Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment.

PubMed

Ceccarelli, Fulvia; Perricone, Carlo; Cipriano, Enrica; Massaro, Laura; Natalucci, Francesco; Capalbo, Giuseppe; Leccese, Ilaria; Bogdanos, Dimitrios; Spinelli, Francesca Romana; Alessandri, Cristiano; Valesini, Guido; Conti, Fabrizio

2017-08-01

In the present review, the different phenotypes, clinimetric and imaging tools able to assess joint involvement in patients affected by Systemic Lupus Erythematosus (SLE) have been described and summarized. Furthermore, the current knowledge about the pathogenic mechanism and the potential biomarkers of this feature is reported. A literature search was done in PubMed, accessed via the National Library of Medicine PubMed interface (http://www.ncbi.nlm.nih.gov/pubmed). Firstly, PubMed was searched using the term "systemic lupus erythematosus" OR "lupus" in combination with (AND) "joint" OR "articular".Secondly, the same PubMed research was combined with other terms, such as "pathogenesis" OR "genetic" OR "antibodies" OR "biomarkers" OR "cytokines" OR "imaging" OR "ultrasonography" OR "magnetic resonance" OR "clinimetry". After a stringent selection, we evaluated in the present review 13 papers concerning clinical phenotypes of SLE joint involvement, 14 concerning clinimetric assessment, 20 concerning imaging, and finally, 28 concerning pathogenesis and biomarkers. Further relevant data were obtained from the reference lists of articles returned using these search terms and from authors own experience and knowledge of the literature. Despite the prevalence and severity of SLE joint involvement, more awareness and a deeper evaluation of the clinical heterogeneity of this manifestation are mandatory. Moreover, longitudinal studies are needed to assess the progression of this manifestation and to provide standard definitions and examination/recording protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

Immunological Mechanisms Implicated in the Pathogenesis of Chronic Urticaria and Hashimoto Thyroiditis.

PubMed

Berghi, Nicolae Ovidiu

2017-08-01

Autoimmunity represents the attack of the immune system of an organism against its own cells and tissues. Autoimmune diseases may affect one organ (Hashimoto thyroiditis) or can be systemic (chronic urticaria). Many factors are implicated in the pathogenesis of autoimmunity (white cells, cytokines, chemokines). Hashimoto thyroiditis has been associated with chronic urticaria in the last 3 decades in a number of clinical studies. Anti-thyroid antibodies have been documented in a proportion ranging from 10% to 30% in chronic urticaria patients in different countries from 3 continents. Two of the factors involved in the mechanism of autoimmunity are present both in the pathophysiology of Hashimoto thyroiditis and chronic urticaria. According to recent studies, IL6 is implicated in the pathogenesis of both diseases. TregsCD4+CD25+Foxp3+ cells have also been implicated in the pathological mechanisms of these 2 entities. This review offers an explanation of the clinical and statistical association between these two diseases from the pathophysiological point of view.

Current perspectives on the epidemiology and pathogenesis of clinically significant Vibrio spp.

PubMed Central

Janda, J M; Powers, C; Bryant, R G; Abbott, S L

1988-01-01

Recent taxonomic advances have now implicated several different Vibrio species as human pathogens. While the most common clinical presentation of Vibrio infection continues to be gastroenteritis, an increasing number of extraintestinal infections are being reported, particularly in immunocompromised individuals. Detection of Vibrio infections requires a good clinical history and the use of appropriate isolation and identification procedures by the laboratory to confirm illnesses attributed to Vibrio species. Except for Vibrio cholerae O1 and Vibrio parahaemolyticus, there is little direct evidence linking the production of a myriad of cell-associated or extracellular factors produced by each species with human disease and pathogenesis. Many questions regarding pathogenic Vibrio species remain unanswered, including their frequency and distribution in environmental specimens (water, shellfish), infective doses, virulence potential of individual isolates, and markers associated with such strains. Images PMID:3058295

[Dandy-Walker complex: a clinicopathologic study of 9 cases].

PubMed

Zhang, Xiao-bo; Gu, Yi-qun; Sun, Xiao-fei; Wang, Ying-nan; Wang, Ai-chun

2013-12-01

To investigate the etiology, pathogenesis, clinicopathologic characteristics, clinical prognosis and treatment of Dandy-Walker syndrome. Nine cases of Dandy-Walker syndrome were included in the study. The autopsy findings and clinical history were evaluated along with review of the literature. The causes, pathogenetic mechanism, pathologic features and prognosis of Dandy-Walker syndrome were analyzed. Among 9 Dandy-Walker syndrome cases, six patients presented with variants of Dandy-Walker complex and 3 cases had classic Dandy-Walker malformation. In addition, 4 patients presented with combined lateral ventricle expansion and multiple malformations were seen in 7 cases. Combined umbilical cord abnormality was noted in 4 patients with variant of Dandy-Walker complex and combined placental abnormality was seen in one classic Dandy-Walker syndrome. Dandy-Walker syndrome is a rare disease. In addition to complex pathogenesis with possible genetic and environmental antigenic etiologies, placental and umbilical cord abnormality may be also related to its development.

Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate.

PubMed

MacDougall, Lori D

2003-03-01

A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed.

Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate

PubMed Central

MacDougall, Lori D.

2003-01-01

A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed. PMID:12677692

[Establishing Individualized Medicine for Intractable Cancer Based on Clinical Molecular Pathogenesis].

PubMed

Jono, Hirofumi

2018-01-01

　Although cancer treatment has dramatically improved with the development of molecular-targeted agents over the past decade, identifying eligible patients and predicting the therapeutic effects remain a major challenge. Because intratumoral heterogeneity represents genetic and molecular differences affecting patients' responses to these therapeutic agents, establishing individualized medicine based on precise molecular pathological analysis of tumors is urgently required. This review focuses on the pathogenesis of oral squamous cell carcinoma (OSCC), a common head and neck neoplasm, and introduces our approaches toward developing novel anticancer therapies particularly based on clinical molecular pathogenesis. Deeper understanding of more precise molecular pathogenesis in clinical settings may open up novel strategies for establishing individualized medicine for OSCC.

Cutaneous Pseudolymphomas.

PubMed

Romero-Pérez, D; Blanes Martínez, M; Encabo-Durán, B

2016-10-01

The term cutaneous pseudolymphoma refers to benign reactive lymphoid proliferations in the skin that simulate cutaneous lymphomas. It is a purely descriptive term that encompasses various reactive conditions with a varied etiology, pathogenesis, clinical presentation, histology, and behavior. We present a review of the different types of cutaneous pseudolymphoma. To reach a correct diagnosis, it is necessary to contrast clinical, histologic, immunophenotypic, and molecular findings. Even with these data, in some cases only the clinical course will confirm the diagnosis, making follow-up essential. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Protein contact dermatitis: allergens, pathogenesis, and management.

PubMed

Levin, Cheryl; Warshaw, Erin

2008-01-01

Protein contact dermatitis is an allergic skin reaction induced principally by proteins of either animal or plant origin. The clinical presentation is that of a chronic dermatitis, and it is often difficult to differentiate between allergic contact dermatitis and other eczematous dermatoses. One distinguishing clinical feature is that acute flares of pruritus, urticaria, edema, or vesiculation are noted minutes after contact with the causative substances. Additionally, the patch-test result is typically negative, and the scratch- or prick-test result is positive. The pathogenesis of protein contact dermatitis is unclear but may involve a type I (immunoglobulin E [IgE], immediate) hypersensitivity reaction, type IV (cell-mediated delayed) hypersensitivity reaction, and/or a delayed reaction due to IgE-bearing Langerhans' cells. Management involves avoidance of the allergen.

Amphetamine-associated ischemic stroke: clinical presentation and proposed pathogenesis.

PubMed

De Silva, Deidre Anne; Wong, Meng Cheong; Lee, Moi Pin; Chen, Christopher Li-Hsian; Chang, Hui Meng

2007-01-01

We report a young lady with acute left middle cerebral artery infarction after acute intake of amphetamine. This is the first case report of amphetamine-induced ischemic stroke with serial angiography and transcranial color-coded Doppler studies. The temporal sequence of stenosis of at least 3 weeks with subsequent complete resolution by 3 months and a "beaded" appearance on angiography support vasculitis or vasospasm as the pathogenesis of ischemic stroke in this patient. The presence of microembolic signals supports acute thrombosis at the site of vasculitis/vasospasm with distal embolism.

Oral Lichen Planus: An Update on Etiology, Pathogenesis, Clinical Presentation, Diagnosis and Management

PubMed Central

Gupta, Sonia; Jawanda, Manveen Kaur

2015-01-01

The mouth is a mirror of health or disease, a sentinel or early warning system. The oral cavity might well be thought as a window to the body because oral manifestations accompany many systemic diseases. In many instances, oral involvement precedes the appearance of other symptoms or lesions at other locations. Oral lichen planus (OLP) is a chronic mucocutaneous disorder of stratified squamous epithelium of uncertain etiology that affects oral and genital mucous membranes, skin, nails, and scalp. LP is estimated to affect 0.5% to 2.0% of the general population. This disease has most often been reported in middle-aged patients with 30-60 years of age and is more common in females than in males. The disease seems to be mediated by an antigen-specific mechanism, activating cytotoxic T cells, and non-specific mechanisms like mast cell degranulation and matrix metalloproteinase activation. A proper understanding of the pathogenesis, clinical presentation, diagnosis of the disease becomes important for providing the right treatment. This article discusses the prevalence, etiology, clinical features, oral manifestations, diagnosis, complications and treatment of oral LP. PMID:26120146

[Hellp syndrome. Presentation of a case and review of the literature].

PubMed

Vargas Hernández, V M; Romo Vázquez, L M; Oros Ramírez, J A

1991-07-01

A severe case of preeclampsia with Hellp Syndrome is reported. Clinical findings, laboratory abnormalities and pathogenesis, were discussed. We concluded that severe preeclampsia and Hellp Syndrome are not different diseases, but the natural course of preeclampsia per se.

Systemic lupus erythematosus: Clinical and experimental aspects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smolen, J.S.

1987-01-01

This text covers questions related to the history, etiology, pathogenesis, clinical aspects and therapy of systematic lupus erythematosus (SLE). Both animal models and human SLE are considered. With regard to basic science, concise information on cellular immunology, autoantibodies, viral aspects and molecular biology in SLE is provided. Clinical topics then deal with medical, dermatologic, neurologic, radiologic, pathologic, and therapeutic aspects. The book not only presents the most recent information on clinical and experimental insights, but also looks at future aspects related to the diagnosis and therapy of SLE.

Pharmacotherapy of Systemic Sclerosis

PubMed Central

Postlethwaite, Arnold E.; Harris, L. Jeff; Raza, Syed H.; Kodura, Swapna; Akhigbe, Titilola

2010-01-01

Importance of the field Systemic-sclerosis (SSc) is an uncommon autoimmune disease with variable degrees of fibroproliferation in blood vessels and certain organs of the body. Presently, there is no cure for SSc. The purpose of this article is to review the current literature regarding pathogenesis and treatment of complications of SSc. Areas covered in this review All available articles regarding research related to SSc pathogenesis and treatment listed in the PubMed.gov database were searched, relevant articles were then reviewed and used as sources of information for this review. What the reader will gain This review attempts for the reader to highlight some current thought regarding mechanisms of SSc pathogenesis and how autoimmunity relates to vascular changes and fibrogenesis of the disease plus provide a review of results of completed clinical trials and current on-going clinical trials that address organ specific or global therapies for this disease which can aid physicians who provide medical care for patients with SSc. Take home message SSc is a complex autoimmune disease, the pathogenesis of which although not completely understood is under active study, and new insights into pathogenesis are continuously being discovered. Although there is no effective disease modifying treatment for patients with SSc, quality of life, morbidity and mortality can be improved by using targeted therapy directed at affecting the consequences of damage to lungs, blood vessels, kidneys and the gastrointestinal tract. Innovative approaches to treating SSc are under intense investigation. PMID:20210685

[Melasma : An update on the clinical picture, treatment, and prevention].

PubMed

Becker, S; Schiekofer, C; Vogt, T; Reichrath, J

2017-02-01

Melasma, also known as chloasma or mask of pregnancy, presents clinically as hyperpigmented skin areas, which develop mostly in the face as a consequence of increased synthesis of melanin. The established treatment options, including topically applied agents and the use of various laser systems, mostly result in improvement but not in complete remission of the lesions. Because of its significant impact on quality of life and the limited effectivity of available treatment options, the management of melasma is challenging for the treating physician. Although many risk factors, including pregnancy and UV exposure, have been identified, the pathogenesis is not yet fully understood. Avoiding solar or artificial UV exposure is of high importance both for the prevention of melasma and for the clinical outcome of existing lesions. In order to avoid vitamin D deficiency, oral vitamin D supplementation should be recommended. In this review, we give an update on clinical aspects, epidemiology, pathogenesis and therapy of melasma and give an outlook on future developments.

Update on Legionnaires’ disease: pathogenesis, epidemiology, detection and control

PubMed Central

Hilbi, Hubert; Jarraud, Sophie; Hartland, Elizabeth; Buchrieser, Carmen

2010-01-01

Summary Legionellosis or Legionnaires’ disease is an emerging and often-fatal form of pneumonia that is most severe in elderly and immunocompromised people, an ever-increasing risk group for infection. In recent years, the genomics of Legionella spp. has significantly increased our knowledge of the pathogenesis of this disease by providing new insights into the evolution and genetic and physiological basis of Legionella–host interactions. The 7th international conference on Legionella, Legionella 2009, illustrated many recent conceptual advances in epidemiology, pathogenesis and ecology. Experts in different fields presented new findings on basic mechanisms of pathogen–host interactions and bacterial evolution, as well as the clinical management and environmental prevalence and persistence of Legionella. The presentations revealed remarkable facts about the genetic and metabolic basis of the intracellular lifestyle of Legionella and reported on its striking ability to manipulate host cell processes by molecular mimicry. Together, these investigations will lead to new approaches for the treatment and prevention of Legionnaires’ disease. PMID:20149105

Adenomyosis and Abnormal Uterine Bleeding (AUB-A)-Pathogenesis, diagnosis, and management.

PubMed

Abbott, Jason A

2017-04-01

The complex pathogenesis and variable presentation of adenomyosis make it one of the most difficult of the FIGO PALM-COIEN abnormal uterine bleeding group to diagnose and treat. Basic clinical parameters such as prevalence are difficult to accurately assess because histological confirmation is usually employed; however, because of the access to and accuracy and utilization of transvaginal ultrasound and other advanced imaging techniques such as MRI, noninvasive diagnosis is recognized to be highly accurate. The clinical symptoms of pain, abnormal uterine bleeding, and subfertility are the primary presentations of adenomyosis with increasing data supporting a substantial role of this disease in reducing fecundity and interfering with assisted reproductive interventions. Treatments have been aimed at managing symptoms and improving fertility options. Management by hysterectomy is not always desired by women, and with many women having children in their fourth and even fifth decades, it is often not reasonable to consider this radical option. Copyright © 2016. Published by Elsevier Ltd.

Endometriosis: Survey of Current Diagnostic and Therapeutic Options and Latest Research Work

PubMed Central

Juhasz-Böss, I.; Laschke, M. W.; Müller, F.; Rosenbaum, P.; Baum, S.; Solomayer, E. F.; Ulrich, U.

2014-01-01

Endometriosis is one of the most frequent benign diseases in women of child-bearing age. The main symptoms are chronic upper abdominal pain and infertility. However, the aetiology and pathogenesis of endometriosis are as yet insufficiently clarified. Thus, therapy is mainly symptomatic with laparoscopic surgery being the gold standard. The aim of drug therapy is to achieve a hypo-oestrogenic condition. In cases of severe endometriosis and a desire to have children there is often an indication for assisted reproduction. The present article illustrates almost all current aspects on the diagnosis of and therapy of endometriosis. From the clinical viewpoint, emphasis is placed on the rare cases of deeply infiltrating endometriosis that are, however, accompanied with a high morbidity. Current therapeutic options in cases of infertility are also presented in more detail. Furthermore, special attention is paid to the latest research results from both clinical and basic research fields in order to demonstrate our current knowledge on the pathogenesis and, where possible, potentially related therapeutic options. PMID:25221341

Role of phosphoinositide 3-kinase in the pathogenesis of acute pancreatitis.

PubMed

Lupia, Enrico; Pigozzi, Luca; Goffi, Alberto; Hirsch, Emilio; Montrucchio, Giuseppe

2014-11-07

A large body of experimental and clinical data supports the notion that inflammation in acute pancreatitis has a crucial role in the pathogenesis of local and systemic damage and is a major determinant of clinical severity. Thus, research has recently focused on molecules that can regulate the inflammatory processes, such as phosphoinositide 3-kinases (PI3Ks), a family of lipid and protein kinases involved in intracellular signal transduction. Studies using genetic ablation or pharmacologic inhibitors of different PI3K isoforms, in particular the class I PI3Kδ and PI3Kγ, have contributed to a greater understanding of the roles of these kinases in the modulation of inflammatory and immune responses. Recent data suggest that PI3Ks are also involved in the pathogenesis of acute pancreatitis. Activation of the PI3K signaling pathway, and in particular of the class IB PI3Kγ isoform, has a significant role in those events which are necessary for the initiation of acute pancreatic injury, namely calcium signaling alteration, trypsinogen activation, and nuclear factor-κB transcription. Moreover, PI3Kγ is instrumental in modulating acinar cell apoptosis, and regulating local neutrophil infiltration and systemic inflammatory responses during the course of experimental acute pancreatitis. The availability of PI3K inhibitors selective for specific isoforms may provide new valuable therapeutic strategies to improve the clinical course of this disease. This article presents a brief summary of PI3K structure and function, and highlights recent advances that implicate PI3Ks in the pathogenesis of acute pancreatitis.

Role of phosphoinositide 3-kinase in the pathogenesis of acute pancreatitis

PubMed Central

Lupia, Enrico; Pigozzi, Luca; Goffi, Alberto; Hirsch, Emilio; Montrucchio, Giuseppe

2014-01-01

A large body of experimental and clinical data supports the notion that inflammation in acute pancreatitis has a crucial role in the pathogenesis of local and systemic damage and is a major determinant of clinical severity. Thus, research has recently focused on molecules that can regulate the inflammatory processes, such as phosphoinositide 3-kinases (PI3Ks), a family of lipid and protein kinases involved in intracellular signal transduction. Studies using genetic ablation or pharmacologic inhibitors of different PI3K isoforms, in particular the class I PI3Kδ and PI3Kγ, have contributed to a greater understanding of the roles of these kinases in the modulation of inflammatory and immune responses. Recent data suggest that PI3Ks are also involved in the pathogenesis of acute pancreatitis. Activation of the PI3K signaling pathway, and in particular of the class IB PI3Kγ isoform, has a significant role in those events which are necessary for the initiation of acute pancreatic injury, namely calcium signaling alteration, trypsinogen activation, and nuclear factor-κB transcription. Moreover, PI3Kγ is instrumental in modulating acinar cell apoptosis, and regulating local neutrophil infiltration and systemic inflammatory responses during the course of experimental acute pancreatitis. The availability of PI3K inhibitors selective for specific isoforms may provide new valuable therapeutic strategies to improve the clinical course of this disease. This article presents a brief summary of PI3K structure and function, and highlights recent advances that implicate PI3Ks in the pathogenesis of acute pancreatitis. PMID:25386068

New and emerging pathogens in canine infectious respiratory disease.

PubMed

Priestnall, S L; Mitchell, J A; Walker, C A; Erles, K; Brownlie, J

2014-03-01

Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings.

Thyroid emergencies.

PubMed

Klubo-Gwiezdzinska, Joanna; Wartofsky, Leonard

2012-03-01

This review presents current knowledge about the thyroid emergencies known as myxedema coma and thyrotoxic storm. Understanding the pathogenesis of these conditions, appropriate recognition of the clinical signs and symptoms, and their prompt and accurate diagnosis and treatment are crucial in optimizing survival. Copyright © 2012 Elsevier Inc. All rights reserved.

Diagnosis, pathogenesis and treatment of myositis: recent advances

PubMed Central

Carstens, P-O; Schmidt, J

2014-01-01

Dermatomyositis (DM), polymyositis (PM), necrotizing myopathy (NM) and inclusion body myositis (IBM) are four distinct subtypes of idiopathic inflammatory myopathies – in short myositis. Recent studies have shed some light on the unique pathogenesis of each entity. Some of the clinical features are distinct, but muscle biopsy is indispensable for making a reliable diagnosis. The use of magnetic resonance imaging of skeletal muscles and detection of myositis-specific autoantibodies have become useful additions to our diagnostic repertoire. Only few controlled trials are available to substantiate current treatment approaches for myositis and hopes are high that novel modalities will become available within the next few years. In this review we provide an up-to-date overview of the pathogenesis and diagnostic approach of myositis. We aim to present a guide towards therapeutic and general management. PMID:23981102

Diagnosis, pathogenesis and treatment of myositis: recent advances.

PubMed

Carstens, P-O; Schmidt, J

2014-03-01

Dermatomyositis (DM), polymyositis (PM), necrotizing myopathy (NM) and inclusion body myositis (IBM) are four distinct subtypes of idiopathic inflammatory myopathies - in short myositis. Recent studies have shed some light on the unique pathogenesis of each entity. Some of the clinical features are distinct, but muscle biopsy is indispensable for making a reliable diagnosis. The use of magnetic resonance imaging of skeletal muscles and detection of myositis-specific autoantibodies have become useful additions to our diagnostic repertoire. Only few controlled trials are available to substantiate current treatment approaches for myositis and hopes are high that novel modalities will become available within the next few years. In this review we provide an up-to-date overview of the pathogenesis and diagnostic approach of myositis. We aim to present a guide towards therapeutic and general management. © 2013 British Society for Immunology.

Etiology and Pathogenesis of Idiopathic Achalasia.

PubMed

Pressman, Amanda; Behar, Jose

2017-03-01

This review examines the etiology and pathogenesis of idiopathic achalasia. This disease is clinically characterized by dysphagia of solids and liquids due to the presence of simultaneous or absent esophageal contractions and impaired or absent relaxation of the lower esophageal sphincter. It includes a review of (a) etiology and pathogenesis of this inflammatory process that damage the ganglion cells of the Auerbach plexus that is limited to the esophagus; (b) genetic abnormalities and polymorphisms associated with this disease that may help explain its heterogeneity expressed by the different motility abnormalities of its phenotypes as well as differences in its clinical progression. These different genetic abnormalities may be responsible for the slow progression of types I or II phenotypes; (c) indirect evidence of viruses present in these patients that may initiate its development; (d) the abnormalities of the muscle layer that may be responsible for the dilation of the body of the esophagus that ultimately causes the sigmoid-like esophagus in the very last phase of this disease. This progression to the end-stage phase tends to occur in about 5% of patients. And, (e) the chronic inflammatory abnormalities in the squamous mucosa that may be the cause of the dysplastic and neoplastic changes that may lead to squamous cell carcinoma whose incidence in this disease is increased. These mucosal abnormalities are usually present in patients with markedly dilated body of the esophagus and severe food stasis.

East Coast Fever Caused by Theileria parva Is Characterized by Macrophage Activation Associated with Vasculitis and Respiratory Failure

PubMed Central

Schneider, David A.; Frevert, Charles W.; Nelson, Danielle D.; Morrison, W. Ivan; Knowles, Donald P.

2016-01-01

Respiratory failure and death in East Coast Fever (ECF), a clinical syndrome of African cattle caused by the apicomplexan parasite Theileria parva, has historically been attributed to pulmonary infiltration by infected lymphocytes. However, immunohistochemical staining of tissue from T. parva infected cattle revealed large numbers of CD3- and CD20-negative intralesional mononuclear cells. Due to this finding, we hypothesized that macrophages play an important role in Theileria parva disease pathogenesis. Data presented here demonstrates that terminal ECF in both Holstein and Boran cattle is largely due to multisystemic histiocytic responses and resultant tissue damage. Furthermore, the combination of these histologic changes with the clinical findings, including lymphadenopathy, prolonged pyrexia, multi-lineage leukopenia, and thrombocytopenia is consistent with macrophage activation syndrome. All animals that succumbed to infection exhibited lymphohistiocytic vasculitis of small to medium caliber blood and lymphatic vessels. In pulmonary, lymphoid, splenic and hepatic tissues from Holstein cattle, the majority of intralesional macrophages were positive for CD163, and often expressed large amounts of IL-17. These data define a terminal ECF pathogenesis in which parasite-driven lymphoproliferation leads to secondary systemic macrophage activation syndrome, mononuclear vasculitis, pulmonary edema, respiratory failure and death. The accompanying macrophage phenotype defined by CD163 and IL-17 is presented in the context of this pathogenesis. PMID:27195791

East Coast Fever Caused by Theileria parva Is Characterized by Macrophage Activation Associated with Vasculitis and Respiratory Failure.

PubMed

Fry, Lindsay M; Schneider, David A; Frevert, Charles W; Nelson, Danielle D; Morrison, W Ivan; Knowles, Donald P

2016-01-01

Respiratory failure and death in East Coast Fever (ECF), a clinical syndrome of African cattle caused by the apicomplexan parasite Theileria parva, has historically been attributed to pulmonary infiltration by infected lymphocytes. However, immunohistochemical staining of tissue from T. parva infected cattle revealed large numbers of CD3- and CD20-negative intralesional mononuclear cells. Due to this finding, we hypothesized that macrophages play an important role in Theileria parva disease pathogenesis. Data presented here demonstrates that terminal ECF in both Holstein and Boran cattle is largely due to multisystemic histiocytic responses and resultant tissue damage. Furthermore, the combination of these histologic changes with the clinical findings, including lymphadenopathy, prolonged pyrexia, multi-lineage leukopenia, and thrombocytopenia is consistent with macrophage activation syndrome. All animals that succumbed to infection exhibited lymphohistiocytic vasculitis of small to medium caliber blood and lymphatic vessels. In pulmonary, lymphoid, splenic and hepatic tissues from Holstein cattle, the majority of intralesional macrophages were positive for CD163, and often expressed large amounts of IL-17. These data define a terminal ECF pathogenesis in which parasite-driven lymphoproliferation leads to secondary systemic macrophage activation syndrome, mononuclear vasculitis, pulmonary edema, respiratory failure and death. The accompanying macrophage phenotype defined by CD163 and IL-17 is presented in the context of this pathogenesis.

Chorea revealing systemic lupus erythematosus in a 13-year old boy: A case report and short review of the literature.

PubMed

Athanasopoulos, E; Kalaitzidou, I; Vlachaki, G; Stefanaki, S; Tzagkaraki, A; Niotakis, G; Tritou, I; Ladomenou, F

2018-03-29

Among the neurological manifestations of systemic lupus erythematosus (SLE), chorea is rare, presenting in less than 7% of the pediatric SLE patients. It can appear early in the onset of SLE, be the first or even the sole clinical feature of the illness and has strongly been associated with the presence of antiphospholipid antibodies. We report on the case of a 13-year old boy, admitted with acute onset chorea and finally diagnosed with SLE. Subsequently, we present a short review of the literature on the epidemiology, suggested pathogenesis, clinical presentation and treatment of this rare presentation of SLE.

Smoking and nonsmoking asthma: differences in clinical outcome and pathogenesis.

PubMed

Fattahi, Fatemeh; Hylkema, Machteld N; Melgert, Barbro N; Timens, Wim; Postma, Dirkje S; ten Hacken, Nick H T

2011-02-01

Cigarette smoking in asthma is frequently present and is associated with worsening of symptoms, accelerated lung-function decline, a higher frequency of hospital admissions, a higher degree of asthma severity, poorer asthma control and reduced responsiveness to corticosteroids. Furthermore, it is associated with reduced numbers of eosinophils and higher numbers of mast cells in the submucosa of the airway wall. Airway remodeling is increased as evidenced by increased epithelial thickness and goblet cell hyperplasia in smoking asthmatics. The pathogenesis responsible for smoking-induced changes in airway inflammation and remodeling in asthma is complex and largely unknown. The underlying mechanism of reduced corticosteroid responsiveness is also unknown. This article discusses differences between smoking and nonsmoking asthmatics regarding the clinical expression of asthma, lung function, response to corticosteroids, airway inflammation and remodeling processes. Possible pathogenetic mechanisms that may explain the links between cigarette smoking and changes in the clinical expression of asthma will be discussed, as well as the beneficial effects of smoking cessation.

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

PubMed Central

Becker, Karsten; Löffler, Bettina

2016-01-01

SUMMARY Small colony variants (SCVs) were first described more than 100 years ago for Staphylococcus aureus and various coagulase-negative staphylococci. Two decades ago, an association between chronic staphylococcal infections and the presence of SCVs was observed. Since then, many clinical studies and observations have been published which tie recurrent, persistent staphylococcal infections, including device-associated infections, bone and tissue infections, and airway infections of cystic fibrosis patients, to this special phenotype. By their intracellular lifestyle, SCVs exhibit so-called phenotypic (or functional) resistance beyond the classical resistance mechanisms, and they can often be retrieved from therapy-refractory courses of infection. In this review, the various clinical infections where SCVs can be expected and isolated, diagnostic procedures for optimized species confirmation, and the pathogenesis of SCVs, including defined underlying molecular mechanisms and the phenotype switch phenomenon, are presented. Moreover, relevant animal models and suggested treatment regimens, as well as the requirements for future research areas, are highlighted. PMID:26960941

Dialysis-associated steal syndrome (DASS).

PubMed

Mohamed, Ahmed S; Peden, Eric K

2017-03-06

In this article, we will review the clinical symptoms of dialysis access steal syndrome (DASS), evaluation, treatment options, and our approach and treatment algorithm. We reviewed the literature discussing different aspects of DASS including its epidemiology, pathogenesis, clinical presentation, evaluation and management options. DASS is the most dreaded complication of access surgery. Although the incidence is low, all providers caring for dialysis patients should be aware of this problem. Symptoms can range from mild to limb threatening. Although various tests are available, the diagnosis of DASS remains a clinical one and requires thoughtful management to have the best outcomes. Multiple treatment options exist for steal. We present diagnostic evaluation and management algorithm.

[Pathogenesis of hypophosphatemia].

PubMed

Takeuchi, Yasuhiro

2016-02-01

Chronic hypophosphatemia is seriously involved in several disorders of musculoskeletal system. Symptoms of patients are usually non-specific, such as pain with or without muscle weakness on lower extremities and are often hard to be correctly diagnosed. It is clinically important for physicians to understand pathogenesis and clinical features of hypophosphatemia and its related diseases.

Clinical implications of miRNAs in the pathogenesis, diagnosis and therapy of pancreatic cancer

PubMed Central

Rachagani, Satyanarayana; Macha, Muzafar A.; Heimann, Nicholas; Seshacharyulu, Parthasarathy; Haridas, Dhanya; Chugh, Seema; Batra, Surinder K.

2014-01-01

Despite considerable progress being made in understanding pancreatic cancer (PC) pathogenesis, it still remains the 10th most often diagnosed malignancy in the world and 4th leading cause of cancer related deaths in the United States with a five year survival rate of only 6%. The aggressive nature, lack of early diagnostic and prognostic markers, late clinical presentation, and limited efficacy of existing treatment regimens makes PC a lethal cancer with high mortality and poor prognosis. Therefore, novel reliable biomarkers and molecular targets are urgently needed to combat this deadly disease. MicroRNAs (miRNAs) are short (19–24 nucleotides) non-coding RNA molecules implicated in the regulation of gene expression at post-transcriptional level and play significant roles in various physiological and pathological conditions. Aberrant expression of miRNAs has been reported in several cancers including PC and is implicated in PC pathogenesis and progression, suggesting their utility in diagnosis, prognosis and therapy. In this review, we summarize the role of several miRNAs that regulate various oncogenes (KRAS) and tumor suppressor genes (p53, p16, SMAD4 etc) involved in PC development, their prospective roles as diagnostic and prognostic markers and their therapeutic targets. PMID:25453266

[The role of stress-induced chronic subclinical inflammation in the pathogenesis of the chronic pelvic pain syndrome IIIB in men].

PubMed

Shormanov, I S; Mozhaev, I I; Sokolova, Kh A; Solovev, A S

2017-12-01

This literature review of recent clinical and experimental studies describes the role of oxidative stress in the multifactorial and interdisciplinary pathogenesis of non-inflammatory chronic pelvic pain syndrome IIIB (CPPS-IIIB) in men. The authors outline general biological nature of oxidative stress and its mechanisms. More detailed information is presented on cytokine-mediated chronic subclinical inflammation, one of the key mechanisms of oxidative stress, which is currently being actively studied. It is shown that the imbalance between pro- and anti-inflammatory cytokines observed in patients with CPPS-IIIB can explain some features of the clinical course (in particular, the characteristics of the pain syndrome) and the progression of this disease. In this regard, cytokine profiling of prostatic secretion can provide valuable diagnostic, prognostic and monitoring information in the management of this category of patients. Recently published evidence has demonstrated the essential role of the cytokine-mediated chronic inflammatory response as a mechanism of oxidative stress in the pathogenesis of CPPS-IIIB. Further studies in this area are warranted and in the long term may become a basis for the development of new effective pathogenetic pharmacotherapy of CPPS-IIIB.

Central nervous system manifestations of Angiostrongylus cantonensis infection.

PubMed

Martins, Yuri C; Tanowitz, Herbert B; Kazacos, Kevin R

2015-01-01

Over 20 species of Angiostrongylus have been described from around the world, but only Angiostrongylus cantonensis has been confirmed to cause central nervous system disease in humans. A neurotropic parasite that matures in the pulmonary arteries of rats, A. cantonensis is the most common cause of eosinophilic meningitis in southern Asia and the Pacific and Caribbean islands. The parasite can also cause encephalitis/encephalomyelitis and rarely ocular angiostrongyliasis. The present paper reviews the life cycle, epidemiology, pathogenesis, clinical features, diagnosis, treatment, prevention and prognosis of A. cantonesis infection. Emphasis is given on the spectrum of central nervous system manifestations and disease pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

Inflammatory bowel disease pathogenesis: where are we?

PubMed

Fiocchi, Claudio

2015-03-01

Inflammatory bowel disease (IBD) is presently one of the most investigated human disorders. Expansion of knowledge of its pathophysiology has helped in developing novel medications to combat gut inflammation with a considerably degree of success. Despite this progress, much more remains to be done in regard to gaining a more profound understanding of IBD pathogenesis, detecting inflammation before it clinically manifests, implementing lifestyle modifications, and developing agents that can modify the natural course of the disease. One of the limitations to achieve these goals is the lack of integration of the major components of IBD pathogenesis, that is the exposome, the genome, the gut microbiome, and the immunome. An "IBD integrome" approach that takes advantage of all functional information derived from the detailed investigation of each single pathogenic component through the use of systems biology may offer the solution to understand IBD and cure it. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Oral submucous fibrosis: An update on current theories of pathogenesis.

PubMed

Arakeri, Gururaj; Rai, Kirthi Kumar; Hunasgi, Santosh; Merkx, M A W; Gao, Shan; Brennan, Peter A

2017-07-01

Over the last 40 years, many theories linking oral submucous fibrosis (OSMF) to various risk factors have been proposed. Spicy, pungent foods and irritants such as supari (areca nut), paan (betel leaves), tobacco (through chewing or smoking)-the common Asian habits of chewing the aforementioned agents-have all been incriminated as causative agents. Systemic factors such as nutritional deficiency, genetic predisposition and autoimmunity have also been proposed in the pathogenesis of OSMF. However, the precise aetiology of OSMF is still unknown, and no conclusive evidence has been found despite many extensive investigations on implicated factors. Most of the ideas proposed have been derived from the existing clinical and epidemiological data. We present a comprehensive review of the various theories regarding the pathogenesis of the condition, but have not concentrated on malignant transformation in this article. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Progression of understanding for the role of Epstein-Barr virus and management of nasopharyngeal carcinoma.

PubMed

Nakanishi, Yosuke; Wakisaka, Naohiro; Kondo, Satoru; Endo, Kazuhira; Sugimoto, Hisashi; Hatano, Miyako; Ueno, Takayoshi; Ishikawa, Kazuya; Yoshizaki, Tomokazu

2017-09-01

Nasopharyngeal carcinoma (NPC) is very common in southern China and Southeast Asia. In regions where NPC is endemic, undifferentiated subtypes constitute most cases and are invariably associated with Epstein-Barr virus (EBV) infection, whereas the differentiated subtype is more common in other parts of the world. Undifferentiated NPC is a unique malignancy with regard to its epidemiology, etiology, and clinical presentation. Clinically, NPC is highly invasive and metastatic, but sensitive to both chemotherapy and radiotherapy (RT). Overall prognosis has dramatically improved over the past three decades because of advances in management, including the improvement of RT technology, the broader application of chemotherapy, and more accurate disease staging. Despite the excellent local control with modern RT, distant failure remains a challenging problem. Advances in molecular technology have helped to elucidate the molecular pathogenesis of NPC. This article reviews the contribution of EBV gene products to NPC pathogenesis and the current management of NPC.

The Immune System in the Pathogenesis of Ovarian Cancer

PubMed Central

Charbonneau, Bridget; Goode, Ellen L.; Kalli, Kimberly R.; Knutson, Keith L.; DeRycke, Melissa S.

2014-01-01

Clinical outcomes in ovarian cancer are heterogeneous even when considering common features such as stage, response to therapy, and grade. This disparity in outcomes warrants further exploration into tumor and host characteristics. One compelling host characteristic is the immune response to ovarian cancer. While several studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease, recent genetic and protein analyses also suggest a role in disease incidence. Recent studies also show that anti-tumor immunity is often negated by immune suppressive cells present in the tumor microenvironment. These suppressive immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, future research into immunotherapy targeting ovarian cancer will likely become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression or by disrupting critical cytokine networks. PMID:23582060

An overview of burning mouth syndrome for the dermatologist.

PubMed

Lewis, A K; Prime, S S; Cohen, S N

2016-03-01

Burning mouth syndrome is characterized by an idiopathic burning pain affecting the oral mucosa, with no clinically apparent changes. It can present to a variety of health professionals including dermatologists. This article summarizes the important aspects of the condition, including theories of pathogenesis, diagnosis and management. © 2016 British Association of Dermatologists.

Bacterial reproductive pathogens of cats and dogs.

PubMed

Graham, Elizabeth M; Taylor, David J

2012-05-01

With the notable exception of Brucella canis, exogenous bacterial pathogens are uncommon causes of reproductive disease in cats and dogs. Most bacterial reproductive infections are endogenous, and predisposing factors for infection are important. This article reviews the etiology, pathogenesis, clinical presentation, diagnosis, treatment, and public health significance of bacterial reproductive pathogens in cats and dogs.

Potential association of reduced cholinesterase activity with Trypanosoma evansi pathogenesis in buffaloes.

PubMed

Singh, Shanker K; Singh, Vivek K; Yadav, Brajesh K; Nakade, Udayraj P; Kumari, Priyambada; Srivastava, Mukesh K; Sharma, Abhishek; Choudhary, Soumen; Swain, Dilip; Garg, Satish K

2016-07-30

The present study aimed to investigate the association of cholinesterase activity with trypanosomosis in buffaloes. Thirty-three clinical cases of trypanosomosis in water buffaloes, found positive for trypomastigotes of T. evansi on blood smear examination, were divided into two groups based on clinical manifestations. Twenty diseased buffaloes revealing only common clinical signs were allocated to Group I, while the remaining 13 buffaloes showing common clinical manifestations along with neurological disturbances were allocated to Group II. Twelve clinically healthy buffaloes, free from any haemoprotozoa infection, were kept as healthy control (Group III). Blood samples were collected from buffaloes of all three groups to determine serum cholinesterase activity. Compared to buffaloes of healthy control group, cholinesterase activity in T. evansi-infected buffaloes of Group I and II was significantly (P<0.001) lower. However, no significant difference was observed in cholinesterase activity between the T. evansi-infected buffaloes exhibiting neurological disorders and no neurological disorders. Summing up, reduced cholinesterase activity seems to be associated with the pathogenesis of natural T. evansi infection and its clinical manifestations in buffaloes possibly by evading immune response. Further studies are warranted on association of cholinesterase activity in T. evansi-infected buffaloes with neurological disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Sarcoidosis with prominent necrosis on histopathology.

PubMed

Rosenstein, Rachel; Orme, Charisse; Kim, Randie H; Meehan, Shane A; Femia, Alisa

2016-12-15

Sarcoidosis is a multiorgan inflammatory diseasewith variable clinical presentations and the commonhistopathologic finding of noncaseating granulomas.The etiology of the disease is not known, butevidence suggests both environmental and geneticcontributions to the pathogenesis. Depending onthe severity of cutaneous disease and extent ofextracutaneous involvement, therapies range fromtopical and intralesional glucocorticoids to systemicimmunomodulatory and immunosuppressiveagents. We present the case of a patient withcutaneous sarcoidosis with prominent necrosis onhistopathologic examination in the setting of severepulmonary sarcoidosis.

Osteochondral injuries of the foot and ankle.

PubMed

Frost, Andrew; Roach, Richard

2009-06-01

Osteochondral injuries commonly affect the ankle joint and involve the dome of the talus. This article describes the etiology and pathogenesis of these injuries. Their clinical presentation is described and advice is given on how to diagnose and investigate suspected osteochondral injuries. The various treatment options currently available are briefly reviewed. There is some attempt made to give consensus on optimal treatment of this condition at the present time.

Black esophagus syndrome associated with diabetic ketoacidosis

PubMed Central

Rigolon, Riccardo; Fossà, Irene; Rodella, Luca; Targher, Giovanni

2016-01-01

Acute esophageal necrosis, also known as “black esophagus syndrome”, is a rare acute esophageal disease that is often associated with vomiting and upper gastrointestinal haemorrhage. At present, little is known regarding the pathogenesis of this disease. We present the case of a 50-year-old white male patient with diabetic ketoacidosis suffering from acute esophageal necrosis with nausea and vomiting but without any clinical signs of upper gastrointestinal bleeding. PMID:26881192

Systemic lupus erythematosus associated with acute Epstein-Barr virus infection.

PubMed

Dror, Y; Blachar, Y; Cohen, P; Livni, N; Rosenmann, E; Ashkenazi, A

1998-11-01

Systemic lupus erythematosus (SLE) is a multisystem disease of unknown origin, characterized by a variety of autoimmune phenomena. Viruses have long been postulated to play a role in its pathogenesis. Several observations suggested a link between Epstein-Barr virus (EBV) and SLE. We describe a 14-year-old girl who presented with acute onset of SLE concurrently with clinical and laboratory findings consistent with EBV-induced infectious mononucleosis (IM). Evidence for acute EBV infection was confirmed by serological studies and detection of specific EBV antigens on kidney biopsy. This close association between EBV and SLE suggests a possible role of the virus in the pathogenesis of SLE in this patient.

Neuroblastoma pathogenesis: deregulation of embryonic neural crest development.

PubMed

Tomolonis, Julie A; Agarwal, Saurabh; Shohet, Jason M

2018-05-01

Neuroblastoma (NB) is an aggressive pediatric cancer that originates from neural crest tissues of the sympathetic nervous system. NB is highly heterogeneous both from a clinical and a molecular perspective. Clinically, this cancer represents a wide range of phenotypes ranging from spontaneous regression of 4S disease to unremitting treatment-refractory progression and death of high-risk metastatic disease. At a cellular level, the heterogeneous behavior of NB likely arises from an arrest and deregulation of normal neural crest development. In the present review, we summarize our current knowledge of neural crest development as it relates to pathways promoting 'stemness' and how deregulation may contribute to the development of tumor-initiating CSCs. There is an emerging consensus that such tumor subpopulations contribute to the evolution of drug resistance, metastasis and relapse in other equally aggressive malignancies. As relapsed, refractory disease remains the primary cause of death for neuroblastoma, the identification and targeting of CSCs or other primary drivers of tumor progression remains a critical, clinically significant goal for neuroblastoma. We will critically review recent and past evidence in the literature supporting the concept of CSCs as drivers of neuroblastoma pathogenesis.

Clinical "pneumococcal pneumonia" due to Moraxella osloensis: case report and a review.

PubMed

Vuori-Holopainen, E; Salo, E; Saxen, H; Vaara, M; Tarkka, E; Peltola, H

2001-01-01

A previously healthy 6-y-old girl presented with a disease very similar to pneumococcal pneumonia. However, Moraxella osloensis was isolated by lung tap. The patient responded well to a course of parenteral penicillin. This is probably the first documented case of community-acquired pneumonia associated with this agent. Clinical isolates of M. osloensis are rare and its pathogenesis has not been delineated; however, a literature review suggests that the organism is more common than is generally recognized.

Fundus autofluorescence applications in retinal imaging

PubMed Central

Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo

2015-01-01

Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications. PMID:26139802

Oral lichenoid lesions: distinguishing the benign from the deadly.

PubMed

Müller, Susan

2017-01-01

Oral lichen planus is a chronic inflammatory disease of unknown etiology or pathogenesis with varied disease severity that waxes and wanes over a long period of time. Although a common oral mucosal disease, accurate diagnosis is often challenging due to the overlapping clinical and histopathological features of oral lichen planus and other mucosal diseases. Other immune-mediated mucocutaneous diseases can exhibit lichenoid features including mucous membrane pemphigoid, chronic graft-versus-host disease, and discoid lupus erythematosus. Reactive changes to dental materials or to systemic medications can mimic oral lichen planus both clinically and histologically. In these situations the clinical presentation can be useful, as oral lichen planus presents as a multifocal process and is usually symmetrical and bilateral. Dysplasia of the oral cavity can exhibit a lichenoid histology, which may mask the potentially premalignant features. Proliferative verrucous leukoplakia, an unusual clinical disease, can often mimic oral lichen planus clinically, requiring careful correlation of the clinical and pathologic features.

Peste des Petits Ruminants Virus Tissue Tropism and Pathogenesis in Sheep and Goats following Experimental Infection

PubMed Central

Truong, Thang; Boshra, Hani; Embury-Hyatt, Carissa; Nfon, Charles; Gerdts, Volker; Tikoo, Suresh; Babiuk, Lorne A.; Kara, Pravesh; Chetty, Thireshni; Mather, Arshad; Wallace, David B.; Babiuk, Shawn

2014-01-01

Peste des petits ruminants (PPR) is a viral disease which primarily affects small ruminants, causing significant economic losses for the livestock industry in developing countries. It is endemic in Saharan and sub-Saharan Africa, the Middle East and the Indian sub-continent. The primary hosts for peste des petits ruminants virus (PPRV) are goats and sheep; however recent models studying the pathology, disease progression and viremia of PPRV have focused primarily on goat models. This study evaluates the tissue tropism and pathogenesis of PPR following experimental infection of sheep and goats using a quantitative time-course study. Upon infection with a virulent strain of PPRV, both sheep and goats developed clinical signs and lesions typical of PPR, although sheep displayed milder clinical disease compared to goats. Tissue tropism of PPRV was evaluated by real-time RT-PCR and immunohistochemistry. Lymph nodes, lymphoid tissue and digestive tract organs were the predominant sites of virus replication. The results presented in this study provide models for the comparative evaluation of PPRV pathogenesis and tissue tropism in both sheep and goats. These models are suitable for the establishment of experimental parameters necessary for the evaluation of vaccines, as well as further studies into PPRV-host interactions. PMID:24498032

Peste des petits ruminants virus tissue tropism and pathogenesis in sheep and goats following experimental infection.

PubMed

Truong, Thang; Boshra, Hani; Embury-Hyatt, Carissa; Nfon, Charles; Gerdts, Volker; Tikoo, Suresh; Babiuk, Lorne A; Kara, Pravesh; Chetty, Thireshni; Mather, Arshad; Wallace, David B; Babiuk, Shawn

2014-01-01

Peste des petits ruminants (PPR) is a viral disease which primarily affects small ruminants, causing significant economic losses for the livestock industry in developing countries. It is endemic in Saharan and sub-Saharan Africa, the Middle East and the Indian sub-continent. The primary hosts for peste des petits ruminants virus (PPRV) are goats and sheep; however recent models studying the pathology, disease progression and viremia of PPRV have focused primarily on goat models. This study evaluates the tissue tropism and pathogenesis of PPR following experimental infection of sheep and goats using a quantitative time-course study. Upon infection with a virulent strain of PPRV, both sheep and goats developed clinical signs and lesions typical of PPR, although sheep displayed milder clinical disease compared to goats. Tissue tropism of PPRV was evaluated by real-time RT-PCR and immunohistochemistry. Lymph nodes, lymphoid tissue and digestive tract organs were the predominant sites of virus replication. The results presented in this study provide models for the comparative evaluation of PPRV pathogenesis and tissue tropism in both sheep and goats. These models are suitable for the establishment of experimental parameters necessary for the evaluation of vaccines, as well as further studies into PPRV-host interactions.

Sclerosing bone dysplasias: genetic, clinical and radiology update of hereditary and non-hereditary disorders

PubMed Central

Boulet, Cedric; Madani, Hardi; Lenchik, Leon; Vanhoenacker, Filip; Amalnath, Deepak S; de Mey, Johan

2016-01-01

There is a wide variety of hereditary and non-hereditary bone dysplasias, many with unique radiographic findings. Hereditary bony dysplasias include osteopoikilosis, osteopathia striata, osteopetrosis, progressive diaphyseal dysplasia, hereditary multiple diaphyseal sclerosis and pyknodysostosis. Non-hereditary dysplasias include melorheostosis, intramedullary osteosclerosis and overlap syndromes. Although many of these dysplasias are uncommon, radiologists should be familiar with their genetic, clinical and imaging findings to allow for differentiation from acquired causes of bony sclerosis. We present an overview of hereditary and non-hereditary bony dysplasias with focus on the pathogenesis, clinical and radiographic findings of each disorder. PMID:26898950

Biological features of hepatitis B virus isolates from patients based on full-length genomic analysis.

PubMed

Wen, Yu-Mei; Wang, Yong-Xiang

2009-01-01

The mechanisms for HBV persistence and the pathogenesis of chronic HB have been shown mainly due to defects in host immune responses. However, HBV isolates with different biological features may also contribute to different clinical outcomes and epidemiological implications in viral hepatitis B (HB). This review presents interesting biological features of HBV isolates based on the structural and functional analysis of full-length HBV isolates from various patients. Among isolates from children after failure of HB vaccination, 129L mutant at the 'a' determinant was found with normal binding efficiency to anti-HBs, but with reduced immunogenicity, which could initiate persistent HBV infections. Isolates from fulminant hepatitis (FH) B patients were not all highly replicative, but differences in capacities of anti-HBs induction could be involved in the pathogenesis of FH. The high replicative competency of isolates from hepatocellular carcinoma (HCC) patients could result in enhanced immune-mediated cytopathic effects against HBV viral proteins, and increased transactivating activity by the X protein. The mechanism of a double-spliced variant in enhancing replication of the wild-type virus is presented. The importance of integrating structural and functional analysis to reveal biological features of HBV isolates in viral pathogenesis is discussed.

Exuberant juvenile hyaline fibromatosis in two patients.

PubMed

Muniz, Mariela Leão; Lobo, Alice Zoghbi Coelho; Machado, Maria Cecília da Matta Rivitti; Valente, Neusa Yuriko Sakai; Kim, Chong Ae; Lourenço, Sílvia Vanessa; Nico, Marcello Menta Simonsen

2006-01-01

Juvenile hyaline fibromatosis and infantile systemic hyalinosis are rare autosomal recessive disorders of infancy and early childhood that are histologically characterized by deposition of hyaline material. The main clinical features are papulo-nodular skin lesions, gingival hypertrophy, joint contractures, and bone abnormalities. However, infantile systemic hyalinosis has a more severe clinical presentation, including visceral involvement and premature death. Very recently, genetic studies identified mutations in the same gene in patients with both conditions, strongly suggesting that they belong to the same disease spectrum. We report two new nonrelated patients who met the criteria for the diagnosis of juvenile hyaline fibromatosis/infantile systemic hyalinosis. Clinical, histopathologic, immunohistochemical, and ultrastructural findings are presented, as well as an extensive review of the literature. Recent information regarding pathogenesis and treatment is discussed.

The Roles of Cigarette Smoking and the Lung in the Transitions between Phases of Preclinical Rheumatoid Arthritis

PubMed Central

Sparks, Jeffrey A.; Karlson, Elizabeth W.

2016-01-01

While the etiology of rheumatoid arthritis (RA) remains to be fully elucidated, recent research has advanced the understanding of RA pathogenesis to the point where clinical trials for RA prevention are underway. The current paradigm for RA pathogenesis is that individuals progress through distinct preclinical stages prior to the onset of clinically apparent RA. These preclinical RA phases consist of genetic risk, local inflammation, presence of RA-related autoantibodies, asymptomatic systemic inflammation, and early non-specific symptoms prior to clinical seropositive RA. Epidemiologic studies have been important in forming hypotheses related to the biology occurring in preclinical RA. Specifically, studies associating cigarette smoking with overall RA risk as well as transitions between phases of preclinical RA were vital in helping to establish the lung as a potential important initiating site in the pathogenesis of seropositive RA. Herein, we review the epidemiology associating smoking with transitions in preclinical phases of RA as well as the recent literature supporting the lung as a critical site in RA pathogenesis. PMID:26951253

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

PubMed Central

Gao, Bin; Xu, Ming-Jiang; Bertola, Adeline; Wang, Hua; Zhou, Zhou; Liangpunsakul, Suthat

2017-01-01

Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals. All of these models recapitulate some features of the different stages of ALD and have been widely used by many investigators to study the pathogenesis of ALD and to test for therapeutic drugs/components. However, these models are somewhat variable, depending on mouse genetic background, ethanol dose, and animal facility environment. This review focuses on these models and discusses these variations and some methods to improve the feeding protocol. The pathogenesis, clinical relevance, and translational studies of these models are also discussed. PMID:28411363

Far East Scarlet-Like Fever: A Review of the Epidemiology, Symptomatology, and Role of Superantigenic Toxin: Yersinia pseudotuberculosis-Derived Mitogen A

PubMed Central

Amphlett, A.

2016-01-01

Far East scarlet-like fever (FESLF) is a severe inflammatory disease that occurs sporadically and in outbreaks in Russia and Japan. Far East scarlet-like fever is caused by Yersinia pseudotubuclosis infection, an organism that typically causes self-limiting gastroenteritis in Europe. Studies suggest the ability of Far Eastern strains to produce superantigen toxin Y pseudotuberculosis-derived mitogen A is integral to FESLF pathogenesis. In Europe, human Y pseudotuberculosis infection typically occurs sporadically, in the form of a self-limiting gastroenteritis. In Russia and Japan, outbreaks of Y pseudotuberculosis infection cause severe systemic inflammatory symptoms. This disease variant is called FESLF. Geographical heterogeneity exists between virulence factors produced by European and Far Eastern Y pseudotuberculosis strains, implicating superantigen Y pseudotuberculosis-derived mitogen A (YPMa) in the pathogenesis of FESLF. This article describes the epidemiology and clinical features of FESLF, and it presents the evidence for the role of YPMa in FESLF pathogenesis. PMID:26819960

Far East Scarlet-Like Fever: A Review of the Epidemiology, Symptomatology, and Role of Superantigenic Toxin: Yersinia pseudotuberculosis-Derived Mitogen A.

PubMed

Amphlett, A

2016-01-01

Far East scarlet-like fever (FESLF) is a severe inflammatory disease that occurs sporadically and in outbreaks in Russia and Japan. Far East scarlet-like fever is caused by Yersinia pseudotubuclosis infection, an organism that typically causes self-limiting gastroenteritis in Europe. Studies suggest the ability of Far Eastern strains to produce superantigen toxin Y pseudotuberculosis-derived mitogen A is integral to FESLF pathogenesis. In Europe, human Y pseudotuberculosis infection typically occurs sporadically, in the form of a self-limiting gastroenteritis. In Russia and Japan, outbreaks of Y pseudotuberculosis infection cause severe systemic inflammatory symptoms. This disease variant is called FESLF. Geographical heterogeneity exists between virulence factors produced by European and Far Eastern Y pseudotuberculosis strains, implicating superantigen Y pseudotuberculosis-derived mitogen A (YPMa) in the pathogenesis of FESLF. This article describes the epidemiology and clinical features of FESLF, and it presents the evidence for the role of YPMa in FESLF pathogenesis.

A native interactor scaffolds and stabilizes toxic ATAXIN-1 oligomers in SCA1

PubMed Central

Lasagna-Reeves, Cristian A; Rousseaux, Maxime WC; Guerrero-Muñoz, Marcos J; Park, Jeehye; Jafar-Nejad, Paymaan; Richman, Ronald; Lu, Nan; Sengupta, Urmi; Litvinchuk, Alexandra; Orr, Harry T; Kayed, Rakez; Zoghbi, Huda Y

2015-01-01

Recent studies indicate that soluble oligomers drive pathogenesis in several neurodegenerative proteinopathies, including Alzheimer and Parkinson disease. Curiously, the same conformational antibody recognizes different disease-related oligomers, despite the variations in clinical presentation and brain regions affected, suggesting that the oligomer structure might be responsible for toxicity. We investigated whether polyglutamine-expanded ATAXIN-1, the protein that underlies spinocerebellar ataxia type 1, forms toxic oligomers and, if so, what underlies their toxicity. We found that mutant ATXN1 does form oligomers and that oligomer levels correlate with disease progression in the Atxn1154Q/+ mice. Moreover, oligomeric toxicity, stabilization and seeding require interaction with Capicua, which is expressed at greater ratios with respect to ATXN1 in the cerebellum than in less vulnerable brain regions. Thus, specific interactors, not merely oligomeric structure, drive pathogenesis and contribute to regional vulnerability. Identifying interactors that stabilize toxic oligomeric complexes could answer longstanding questions about the pathogenesis of other proteinopathies. DOI: http://dx.doi.org/10.7554/eLife.07558.001 PMID:25988806

Mechanisms of mutations in myeloproliferative neoplasms.

PubMed

Levine, Ross L

2009-12-01

In recent years, a series of studies have provided genetic insight into the pathogenesis of myeloproliferative neoplasms (MPNs). It is now known that JAK2V617F mutations are present in 90% of patients with polycythaemia vera (PV), 60% of patients with essential thrombocytosis (ET) and 50% of patients with myelofibrosis (MF). Despite the high prevalence of JAK2V617F mutations in these three myeloid malignancies, several questions remain. For example, how does one mutation contribute to the pathogenesis of three clinically distinct diseases, and how do some patients develop these diseases in the absence of a JAK2V617F mutation? Single nucleotide polymorphisms at various loci and somatic mutations, such as those in MPLW515L/K, TET2 and in exon 12 of JAK2, may also contribute to the pathogenesis of these MPNs. There are likely additional germline and somatic genetic factors important to the MPN phenotype. Additional studies of large MPN and control cohorts with new techniques will help identify these factors.

B Cells Are Multifunctional Players in Multiple Sclerosis Pathogenesis: Insights from Therapeutic Interventions

PubMed Central

Claes, Nele; Fraussen, Judith; Stinissen, Piet; Hupperts, Raymond; Somers, Veerle

2015-01-01

Multiple sclerosis (MS) is a severe disease of the central nervous system (CNS) characterized by autoimmune inflammation and neurodegeneration. Historically, damage to the CNS was thought to be mediated predominantly by activated pro-inflammatory T cells. B cell involvement in the pathogenesis of MS was solely attributed to autoantibody production. The first clues for the involvement of antibody-independent B cell functions in MS pathology came from positive results in clinical trials of the B cell-depleting treatment rituximab in patients with relapsing-remitting (RR) MS. The survival of antibody-secreting plasma cells and decrease in T cell numbers indicated the importance of other B cell functions in MS such as antigen presentation, costimulation, and cytokine production. Rituximab provided us with an example of how clinical trials can lead to new research opportunities concerning B cell biology. Moreover, analysis of the antibody-independent B cell functions in MS has gained interest since these trials. Limited information is present on the effects of current immunomodulatory therapies on B cell functions, although effects of both first-line (interferon, glatiramer acetate, dimethyl fumarate, and teriflunomide), second-line (fingolimod, natalizumab), and even third-line (monoclonal antibody therapies) treatments on B cell subtype distribution, expression of functional surface markers, and secretion of different cytokines by B cells have been studied to some extent. In this review, we summarize the effects of different MS-related treatments on B cell functions that have been described up to now in order to find new research opportunities and contribute to the understanding of the pathogenesis of MS. PMID:26734009

Gastroduodenal neuroendocrine neoplasms, including gastrinoma - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

PubMed

Lipiński, Michał; Rydzewska, Grażyna; Foltyn, Wanda; Andrysiak-Mamos, Elżbieta; Bałdys-Waligórska, Agata; Bednarczuk, Tomasz; Blicharz-Dorniak, Jolanta; Bolanowski, Marek; Boratyn-Nowicka, Agnieszka; Borowska, Małgorzata; Cichocki, Andrzej; Ćwikła, Jarosław B; Falconi, Massimo; Handkiewicz-Junak, Daria; Hubalewska-Dydejczyk, Alicja; Jarząb, Barbara; Junik, Roman; Kajdaniuk, Dariusz; Kamiński, Grzegorz; Kolasińska-Ćwikła, Agnieszka; Kowalska, Aldona; Król, Robert; Królicki, Leszek; Kunikowska, Jolanta; Kuśnierz, Katarzyna; Lampe, Paweł; Lange, Dariusz; Lewczuk-Myślicka, Anna; Lewiński, Andrzej; Londzin-Olesik, Magdalena; Marek, Bogdan; Nasierowska-Guttmejer, Anna; Nowakowska-Duława, Ewa; Pilch-Kowalczyk, Joanna; Poczkaj, Karolina; Rosiek, Violetta; Ruchała, Marek; Siemińska, Lucyna; Sowa-Staszczak, Anna; Starzyńska, Teresa; Steinhof-Radwańska, Katarzyna; Strzelczyk, Janusz; Sworczak, Krzysztof; Syrenicz, Anhelli; Szawłowski, Andrzej; Szczepkowski, Marek; Wachuła, Ewa; Zajęcki, Wojciech; Zemczak, Anna; Zgliczyński, Wojciech; Kos-Kudła, Beata

2017-01-01

This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis, and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological, and localisation diagnoses. The principles of treatment are discussed, including endoscopic, surgical, pharmacological, and radionuclide treatments. Finally, there are also recommendations on patient monitoring.

The treatment of psychogenic polydipsia with risperidone in two children diagnosed with schizophrenia.

PubMed

Dogangün, Burak; Hergüner, Sabri; Atar, Murat; Kara, Bülent; Aksoy, M Umut; Kayaalp, Levent; Tüzün, Umran

2006-08-01

Polydipsia is a well-known phenomenon in adult psychiatry, but the literature regarding children is very limited. Just as the pathogenesis remains poorly understood, so does its management remain a clinical challenge. Data regarding the effect of risperidone on polydipsia are contradictory. We present case studies of remission of severe polydipsia with risperidone in two children.

Vitamin D/dietary calcium deficiency rickets and pseudo-vitamin D deficiency rickets

PubMed Central

Glorieux, Francis H; Pettifor, John M

2014-01-01

This review describes the pathogenesis, clinical presentation and biochemical perturbations found in privational (nutritional) rickets and pseudo-vitamin D deficiency rickets (PDDR), an autosomal recessive condition with loss of function mutations in CYP27B1. It may seem strange to combine a discussion on privational rickets and PDDR as a single topic, but privational rickets and PDDR present with similar clinical signs and symptoms and with similar perturbations in bone and mineral metabolism. Of interest is the characteristic lack of features of rickets at birth in infants with PDDR, a finding which has also been reported in infants born to vitamin D-deficient mothers. This highlights the independence of the fetus and neonate from the need for vitamin D to maintain calcium homeostasis during this period. The variable roles of vitamin D deficiency and dietary calcium deficiency in the pathogenesis of privational rickets are discussed and the associated alterations in vitamin D metabolism highlighted. Although PDDR is a rare autosomal recessive disorder, results of long-term follow-up are now available on the effect of treatment with calcitriol, and these are discussed. Areas of uncertainty, such as should affected mothers breastfeed their infants, are emphasized. PMID:24818008

Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

PubMed

Milo, Ron

2015-04-01

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

Recent advances in understanding dengue

PubMed Central

Yacoub, Sophie; Mongkolsapaya, Juthathip; Screaton, Gavin

2016-01-01

Dengue is an emerging threat to billions of people worldwide. In the last 20 years, the incidence has increased four-fold and this trend appears to be continuing. Caused by one of four viral serotypes, dengue can present as a wide range of clinical phenotypes with the severe end of the spectrum being defined by a syndrome of capillary leak, coagulopathy, and organ impairment. The pathogenesis of severe disease is thought to be in part immune mediated, but the exact mechanisms remain to be defined. The current treatment of dengue relies on supportive measures with no licensed therapeutics available to date. There have been recent advances in our understanding of a number of areas of dengue research, of which the following will be discussed in this review: the drivers behind the global dengue pandemic, viral structure and epitope binding, risk factors for severe disease and its pathogenesis, as well as the findings of recent clinical trials including therapeutics and vaccines. We conclude with current and future dengue control measures and key areas for future research. PMID:26918159

Fibromyalgia Pathogenesis and Treatment Options Update.

PubMed

Chinn, Steven; Caldwell, William; Gritsenko, Karina

2016-04-01

This review article presents and summarizes up-to-date literature on the clinical manifestations, diagnosis, pathophysiological mechanisms, and treatment options for fibromyalgia patients. First, the most recent diagnostic criteria for fibromyalgia, as put forth by the American College of Rheumatology will be summarized. Clinical features, including chronic widespread pain, hyperalgesia, mood disorders, anxiety, and disturbed sleep patterns will be explored in-depth. The pathogenesis and pathophysiology of fibromyalgia involves alterations in multiple ascending and descending central nervous system pathways, as well as peripheral pathways, leading to heightened pain sensitivity. Risk factors have been studied extensively, and the most recent research focuses on various genetic influences and the contributions of stress and poor sleep. Lastly, the discussion in this article focuses on treatment options for fibromyalgia; some have been mainstay options for many years. Pharmacological agents include tricyclic antidepressants, anti-epileptic drugs, selective serotonin reuptake inhibitors, norepinephrine/serotonin reuptake inhibitors, as well as some investigational agents. The evidence behind non-pharmacologic treatments, including massage therapy, exercise, and acupuncture, are discussed.

Review article: pathogenesis and clinical manifestations of gastrointestinal involvement In systemic sclerosis

PubMed Central

Kumar, Sumit; Singh, Jagmohan; Rattan, Satish; DiMarino, Anthony J; Cohen, Sidney; Jimenez, Sergio A.

2017-01-01

SUMMARY Background Gastrointestinal tract involvement is a common cause of debilitating symptoms in patients with systemic sclerosis. There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis. Aim To investigate novel aspects of the pathogenesis of gastrointestinal involvement in systemic sclerosis To summarize existing knowledge regarding the cardinal clinical gastrointestinal manifestations of systemic sclerosis and its pathogenesis, emphasizing recent investigations that may be valuable in identifying potentially novel therapeutic targets. Methods Electronic (Pubmed/Medline) and manual Google search Results The gastrointestinal tract is the most common internal organ involved in systemic sclerosis. Any part of the gastrointestinal tract from the mouth to the anus can be affected. There is substantial variability in clinical manifestations and disease course and symptoms are non-specific and overlapping for a particular anatomical site. Gastrointestinal involvement can occur in the in the absence of cutaneous disease. Up to 8% of systemic sclerosis patients develop severe gastrointestinal tract symptoms. This subset of patients display increased mortality with only 15% survival at 9 years. Dysmotiity of the gastrointestinal tract causes the majority of symptoms. Recent investigations have identified a novel mechanism in the pathogenesis of gastrointestinal tract dysmotility mediated by functional anti-muscarinic receptor autoantibodies. Conclusion Despite extensive investigation the pathogenesis of gastrointestinal involvement in systemic sclerosis remains elusive. Although treatment currently remains symptomatic, an improved understanding of novel pathogenic mechanisms may allow the development of potentially highly effective approaches including intravenous immunoglobulin and microRNA based therapeutic interventions. PMID:28185291

One year in review 2016: systemic lupus erythematosus.

PubMed

Adinolfi, Antonella; Valentini, Eleonora; Calabresi, Emanuele; Tesei, Giulia; Signorini, Viola; Barsotti, Simone; Tani, Chiara

2016-01-01

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a highly variable course and prognosis. The management of the disease is still a clinical challenge for the treating physicians as many aspects regarding the disease pathogenesis, clinical picture and outcomes remain to be elucidated. New and interesting data are emerging; here the recent literature on SLE pathogenesis, clinical and laboratory aspects, as well as treatments and comorbidities, are reviewed and the main findings summarised in order to provide a bird's eye on the relevant papers on these topics.

Tendinopathy: Investigating the Intersection of Clinical and Animal Research to Identify Progress and Hurdles in the Field

PubMed Central

Titan, Ashley; Andarawis-Puri, Nelly

2017-01-01

Biological treatments, surgical interventions, and rehabilitation exercises have been successfully used to treat tendinopathy, but the development of effective treatments has been hindered by the lack of mechanistic data regarding the pathogenesis of the disease.While insightful, clinical studies are limited in their capacity to provide data regarding the pathogenesis of tendinopathies, emphasizing the value of animal models and cell culture studies to fill this essential gap in knowledge.Clinical pathological findings from imaging studies or histological analysis are not universal across patients with tendinopathy and have not been clearly associated with the onset of symptoms.There are several unresolved controversies, including the cellular changes that accompany the tendinopathic disease state and the role of inflammation.Additional research is needed to correlate the manifestations of the disease with its pathogenesis, with the goal of reaching a field-wide consensus on the pathology of the disease state. Such a consensus will allow standardized clinical practices to more effectively diagnose and treat tendinopathy. PMID:27792676

Hypohidrotic and hidrotic ectodermal dysplasia: a report of two cases.

PubMed

Vasconcelos Carvalho, Marianne; Romero Souto de Sousa, José; Paiva Correa de Melo, Filipe; Fonseca Faro, Tatiane; Nunes Santos, Ana Clara; Carvalho, Silvia; Veras Sobral, Ana Paula

2013-07-14

Ectodermal dysplasias are a large group of syndromes characterized by anomalies in the structures of ectodermal origin. There are 2 major types of this disorder, based on clinical findings: hypohidrotic ectodermal dysplasia and hidrotic ectodermal dysplasia. This clinical classification is very important because clinical professionals involved with this disease need first a clear and practical method of diagnosis. The main oral manifestation of ectodermal dysplasia may be expressed as hypodontia. Thus, dental professionals may be the first to diagnose ectodermal dysplasia. The present article reports one case of each of the main types (hypohidrotic and hidrotic) of ectodermal dysplasia and the authors review the literature regarding the pathogenesis, clinical features, and therapeutic management of this condition.

[Cardio-hepatic Syndrome in Heart Failure: Prevalence, Pathogenesis and Prognostic Significance].

PubMed

Kobalava, Zh D; Villevalde, S V; Soloveva, A E

2016-12-01

In a framework of the concept of organ interactions great attention has been paid during recent years to interaction of the heart and liver. The term cardio-hepatic syndrome (CHS) designates the combination of clinical-laboratory signs of liver dysfunction and acute or chronic cardiac pathology. In this article, we present mechanisms and characteristics of CHS in acute and chronic heart failure (HF), data of large clinical studies and registries on prevalence, associations, and prognostic significance of cardiogenic disturbances of liver function in patients with HF.

[Hypertensive crisis: pathogenesis, clinic, treatment].

PubMed

Vertkin, A L; Topolianskiĭ, A V; Abdullaeva, A U; Alekseev, M A; Shakhmanaev, Kh A

2013-01-01

Contemporary data on mechanisms of development, types, and clinical picture of hypertensive crisis (HC) are presented. Algorithms of rational therapy of uncomplicated and complicated HC are considered. Appropriateness of the use in HC of antihypertensive drugs with multifactorial action is stressed. These drugs include urapidil - an antihypertensive agent with complex mechanism of action. Blocking mainly the postsynaptic 1-adrenoreceptors urapidil attenuates vasoconstrictor effect of catecholamines and decreases total peripheral resistance. Stimulation of 5HT1-receptors of medullary vasculomotor center promotes lowering of elevated vascular tone and prevents development of reflex tachycardia.

Amyloid is essential but insufficient for Alzheimer causation: addition of subcellular cofactors is required for dementia.

PubMed

Fessel, Jeffrey

2018-01-01

The aim of this study is to examine the hypotheses stating the importance of amyloid or of its oligomers in the pathogenesis of Alzheimer's disease (AD). Published studies were examined. The importance of amyloid in the pathogenesis of AD is well established, yet accepting it as the main cause for AD is problematic, because amyloid-centric treatments have provided no clinical benefit and about one-third of cognitively normal, older persons have cerebral amyloid plaques. Also problematic is the alternative hypothesis that, instead of amyloid plaques, it is oligomers of amyloid precursor protein that cause AD.Evidence is presented suggesting amyloid/oligomers as necessary but insufficient causes of the dementia and that, for dementia to develop, requires the addition of cofactors known to be associated with AD. Those cofactors include several subcellular processes: mitochondrial impairments; the Wnt signaling system; the unfolded protein response; the ubiquitin proteasome system; the Notch signaling system; and tau, calcium, and oxidative damage. A modified amyloid/oligomer hypothesis for the pathogenesis of AD is that activation of one or more of the aforementioned cofactors creates a burden of functional impairments that, in conjunction with amyloid/oligomers, now crosses a threshold of dysfunction that results in clinical dementia. Of considerable importance, several treatments that might reverse the activation of some of the subcellular processes are available, for example, lithium, pioglitazone, erythropoietin, and prazosin; they should be given in combination in a clinical trial to test their safety and efficacy. © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Basal Cell Carcinoma: Pathogenesis, Epidemiology, Clinical Features, Diagnosis, Histopathology, and Management

PubMed Central

Marzuka, Alexander G.; Book, Samuel E.

2015-01-01

Basal cell carcinoma (BCC) is the most common malignancy. Exposure to sunlight is the most important risk factor. Most, if not all, cases of BCC demonstrate overactive Hedgehog signaling. A variety of treatment modalities exist and are selected based on recurrence risk, importance of tissue preservation, patient preference, and extent of disease. The pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management of BCC will be discussed in this review. PMID:26029015

Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

PubMed Central

Zielinski, Daniel C.; Filipp, Fabian V.; Bordbar, Aarash; Jensen, Kasper; Smith, Jeffrey W.; Herrgard, Markus J.; Mo, Monica L.; Palsson, Bernhard O.

2015-01-01

Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways dysregulated by drugs are linked to the development of side effects. We show such dysregulated metabolic pathways contain genes with sequence variants affecting side effect incidence, play established roles in pathophysiology, have significantly altered activity in corresponding diseases, are susceptible to metabolic inhibitors and are effective targets for therapeutic nutrient supplementation. Our results indicate that metabolic dysregulation represents a common mechanism underlying side effect pathogenesis that is distinct from the role of metabolism in drug clearance. We suggest that elucidating the relationships between the cellular response to drugs, genetic variation of patients and cell metabolism may help managing side effects by personalizing drug prescriptions and nutritional intervention strategies. PMID:26055627

Granulomatous mastitis: a report of seven cases

PubMed Central

Fletcher, A; Magrath, IM; Riddell, RH; Talbot, IC

1982-01-01

The clinical history and histological features of seven cases of granulomatous mastitis are presented. The lesion occurs in young parous women as a tender extra-areolar breast lump. Histologically, non-caseating discrete granulomas are present, confined to breast lobules with, in three cases, coalescence of the granulomas and microabscess formation. Pathogenesis of the changes is discussed. It is thought that granulomatous mastitis is an entity morphologically distinct from duct ectasia/plasma cell mastitis and the commoner forms of granulomatous breast diseases. Images PMID:6889612

Pathogenesis of Taenia solium taeniasis and cysticercosis.

PubMed

Gonzales, I; Rivera, J T; Garcia, H H

2016-03-01

Taenia solium infections (taeniasis/cysticercosis) are a major scourge to most developing countries. Neurocysticercosis, the infection of the human nervous system by the cystic larvae of this parasite, has a protean array of clinical manifestations varying from entirely asymptomatic infections to aggressive, lethal courses. The diversity of clinical manifestations reflects a series of contributing factors which include the number, size and location of the invading parasites, and particularly the inflammatory response of the host. This manuscript reviews the different presentations of T. solium infections in the human host with a focus on the mechanisms or processes responsible for their clinical expression. © 2016 John Wiley & Sons Ltd.

[A disseminated form of Langerhans histiocytosis associated with diabetes insipidus and diabetes mellitus].

PubMed

Ben Ghorbel, I; Houman, M H; B'chir, S; Chamakhi, S; Miled, M

2001-05-01

Langerhans' cell histiocytosis is a rare disorder of unknown etiology characterized by a wide clinical spectrum and varied behavior. Diabetes insipidus is a relatively common feature in Langerhans' cell histiocytosis. The presence of both diabetes insipidus and mellitus associated with histiocytosis in an adult is rare. To our knowledge, only three previous cases have been reported. We report the clinical presentation, pathologic findings and clinical progress in an adult female who had disseminated Langerhans' cell histiocytosis (hypothalamic infiltration, multifocal bone involvement) associated with both diabetes insipidus and mellitus. The pathogenesis of diabetes mellitus in such an association will be discussed.

HLA-C and guttate psoriasis.

PubMed

Mallon, E; Bunce, M; Savoie, H; Rowe, A; Newson, R; Gotch, F; Bunker, C B

2000-12-01

Psoriasis is a heterogeneous disease in its clinical expression. Both genetic and environmental factors are thought to contribute to the pathogenesis of the inflammatory and hyperproliferative components of the typical skin lesions. Predisposing genetic influences include associations with human leucocyte antigens (HLA) of which that with HLA-Cw6 is the strongest. Guttate psoriasis is a specific clinical manifestation of psoriasis frequently associated with group A beta-haemolytic streptococcal throat infection. We set out to determine whether further clinical subdivision of psoriasis is associated with tighter correlation with HLA-C alleles. We determined the HLA-C locus genotype of 29 caucasian patients with guttate psoriasis presenting consecutively with guttate psoriasis associated with a history of a sore throat and/or an antistreptolysin O titre > 200 IU mL-1. Polymerase chain reaction typing using sequence-specific primers was used to detect all known HLA-C alleles. These data were compared with a control population of 604 random caucasian cadaver donors. All patients (100%) with guttate psoriasis carried the Cw*0602 allele compared with 20% of the control population (odds ratio = infinity; 95% confidence limits 25.00-infinity; Pcorrected < 0.0000002). This result is consistent with HLA-Cw*0602 playing a part directly in the pathogenesis of guttate psoriasis.

[History of the Department of Neurology at the University of Buenos Aires (1887-2007)].

PubMed

Allegri, Ricardo F; Bartoloni, Leonardo; Sica, Roberto E

2016-07-01

In 1887, only five years after Jean-Martin Charcot was awarded the Head of Neurology at "La Salpetrière" in Paris, José María Ramos Mejía became the first professor of Neurology in South America, at the School of Medicine of the University of Buenos Aires. Ramos Mejía convoked three assistants, the neuropathologist Christofredo Jakob, the clinician José A. Esteves and José Ingenieros. Hence it followed that Neurology in Argentina took a stand based on a clinical neurology-neuropathology approach (1941-1987) followed by a clinical-semiological attitude, finally inserting itself within the modern times (1987-present) by creating subspecialties. Throughout its history, Argentina has made remarkable contributions to Neurology, such as the diagnosis and pathogenesis of the nervous system involvement occurring in some regional endemic disorders -for instance, Chagas' disease-, the clinical approach to the diagnosis of dementias, and the pathogenesis of extrapyramidal illnesses and other primary degenerative diseases of the central nervous system, mainly amyotrophic lateral sclerosis. On the other hand, in recent years globalization allowed neurologists to participate in international cooperative projects, favoring a swifter development in the practice of this discipline.

[Leber hereditary optic neuropathy].

PubMed

Mazunin, I O; Volodko, N V

2018-01-01

Leber hereditary optic neuropathy is characterized by bilateral, painless loss of vision in children and young adults (generally up to 25 years old). Since its first description in 1871, the understanding of its etiology and pathogenesis has improved considerably. The article considers Leber neuropathy from the points of view of ophthalmology, neurology and molecular genetics, and presents data on experimental treatment methods, one of which is undergoing clinical trial.

Recognizing and preventing refeeding syndrome.

PubMed

Adkins, Susan M

2009-01-01

Refeeding syndrome is an uncommon but potentially fatal phenomenon that can occur in patients receiving parenteral, enteral, or oral feedings after a period of sustained malnutrition or starvation. This syndrome is characterized by hypophosphatemia, hypokalemia, and hypomagnesemia. The purpose of this article was to bring an acute awareness of refeeding syndrome to the critical care nurse. The recognition, pathogenesis, clinical manifestations, potential life threatening complications, and treatment are presented.

New Metrics for Evaluating Viral Respiratory Pathogenesis

PubMed Central

Menachery, Vineet D.; Gralinski, Lisa E.; Baric, Ralph S.; Ferris, Martin T.

2015-01-01

Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis. PMID:26115403

Severe optic neuritis in infectious mononucleosis.

PubMed

Jones, J; Gardner, W; Newman, T

1988-04-01

Because the presentation and clinical features of infectious mononucleosis can be misleading in the elderly, a significant number of infections may go unrecognized. We report an unusual case of infectious mononucleosis in a 61-year-old man in whom marked visual impairment was the presenting complaint and severe optic neuritis was the only prominent finding. Confirmation of the diagnosis was made by serologic testing for Epstein-Barr virus antibody. Recovery of visual function was near complete, but optic atrophy persisted. We reviewed the English literature and collected seven cases of well-documented optic neuritis associated with infectious mononucleosis. A clinical profile of parainfectious optic neuritis is discussed along with the likely pathogenesis for this complication.

Novel therapeutic approaches in chondrosarcoma.

PubMed

Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M; Huang, Paul H; Lee, Alex; Jones, Robin L

2017-03-01

Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

Necrotizing Enterocolitis in the Premature Infant

PubMed Central

Gregory, Katherine E.; DeForge, Christine E.; Natale, Kristan M.; Phillips, Michele; Van Marter, Linda J.

2013-01-01

Necrotizing enterocolitis (NEC) remains one of the most catastrophic comorbidities associated with prematurity. In spite of extensive research, the disease remains unsolved. The aims of this paper are to present the current state of the science on the pathogenesis of NEC, summarize the clinical presentation and severity staging of the disease, and highlight the nursing assessments required for early identification of NEC and ongoing care for infants diagnosed with this gastrointestinal disease. The distributions of systemic and intestinal clinical signs that are most sensitive to nursing assessment and associated with Bell Staging Criteria are presented. This descriptive data is representative of 117 cases of NEC diagnosed in low gestational age infants (<29 weeks gestation). The data highlights the clinical signs most commonly observed in infants with NEC, and thus, provides NICU nurses an evidence-based guide for assessment and care of infants with NEC. PMID:21730907

The pathophysiology of Peyronie's disease.

PubMed

El-Sakka, Ahmed I; Salabas, Emre; Dinçer, Murat; Kadioglu, Ates

2013-09-01

To review the contemporary knowledge of the pathophysiology of Peyronie's disease (PD). Medline was searched for papers published in English from 2000 to March 2013, using the keywords 'Peyronie's disease' and 'pathophysiology'. More than 300 relevant articles were identified for the purpose of this review. Unfortunately only a few studies had a high level of evidence, and the remaining studies were not controlled in their design. Many theories have been proposed to explain the cause of PD, but the true pathogenesis of PD remains an enigma. Identifying particular growth factors and the specific genes responsible for the induction of PD have been the ultimate goal of research over the past several decades. This would provide the means to devise a possible gene therapy for this devastating condition. We discuss present controversies and new discoveries related to the pathophysiology of this condition. PD is one of the most puzzling diseases in urology. The pathogenesis remains uncertain and there is still controversy about the best management. The pathogenesis of PD has been explored in animal models, cell cultures and clinical trials, but the results have led to further questions. New research on the aetiology and pathogenesis of PD is needed, and which will hopefully improve the understanding and management for patients with this frustrating disease.

Mesomelic skeletal dysplasias.

PubMed

Kaitila, I; Leisti, J T; Rimoin, D L

1976-01-01

Mesomelic shortening of the extremities lends itself as a useful clinical and/or radiologic sign to characterize a group of hereditary bone dysplasias. Table 1 and Figure 4 are presented to facilitate the comparison between the many different types of mesomelic dwarfism. Differential diagnosis between these types is not difficult because of the specific bone changes and extraskeletal malformations present. As in many hereditary syndromes, however, there may be wide clinical variability within a single entity, and meticulous clinical and radiologic examination must be done to arrive at the correct diagnosis. Certain other forms of chondrodystrophies, such as achondroplasia, hypochondroplasia, pseudoachondroplasia and distrophic dwarfism, can be easily differentiated from the mesomelic dysplasias by their clinical features and skeletal radiographs. Nothing is known about the pathogenesis of the various forms of mesomelic dysplasias. There is no available specific treatment, although corrective surgery has benefited selected patients. The correct diagnosis is, however, important both for prognostication and accurate genetic counseling.

The pathogenesis of Foot-and-Mouth Disease in pigs

USDA-ARS?s Scientific Manuscript database

The greatest segment of foot-and-mouth disease (FMD) clinical research has been dedicated to elucidating pathogenesis and enhancing vaccine protection in cattle with less efforts invested in studies that are specific to pigs. However, accumulated evidence from FMD outbreaks and experimental invest...

Citation classics in neuro-oncology: assessment of historical trends and scientific progress.

PubMed

Hachem, Laureen D; Mansouri, Alireza; Juraschka, Kyle; Taslimi, Shervin; Pirouzmand, Farhad; Zadeh, Gelareh

2017-09-01

Citation classics represent the highest cited works in a field and are often regarded as the most influential literature. Analyzing thematic trends in citation classics across eras enables recognition of important historical advances within a field. We present the first analysis of the citation classics in neuro-oncology. The Web of Science database was searched using terms relevant to "neuro-oncology." Articles with >400 citations were identified and the top 100 cited articles were evaluated. The top 100 neuro-oncology citation classics consisted of 43 clinical studies (17 retrospective, 10 prospective, 16 randomized trials), 43 laboratory investigations, 8 reviews/meta-analyses, and 6 guidelines/consensus statements. Articles were classified into 4 themes: 13 pertained to tumor classification, 37 to tumor pathogenesis/clinical presentation, 6 to imaging, 44 to therapy (15 chemotherapy, 10 radiotherapy, 5 surgery, 14 new agents). Gliomas were the most common tumor type examined, with 70 articles. There was a significant increase in the number of citation classics in the late 1990s, which was paralleled by an increase in studies examining tumor pathogenesis, chemotherapy, and new agents along with laboratory and randomized studies. The majority of citation classics in neuro-oncology are related to gliomas and pertain to tumor pathogenesis and treatment. The rise in citation classics in recent years investigating tumor biology, new treatment agents, and chemotherapeutics may reflect increasing scientific interest in nonsurgical treatments for CNS tumors and the need for fundamental investigations into disease processes. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Apoptosis in the cerebellum of dogs with distemper.

PubMed

Moro, L; Martins, A S; Alves, C M; Santos, F G A; Del Puerto, H L; Vasconcelos, A C

2003-06-01

Canine distemper virus (CDV) may induce multifocal demyelination in the central nervous system of infected dogs. The pathogenesis of this process is not clear. The present work identifies the presence of apoptotic cells in white and grey matter of dogs'cerebellum, naturally infected with CDV. Fifteen dogs with clinical signs of canine distemper that tested positive for CDV nucleoprotein were used. Brain specimens were processed and embedded in paraffin. Sections 5 microm thick were stained with hematoxylin-eosin and Shorr. Other sections were submitted to TUNEL reaction and to immunohistochemistry for CDV nucleoprotein detection. Acute and chronic demyelinated plaques were observed in the white matter, while apoptosis occurred particularly in the granular layer of grey matter. Apoptosis seems to play an important role in the pathogenesis of canine distemper demyelination.

Hepatic sarcoidosis: pathogenesis, clinical context, and treatment options.

PubMed

Syed, Umer; Alkhawam, Hassan; Bakhit, Mena; Companioni, Rafael A Ching; Walfish, Aron

2016-09-01

Sarcoidosis is typically characterized as a non-caseating granulomatous disease that has the ability to affect multiple different organ systems. Although extra-thoracic sarcoidosis can occur in the presence and also without lung involvement, isolated extra-pulmonary disease is rare. The liver is the third most commonly affected organ system after the lungs and lymph nodes. When discussing hepatic sarcoidosis it is important to keep in mind that many patients in this population may not present as one would typically expect since most of the patients are asymptomatic or have mild presentations. Therefore, the diagnosis can be difficult at times since no single laboratory or imaging study can definitively diagnose this systemic disease. In the rare case of some patients where there is difficulty in discerning between different pathologies, the use of image-guided tissue biopsy may be necessary to establish a diagnosis. At the current time, there are no clear guidelines for the management of hepatic sarcoidosis and are mostly dependent on a patient's clinical status at time of presentation. The current body of research in regard to treatment suggests steroids to be the mainstay of therapy. However, there is a role for additional immunosuppressive therapy in cases where the initial treatment is refractory to steroids. In this manuscript, we discussed the pathogenesis of liver sarcoidosis and context of its presentation. In addition, the differential diagnosis and imaging evaluation in this population is discussed. Finally, treatment options are reviewed in setting of previous studies for liver sarcoidosis.

Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy.

PubMed

Vitale, Giovanni; Dicitore, Alessandra; Messina, Erika; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

2016-01-01

Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC. The present review reports a detailed description of epigenetic abnormalities (DNA methylation, histone modifications and miRNA profile), probably involved in the pathogenesis and progression of MTC. A systematic review was performed using Pubmed and Google patents databases. We report the current understanding of epigenetic patterns in MTC and discuss the potential use of current knowledge in designing novel therapeutic strategies through epigenetic drugs, focusing on recent patents in this field. Taking into account the reversibility of epigenetic alterations and the recent development in this field, epigenetic therapy may emerge for clinical use in the near future for patients with advanced MTC.

Pathogenesis and treatment modalities of localized scleroderma.

PubMed

Valančienė, Greta; Jasaitienė, Daiva; Valiukevičienė, Skaidra

2010-01-01

Localized scleroderma is a chronic inflammatory disease primarily of the dermis and subcutaneous fat that ultimately leads to a scar-like sclerosis of connective tissue. The disorder manifests as various plaques of different shape and size with signs of skin inflammation, sclerosis, and atrophy. This is a relatively rare inflammatory disease characterized by a chronic course, unknown etiology, and insufficiently clear pathogenesis. Many factors may influence its appearance: trauma, genetic factors, disorders of the immune system or hormone metabolism, viral infections, toxic substances or pharmaceutical agents, neurogenic factors, and Borrelia burgdorferi infection. Various therapeutic modalities are being used for the treatment of localized scleroderma. There is no precise treatment scheme for this disease. A majority of patients can be successfully treated with topical pharmaceutical agents and phototherapy, but some of them with progressive, disseminated, and causing disability localized scleroderma are in need of systemic treatment. The aim of this article is not only to dispute about the clinical and morphological characteristics of localized scleroderma, but also to present the newest generalized data about the possible origin, pathogenesis, and treatment modalities of this disease.

Biomarker identification and pathway analysis of preeclampsia based on serum metabolomics.

PubMed

Chen, Tingting; He, Ping; Tan, Yong; Xu, Dongying

2017-03-25

Preeclampsia presents serious risk of both maternal and fetal morbidity and mortality. Biomarkers for the detection of preeclampsia are critical for risk assessment and targeted intervention. The goal of this study is to screen potential biomarkers for the diagnosis of preeclampsia and to illuminate the pathogenesis of preeclampsia development based on the differential expression network. Two groups of subjects, including healthy pregnant women, subjects with preeclampsia, were recruited for this study. The metabolic profiles of all of the subjects' serum were obtained by liquid chromatography quadruple time-of-flight mass spectrometry. Correlation between metabolites was analyzed by bioinformatics technique. Results showed that the PC(14:0/00), proline betaine and proline were potential sensitive and specific biomarkers for preeclampsia diagnosis and prognosis. Perturbation of corresponding biological pathways, such as iNOS signaling, nitric oxide signaling in the cardiovascular system, mitochondrial dysfunction were responsible for the pathogenesis of preeclampsia. This study indicated that the metabolic profiling had a good clinical significance in the diagnosis of preeclampsia as well as in the study of its pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Candida albicans importance to denture wearers. A literature review.

PubMed

Gleiznys, Alvydas; Zdanavičienė, Eglė; Žilinskas, Juozas

2015-01-01

Opportunistic oral fungal infections have spred, especially in denture wearers. Denture stomatitis is a common inflammatory reaction, multifactorial etiology, which is usually associated with Candida species, particularly Candida albicans, due to its high virulence, ability to adhere and form biofilms on oral cavity tissues and denture surfaces. This article highlights the pathogenesis, clinical presentation, and management strategies of Candida-associated denture stomatitis commonly encountered in dental practice.

Leveraging Gene-Environment Interactions and Endotypes for Asthma Gene Discovery

PubMed Central

Bønnelykke, Klaus; Ober, Carole

2016-01-01

Asthma is a heterogeneous clinical syndrome that includes subtypes of disease with different underlying causes and disease mechanisms. Asthma is caused by a complex interaction between genes and environmental exposures; early-life exposures in particular play an important role. Asthma is also heritable, and a number of susceptibility variants have been discovered in genome-wide association studies, although the known risk alleles explain only a small proportion of the heritability. In this review, we present evidence supporting the hypothesis that focusing on more specific asthma phenotypes, such as childhood asthma with severe exacerbations, and on relevant exposures that are involved in gene-environment interactions (GEIs), such as rhinovirus infections, will improve detection of asthma genes and our understanding of the underlying mechanisms. We will discuss the challenges of considering GEIs and the advantages of studying responses to asthma-associated exposures in clinical birth cohorts, as well as in cell models of GEIs, to dissect the context-specific nature of genotypic risks, to prioritize variants in genome-wide association studies, and to identify pathways involved in pathogenesis in subgroups of patients. We propose that such approaches, in spite of their many challenges, present great opportunities for better understanding of asthma pathogenesis and heterogeneity and, ultimately, for improving prevention and treatment of disease. PMID:26947980

Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus

PubMed Central

da Fontoura Budaszewski, Renata; von Messling, Veronika

2016-01-01

Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development. PMID:27727184

Fever of Unknown Origin in a Patient with Confirmed West Nile Virus Meningoencephalitis

PubMed Central

Sabre, Alexander; Farricielli, Laurie

2014-01-01

West Nile Virus (WNV), an RNA arbovirus and member of the Japanese encephalitis virus antigenic complex, causes a wide range of clinical symptoms, from asymptomatic to encephalitis and meningitis. Nearly all human infections of WNV are due to mosquito bites with birds being the primary amplifying hosts. Advanced age is the most important risk factor for neurological disease leading most often to poor prognosis in those afflicted. We report a case of WNV meningoencephalitis in a 93-year-old Caucasian male who presented with fever of unknown origin (FUO) and nuchal rigidity that rapidly decompensated within 24 h to a persistent altered mental state during inpatient stay. The patient's ELISA antibody titers confirmed pathogenesis of disease by WNV; he given supportive measures and advanced to an excellent recovery. In regard to the approach of FUO, it is important to remain impartial yet insightful to all elements when determining pathogenesis in atypical presentation. PMID:25580318

Ebola virus disease - pathogenesis, clinical presentation and management.

PubMed

Bociaga-Jasik, Monika; Piatek, Anna; Garlicki, Aleksander

2014-01-01

On March 2014 the WHO notified the outbreak of Ebola virus disease (EVD) in Guinea, and infection quickly spread to another West African countries including Sierra Leone, Liberia and Nigeria. Current outbreak is the largest in the history, since discovery of the virus in 1976. Imported cases and infection among healthcare workers in Europe and United States have elucidated necessity of better education of medical staff. Clinicians must be familiar with clinical picture of EVD, differential diagnosis and therapeutic approach, as rapid diagnosis and prompt introduction of supportive therapy can have a significant impact on the survival.

Update on the evaluation and treatment of osteogenesis imperfecta.

PubMed

Harrington, Jennifer; Sochett, Etienne; Howard, Andrew

2014-12-01

Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that presents with a wide clinical phenotype spectrum: from perinatal lethality and severe deformities to very mild forms without fractures. Most cases of OI are due to autosomal dominant mutations of the type I collagen genes. A multidisciplinary approach with rehabilitation, orthopedic surgery, and consideration of medical therapy with bisphosphonates underpins current management. Greater understanding of the pathogenesis of OI may lead to novel, therapeutic approaches to help improve clinical symptoms of children with OI in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

Traumatic ulcerative granuloma with stromal eosinophilia - Mystery of pathogenesis revisited.

PubMed

Sarangarajan, R; Vaishnavi Vedam, V K; Sivadas, G; Sarangarajan, Anuradha; Meera, S

2015-08-01

Oral ulcers are a common symptom in clinical practice. Among various causative factors, different types of ulcers in oral cavity exist. Among this, traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) appears to be quite neglected by the clinicians due to the limited knowledge and awareness. On reviewing with a detailed approach to titles and abstracts of articles eliminating duplicates, 40 relevant articles were considered. Randomized studies, review articles, case reports and abstracts were included while conference papers and posters were excluded. Of importance, TUGSE cases been reported only to a minimal extent in the literature. Lack of its awareness tends to lead clinicians to a misconception of cancer. Thus, this particular lesion needs to be differentiated from other malignant lesions to provide a proper mode of treatment. The present article reviews various aspects of the TUGSE with emphasis on the clinical manifestation, pathogenesis, histological, and immunohistochemical study. This study provides the clinician contemporaries, a humble expansion to their knowledge of the disease, based on the searched literature, enabling a more comprehensive management of this rare occurrence.

Cholera.

PubMed Central

Kaper, J B; Morris, J G; Levine, M M

1995-01-01

Despite more than a century of study, cholera still presents challenges and surprises to us. Throughout most of the 20th century, cholera was caused by Vibrio cholerae of the O1 serogroup and the disease was largely confined to Asia and Africa. However, the last decade of the 20th century has witnessed two major developments in the history of this disease. In 1991, a massive outbreak of cholera started in South America, the one continent previously untouched by cholera in this century. In 1992, an apparently new pandemic caused by a previously unknown serogroup of V. cholerae (O139) began in India and Bangladesh. The O139 epidemic has been occurring in populations assumed to be largely immune to V. cholerae O1 and has rapidly spread to many countries including the United States. In this review, we discuss all aspects of cholera, including the clinical microbiology, epidemiology, pathogenesis, and clinical features of the disease. Special attention will be paid to the extraordinary advances that have been made in recent years in unravelling the molecular pathogenesis of this infection and in the development of new generations of vaccines to prevent it. PMID:7704895

Recent advances in hepatocellular carcinoma therapy☆

PubMed Central

Dutta, Rinku; Mahato, Ram I.

2017-01-01

Hepatocellular carcinoma (HCC), also called malignant hepatoma, is one of the deadliest cancers due to its complexities, reoccurrence after surgical resection, metastasis and heterogeneity. Incidence and mortality of HCC are increasing in Western countries and are expected to rise as a consequence of the obesity epidemic. Multiple factors trigger the initiation and progression of HCC including chronic alcohol consumption, viral hepatitis B and C infection, metabolic disorders and age. Although Sorafenib is the only FDA approved drug for the treatment of HCC, numerous treatment modalities such as transcatheter arterial chemoembolization/transarterial chemoembolization (TACE), radiotherapy, locoregional therapy and chemotherapy have been tested in the clinics. Polymeric nanoparticles, liposomes, and micelles carrying small molecules, proteins, peptides and nucleic acids have attracted great attention for the treatment of various cancers including HCC. Herein, we discuss the pathogenesis of HCC in relation to its various recent treatment methodologies using nanodelivery of monoclonal antibodies (mAbs), small molecules, miRNAs and peptides. Synopsis of recent clinical trials of mAbs and peptide drugs has been presented with a broad overview of the pathogenesis of the disease and treatment efficacy. PMID:28174094

Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation

PubMed Central

2010-01-01

Air pollutant exposure has been linked to a rise in wheezing illnesses. Clinical data highlight that exposure to mainstream tobacco smoke (MS) and environmental tobacco smoke (ETS) as well as exposure to diesel exhaust particles (DEP) could promote allergic sensitization or aggravate symptoms of asthma, suggesting a role for these inhaled pollutants in the pathogenesis of asthma. Mouse models are a valuable tool to study the potential effects of these pollutants in the pathogenesis of asthma, with the opportunity to investigate their impact during processes leading to sensitization, acute inflammation and chronic disease. Mice allow us to perform mechanistic studies and to evaluate the importance of specific cell types in asthma pathogenesis. In this review, the major clinical effects of tobacco smoke and diesel exhaust exposure regarding to asthma development and progression are described. Clinical data are compared with findings from murine models of asthma and inhalable pollutant exposure. Moreover, the potential mechanisms by which both pollutants could aggravate asthma are discussed. PMID:20092634

[Hernia surgery in urology: part 1: inguinal, femoral and umbilical hernias - fundamentals of clinical diagnostics and treatment].

PubMed

Franz, T; Schwalenberg, T; Dietrich, A; Müller, J; Stolzenburg, J-U

2013-05-01

Hernias are a common occurrence with correspondingly huge clinical and economic impacts on the healthcare system. The most common forms of hernia which need to be diagnosed and treated in routine urological work are inguinal and umbilical hernias. With the objective of reconstructing and stabilizing the inguinal canal there are the possibilities of open and minimally invasive surgery and both methods can be performed with suture or mesh repair. Indications for surgery of umbilical hernias are infrequent although this is possible with little effort under local anesthesia. This article presents an overview of the epidemiology, pathogenesis, clinical symptoms, diagnostics and therapy of inguinal, femoral and umbilical hernias.

Neurological Manifestations of Dengue Infection.

PubMed

Li, Guo-Hong; Ning, Zhi-Jie; Liu, Yi-Ming; Li, Xiao-Hong

2017-01-01

Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS), peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

[Invasive aspergillosis with extrapulmonary involvement: pathogenesis, clinical characteristics and prognosis].

PubMed

López-Cortés, Luis Eduardo; Garcia-Vidal, Carolina; Ayats, Josefina; Gudiol, Carlota; Bodro, Marta; Sánchez-Ortega, Isabel; Peña, Carmen; Carratalá, Jordi

2012-01-01

The incidence of invasive aspergillosis has increased worldwide. Information regarding the clinical characteristics of patients with extrapulmonary involvement is scarce. We aimed to describe the pathogenesis, characteristics and outcomes of patients with invasive aspergillosis and extrapulmonary disease. A retrospective study conducted in a university hospital in Barcelona, Spain (1995-2011). A total of 12 cases of invasive aspergillosis and extrapulmonary involvement were found. The most common clinical manifestations were invasive sinusitis, early postoperative prosthetic valve endocarditis, fungaemia, postoperative meningitis, multiple brain abscesses and lumbar spondylitis with epidural abscess. Sinusitis occurred frequently in patients without immunosuppression and had invasive brain involvement in one case. Endocarditis was associated with multiple septic metastases. Concomitant lung involvement was documented in 5 cases. The strains isolated were Aspergillus fumigatus (5), Aspergillus flavus (3), and Aspergillus niger (2). The species of Aspergillus was not established for 3 isolates. All patients were treated with antifungals and surgery was performed in 8 cases. Outcome was related with the source of infection; all patients with invasive sinusitis survived, while the remaining patients had a high mortality rate (88%). Invasive aspergillosis with extrapulmonary involvement is rare. The most common presentation is invasive sinusitis, which has a lower mortality. Other clinical forms with extrapulmonary involvement were associated with severe immunosuppression or previous surgery, and had a poor outcome. Copyright © 2011 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

An update on Legionella.

PubMed

Carratalà, Jordi; Garcia-Vidal, Carolina

2010-04-01

Legionella pneumophila is increasingly recognized as a significant cause of sporadic and epidemic community-acquired and nosocomial-acquired pneumonia. This review focuses on the latest literature concerning the epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of Legionnaires' disease. A significant increase in the incidence of Legionnaires' disease in the United States has been documented over the last years. L. pneumophila has recently been found to be a leading cause of community-acquired pneumonia in hospitalized and ambulatory patients in Germany. Recent studies provide insight into the understanding of the pathogenesis of Legionnaires' disease and the relevance of the formation of biofilms. Clinical manifestations of Legionnaires' disease are not specific and current diagnostic scores are of limited use. Several recent studies offer useful information concerning Legionnaires' disease in immunosuppressed patients. A systematic review of English literature performed to assess test characteristics of Legionella urinary antigen has found that the pooled sensitivity of the test was 0.74 and specificity was 0.991. Improved clinical response has been observed for patients with Legionnaires' disease treated with highly active antimicrobial agents against Legionella. Legionnaires' disease is a significant health problem in many countries. Clinical manifestations are unreliable in diagnosing Legionnaires' disease. Therefore, diagnostic laboratory tests for Legionella, including the urinary antigen test, should be applied to all patients with pneumonia. Levofloxacin (or other fluoroquinolone) or azithromycin are the current drugs of choice for treatment of Legionnaires' disease. Effective preventive strategies are needed.

Potential role of the Virchow Robin space in the pathogenesis of bacterial meningitis.

PubMed

Chan, Patrick; Meerdink, Denis J; Uchizono, James A

2017-11-01

Meningitis is an infectious disease commonly arising from a bacterial etiology. The rapid progression of morbidity and mortality due to bacterial meningitis requires critical and imminent time-dependent clinical intervention. Although it is unambiguously clear that bacteria must infiltrate the cerebrospinal fluid, the sequence of events in the pathogenesis of bacterial meningitis has not been fully elucidated. Most reviews of the pathogenesis of bacterial meningitis do not specify the anatomical location of bacteria following BBB traversal. We propose an additional hypothesis focusing on the Virchow-Robin space (VRS). The VRS consists of a small, but identifiable perivascular space formed by a sheath of cells derived from the pia mater. The VRS has been described as an immunological space and possibly having a role in several neuropathological diseases. Solute exchange between cerebrospinal fluid and extracellular fluid occurs at the VRS, with subsequent drainage into the subarachnoid space. Because the VRS is continuous with the subpial space, a more direct route to the meninges is facilitated. The involvement of the VRS may have profound implications on the pathogenesis and therapeutic strategies: (1) nasopharyngeal colonization; (2) penetration into the blood stream after crossing the mucosal and epithelial membranes; (3) proliferation in the bloodstream; (4) extravasations through the endothelium of the post-capillary venules to the perivascular VRS; (5) migration from VRS to subpial space; (6) traversal through pia mater, entering the CSF in the subarachnoid space; (7) invasion of the meninges. The implication of the VRS in the pathogenesis of bacterial meningitis would be twofold. First, the VRS could provide an additional route of entry of bacteria into the brain. Second, the VRS could provide an area for bacterial proliferation, and thereby serve as a bacterial reservoir in relatively close proximity to the meninges. The clinical consequences of this hypothesis are: 1) clinical interpretation of laboratory findings, and 2) effective antibiotic delivery into the VRS. If the role of the VRS is established as part of bacterial meningitis pathogenesis, antibiotic pharmacokinetics and pharmacodynamics in the VRS need to be determined. This may result in developing novel antibiotic delivery and clinical strategies to improve morbidity and mortality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immunoglobulin A Nephropathy: Advances in Understanding of Pathogenesis and Treatment.

PubMed

Lafayette, Richard A; Kelepouris, Ellie

2018-05-31

Immunoglobulin A (IgA) nephropathy is the most common form of primary glomerulonephritis and has clinical associations with a wide range of inflammatory and infectious diseases. There is a substantial variation in clinical course and outcomes, with many patients not diagnosed until they present with sequelae, which may include gross hematuria, hypertension, renal insufficiency, and/or significant proteinuria. Treatment options are currently limited and directed mainly toward control of these sequelae and have limited ability to reduce the incidence of end-stage renal disease or treat the primary IgA defect. Growing knowledge about the pathogenesis of IgA nephropathy and research into its genetic basis are helping to elucidate the course of this widely variable disease. IgA accumulation in the kidneys is thought to be the result of a number of different pathways in a "multi-hit" process that includes an initial traumatic trigger (often infection related) and subsequent memory responses that are amplified in those with a genetic predisposition to the disease and lead to an inflammatory response in susceptible individuals. Genome-wide association studies are providing new insights into the genetic variance of this autoimmune disease and are yielding information that may address both its causes and consequences. Key Messages: New treatment approaches are urgently required for the management of patients with IgA nephropathy. Novel interventions based around its inflammatory nature and "multi-hit" pathogenesis are being investigated to potentially limit disease progression. © 2018 S. Karger AG, Basel.

Immune mechanisms in the pathogenesis of bronchiolitis obliterans syndrome after lung transplantation.

PubMed

Jaramillo, Andrés; Fernández, Félix G; Kuo, Elbert Y; Trulock, Elbert P; Patterson, G A; Mohanakumar, T

2005-02-01

Lung transplantation is recognized as the only viable treatment option in a variety of end-stage pulmonary diseases. However, the long-term survival after lung transplantation is limited by the development of obliterative bronchiolitis, and its clinical correlate bronchiolitis obliterans syndrome (BOS), which is considered to represent chronic lung allograft rejection. Histopathologically, BOS is an inflammatory process that leads to fibrous scarring of the terminal and respiratory bronchioles and subsequent total occlusion of the airways. The specific etiology and pathogenesis of BOS are not well understood. The current premise is that BOS represents a common lesion in which different inflammatory insults such as ischemia-reperfusion, rejection, and infection can lead to a similar histological and clinical outcome. However, the low incidence of BOS in non-transplanted individuals and the observation that early development of BOS is predicted by the frequency and severity of acute rejection episodes indicate that alloimmune-dependent mechanisms play a crucial role in the pathogenesis of BOS. The evidence presented in this review indicates that BOS is the result of humoral and cellular immune responses developed against major histocompatibility complex molecules expressed by airway epithelial cells of the lung allograft. This process is aggravated by alloimmune-independent mechanisms such as ischemia-reperfusion and infection. Currently, treatment of BOS is frequently unsuccessful. Therefore, a better understanding of the immunopathogenesis of BOS is of paramount importance toward improving long-term patient and graft survival after lung transplantation.

Gene knockout of tau expression does not contribute to the pathogenesis of prion disease.

PubMed

Lawson, Victoria A; Klemm, Helen M; Welton, Jeremy M; Masters, Colin L; Crouch, Peter; Cappai, Roberto; Ciccotosto, Giuseppe D

2011-11-01

Prion diseases or transmissible spongiform encephalopathies are a group of fatal and transmissible disorders affecting the central nervous system of humans and animals. The principal agent of prion disease transmission and pathogenesis is proposed to be an abnormal protease-resistant isoform of the normal cellular prion protein. The microtubule-associated protein tau is elevated in patients with Creutzfeldt-Jakob disease. To determine whether tau expression contributes to prion disease pathogenesis, tau knockout and control wild-type mice were infected with the M1000 strain of mouse-adapted human prions. Immunohistochemical analysis for total tau expression in prion-infected wild-type mice indicated tau aggregation in the cytoplasm of a subpopulation of neurons in regions associated with spongiform change. Western immunoblot analysis of brain homogenates revealed a decrease in total tau immunoreactivity and epitope-specific changes in tau phosphorylation. No significant difference in incubation period or other disease features were observed between tau knockout and wild-type mice with clinical prion disease. These results demonstrate that, in this model of prion disease, tau does not contribute to the pathogenesis of prion disease and that changes in the tau protein profile observed in mice with clinical prion disease occurs as a consequence of the prion-induced pathogenesis.

Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma.

PubMed

Mariño-Enríquez, Adrián; Bovée, Judith V M G

2016-09-01

Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of cytokines in the pathogenesis and staging of Trypanosoma brucei rhodesiense sleeping sickness.

PubMed

Kato, Charles D; Matovu, Enock; Mugasa, Claire M; Nanteza, Ann; Alibu, Vincent P

2016-01-01

Human African trypanosomiasis due to Trypanosoma brucei rhodesiense is invariably fatal if untreated with up to 12.3 million people at a risk of developing the disease in Sub-Saharan Africa. The disease is characterized by a wide spectrum of clinical presentation coupled with differences in disease progression and severity. While the factors determining this varied response have not been clearly characterized, inflammatory cytokines have been partially implicated as key players. In this review, we consolidate available literature on the role of specific cytokines in the pathogenesis of T. b. rhodesiense sleeping sickness and further discuss their potential as stage biomarkers. Such information would guide upcoming research on the immunology of sleeping sickness and further assist in the selection and evaluation of cytokines as disease stage or diagnostic biomarkers.

The lung may play a role in the pathogenesis of rheumatoid arthritis

PubMed Central

Demoruelle, M Kristen; Solomon, Joshua J; Fischer, Aryeh; Deane, Kevin D

2015-01-01

Multiple studies have identified strong associations between the lung and rheumatoid arthritis (RA). Such studies identify a high prevalence of lung disease, both airways and parenchymal disease, in subjects with clinically classifiable RA. It has been suggested that lung disease in RA results from targeting of the lung from circulating autoimmunity or other factors such as medications. However, findings that lung disease, specifically inflammatory airways disease, and lung generation of autoimmunity can be present before the onset of joint symptoms suggest that immune reactions in the lung may be involved in the initial development of RA-related autoimmunity. Herein we review these issues in detail, as well as outline a potential research agenda to understand the natural history of lung involvement in RA and its relation to the overall pathogenesis of RA. PMID:26089988

Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN.

PubMed

Sethi, Sanjeev; Haas, Mark; Markowitz, Glen S; D'Agati, Vivette D; Rennke, Helmut G; Jennette, J Charles; Bajema, Ingeborg M; Alpers, Charles E; Chang, Anthony; Cornell, Lynn D; Cosio, Fernando G; Fogo, Agnes B; Glassock, Richard J; Hariharan, Sundaram; Kambham, Neeraja; Lager, Donna J; Leung, Nelson; Mengel, Michael; Nath, Karl A; Roberts, Ian S; Rovin, Brad H; Seshan, Surya V; Smith, Richard J H; Walker, Patrick D; Winearls, Christopher G; Appel, Gerald B; Alexander, Mariam P; Cattran, Daniel C; Casado, Carmen Avila; Cook, H Terence; De Vriese, An S; Radhakrishnan, Jai; Racusen, Lorraine C; Ronco, Pierre; Fervenza, Fernando C

2016-05-01

Renal pathologists and nephrologists met on February 20, 2015 to establish an etiology/pathogenesis-based system for classification and diagnosis of GN, with a major aim of standardizing the kidney biopsy report of GN. On the basis of etiology/pathogenesis, GN is classified into the following five pathogenic types, each with specific disease entities: immune-complex GN, pauci-immune GN, antiglomerular basement membrane GN, monoclonal Ig GN, and C3 glomerulopathy. The pathogenesis-based classification forms the basis of the kidney biopsy report. To standardize the report, the diagnosis consists of a primary diagnosis and a secondary diagnosis. The primary diagnosis should include the disease entity/pathogenic type (if disease entity is not known) followed in order by pattern of injury (mixed patterns may be present); score/grade/class for disease entities, such as IgA nephropathy, lupus nephritis, and ANCA GN; and additional features as detailed herein. A pattern diagnosis as the sole primary diagnosis is not recommended. Secondary diagnoses should be reported separately and include coexisting lesions that do not form the primary diagnosis. Guidelines for the report format, light microscopy, immunofluorescence microscopy, electron microscopy, and ancillary studies are also provided. In summary, this consensus report emphasizes a pathogenesis-based classification of GN and provides guidelines for the standardized reporting of GN. Copyright © 2016 by the American Society of Nephrology.

Self-care interventions for the school-aged child with encopresis.

PubMed

Vitito, L M

2000-01-01

Encopresis, an elimination disorder in children, presents as a challenging problem for gastroenterology nurses working with patients and families confronted with this disorder. This article offers a summary of the literature on encopresis, including pathogenesis, causative factors, early treatment, and clinical interventions focused on self-care. The antecedent factors that facilitate the child's participation in self-care are summarized, along with the intended outcomes of the self-care intervention plan.

Measurement of Circulating Cytokines and Immune-Activation Markers by Multiplex Technology in the Clinical Setting: What Are We Really Measuring?

PubMed

Aziz, Najib

2015-01-01

Measurement of circulating cytokine levels can provide important information in the study of the pathogenesis of disease. John L. Fahey was a pioneer in the measurement of circulating cytokines and immune-activation markers and a leader in the quality assessment/control of assays for measurement of circulating cytokines. Insights into the measurement of circulating cytokines, including consideration of multiplex assays, are presented here.

Mumps virus pathogenesis: Insights and knowledge gaps.

PubMed

Gouma, Sigrid; Koopmans, Marion P G; van Binnendijk, Rob S

2016-12-01

The recent mumps outbreaks among MMR vaccinated persons have raised questions about the biological mechanisms related to mumps symptoms and complications in the background of waning immunity. Contrary to other paramyxoviruses, the understanding of mumps virus pathogenesis is limited, and further in-depth clinical studies are required to provide answers to important research questions.

Pathogenesis of infectious disease of mice caused by H5N1 avian influenza virus.

PubMed

Evseenko, V A; Sharshov, K A; Bukin, E K; Zaykovskaya, A V; Ternovoy, V A; Ignatyev, G M; Shestopalov, A M; Netesov, S V; Shkurupiy, V A; Drozdov, I G

2008-12-01

The pathogenesis of a disease caused by Qinghai-like H5N1 influenza virus in BALB/c mice was studied. Clinical, morphological, and immunological characteristics of the experimental infection caused by highly pathogenic A/duck/Tuva/01/06/ (H5N1) virus are described.

Urinary Tract Infection: Pathogenesis and Outlook

PubMed Central

McLellan, Lisa K.; Hunstad, David A.

2016-01-01

The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities. PMID:27692880

Proximal tubulopathies associated with monoclonal light chains: the spectrum of clinicopathologic manifestations and molecular pathogenesis.

PubMed

Herrera, Guillermo A

2014-10-01

Lesions associated with monoclonal light and heavy chains display a variety of glomerular, tubular interstitial, and vascular manifestations. While some of the entities are well recognized, including light and heavy chain deposition diseases, AL (light chain) and AH (heavy chain) amyloidosis, and light chain ("myeloma") cast nephropathy, other lesions centered on proximal tubules are much less accurately identified, properly diagnosed, and adequately understood in terms of pathogenesis and molecular mechanisms involved. These proximal tubule-centered lesions are typically associated with monoclonal light chains and have not been reported in patients with circulating monoclonal heavy chains. To determine the incidence of proximal tubulopathies in a series of patients with monoclonal light chain-related renal lesions and characterize them with an emphasis on clinical correlations and elucidation of molecular mechanisms involved in their pathogenesis. A study of 5410 renal biopsies with careful evaluation of light microscopic, immunofluorescence, and electron microscopic findings was conducted to identify these monoclonal light/heavy chain-related lesions. In selected cases, ultrastructural immunolabeling was performed to better illustrate and understand molecular mechanisms involved or to resolve specific diagnostic difficulties. In all, 2.5% of the biopsies were diagnosed as demonstrating renal pathology associated with monoclonal light or heavy chains. Of these, approximately 46% were classified as proximal tubule-centered lesions, also referred to as monoclonal light chain-associated proximal tubulopathies. These proximal tubulopathies were divided into 4 groups defined by characteristic immunomorphologic manifestations associated with specific clinical settings. These are important lesions whose recognition in the different clinical settings is extremely important for patients' clinical management, therapeutic purposes, and prognosis. These entities have been segregated into 4 distinct variants, conceptualized morphologically and clinically. Specific mechanisms involved in their pathogenesis are proposed.

Gallbladder Cancer in the 21st Century

PubMed Central

Kanthan, Rani; Senger, Jenna-Lynn; Ahmed, Shahid; Kanthan, Selliah Chandra

2015-01-01

Gallbladder cancer (GBC) is an uncommon disease in the majority of the world despite being the most common and aggressive malignancy of the biliary tree. Early diagnosis is essential for improved prognosis; however, indolent and nonspecific clinical presentations with a paucity of pathognomonic/predictive radiological features often preclude accurate identification of GBC at an early stage. As such, GBC remains a highly lethal disease, with only 10% of all patients presenting at a stage amenable to surgical resection. Among this select population, continued improvements in survival during the 21st century are attributable to aggressive radical surgery with improved surgical techniques. This paper reviews the current available literature of the 21st century on PubMed and Medline to provide a detailed summary of the epidemiology and risk factors, pathogenesis, clinical presentation, radiology, pathology, management, and prognosis of GBC. PMID:26421012

Recent progress in melasma pathogenesis.

PubMed

Lee, Ai-Young

2015-11-01

Melasma is a common skin pigmentation condition. Given therapeutic difficulty as one of the biggest concerns, understanding of the etiology and pathogenesis of melasma becomes essential. UV irradiation, female sex hormones, and inflammatory processes are addressed as triggering factors with genetic predisposition. The mechanism of UV-induced melanogenesis has been extensively investigated as a model system to study melasma pathogenesis. Hitherto, treatment modalities for melasma are similar to other hyperpigmentation disorders. However, individual triggering factors induce a separate pigmentation disease, whose pathogenic mechanisms and clinical phenotypes are different from the ones encountered in melasma. Fortunately, there have been ongoing updates on melasma pathogenesis with regard to major triggering factors. Presence of certain factors working independently of UV exposure and role of dermal factors and microRNAs are being identified as novel discoveries about melasma pathogenesis. In this review, the melasma pathogenesis is reviewed in association with updated and new findings. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neuropathies in the setting of Neurofibromatosis tumor syndromes: Complexities and opportunities.

PubMed

Schulz, Alexander; Grafe, Peter; Hagel, Christian; Bäumer, Philipp; Morrison, Helen; Mautner, Victor-Felix; Farschtschi, Said

2018-01-01

The term 'Neurofibromatosis' (NF) comprises a group of rare diseases with related clinical presentations but distinct genetic conditions. All currently known types - NF1, NF2 and Schwannomatosis - predispose afflicted individuals to the development of glial cell-derived (gliogenic) tumors. Furthermore, the occurrence of neuropathic symptoms, which add to the overall neurologic disability of patients, has been described in all disease entities. We show that neuropathic symptoms are a common and clinically important, yet infrequently studied feature in the NF spectrum. However, the clinical relevance and respective underlying pathogenesis, varies greatly among the different NF types. In this review, we summarize and interpret the latest basic research findings, as well as clinical observations, in respect of Neurofibromatosis-associated neuropathies. Copyright © 2017 Elsevier Inc. All rights reserved.

Isolated acquired factor VII deficiency: review of the literature.

PubMed

Mulliez, Sylvie M N; Devreese, Katrien M J

2016-04-01

Isolated acquired factor VII (FVII) deficiency is a rare haemorrhagic disorder. We report what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of acquired FVII deficiency. We performed a literature search and included all articles published between 1980 and August 2015. Acquired FVII deficiency has been reported in 42 patients. There are well-established clinical diseases associated with acquired FVII deficiency, most notably infections, malignancy and haematological stem cell transplantation. The exact pathogenesis of the diseases is still unknown, but different pathophysiological hypotheses have been suggested. The clinical manifestation of acquired FVII deficiency varies greatly in severity; asymptomatic course as well as severe life-threatening bleeding diathesis and fatal bleedings have been described.

[Morphology and pathogenesis of visceral manifestations of chronic alcoholism].

PubMed

Lebedev, S P

1982-01-01

Chronic alcoholism is accompanied by systemic involvement of the internal organs. Clinico-morphological forms of chronic alcoholism are distinguished on the basis of the prevailing organ pathology, Morphological data are presented, and pathogenesis of the lesions of the liver, heart, pancreas, and kidneys in patients with chronic alcoholism is analysed. The hepatic form may present alcoholic dystrophy, hepatitis or cirrhosis which are stages of progressing hepatopathy. The toxic and metabolic effect of ethanol is important in the pathogenesis of liver lesion. The cardiac form is characterized by the development of alcoholic myocardiodystrophy. In addition to the toxic influence of ethanol, hormonal and electrolyte changes and microcirculatory disorders play a role in its pathogenesis. Chronic calcifying pancreatitis in chronic alcoholism is associated with the effect of ethanol on the mediatory system. The renal form any present necronephrosis, hepatorenal syndrome, glomerulonephritis or pyelonephritis. Their pathogenesis is determined by toxicity of ethanol, circulation of immune complexes in the blood, or immunosuppression.

[Non-AIDS-associated cancer disorders. A novel scenario after over thirty years from HIV discovery? Clinical experience and literature appraisal].

PubMed

Manfredi, Roberto; Cascavilla, Alessandra; Calza, Leonardo

2015-08-01

Both natural history and epidemiological trend of HIV infection have been deeply modified by the introduction of highly active antiretroviral therapy (HAART), around twenty years ago. However, despite a rapid drop of the incidence of the large majority of opportunistic infections, a slow, but continued increase of malignancies occurred, with particular evidence focused on cancers which are not strictly related to the definition of full blown AIDS (the so called non-AIDS-defining malignancies). The unique clinical occurrence of HIV infection complicated by even four non-AIDS-defining cancers prompted us to re-discuss the epidemiology and the possible pathogenesis, the clinical presentation, and the differential diagnosis of this pathologic presentation. On the ground of our experience in this field, and the available literature evidences, we discuss how this clinical occurrence is acting on HIV infection presentation during the HAART era of the third millennium. These changes need broad scale studies, and promise relevant consequences on etiopathogenetic, prevention, therapeutic, and management aspects of HIV disease in the next future.

Bartonella Species, an Emerging Cause of Blood-Culture-Negative Endocarditis.

PubMed

Okaro, Udoka; Addisu, Anteneh; Casanas, Beata; Anderson, Burt

2017-07-01

Since the reclassification of the genus Bartonella in 1993, the number of species has grown from 1 to 45 currently designated members. Likewise, the association of different Bartonella species with human disease continues to grow, as does the range of clinical presentations associated with these bacteria. Among these, blood-culture-negative endocarditis stands out as a common, often undiagnosed, clinical presentation of infection with several different Bartonella species. The limitations of laboratory tests resulting in this underdiagnosis of Bartonella endocarditis are discussed. The varied clinical picture of Bartonella infection and a review of clinical aspects of endocarditis caused by Bartonella are presented. We also summarize the current knowledge of the molecular basis of Bartonella pathogenesis, focusing on surface adhesins in the two Bartonella species that most commonly cause endocarditis, B. henselae and B. quintana . We discuss evidence that surface adhesins are important factors for autoaggregation and biofilm formation by Bartonella species. Finally, we propose that biofilm formation is a critical step in the formation of vegetative masses during Bartonella -mediated endocarditis and represents a potential reservoir for persistence by these bacteria. Copyright © 2017 American Society for Microbiology.

Activation of Type I Interferon Pathway in Systemic Lupus Erythematosus: Association with Distinct Clinical Phenotypes

PubMed Central

Karageorgas, Theophanis P.; Tseronis, Dimitrios D.; Mavragani, Clio P.

2011-01-01

Growing evidence over the last few years suggests a central role of type I IFN pathway in the pathogenesis of systemic autoimmune disorders. Data from clinical and genetic studies in patients with systemic lupus erythematosus (SLE) and lupus-prone mouse models, indicates that the type I interferon system may play a pivotal role in the pathogenesis of several lupus and associated clinical features, such as nephritis, neuropsychiatric and cutaneous lupus, premature atherosclerosis as well as lupus-specific autoantibodies particularly against ribonucleoproteins. In the current paper, our aim is to summarize the latest findings supporting the association of type I IFN pathway with specific clinical manifestations in the setting of SLE providing insights on the potential use of type I IFN as a therapeutic target. PMID:22162633

Pathogenesis of coxsackievirus B2 in mice: characterization of clinical isolates of the coxsackievirus B2 from patients with myocarditis and aseptic meningitis in Korea.

PubMed

Hong, Jiyoung; Kang, Bunghak; Yeo, Sanggu; Jee, Youngmee; Park, Jae-Hak

2017-12-31

Group B coxsackieviruses (CVBs) are a group of common human pathogens producing various clinical symptoms. Although the virology of CVB is well known, there is limited information on viral pathogenesis and the relationship between clinical symptoms and viral phenotype, particularly for CVB type 2 (CVB2). In 2004 in Korea, two CVB2 strains were isolated: CB2/04/279 from stool of an acute myocarditis patient with heart failure and CB2/04/243 from an aseptic meningitis patient. In this study, a high degree of homology was observed between the CB2/04/279 and CB2/04/243 full genome sequences. The two Korean CVB2 isolates had 93.1% homology compared to 82.1%-82.5% nucleotide sequence identity with the cardiovirulence-associated reference CVB strain Ohio-1 (CVB/O). CVB2-induced pathogenesis was analyzed, focusing on virus-induced pathology of various tissues in 4-week-old BALB/c inbred male mice. Myocarditis developed and extensive pancreatic inflammation was observed in all mice infected with CB2/04/279 or CVB/O, but not in animals infected with CB2/04/243. This is the first report of the full-genomic sequence and pathogenesis of the CVB2 strain isolated from an acute myocarditis patient in Korea.

Chronic Inflammatory Demyelinating Polyneuropathy

PubMed Central

Dimachkie, Mazen M.; Barohn, Richard J.

2014-01-01

Opinion statement Chronic Inflammatory polyneuropathies are an important group of neuromuscular disorders that present chronically and progress over more than 8 weeks, being referred to as chronic inflammatory demyelinating polyneuropathy (CIDP). Despite tremendous progress in elucidating disease pathogenesis, the exact triggering event remains unknown. Our knowledge regarding diagnosis and management of CIDP and its variants continues to expand, resulting in improved opportunities for identification and treatment. Most clinical neurologists will be involved in the management of patients with these disorders, and should be familiar with available therapies for CIDP. We review the distinctive clinical, laboratory, and electro-diagnostic features that aid in diagnosis. We emphasize the importance of clinical patterns that define treatment responsiveness and the most appropriate therapies in order to improve prognosis. PMID:23564314

Two cases of traumatic head injury mimicking acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Nishiyama, Masahiro; Fujita, Kyoko; Maruyama, Azusa; Nagase, Hiroaki

2014-11-01

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) presents a distinct clinical course of biphasic seizures and impaired consciousness. These symptoms are followed by reduced diffusion in the subcortical white matter on magnetic resonance imaging that is typically observed between 3 and 9 days after illness onset. Here, we report two cases of traumatic head injury with clinical and radiological features similar to those for AESD. The similarities between our cases and AESD may be useful in understanding the pathogenesis of AESD. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Molecular pathogenesis of viral hemorrhagic fever.

PubMed

Basler, Christopher F

2017-07-01

The clinical syndrome referred to as viral hemorrhagic fever (VHF) can be caused by several different families of RNA viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. VHF is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. Study of the filovirus Ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenesis. Additionally, antigen-presenting cells are targets of productive infection and immune dysregulation. Among these cell populations, monocytes and macrophages are proposed to produce damaging inflammatory cytokines, while infected dendritic cells fail to undergo proper maturation, potentially impairing adaptive immunity. Uncontrolled virus replication and accompanying inflammatory responses are thought to promote vascular leakage and coagulopathy. However, the specific molecular pathways that underlie these features of VHF remain poorly understood. The arenavirus Lassa virus and the flavivirus yellow fever virus exhibit similar molecular pathogenesis suggesting common underlying mechanisms. Because non-human primate models that closely mimic VHF are available for Ebola, Lassa, and yellow fever viruses, we propose that comparative molecular studies using these models will yield new insights into the molecular underpinnings of VHF and suggest new therapeutic approaches.

Investigating the Pathogenesis of Severe Malaria: A Multidisciplinary and Cross-Geographical Approach

PubMed Central

Wassmer, Samuel C.; Taylor, Terrie E.; Rathod, Pradipsinh K.; Mishra, Saroj K.; Mohanty, Sanjib; Arevalo-Herrera, Myriam; Duraisingh, Manoj T.; Smith, Joseph D.

2015-01-01

More than a century after the discovery of Plasmodium spp. parasites, the pathogenesis of severe malaria is still not well understood. The majority of malaria cases are caused by Plasmodium falciparum and Plasmodium vivax, which differ in virulence, red blood cell tropism, cytoadhesion of infected erythrocytes, and dormant liver hypnozoite stages. Cerebral malaria coma is one of the most severe manifestations of P. falciparum infection. Insights into its complex pathophysiology are emerging through a combination of autopsy, neuroimaging, parasite binding, and endothelial characterizations. Nevertheless, important questions remain regarding why some patients develop life-threatening conditions while the majority of P. falciparum-infected individuals do not, and why clinical presentations differ between children and adults. For P. vivax, there is renewed recognition of severe malaria, but an understanding of the factors influencing disease severity is limited and remains an important research topic. Shedding light on the underlying disease mechanisms will be necessary to implement effective diagnostic tools for identifying and classifying severe malaria syndromes and developing new therapeutic approaches for severe disease. This review highlights progress and outstanding questions in severe malaria pathophysiology and summarizes key areas of pathogenesis research within the International Centers of Excellence for Malaria Research program. PMID:26259939

Helicobacter pylori virulence and cancer pathogenesis

PubMed Central

Yamaoka, Yoshio; Graham, David Y

2014-01-01

Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro–in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies. PMID:25052757

Helicobacter pylori virulence and cancer pathogenesis.

PubMed

Yamaoka, Yoshio; Graham, David Y

2014-06-01

Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.

Anti-EGFR Agents: Current Status, Forecasts and Future Directions.

PubMed

Kwapiszewski, Radoslaw; Pawlak, Sebastian D; Adamkiewicz, Karolina

2016-12-01

The epidermal growth factor receptor (EGFR) is one of the most important and attractive targets for specific anticancer therapies. It is a robust regulator of pathways involved in cancer pathogenesis and progression. Thus far, clinical trials have demonstrated the benefits of monoclonal antibodies and synthetic tyrosine kinase inhibitors in targeting this receptor; however, novel strategies are still being developed. This article reviews the current state of efforts in targeting the EGFR in cancer therapy. Following a brief characterization of EGFR, we will present a complete list of anti-EGFR agents that are already approved, and available in clinical practice. Aside from the indications, we will present the sales forecasts and expiry dates of product patents for the selected agents. Finally, we discuss the novel anti-EGFR strategies that are currently in preclinical development.

[Giant epidermoid cyst of the skull with extra and intracranial extension. A case report].

PubMed

Akhaddar, A; Gazzaz, M; El Mostarchid, B; Kadiri, B; Lrhezzioui, J; Boucetta, M

2002-09-01

Intradiploic epidermoid cyst of the skull is a rare clinical entity that can exceptionally grow to a large size with intracranial extension. The authors report the case of a 38-year-old man with a giant epidermoid cyst of the parietal bone with extra and intracranial extension, presenting with focal neurological symptoms. The diagnosis was suggested at imaging (skull radiographs, CT and MRI), and confirmed at histology. Complete removal of the cyst and its capsule was performed followed by cranioplasty. Postoperatively, the patient was discharged free of symptoms. CT scan provides good evaluation of the bony lesion and may suggest intracranial extension. MRI is superior for evaluation of cerebral compression. The pathogenesis, clinical presentation, diagnostic evaluation and therapeutic management of these rare lesions are reviewed.

[The feasibility of the application of cryotherapy and radonotherapy for the treatment of the patients presenting with osteoarthritis].

PubMed

Vakulenko, O Y; Rassulova, M A; Razumov, A N

2017-12-05

Osteoarthritis (OA) is currently considered to be one of the most widespread diseases. Its main clinical symptoms include pain and dysfunction of joints. In the present review of the foreign and domestic literature, the questions of pathogenesis and risk factors underlying the development of osteoarthritis are discussed. The understanding of OA pathogenesis have altered essentially in the recent years which made necessary the search for the novel approaches to the treatment of this pathology. According to the modern views of OA origin and progression, its therapy should be based on the application of the combination of medicamentous and non-medicamentous modalities including, in particular, collective and individual activities focused on the implementation of the programs of therapeutic physical training as an obligatory component of ОА prophylaxis and treatment. The present review gives evidence of the feasibility of the application of the methods of cryotherapy and radonotherapy for the management of the patients suffering from osteoarthritis. It is emphasized that many recent publications report extensive investigations of the clinical and pathogenetic aspects of the application of these methods for the combined regenerative treatment of the patients presenting with gonarthrosis. The influence of cryotherapy and radonotherapy on the neuroendocrine and immune systems is discussed with special reference to the possibility of regulation of the metabolic processes and retardation of inflammation. It is concluded that the introduction of the above methods into the compulsory individual program for the regenerative treatment of patients presenting with osteoarthritis is pathologically substantiated since it greatly contributes to the reduction of pain and retardation of the progress of the disease. The main pharmaceutical preparations for the OA treatment remain to be slow-acting symptomatic medicines possessed of the chondro-protective effect.

Identification of syncytial mutations in a clinical isolate of herpes simplex virus 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muggeridge, Martin I.; Grantham, Michael L.; Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130

2004-10-25

Small polykaryocytes resulting from cell fusion are found in herpes simplex virus (HSV) lesions in patients, but their significance for viral spread and pathogenesis is unclear. Although syncytial variants causing extensive fusion in tissue culture can be readily isolated from laboratory strains, they are rarely found in clinical isolates, suggesting that extensive cell fusion may be deleterious in vivo. Syncytial mutations have previously been identified for several laboratory strains, but not for clinical isolates of HSV type 2. To address this deficiency, we studied a recent syncytial clinical isolate, finding it to be a mixture of two syncytial and onemore » nonsyncytial strain. The two syncytial strains have novel mutations in glycoprotein B, and in vitro cell fusion assays confirmed that they are responsible for syncytium formation. This panel of clinical strains may be ideal for examining the effect of increased cell fusion on pathogenesis.« less

What’s New in Neurofibromatosis? Proceedings From The 2009 NF Conference: New Frontiers

PubMed Central

Kissil, Joseph; Blakeley, Jaishri; Ferner, Rosalie; Huson, Susan; Kalamarides, Michel; Mautner, Victor-Felix; McCormick, Frank; Morrison, Helen; Packer, Roger; Ramesh, Vijaya; Ratner, Nancy; Rauen, Katherine A.; Stevenson, David; Hunter-Schaedle, Kim; North, Kathryn

2009-01-01

The NF Conference is the largest annual gathering of researchers and clinicians focused on neurofibromatosis and has been convened by the Children’s Tumor Foundation for over 20 years. The 2009 NF Conference was held in Portland, Oregon from June 13th – June 16th, 2009 and co-chaired by Kathryn North from the University of Sydney and The Children’s Hospital at Westmead, Sydney, Australia; and Joseph Kissil from the Wistar Institute, Philadelphia. The Conference included 80 platform presentations in 9 sessions over 4 days; over 100 abstracts presented as posters; and three Keynote presentations. To date, there have been tremendous advances in basic research in the pathogenesis of neurofibromatosis, and more recently in progress toward identifying effective drug therapies and the commencement of neurofibromatosis clinical trials. The NF Conference attendees have significantly increased (doubling from 140 in 2005 to 280 attending in 2009) with a significant increase in attendance of physicians and clinical researchers. Correspondingly the NF Conference scope has expanded to include translational research, clinical trials and clinical management issues while retaining a core of basic research. These themes are reflected in the highlights from the 2009 NF Conference presented here. PMID:20082461

Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

PubMed Central

Whitmore, S.Scott; Sohn, Elliott H.; Chirco, Kathleen R.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Mullins, Robert F.

2015-01-01

Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies. PMID:25486088

Complement activation and choriocapillaris loss in early AMD: implications for pathophysiology and therapy.

PubMed

Whitmore, S Scott; Sohn, Elliott H; Chirco, Kathleen R; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Mullins, Robert F

2015-03-01

Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

PubMed Central

Crampton, Steve P.; Morawski, Peter A.; Bolland, Silvia

2014-01-01

Systemic lupus erythematosus (SLE) represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS) and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease. PMID:25147296

EZH2 in Bladder Cancer, a Promising Therapeutic Target

PubMed Central

Martínez-Fernández, Mónica; Rubio, Carolina; Segovia, Cristina; López-Calderón, Fernando F.; Dueñas, Marta; Paramio, Jesús M.

2015-01-01

Bladder Cancer (BC) represents a current clinical and social challenge. The recent studies aimed to describe the genomic landscape of BC have underscored the relevance of epigenetic alterations in the pathogenesis of these tumors. Among the epigenetic alterations, histone modifications occupied a central role not only in cancer, but also in normal organism homeostasis and development. EZH2 (Enhancer of Zeste Homolog 2) belongs to the Polycomb repressive complex 2 as its catalytic subunit, which through the trimethylation of H3 (Histone 3) on K27 (Lysine 27), produces gene silencing. EZH2 is frequently overexpressed in multiple tumor types, including BC, and plays multiple roles besides the well-recognized histone mark generation. In this review, we summarize the present knowledge on the oncogenic roles of EZH2 and its potential use as a therapeutic target, with special emphasis on BC pathogenesis and management. PMID:26580594

The role of microbiota in the pathogenesis of schizophrenia and major depressive disorder and the possibility of targeting microbiota as a treatment option.

PubMed

Lv, Fengli; Chen, Suling; Wang, Lina; Jiang, Ronghuan; Tian, Hongjun; Li, Jie; Yao, Yudong; Zhuo, Chuanjun

2017-11-21

The importance of interactions between the brain and the gastrointestinal tract has been increasingly recognized in recent years. It has been proposed that dysregulation and abnormalities in the brain-gut axis contribute to the etiology of a variety of central nervous system disorders. Particularly, dysbiosis, or impaired microbiota, has been implicated in multiple neurological and psychological disorders. The present paper reviews current evidence and theories concerning the possible mechanisms by which microbiota dysfunction contributes to the pathogenesis of schizophrenia and major depressive disorder. Clinical trials that investigated the possibility of treating both illnesses by correcting and rebalancing microbiota with probiotics are also reviewed. Overall, despite the accumulated knowledge in this field, more studies are warranted and required to further our understanding of the brain-gut axis and the possibility of targeting microbiota as a treatment option for schizophrenia and major depressive disorder.

Urinary Tract Infection: Pathogenesis and Outlook.

PubMed

McLellan, Lisa K; Hunstad, David A

2016-11-01

The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oral lichen planus: focus on etiopathogenesis.

PubMed

Payeras, Márcia Rodrigues; Cherubini, Karen; Figueiredo, Maria Antonia; Salum, Fernanda Gonçalves

2013-09-01

Lichen planus is a chronic mucocutaneous inflammatory disease, which frequently affects the oral mucosa of white females over 40 years old. Its aetiology remains uncertain and the pathogenesis is still the object of much speculation. The present paper presents the most well known antigens, and describes the action of different cells and proteins associated with the development of that disease, as well as the possible agents involved with its malignant transformation. Different external agents, especially virus, and internal agents, like stress, and the heat shock protein antigen expression, associated or not, can alter the basal keratinocytes of the oral mucosa making them susceptible to apoptosis by CD8(+) cytotoxic T cell as well as activate matrix metalloproteinase and mast cell degranulation, which produce a great range of inflammatory mediators and cytokines determining the clinical onset of the disease. Regarding carcinogenesis, since it is a complex process and presents multifactorial origin, it is believed that there may be a synergism between intrinsic, such as inflammation mediators, and extrinsic agents (tobacco, alcohol, viral infections) for the OLP malignant transformation to occur. However, further studies are needed to better understand the origin, pathogenesis and process of malignant transformation of OLP. Copyright © 2013 Elsevier Ltd. All rights reserved.

Selected clinical chemistry analytes correlate with the pathogenesis of inclusion body hepatitis experimentally induced by fowl aviadenoviruses.

PubMed

Matos, Miguel; Grafl, Beatrice; Liebhart, Dieter; Schwendenwein, Ilse; Hess, Michael

2016-10-01

In the present study, clinical chemistry was applied to assess the pathogenesis and progression of experimentally induced inclusion body hepatitis (IBH). For this, five fowl aviadenovirus (FAdV) strains from recent IBH field outbreaks were used to orally inoculate different groups of day-old specific pathogen-free chickens, which were weighed, sampled and examined during necropsy by sequential killing. Mortalities of 50% and 30% were recorded in two groups between 6 and 9 days post-infection (dpi), along with a decreased weight of 23% and 20%, respectively, compared to the control group. Macroscopical changes were seen in the liver and kidney between 6 and 10 dpi, with no lesions being observed in the other organs. Histological lesions were observed in the liver and pancreas during the same period. Plasma was collected from killed birds of each group at each time point and the following clinical chemistry analytes were investigated: aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), bile acids, total protein, albumin, uric acid and lipase. Plasma protein profile, AST and GLDH, together with bile acids values paralleled the macroscopical and histopathological lesions in the liver, while plasma lipase activity levels coincided with lesions observed in pancreas. In agreement with the histology and clinical chemistry, viral load in the target organs, liver and pancreas, was highest at 7 dpi. Thus, clinical chemistry was found to be a valuable tool in evaluating and monitoring the progression of IBH in experimentally infected birds, providing a deeper knowledge of the underlying pathophysiological mechanisms of a FAdV infection in chickens.

Acute urinary retention in women due to urethral calculi: A rare case

PubMed Central

Turo, Rafal; Smolski, Michal; Kujawa, Magda; Brown, Stephen C.W.; Brough, Richard; Collins, Gerald N.

2014-01-01

We present a case of a 51-year-old woman with acute urinary retention caused by a urethral calculus. Urethral calculi in women are extremely rare and are usually formed in association with underlying genitourinary pathology. In this case, however, no pathology was detected via thorough urological evaluation. We discuss the pathogenesis, clinical presentation and treatment of urethral calculi. To our knowledge, this is the second reported case of a primary urethral calculus in a female with an anatomically normal urinary tract and the first in a middle-aged Caucasian female. PMID:24554984

Is Multiple Sclerosis an Autoimmune Disease?

PubMed Central

Wootla, Bharath; Eriguchi, Makoto; Rodriguez, Moses

2012-01-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS. PMID:22666554

An unusual case of osteonecrosis of the jaw associated with dengue fever and periodontitis.

PubMed

Indurkar, M S; Sethi, R

2016-03-01

Osteonecrosis is a disorder rarely occurring in the jaw. Dengue fever is a common mosquito-borne disease prevalent in many countries including India. The following report presents an interesting case of maxillary osteonecrosis in a middle aged male with a history of dengue infection. We also diagnosed symptoms of chronic periodontitis, which may have potentiated the necrosis. This case report will describe a novel clinical presentation and management of osteonecrosis of the jaw (ONJ) of unknown origin and a possible pathogenesis explaining the association of ONJ with dengue fever and periodontitis. © 2015 Australian Dental Association.

Management of hyperthyroidism due to Graves' disease: frequently asked questions and answers (if any).

PubMed

Bartalena, L; Chiovato, L; Vitti, P

2016-10-01

Graves' disease is the most common cause of hyperthyroidism in iodine-replete areas. Although progress has been made in our understanding of the pathogenesis of the disease, no treatment targeting pathogenic mechanisms of the disease is presently available. Therapies for Graves' hyperthyroidism are largely imperfect because they are bound to either a high rate of relapsing hyperthyroidism (antithyroid drugs) or lifelong hypothyroidism (radioiodine treatment or thyroidectomy). Aim of the present article is to offer a practical guidance to the reader by providing evidence-based answers to frequently asked questions in clinical practice.

Pathology and differential diagnosis of chronic, noninfectious gastritis.

PubMed

Polydorides, Alexandros D

2014-03-01

The histologic finding of chronic inflammation in an endoscopic mucosal biopsy of the stomach (chronic gastritis) is very common and usually reflects the presence of Helicobacter pylori infection. However, infectious organisms are not always present in biopsy material, and some cases of chronic gastritis do not result from H. pylori infection. Thus, the differential diagnosis of this finding is an important one for pathologists to keep in mind. This review presents the three most common and clinically significant causes of chronic, noninfectious gastritis, namely, autoimmune atrophic gastritis, lymphocytic gastritis, and gastric involvement in the setting of inflammatory bowel disease, especially Crohn disease. For each entity, a brief discussion of its etiology and pathogenesis, a review of the clinical and endoscopic features, and a description of the microscopic findings are presented in the context of the differential diagnosis of chronic gastritis with emphasis on helpful histopathologic hints and long-term sequelae. Copyright © 2014 Elsevier Inc. All rights reserved.

Animal models of Parkinson's disease: limits and relevance to neuroprotection studies.

PubMed

Bezard, Erwan; Yue, Zhenyu; Kirik, Deniz; Spillantini, Maria Grazia

2013-01-01

Over the last two decades, significant strides has been made toward acquiring a better knowledge of both the etiology and pathogenesis of Parkinson's disease (PD). Experimental models are of paramount importance to obtain greater insights into the pathogenesis of the disease. Thus far, neurotoxin-based animal models have been the most popular tools employed to produce selective neuronal death in both in vitro and in vivo systems. These models have been commonly referred to as the pathogenic models. The current trend in modeling PD revolves around what can be called the disease gene-based models or etiologic models. The value of utilizing multiple models with a different mechanism of insult rests on the premise that dopamine-producing neurons die by stereotyped cascades that can be activated by a range of insults, from neurotoxins to downregulation and overexpression of disease-related genes. In this position article, we present the relevance of both pathogenic and etiologic models as well as the concept of clinically relevant designs that, we argue, should be utilized in the preclinical development phase of new neuroprotective therapies before embarking into clinical trials. Copyright © 2013 Movement Disorders Society.

The Pathogenesis of Ebola Virus Disease.

PubMed

Baseler, Laura; Chertow, Daniel S; Johnson, Karl M; Feldmann, Heinz; Morens, David M

2017-01-24

For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.

Occult Hepatitis B (OBH) in Clinical Settings

PubMed Central

Alavian, Seyed Moayed; Miri, Seyed Mohammad; Hollinger, F. Blaine; Jazayeri, Seyed Mohammad

2012-01-01

Context Occult hepatitis B (OHB), or persistent HBV DNA in patients who are hepatitis B surface antigen (HBsAg) negative, is a recently recognized entity. In an attempt to summarize the issues, this review presents an overview of the current proposed hypothesis on the clinical relevance and also updates the knowledge on the classification of OHB in different clinical settings. Evidence Acquisition OHB could be found in different population and clinical backgrounds including: viral co-infections (with either human immunodeficiency or hepatitis C viruses), HBV chronic carriers, dialysis patients, transplantation settings and certain clinical situations (named in here: special clinical settings) with no apparent distinguishable clinical parameters. Results The exact magnitude, pathogenesis, and clinical relevance of OHB are unclear. Even the possible role exerted by this cryptic infection on liver disease outcome, and hepatocellular carcinoma development remains unknown. Conclusions Monitoring of Individuals with positive anti-HBc, mass immunization programs and improvement in diagnostic tools seem to be important to control the probability of transmission of HBV through cryptic HBV infection. PMID:23087749

[Functional (psychogenic) vertigo].

PubMed

Diukova, G M; Zamergrad, M V; Golubev, V L; Adilova, S M; Makarov, S A

Psychogenic (functional) vertigo is in second place by frequency after benign positional paroxysmal vertigo. It is often difficult to make the diagnosis, diagnostic program is expensive and traditional treatment often is not effective. This literature review covers current concepts on the terminology, clinical signs, pathogenesis and treatment approaches with regard to functional vertigo. Special attention is given to cerebral mechanisms of the pathogenesis including cognitive aspects.

Role of natural killer cells in lung cancer.

PubMed

Aktaş, Ozge Nur; Öztürk, Ayşe Bilge; Erman, Baran; Erus, Suat; Tanju, Serhan; Dilege, Şükrü

2018-06-01

One of the key immune cells involved in the pathogenesis of lung cancer is natural killer (NK) cells and these cells are novel targets for therapeutic applications in lung cancer. The purpose of this review is to summarize the current literature on lung cancer pathogenesis with a focus on the interaction between NK cells and smoking, how these factors are related to the pathogenesis of lung cancer and how NK cell-based immunotherapy effect lung cancer survival. The relevant literature from PubMed and Medline databases is reviewed in this article. The cytolytic potential of NK cells are reduced in lung cancer and increasing evidence suggests that improving NK cell functioning may induce tumor regression. Recent clinical trials on NK cell-based novel therapies such as cytokines including interleukin (IL)-15, IL-12 and IL-2, NK-92 cell lines and allogenic NK cell immunotherapy showed promising results with less adverse effects on the lung cancer survival. The NK cell targeting strategy has not yet been approved for lung cancer treatment. More clinical studies focusing on the role of NK cells in lung cancer pathogenesis are warranted to develop novel NK cell-based therapeutic approaches for the treatment of lung cancer.

Treatment and pathogenesis of acute hyperkalemia

PubMed Central

Mushiyakh, Yelena; Dangaria, Harsh; Qavi, Shahbaz; Ali, Noorjahan; Pannone, John; Tompkins, David

2012-01-01

This article focuses on the pathogenesis, clinical manifestations, and various treatment modalities for acute hyperkalemia and presents a systematic approach to selecting a treatment strategy. Hyperkalemia, a life-threatening condition caused by extracellular potassium shift or decreased renal potassium excretion, usually presents with non-specific symptoms. Early recognition of moderate to severe hyperkalemia is vital in preventing fatal cardiac arrhythmias and muscle paralysis. Management of hyperkalemia includes the elimination of reversible causes (diet, medications), rapidly acting therapies that shift potassium into cells and block the cardiac membrane effects of hyperkalemia, and measures to facilitate removal of potassium from the body (saline diuresis, oral binding resins, and hemodialysis). Hyperkalemia with potassium level more than 6.5 mEq/L or EKG changes is a medical emergency and should be treated accordingly. Treatment should be started with calcium gluconate to stabilize cardiomyocyte membranes, followed by insulin injection, and b-agonists administration. Hemodialysis remains the most reliable method to remove potassium from the body and should be used in cases refractory to medical treatment. Prompt detection and proper treatment are crucial in preventing lethal outcomes. PMID:23882341

Pathogenesis and morbidity of autoantibody syndromes in Waldenstrom's macroglobulinemia.

PubMed

Stone, Marvin J

2011-02-01

A number of autoantibody syndromes have been identified that are mediated by monoclonal macroglobulins. Chronic cold agglutinin disease (CAD), mixed cryoglobulinemia (MC), and various polyneuropathies produce symptoms and signs such as cold sensitivity and sensorimotor neuropathies that bring the patients to attention ("the patients tell you"). Many of these patients would be classified as having monoclonal gammopathy of undetermined significance (MGUS) were it not for the consequences of antigen-antibody interaction. Other patients with autoantibody syndromes have overt Waldenström's macroglobulinemia (WM). These individuals present at an earlier stage than WM patients who do not have evident antibody activity. Thus the presence of autoreactive antibodies influences clinical presentation and natural history of the disorder. The frequency of monoclonal IgMs with functional antibody activity is unknown. The principal problem is detection. New methods have been described which may more precisely identify the antigens reacting with M-proteins. Some "autoimmune" disorders may represent cross-reactions to exogenous antigens. Elucidation of antigens reacting with monoclonal IgM proteins may provide important insights into the pathogenesis of WM.

Biological and Clinical Implications of Comorbidities in Parkinson’s Disease

PubMed Central

Santiago, Jose A.; Bottero, Virginie; Potashkin, Judith A.

2017-01-01

A wide spectrum of comorbidities has been associated with Parkinson’s disease (PD), a progressive neurodegenerative disease that affects more than seven million people worldwide. Emerging evidence indicates that chronic diseases including diabetes, depression, anemia and cancer may be implicated in the pathogenesis and progression of PD. Recent epidemiological studies suggest that some of these comorbidities may increase the risk of PD and precede the onset of motor symptoms. Further, drugs to treat diabetes and cancer have elicited neuroprotective effects in PD models. Nonetheless, the mechanisms underlying the occurrence of these comorbidities remain elusive. Herein, we discuss the biological and clinical implications of comorbidities in the pathogenesis, progression, and clinical management, with an emphasis on personalized medicine applications for PD. PMID:29255414

Inhibition of plasma lipid oxidation induced by peroxyl radicals, peroxynitrite, hypochlorite, 15-lipoxygenase, and singlet oxygen by clinical drugs.

PubMed

Morita, Mayuko; Naito, Yuji; Yoshikawa, Toshikazu; Niki, Etsuo

2016-11-15

With increasing evidence showing the involvement of oxidative stress in the pathogenesis of various diseases, the effects of clinical drugs possessing antioxidant functions have received much attention. The unregulated oxidative modification of biological molecules leading to diseases is mediated by multiple oxidants including free radicals, peroxynitrite, hypochlorite, lipoxygenase, and singlet oxygen. The capacity of antioxidants to scavenge or quench oxidants depends on the nature of oxidants. In the present study, the antioxidant effects of several clinical drugs against plasma lipid oxidation induced by the aforementioned five kinds of oxidants were investigated from the production of lipid hydroperoxides, which have been implicated in the pathogenesis of various diseases. Troglitazone acted as a potent peroxyl radical scavenger, whereas probucol and edaravone showed only moderate reactivity and carvedilol, pentoxifylline, and ebselen did not act as radical scavenger. Probucol and edaravone suppressed plasma oxidation mediated by peroxynitrite and hypochlorite. Troglitazone and edaravone inhibited 15-lipoxygenase mediated plasma lipid oxidation, the IC 50 being 20 and 34μM respectively. None of the drugs used in this study suppressed plasma lipid oxidation by singlet oxygen. This study shows that the antioxidant effects of drugs depend on the nature of oxidants and that antioxidants against multiple oxidants are required to cope with oxidative stress in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

New testing options for diagnosing and grading dry eye disease.

PubMed

Foulks, Gary N; Pflugfelder, Stephen C

2014-06-01

To describe new options for diagnosis and severity grading of dry eye disease. Perspective on technological advancements to identify tear dysfunction and their value in diagnosing and grading dry eye disease. Evidence is presented on new and evolving technologies to measure tear stability, composition, and meniscus height and their role in dry eye diagnosis and therapeutic efficacy grading is assessed. Evolving concepts regarding pathogenesis and new technologies to evaluate the tears and ocular surface have improved the ability to diagnose, classify, and grade the severity of dry eye disease. New technologies include noninvasive imaging of tear stability and tear meniscus height as a measure of tear volume and tear composition (osmolarity, lacrimal factors, inflammatory mediators, growth and differentiation factors). Approved tests, such as tear osmolarity and tear imaging, are being integrated into clinical practice and may eventually supplant certain traditional tests that have greater variability and less sensitivity. Other tests, such as molecular assays of tears and conjunctival cells, are currently being used in studies investigating pathogenesis and therapeutic mechanism of action. They may eventually translate to routine clinical practice. New technologies have emerged that can noninvasively evaluate the tears and measure disease-associated compositional changes. These tests are being integrated into clinical practice and therapeutic trials for diagnosis, classification, and severity grading of dry eye disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Hyperammonemia and Systemic Inflammatory Response Syndrome Predicts Presence of Hepatic Encephalopathy in Dogs with Congenital Portosystemic Shunts

PubMed Central

Tivers, Mickey S.; Handel, Ian; Gow, Adam G.; Lipscomb, Vicky J.; Jalan, Rajiv; Mellanby, Richard J.

2014-01-01

Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced. PMID:24392080

Hyperammonemia and systemic inflammatory response syndrome predicts presence of hepatic encephalopathy in dogs with congenital portosystemic shunts.

PubMed

Tivers, Mickey S; Handel, Ian; Gow, Adam G; Lipscomb, Vicky J; Jalan, Rajiv; Mellanby, Richard J

2014-01-01

Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced.

Fluctuating lesion of the scalp after a journey to the tropics: a case of furunculoid myiasis.

PubMed

Geyer, Sara; Balakirski, Galina; Tappe, Dennis; Cacch, Claudio; Knüchel-Clarke, Ruth; Schmit, Laurenz

2018-02-15

Fluctuating lesions or furuncles of the scalp occur frequently in dermatological practice. This clinical condition is often caused by gram positive bacteria (e.g. staphylococcal or streptococcal skin infection) or fungal infection (e.g. Kerion celsi). However, a rare diagnosis such as myiasis might be considered, especially if a journey to an endemic area is reported. Herein, we present a case of furunculoid myiasis of the scalp and review the pathogenesis and therapeutic options to treat this condition.

Folliculitis decalvans: the use of dermatoscopy as an auxiliary tool in clinical diagnosis*

PubMed Central

Fabris, Mariana Rocha; Melo, Clarisse Pereira; Melo, Daniel Fernandes

2013-01-01

Folliculitis decalvans is an inflammatory presentation of cicatrizing alopecia characterized by inflammatory perifollicular papules and pustules. It generally occurs in adult males, predominantly involving the vertex and occipital areas of the scalp. The use of dermatoscopy in hair and scalp diseases improves diagnostic accuracy. Some trichoscopic findings, such as follicular tufts, perifollicular erythema, crusts and pustules, can be observed in folliculitis decalvans. More research on the pathogenesis and treatment options of this disfiguring disease is required for improving patient management. PMID:24173192

[Head posture in orthodontics: physiopathology and clinical aspects 2].

PubMed

Caltabiano, M; Verzi, P; Scire Scappuzzo, G

1989-01-01

The Authors review in orthodontic respects present knowledges about head posture involvement in craniofacial morphogenesis and pathology. Relationships between craniofacial morphology, craniocervical posture, craniomandibular posture, cervical spine curvature, hyoid bone position and posture of whole body in space are shown, in attempt to explain conditions such as "forward head posture", mouth breathing and some occlusal disorders. Main methods to evaluate craniocervical relations on lateral skull radiographs are analysed. Pathogenesis of pain syndromes associated with abnormal craniocervical and craniomandibular mechanics are also briefly treated.

Gene clusters of Hafnia alvei strain FB1 important in survival and pathogenesis: a draft genome perspective.

PubMed

Tan, Jia-Yi; Yin, Wai-Fong; Chan, Kok-Gan

2014-01-01

Hafnia alvei is an opportunistic pathogen involved in various types of nosocomical infections. The species has been found to inhabit food and mammalian guts. However, its status as an enteropathogen, and whether the food-inhabiting strains could be a source of gastrointestinal infection remains obscure. In this report we present a draft genome of H. alvei strain FB1 isolated from fish paste meatball, a food popular among Malaysian and Chinese populations. The data was generated on the Illumina MiSeq platform. A comparative study was carried out on FB1 against two other previously sequenced H. alvei genomes. Several gene clusters putatively involved in survival and pathogenesis of H. alvei FB1 in food and gut environment were characterised in this study. These include the widespread colonisation island (WCI), the tad locus that is known to play an essential role in biofilm formation, a eut operon that might contribute to advantage in nutrient acquisition in gut environment, and genes responsible for siderophore production This features enable the bacteria to successful colonise in the host gut environment. With the whole genome data of H. alvei FB1 presented in this study, we hope to provide an insight into future studies on this candidate of enteropathogen by looking into the possible mechanisms employed to survive stresses and gain advantage in competitions, which eventually leads to successful colonisation and pathogenesis. This is to serve as the basis for more effective clinical diagnosis and treatment.

Enterocolic lymphocytic phlebitis: clinicopathologic features and review of the literature.

PubMed

Ngo, Nyethane; Chang, Fuju

2007-07-01

Enterocolic lymphocytic phlebitis (ELP) is a recently described entity and is of unknown etiology and pathogenesis. It is characterized by phlebitis of the bowel wall and mesentery, without arterial involvement or evidence of systemic vasculitis. The clinical presentation of ELP is varied, but it most commonly manifests with signs of an acute abdomen. Clinical, radiologic, and endoscopic findings are often conflicting and misdiagnosis is common as venous thrombosis is not suspected. The diagnosis of ELP is obtained histologically. There is a spectrum of histologic features associated with ELP, which includes lymphocytic phlebitis, necrotizing phlebitis, granulomatous phlebitis, and myointimal hyperplasia. Other features include venous thrombi and acute ischemic changes of the intestine. Surgical resection of the affected bowel is usually curative and recurrences are rare. The clinical and histopathologic features of ELP are reviewed.

Pathogenesis of Salmonellosis: Salmonella Exotoxins

DTIC Science & Technology

1982-03-08

of Salmonella enteritidis , which included 9630 serotype newport, 9136 serotype newport, 10016 serotype javiana, and 8832, serotype javiana were also...supplied by Dr. T. Huber. Additionally, four clinical isolates of Salmonella enteritidis , which included 986 serotype typhimurium, 2000 serotype...77Z7I AD _ REPORT NUMBER 3 0 Pathogenesis of Salmonellosis: Salmonella Exotoxins Annual Progress Report (9/1/79-8/31/80) M Johnny W. Peterson, Ph.D

Differences in genetic background influence the induction of innate and acquired immune responses in chickens depending on the virulence of the infecting infectious bursal disease virus (IBDV) strain.

PubMed

Aricibasi, Merve; Jung, Arne; Heller, E Dan; Rautenschlein, Silke

2010-05-15

Previous studies and field observations have suggested that genetic background influences infectious bursal disease virus (IBDV) pathogenesis. However, the influence of the virulence of the infecting IBDV strain and the mechanisms underlying the differences in susceptibility are not known. In the present study IBDV pathogenesis was compared between specific-pathogen-free layer-type (LT) chickens, which are the most susceptible chicken for IBDV and have been used as the model for pathogenesis studies, and broiler-type (BT) chickens, which are known to be less susceptible to clinical infectious bursal disease (IBD). The innate and acquired immune responses were investigated after inoculation of an intermediate (i), virulent (v) or very virulent (vv) strain of IBDV. IBDV pathogenesis was comparable among genetic backgrounds after infection with iIBDV. After infection with vIBDV and vvIBDV, LT birds showed severe clinical disease and mortality, higher bursal lesion scores and IBDV-antigen load relative to BT birds. Circulating cytokine induction varied significantly in both timing and quantity between LT and BT birds and among virus strains (P<0.05). Evaluation of different immune cell populations by flow-cytometric analysis in the bursa of Fabricius provided circumstantial evidence of a stronger local T cell response in BT birds vs. LT birds after infection with the virulent strain. On the other hand, LT birds showed a more significant increase in circulating macrophage-derived immune mediators such as total interferon (IFN) and serum nitrite than BT birds on days 2 and 3 post-vIBDV infection (P<0.05). Stronger stimulation of innate immune reactions especially after vIBDV infection in the early phase may lead to faster and more severe lesion development accompanied by clinical disease and death in LT chickens relative to BT chickens. Interestingly, no significant differences were seen between genetic backgrounds in induction of the IBDV-specific humoral response: timing of IBDV-antibody induction and antibody levels were comparable between BT and LT birds. This study clearly demonstrates a significant influence of chickens' genetic background on disease outcome. The difference between backgrounds in IBDV susceptibility is further influenced by the virulence of the infecting virus strain. Copyright 2009 Elsevier B.V. All rights reserved.

Epithelioid inflammatory myofibroblastic sarcoma: a case report

PubMed Central

Clevenger, Jessica A.; Masters, Gregory A.; Bauer, Thomas L.; Nam, Brian T.

2015-01-01

Inflammatory myofibroblastic tumor (IMT) of the lung is a rare malignancy with few cases reported in the literature. Histologically, it is composed by spindle cells and an infiltrate of inflammatory cells. Children and young, non-smoking adults constitute the majority of cases, the clinical behavior ranges from a benign entity to a malignant process with rapid recurrence and metastatic progression. We present a case of epithelioid inflammatory myofibroblastic sarcoma (EIMS) of the pleura, a malignant variant of IMT, which was initially treated with debulking surgical resection followed by systemic chemotherapy. The tumor was found to have an anaplastic lymphoma kinase (ALK) gene rearrangement. An ALK directed tyrosine kinase inhibitor was used with an impressive response, the patient remains in remission nearly 1 year after presentation. The pathogenesis, pathologic findings, clinical behavior and imaging of pulmonary EIMS are discussed. PMID:26623133

A Case of Neuro-Behcet’s Disease Presenting with Central Neurogenic Hyperventilation

PubMed Central

Alkhachroum, Ayham M.; Saeed, Saba; Kaur, Jaspreet; Shams, Tanzila; De Georgia, Michael A.

2016-01-01

Patient: Female, 46 Final Diagnosis: Central hyperventilation Symptoms: Hyperventilation Medication: — Clinical Procedure: None Specialty: Neurology Objective: Unusual clinical course Background: Behcet’s disease is a chronic inflammatory disorder usually characterized by the triad of oral ulcers, genital ulcers, and uveitis. Central to the pathogenesis of Behcet’s disease is an autoimmune vasculitis. Neurological involvement, so called “Neuro-Behcet’s disease”, occurs in 10–20% of patients, usually from a meningoencephalitis or venous thrombosis. Case Report: We report the case of a 46-year-old patient with Neuro-Behcet’s disease who presented with central neurogenic hyperventilation as a result of brainstem involvement from venulitis. Conclusions: To the best of our knowledge, central neurogenic hyperventilation has not previously been described in a patient with Neuro-Behcet’s disease. PMID:26965646

The role of Epstein-Barr virus in systemic lupus erythematosus.

PubMed

McClain, M T; Harley, J B; James, J A

2001-10-01

Systemic lupus erythematosus (SLE) is a devastating autoimmune disease with no known cure. Lupus patients suffer from a myriad of clinical symptoms which variably include arthritis, pleuritis, pericarditis, vasculitis, and nephritis. The underlying mechanisms behind these clinical findings and the etiologic events preceding and causing disease onset, however, remain largely unknown. For many years, investigators have suspected that Epstein-Barr virus might somehow be involved in the etiology and/or pathogenesis of systemic lupus. Numerous studies have examined this possibility from various angles and have arrived at different conclusions. This work reviews these historical papers in the context of new results and presents a hypothetical role for this virus as an etiological environmental trigger for SLE.

An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock.

PubMed

Martillo, Miguel; Abed, Jean; Herman, Michael; Abed, Elie; Shi, Wenjing; Munot, Khushboo; Mankal, Pavan Kumar; Gurunathan, Rajan; Ionescu, Gabriel; Kotler, Donald P

2015-01-01

Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration.

Is irritable bowel syndrome also present in dogs?

PubMed

Cerquetella, Matteo; Rossi, Giacomo; Spaterna, Andrea; Tesei, Beniamino; Jergens, Albert E; Suchodolski, Jan S; Bassotti, Gabrio

2018-06-01

Irritable bowel syndrome (IBS) in humans is described as the recurrent presence of gastrointestinal signs, without gross histopathologic evidence of inflammation and of other morphologic lesions; however, it is a syndrome not unanimously defined in veterinary medicine. There is some evidence that dysmotility could be related to stressors in some dogs that present with clinical signs (e.g. chronic idiopathic large-bowel diarrhea) that share overlapping aspects with human IBS. The authors hypothesize that an IBS-like condition, similar to that described in humans, might also be present in dogs. Nevertheless, the diagnostic path for canine IBS needs to be further elucidated and its pathogenesis better defined for a more rational therapeutic approach. Schattauer GmbH.

Clinical Forms of Canine Visceral Leishmaniasis in Naturally Leishmania infantum–Infected Dogs and Related Myelogram and Hemogram Changes

PubMed Central

Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Reis, Levi Eduardo Soares; Carvalho, Maria das Graças; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Bouillet, Leoneide Erica Maduro; Lemos, Denise Silveira; Coura-Vital, Wendel; Reis, Alexandre Barbosa

2013-01-01

Hematological analysis has limited applications for disease diagnosis in Leishmania infantum–infected dogs, but it can be very important in evaluating the clinical forms of the disease and in understanding the evolution of canine visceral leishmaniasis (CVL) pathogenesis. Recently, we demonstrated that alterations in leucopoiesis and erythropoiesis are related to clinical status and bone marrow parasite density in dogs naturally infected by L. infantum. To further characterize these alterations, we evaluated the association between the hematological parameters in bone marrow and peripheral blood alterations in groups of L. infantum–infected dogs: asymptomatic I (AD-I: serum negative/PCR+), asymptomatic II (AD-II: serum positive), oligosymptomatic (OD), and symptomatic (SD). Results were compared with those from noninfected dogs (NID). The SD group was found to present a decrease in erythropoietic lineage with concomitant reductions in erythrocytes, hemoglobin, and hematocrit parameters, resulting in anemia. The SD group also had increased neutrophils and precursors and decreased band eosinophils and eosinophils, leading to peripheral blood leucopenia. In the AD-II group, lymphocytosis occurred in both the peripheral blood and the bone marrow compartments. The SD group exhibited lymphocytosis in the bone marrow, with lymphopenia in the peripheral blood. In contrast, the AD-I group, showed no significant changes suggestive of CVL, presenting normal counts in bone marrow and peripheral blood. Our results showed for the first time that important changes in hematopoiesis and hematological parameters occur during ongoing CVL in naturally infected dogs, mainly in symptomatic disease. Taken together, our results based on myelogram and hemogram parameters enable better understanding of the pathogenesis of the anemia, lymphocytosis, and lymphopenia, as well as the leucopenia (eosinopenia and monocytopenia), that contribute to CVL prognosis. PMID:24376612

Immunopathogenesis of Dengue Virus-Induced Redundant Cell Death: Apoptosis and Pyroptosis.

PubMed

Suwanmanee, San; Luplertlop, Natthanej

Dengue virus infection is a self-limited condition, which is of particular importance in tropical and subtropical regions and for which no specific treatment or effective vaccine is available. There are several hypotheses explaining dengue pathogenesis. These usually refer to host immune responses, including antibody-dependent enhancement, cytokine expression, and dengue virus particles including NS1 protein, which lead to cell death by both apoptosis and pyroptosis. A clear understanding of the pathogenesis should facilitate the development of vaccines and therapies. This review focuses on the immunopathogenesis in relation to clinical manifestations and patterns of cell death, focusing on the pathogenesis of severe dengue.

Metabolic and Clinical Consequences of Hyperthyroidism on Bone Density

PubMed Central

Gorka, Jagoda; Taylor-Gjevre, Regina M.

2013-01-01

In 1891, Von Recklinghausen first established the association between the development of osteoporosis in the presence of overt hyperthyroidism. Subsequent reports have demonstrated that BMD loss is common in frank hyperthyroidism, and, to a lesser extent, in subclinical presentations. With the introduction of antithyroid medication in the 1940s to control biochemical hyperthyroidism, the accompanying bone disease became less clinically apparent as hyperthyroidism was more successfully treated medically. Consequently, the impact of the above normal thyroid hormones in the pathogenesis of osteoporosis may be presently underrecognized due to the widespread effective treatments. This review aims to present the current knowledge of the consequences of hyperthyroidism on bone metabolism. The vast number of recent papers touching on this topic highlights the recognized impact of this common medical condition on bone health. Our focus in this review was to search for answers to the following questions. What is the mechanisms of action of thyroid hormones on bone metabolism? What are the clinical consequences of hyperthyroidism on BMD and fracture risk? What differences are there between men and women with thyroid disease and how does menopause change the clinical outcomes? Lastly, we report how different treatments for hyperthyroidism benefit thyroid hormone-induced osteoporosis. PMID:23970897

Host genetic determinants of HIV pathogenesis: an immunologic perspective.

PubMed

Hunt, Peter W; Carrington, Mary

2008-05-01

The purpose of this review is to highlight recent advances in our understanding of host genetic determinants of HIV pathogenesis and to provide a theoretical framework for interpreting these studies in the context of our evolving understanding of HIV immunopathogenesis. The first genome-wide association analysis of host determinants of HIV pathogenesis and other recent studies evaluating the interaction between killer cell immunoglobulin-like receptors and human leukocyte antigen alleles have implicated both adaptive and innate immune responses in the control of HIV replication. Furthermore, genetic variation associated with the expression of CCR5 and its ligand have been strongly associated with both decreased susceptibility to HIV infection and delayed clinical progression, independent of their effects on viral replication, suggesting a potential role for CCR5 inhibitors as immune-based therapies in HIV disease. Host factors associated with the control of HIV replication may help identify important targets for vaccine design, while those associated with delayed clinical progression provide targets for future immune-based therapies against HIV infection.

Molecular biology, pathogenesis and pathology of mumps virus

PubMed Central

Rubin, Steven; Eckhaus, Michael; Rennick, Linda J; Bamford, Connor GG; Duprex, W Paul

2014-01-01

Mumps is caused by the mumps virus (MuV), a member of the Paramyxoviridae family of enveloped, non-segmented, negative-sense RNA viruses. Mumps is characterized by painful inflammatory symptoms, such as parotitis and orchitis. The virus is highly neurotropic, with laboratory evidence of central nervous system (CNS) infection in approximately half of cases. Symptomatic CNS infection occurs less frequently; nonetheless, prior to the introduction of routine vaccination, MuV was a leading cause of aseptic meningitis and viral encephalitis in many developed countries. Despite being one of the oldest recognized diseases, with a worldwide distribution, surprisingly little attention has been given to its study. Cases of aseptic meningitis associated with some vaccine strains and a global resurgence of cases, including in highly vaccinated populations, has renewed interest in the virus, particularly in its pathogenesis and the need for development of clinically relevant models of disease. In this review we summarize the current state of knowledge on the virus, its pathogenesis and its clinical and pathological outcomes. PMID:25229387

Updates of the role of oxidative stress in the pathogenesis of ovarian cancer.

PubMed

Saed, Ghassan M; Diamond, Michael P; Fletcher, Nicole M

2017-06-01

Clinical and epidemiological investigations have provided evidence supporting the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS), collectively known as oxidative stress, in the etiology of cancer. Exogenous factors such as chronic inflammation, infection and hypoxia are major sources of cellular oxidative stress. Specifically, oxidative stress plays an important role in the pathogenesis, neoangiogenesis, and dissemination of local or distant ovarian cancer, as it is known to induce phenotypic modifications of tumor cells by cross talk between tumor cells and the surrounding stroma. Subsequently, the biological significance of the relationship between oxidative stress markers and various stages of epithelial ovarian cancer highlights potential therapeutic interventions as well as provides urgently needed early detection biomarkers. In the light of our scientific research and the most recent experimental and clinical observations, this review provides the reader with up to date most relevant findings on the role of oxidative stress in the pathogenesis of ovarian cancer and the possible therapeutic implications. Copyright © 2017 Elsevier Inc. All rights reserved.

Pigmented well-differentiated hepatocellular neoplasm with beta-catenin mutation.

PubMed

Souza, Lara Neves; de Martino, Rodrigo Bronze; Thompson, Richard; Strautnieks, Sandra; Heaton, Nigel D; Quaglia, Alberto

2015-12-01

According to the most recent WHO classification of hepatocellular adenomas, a small percentage of inflammatory hepatocellular adenomas presents with mutation in the beta-catenin gene and are at higher risk of malignant transformation. It has been recognized that adenoma-like hepatocellular neoplasms with focal atypia, or in unusual clinical context present with similar cytogenetic and immunohistochemistry characteristics to well-differentiated hepatocellular carcinomas. We report a case of a well-differentiated hepatocellular neoplasm with Dubin-Johnson-like pigment displaying histological features overlapping with a beta-catenin mutated inflammatory adenoma and a well-differentiated hepatocellular carcinoma in a non-cirrhotic liver. The patient was a 48-year-old woman, who was asymptomatic, and had a clinical history of intra-uterine exposure to diethylstilbestrol, previous cancers and past oral contraceptive use. The recently proposed term "well-differentiated hepatocellular neoplasm of uncertain malignant potential" should be applied in such cases to highlight the different pathogenesis and risk of malignancy compared to the typical adenomas, and to suggest a careful and customized clinical management.

Characterization of clinical and immunological features in patients coinfected with dengue virus and HIV.

PubMed

Torrentes-Carvalho, Amanda; Hottz, Eugênio Damaceno; Marinho, Cintia Ferreira; da Silva, Jéssica Badolato-Corrêa; Pinto, Luzia Maria de Oliveira; Fialho, Luciana Gomes; Bozza, Fernando Augusto; Cunha, Rivaldo Venâncio; Damasco, Paulo Vieira; Kubelka, Claire Fernandes; de Azeredo, Elzinandes Leal

2016-03-01

The pathogenesis of dengue in subjects coinfected with HIV remains largely unknown. We investigate clinical and immunological parameters in coinfected DENV/HIV patients. According to the new dengue classification, most coinfected DENV/HIV patients presented mild clinical manifestations of dengue infection. Herein, we show that DENV/HIV coinfected patients had higher CD8 T cells percentages reflected as a lower CD4/CD8 ratio. Furthermore, CCR5 expression on CD4 T cells and CD107a expression on both T subsets were significantly higher in coinfected patients when compared with monoinfected DENV and HIV individuals respectively. Increased inflammatory response was observed in treated HAART coinfected patients despite undetectable HIV load. These data indicate that DENV infection may influence the clinical profile and immune response in individuals concomitantly infected with HIV. Copyright © 2016 Elsevier Inc. All rights reserved.

[Research progress of needles with knife-edge for carotid cardiac syndrome].

PubMed

Tan, Lingqiong; Zhao, Yanling

2015-04-01

According to topographic anatomy, pathogenesis and by retrieving, summarizing and analyzing literature regarding needle-knife and needles with knife-edge for carotid cardiac syndrome, it is found out that clinical misdiagnosis rate of carotid cardiac syndrome is considerably high. Needle-knife and needles with knife-edge could significantly improve the clinical symptoms of carotid cardiac syndrome, showing characteristic and advantage in treatment, but it is deficient in technique standard and efficacy criteria that should be united and authoritative. Researches regarding pathogenesis of carotid cardiac syndrome are not systematic. Clinical observation regarding long-term efficacy and relapse of needle-knife and needles with knife-edge treatment is rare. It is believed that the awareness on carotid cardiac syndrome should be increased to reduce misdiagnosis; scientific and standardized technique standard and efficacy criteria should be established; systematic and comprehensive researches regarding mechanism of needle-knife and needles with knife-edge for carotid cardiac syndrome should be launched; besides, clinical discussion regarding its long-term efficacy should start to provide a better clinical guideline.

Update on pathogenesis and clinical management of acute pancreatitis

PubMed Central

Cruz-Santamaría, Dulce M; Taxonera, Carlos; Giner, Manuel

2012-01-01

Acute pancreatitis (AP), defined as the acute nonbacterial inflammatory condition of the pancreas, is derived from the early activation of digestive enzymes found inside the acinar cells, with variable compromise of the gland itself, nearby tissues and other organs. So, it is an event that begins with pancreatic injury, elicits an acute inflammatory response, encompasses a variety of complications and generally resolves over time. Different conditions are known to induce this disorder, although the innermost mechanisms and how they act to develop the disease are still unknown. We summarize some well established aspects. A phase sequence has been proposed: etiology factors generate other conditions inside acinar cells that favor the AP development with some systemic events; genetic factors could be involved as susceptibility and modifying elements. AP is a disease with extremely different clinical expressions. Most patients suffer a mild and limited disease, but about one fifth of cases develop multi organ failure, accompanied by high mortality. This great variability in presentation, clinical course and complications has given rise to the confusion related to AP related terminology. However, consensus meetings have provided uniform definitions, including the severity of the illness. The clinical management is mainly based on the disease´s severity and must be directed to correct the underlying predisposing factors and control the inflammatory process itself. The first step is to determine if it is mild or severe. We review the principal aspects to be considered in this treatment, as reflected in several clinical practice guidelines. For the last 25 years, there has been a global increase in incidence of AP, along with many advances in diagnosis and treatment. However, progress in knowledge of its pathogenesis is scarce. PMID:22737590

Hegemonic structure of basic, clinical and patented knowledge on Ebola research: a US army reductionist initiative.

PubMed

Fajardo-Ortiz, David; Ortega-Sánchez-de-Tagle, José; Castaño, Victor M

2015-04-19

Ebola hemorrhagic fever (Ebola) is still a highly lethal infectious disease long affecting mainly neglected populations in sub-Saharan Africa. Moreover, this disease is now considered a potential worldwide threat. In this paper, we present an approach to understand how the basic, clinical and patent knowledge on Ebola is organized and intercommunicated and what leading factor could be shaping the evolution of the knowledge translation process for this disease. A combination of citation network analysis; analysis of Medical heading Subject (MeSH) and Gene Ontology (GO) terms, and quantitative content analysis for patents and scientific literature, aimed to map the organization of Ebola research was carried out. We found six putative research fronts (i.e. clusters of high interconnected papers). Three research fronts are basic research on Ebola virus structural proteins: glycoprotein, VP40 and VP35, respectively. There is a fourth research front of basic research papers on pathogenesis, which is the organizing hub of Ebola research. A fifth research front is pre-clinical research focused on vaccines and glycoproteins. Finally, a clinical-epidemiology research front related to the disease outbreaks was identified. The network structure of patent families shows that the dominant design is the use of Ebola virus proteins as targets of vaccines and other immunological treatments. Therefore, patents network organization resembles the organization of the scientific literature. Specifically, the knowledge on Ebola would flow from higher (clinical-epidemiology) to intermediated (cellular-tissular pathogenesis) to lower (molecular interactions) levels of organization. Our results suggest a strong reductionist approach for Ebola research probably influenced by the lethality of the disease. On the other hand, the ownership profile of the patent families network and the main researches relationship with the United State Army suggest a strong involvement of this military institution in Ebola research.

Advances in Probes and Methods for Clinical EPR Oximetry

PubMed Central

Hou, Huagang; Khan, Nadeem; Jarvis, Lesley A.; Chen, Eunice Y.; Williams, Benjamin B.; Kuppusamy, Periannan

2015-01-01

EPR oximetry, which enables reliable, accurate, and repeated measurements of the partial pressure of oxygen in tissues, provides a unique opportunity to investigate the role of oxygen in the pathogenesis and treatment of several diseases including cancer, stroke, and heart failure. Building on significant advances in the in vivo application of EPR oximetry for small animal models of disease, we are developing suitable probes and instrumentation required for use in human subjects. Our laboratory has established the feasibility of clinical EPR oximetry in cancer patients using India ink, the only material presently approved for clinical use. We now are developing the next generation of probes, which are both superior in terms of oxygen sensitivity and biocompatibility including an excellent safety profile for use in humans. Further advances include the development of implantable oxygen sensors linked to an external coupling loop for measurements of deep-tissue oxygenations at any depth, overcoming the current limitation of 10 mm. This paper presents an overview of recent developments in our ability to make meaningful measurements of oxygen partial pressures in human subjects under clinical settings. PMID:24729217

The influence of innate and adaptative immune responses on the differential clinical outcomes of leprosy.

PubMed

Fonseca, Adriana Barbosa de Lima; Simon, Marise do Vale; Cazzaniga, Rodrigo Anselmo; de Moura, Tatiana Rodrigues; de Almeida, Roque Pacheco; Duthie, Malcolm S; Reed, Steven G; de Jesus, Amelia Ribeiro

2017-02-06

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. According to official reports from 121 countries across five WHO regions, there were 213 899 newly diagnosed cases in 2014. Although leprosy affects the skin and peripheral nerves, it can present across a spectrum of clinical and histopathological forms that are strongly influenced by the immune response of the infected individuals. These forms comprise the extremes of tuberculoid leprosy (TT), with a M. leprae-specific Th1, but also a Th17, response that limits M. leprae multiplication, through to lepromatous leprosy (LL), with M. leprae-specific Th2 and T regulatory responses that do not control M. leprae replication but rather allow bacterial dissemination. The interpolar borderline clinical forms present with similar, but less extreme, immune biases. Acute inflammatory episodes, known as leprosy reactions, are complications that may occur before, during or after treatment, and cause further neurological damages that can cause irreversible chronic disabilities. This review discusses the innate and adaptive immune responses, and their interactions, that are known to affect pathogenesis and influence the clinical outcome of leprosy.

Langerhans' cell histiocytosis with neurological injuries diagnosed from a single cutaneous lesion*

PubMed Central

Bannach, Andréa Bauer; Garcia, Maria Teresa Fernandes Castilho; Soares, Deusita Fernandes Gandia; Mattos, Antônio Luiz de Arruda; Barrese, Tomás Zecchini; de Abreu, Marilda Aparecida Milanez Morgado

2017-01-01

Histiocytoses are rare diseases caused by the proliferation of histiocytes. The pathogenesis remains unknown and the highest incidence occurs in pediatric patients. The clinical presentations can be varied, in multiple organs and systems, and the skin lesions are not always present. Evolution is unpredictable and treatment depends on the extent and severity of the disease. It is described the case of a patient with various neurological symptoms, extensively investigated, who had its was diagnosed with histiocytosis from a single skin lesion. This report highlights the importance of Dermatology in assisting the investigation of difficult cases in medical practice. PMID:28954107

Hypertriglyceridaemia-induced pancreatitis

PubMed Central

Weston, Natasha; Fernando, Upul; Baskar, Varadarajan

2013-01-01

Hypertriglyceridaemia is the third most common cause of acute pancreatitis but is relatively rare and therefore requires a high level of clinical suspicion to be diagnosed. We discuss the case of a 46-year-old man who initially presented to the accident and emergency department with suspected first presentation of diabetic ketoacidosis (DKA) and a normal amylase but who did not respond to DKA treatment. Further history revealed significant cardiovascular risk factors, examination showed an evidence of hyperlipidaemia and investigations revealed acute pancreatitis secondary to hypertriglyceridaemia. We discuss the causes of hypertriglyceridaemia, the difficulty in differentiating primary versus secondary hypertriglyceridaemia, possible pathogenesis and current evidence-based treatments. PMID:23446049

The past, present and future of renin–angiotensin aldosterone system inhibition☆

PubMed Central

Mentz, Robert J.; Bakris, George L.; Waeber, Bernard; McMurray, John J.V.; Gheorghiade, Mihai; Ruilope, Luis M.; Maggioni, Aldo P.; Swedberg, Karl; Piña, Ileana L.; Fiuzat, Mona; O’Connor, Christopher M.; Zannad, Faiez; Pitt, Bertram

2014-01-01

The renin–angiotensin aldosterone system (RAAS) is central to the pathogenesis of cardiovascular disease. RAAS inhibition can reduce blood pressure, prevent target organ damage in hypertension and diabetes, and improve outcomes in patients with heart failure and/or myocardial infarction. This review presents the history of RAAS inhibition including a summary of key heart failure, myocardial infarction, hypertension and atrial fibrillation trials. Recent developments in RAAS inhibition are discussed including implementation and optimization of current drug therapies. Finally, ongoing clinical trials, opportunities for future trials and issues related to the barriers and approvability of novel RAAS inhibitors are highlighted. PMID:23121914

Filgrastim as a Rescue Therapy for Persistent Neutropenia in a Case of Dengue Hemorrhagic Fever with Acute Respiratory Distress Syndrome and Myocarditis

PubMed Central

Deepak, Desh; Garg, Rakesh; Pawar, Mridula; Banerjee, Neerja; Solanki, Rakesh; Maurya, Indubala

2011-01-01

Pathogenesis of dengue involves suppression of immune system leading to development of characteristic presentation of haematological picture of thrombocytopenia and leucopenia. Sometimes, this suppression in immune response is responsible for deterioration in clinical status of the patient in spite of all specific and supportive therapy. Certain drugs like steroids are used for rescue therapy in conditions like sepsis. We present a novel use of filgrastim as a rescue therapy in a patient with dengue hemorrhagic fever (DHF) with acute respiratory distress syndrome (ARDS), myocarditis, and febrile neutropenia and not responding to standard management. PMID:22606398

Targeting Transfusion-Related Acute Lung Injury: The Journey From Basic Science to Novel Therapies.

PubMed

Semple, John W; McVey, Mark J; Kim, Michael; Rebetz, Johan; Kuebler, Wolfgang M; Kapur, Rick

2018-05-01

Transfusion-related acute lung injury is characterized by the onset of respiratory distress and acute lung injury following blood transfusion, but its pathogenesis remains poorly understood. Generally, a two-hit model is presumed to underlie transfusion-related acute lung injury with the first hit being risk factors present in the transfused patient (such as inflammation), whereas the second hit is conveyed by factors in the transfused donor blood (such as antileukocyte antibodies). At least 80% of transfusion-related acute lung injury cases are related to the presence of donor antibodies such as antihuman leukocyte or antihuman neutrophil antibodies. The remaining cases may be related to nonantibody-mediated factors such as biolipids or components related to storage and ageing of the transfused blood cells. At present, transfusion-related acute lung injury is the leading cause of transfusion-related fatalities and no specific therapy is clinically available. In this article, we critically appraise and discuss recent preclinical (bench) insights related to transfusion-related acute lung injury pathogenesis and their therapeutic potential for future use at the patients' bedside in order to combat this devastating and possibly fatal complication of transfusion. We searched the PubMed database (until August 22, 2017). Using terms: "Transfusion-related acute lung injury," "TRALI," "TRALI and therapy," "TRALI pathogenesis." English-written articles focusing on transfusion-related acute lung injury pathogenesis, with potential therapeutic implications, were extracted. We have identified potential therapeutic approaches based on the literature. We propose that the most promising therapeutic strategies to explore are interleukin-10 therapy, down-modulating C-reactive protein levels, targeting reactive oxygen species, or blocking the interleukin-8 receptors; all focused on the transfused recipient. In the long-run, it may perhaps also be advantageous to explore other strategies aimed at the transfused recipient or aimed toward the blood product, but these will require more validation and confirmation first.

Chemical sensitivity: pathophysiology or pathopsychology?

PubMed

Genuis, Stephen J

2013-05-01

Escalating numbers of people throughout the world are presenting to primary care physicians, allergists, and immunologists with myriad clinical symptoms after low-level exposure to assorted everyday chemicals such as smoke, perfumes, air fresheners, paints, glues, and other products. This clinical state is referred to by various diagnostic labels, including multiple chemical sensitivity disorder, environmental intolerance, chemical sensitivity (CS), and sensitivity-related illness, and has been the subject of much controversy within the health care community. The goal of this study was to provide a brief overview of the etiology, pathogenesis, clinical presentation, and management of CS. An evaluation of the medical community's response to this emerging diagnosis was also explored. This review was prepared by assessing available medical and scientific literature from MEDLINE, as well as by reviewing numerous books, toxicology journals, conference proceedings, government publications, and environmental health periodicals. A primary observation, however, is that there is limited scientific literature available on the issue of CS. The format of a traditional integrated review was chosen because such reviews play a pivotal role in scientific research and professional practice in medical issues with limited primary study and uncharted clinical territory. The sensitization state of CS seems to be initiated by a significant toxic exposure, occurring as a 1-time event, or on surpassing a threshold of toxicity after toxicant accrual from repeated lower-level exposures. Once sensitized through a toxicant-induced loss of tolerance, individuals exposed to inciting triggers such as minute amounts of diverse everyday chemicals may experience various clinical and immune sequelae, sometimes involving lymphocyte, antibody, or cytokine responses. Precautionary avoidance of inciting triggers will prevent symptoms, and desensitization immunotherapy or immune suppression may improve symptoms in some cases. Sustained resolution of the CS state occurs after successful elimination of the accrued body burden of toxicants through natural mechanisms of toxicant bioelimination and/or interventions of clinical detoxification. Despite extensive clinical evidence to support the veracity of this clinical state, many members of the medical community are reluctant to accept this condition as a pathophysiologic disorder. The emerging problem of ubiquitous adverse toxicant exposures in modern society has resulted in escalating numbers of individuals developing a CS disorder. As usual in medical history, iconoclastic ideas and emerging evidence regarding novel disease mechanisms, such as the pathogenesis of CS, have been met with controversy, resistance, and sluggish knowledge translation. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Childhood Ataxia: Clinical Features, Pathogenesis, Key Unanswered Questions, and Future Directions

PubMed Central

Ashley, Claire N.; Hoang, Kelly D.; Lynch, David R.; Perlman, Susan L.; Maria, Bernard L.

2013-01-01

Childhood ataxia is characterized by impaired balance and coordination primarily due to cerebellar dysfunction. Friedreich ataxia, a form of childhood ataxia, is the most common multisystem autosomal recessive disease. Most of these patients are homozygous for the GAA repeat expansion located on the first intron of the frataxin gene on chromosome 9. Mutations in the frataxin gene impair mitochondrial function, increase reactive oxygen species, and trigger redistribution of iron in the mitochondria and cytosol. Targeted therapies for Friedreich ataxia are undergoing testing. In addition, a centralized database, patient registry, and natural history study have been launched to support clinical trials in Friedreich ataxia. The 2011 Neurobiology of Disease in Children symposium, held in conjunction with the 40th annual Child Neurology Society meeting, aimed to (1) describe clinical features surrounding Friedreich ataxia, including cardiomyopathy and genetics; (2) discuss recent advances in the understanding of the pathogenesis of Friedreich ataxia and developments of clinical trials; (3) review new investigations of characteristic symptoms; (4) establish clinical and biochemical overlaps in neurodegenerative diseases and possible directions for future basic, translational, and clinical studies. PMID:22859693

Humoral Epitope Spreading in Autoimmune Bullous Diseases

PubMed Central

Didona, Dario; Di Zenzo, Giovanni

2018-01-01

Autoimmune blistering diseases are characterized by autoantibodies against structural adhesion proteins of the skin and mucous membranes. Extensive characterization of their autoantibody targets has improved understanding of pathogenesis and laid the basis for the study of antigens/epitopes diversification, a process termed epitope spreading (ES). In this review, we have reported and discussed ES phenomena in autoimmune bullous diseases and underlined their functional role in disease pathogenesis. A functional ES has been proposed: (1) in bullous pemphigoid patients and correlates with the initial phase of the disease, (2) in pemphigus vulgaris patients with mucosal involvement during the clinical transition to a mucocutaneous form, (3) in endemic pemphigus foliaceus, underlining its role in disease pathogenesis, and (4) in numerous cases of disease transition associated with an intermolecular diversification of immune response. All these findings could give useful information to better understand autoimmune disease pathogenesis and to design antigen/epitope specific therapeutic approaches. PMID:29719538

Molecular genetics made simple

PubMed Central

Kassem, Heba Sh.; Girolami, Francesca; Sanoudou, Despina

2012-01-01

Abstract Genetics have undoubtedly become an integral part of biomedical science and clinical practice, with important implications in deciphering disease pathogenesis and progression, identifying diagnostic and prognostic markers, as well as designing better targeted treatments. The exponential growth of our understanding of different genetic concepts is paralleled by a growing list of genetic terminology that can easily intimidate the unfamiliar reader. Rendering genetics incomprehensible to the clinician however, defeats the very essence of genetic research: its utilization for combating disease and improving quality of life. Herein we attempt to correct this notion by presenting the basic genetic concepts along with their usefulness in the cardiology clinic. Bringing genetics closer to the clinician will enable its harmonious incorporation into clinical care, thus not only restoring our perception of its simple and elegant nature, but importantly ensuring the maximal benefit for our patients. PMID:25610837

Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease.

PubMed

Wang, Zi-Kai; Yang, Yun-Sheng; Chen, Ye; Yuan, Jing; Sun, Gang; Peng, Li-Hua

2014-10-28

The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models.

New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

PubMed Central

Hernández-Rivas, Jesús María

2018-01-01

The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures. We reviewed the molecular basis of pathways including transcriptional regulation, lymphoid differentiation and development, TP53 and the cell cycle, RAS signaling, JAK/STAT, NOTCH, PI3K/AKT/mTOR, Wnt/β-catenin signaling, chromatin structure modifiers, and epigenetic regulators. The implementation of NGS strategies has enabled important mutated genes in each pathway, their associations with the genetic subtypes of ALL, and their outcomes, which will be described further. We also discuss classic and new cryptic DNA rearrangements in ALL identified by mRNA-seq strategies. Novel cooperative abnormalities in ALL could be key prognostic and/or predictive biomarkers for selecting the best frontline treatment and for developing therapies after the first relapse or refractory disease. PMID:29642462

New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update.

PubMed

Montaño, Adrián; Forero-Castro, Maribel; Marchena-Mendoza, Darnel; Benito, Rocío; Hernández-Rivas, Jesús María

2018-04-07

The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures. We reviewed the molecular basis of pathways including transcriptional regulation, lymphoid differentiation and development, TP53 and the cell cycle, RAS signaling, JAK/STAT, NOTCH, PI3K/AKT/mTOR, Wnt/β-catenin signaling, chromatin structure modifiers, and epigenetic regulators. The implementation of NGS strategies has enabled important mutated genes in each pathway, their associations with the genetic subtypes of ALL, and their outcomes, which will be described further. We also discuss classic and new cryptic DNA rearrangements in ALL identified by mRNA-seq strategies. Novel cooperative abnormalities in ALL could be key prognostic and/or predictive biomarkers for selecting the best frontline treatment and for developing therapies after the first relapse or refractory disease.

Adverse food reactions: Pathogenesis, clinical signs, diagnosis and alternatives to elimination diets.

PubMed

Mueller, R S; Unterer, S

2018-06-01

This review summarises available information about adverse food reactions in dogs and cats. Much of the published information on the pathogenesis of adverse food reactions in these species is transferred from what is known in mice and human beings. Clinical signs affect mostly the integument and gastrointestinal system. Pruritus of the distal limbs, face, ears and ventrum is the most common cutaneous presentation in dogs, although urticaria has also been reported. In cats, all so-called 'cutaneous reaction patterns' may be due to adverse food reactions. The most common gastrointestinal signs in both species are diarrhoea and vomiting. An elimination diet over several weeks using a protein source and a carbohydrate source previously not fed is still the diagnostic tool of choice. Improvement on such a diet, deterioration on re-challenge with the old food and improvement again on the elimination diet confirms the diagnosis of adverse food reaction, whereas alternative tests of blood, serum, saliva and hair have been found to be unsatisfactory. Patch testing with food antigens has been recommended as an aid to choose the elimination diet ingredients, since it has a reasonable negative predictability and likelihood ratio, but is laborious and costly. Copyright © 2018 Elsevier Ltd. All rights reserved.

Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives

PubMed Central

Vannucchi, Alessandro M; Guglielmelli, Paola; Rambaldi, Alessandro; Bogani, Costanza; Barbui, Tiziano

2009-01-01

The classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), which include polycythaemia vera, essential thrombocythaemia and primary myelofibrosis, originate from a stem cell-derived clonal myeloproliferation that manifests itself with variable haematopoietic cell lineage involvement; they are characterized by a high degree of similarities and the chance to transform each to the other and to evolve into acute leukaemia. Their molecular pathogenesis has been associated with recurrent acquired mutations in janus kinase 2 (JAK2) and myeloproliferative leukemia virus oncogene (MPL). These discoveries have simplified the diagnostic approach and provided a number of clues to understanding the phenotypic expression of MPNs; furthermore, they represented a framework for developing and/or testing in clinical trials small molecules acting as tyrosine kinase inhibitors. On the other hand, evidence of abnormal epigenetic gene regulation as a mechanism potentially contributing to the pathogenesis and the phenotypic diversity of MPNs is still scanty; however, study of epigenetics in MPNs represents an active field of research. The first clinical trials with epigenetic drugs have been completed recently, whereas others are still ongoing; results have been variable and at present do not allow any firm conclusion. Novel basic and translational information concerning epigenetic gene regulation in MPNs and the perspectives for therapy will be critically addressed in this review. PMID:19522842

Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease

PubMed Central

Wang, Zi-Kai; Yang, Yun-Sheng; Chen, Ye; Yuan, Jing; Sun, Gang; Peng, Li-Hua

2014-01-01

The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models. PMID:25356041

Ebolavirus: An Overview of Molecular and Clinical Pathogenesis.

PubMed

Vine, Veronica; Scott, Dana P; Feldmann, Heinz

2017-01-01

Ebolaviruses cause severe, often fatal hemorrhagic fever in Central, East, and West Africa. Until recently, they have been viewed as rare but highly pathogenic infections with regional, but limited, global public health impact. This view has changed with the emergence of the first epidemic of Ebola hemorrhagic fever in West Africa. In this chapter we provide an introduction of the pathogenesis of ebolaviruses as well as a description of clinical disease features. We also describe the current animal models used in ebolavirus research, detailing each model's unique strengths and weaknesses. We focus on Ebola virus representing the type species Zaire ebolavirus of the genus Ebolavirus, as most work relates to this pathogen.

New Insights into the Pathogenesis of MDS and the rational therapeutic opportunities.

PubMed

Abou Zahr, Abdallah; Bernabe Ramirez, Carolina; Wozney, Jocelyn; Prebet, Thomas; Zeidan, Amer M

2016-01-01

Myelodysplastic syndromes (MDS) include a heterogeneous group of acquired hematopoietic malignancies characterized by ineffective hematopoiesis, peripheral cytopenias, and a varying propensity for progression to acute myeloid leukemia. The clinical heterogeneity in MDS is a reflection of its molecular heterogeneity. Better understanding of aberrant epigenetics, dysregulation of immune responses, and del(5q) MDS has provided the rationale for well-established treatments in MDS. Further understanding of abnormal signal transduction and aberrant apoptosis pathways has led to development of new rational therapies that are in advanced phases of clinical translation. This review seeks to describe recent developments in our understanding of the pathogenesis of MDS and the potential therapeutic implications of these observations.

Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches

PubMed Central

Sahu, Praveen K.; Satpathi, Sanghamitra; Behera, Prativa K.; Mishra, Saroj K.; Mohanty, Sanjib; Wassmer, Samuel Crocodile

2015-01-01

Cerebral malaria is a severe neuropathological complication of Plasmodium falciparum infection. It results in high mortality and post-recovery neuro-cognitive disorders in children, even after appropriate treatment with effective anti-parasitic drugs. While the complete landscape of the pathogenesis of cerebral malaria still remains to be elucidated, numerous innovative approaches have been developed in recent years in order to improve the early detection of this neurological syndrome and, subsequently, the clinical care of affected patients. In this review, we briefly summarize the current understanding of cerebral malaria pathogenesis, compile the array of new biomarkers and tools available for diagnosis and research, and describe the emerging therapeutic approaches to tackle this pathology effectively. PMID:26579500

Gene clusters of Hafnia alvei strain FB1 important in survival and pathogenesis: a draft genome perspective

PubMed Central

2014-01-01

Background Hafnia alvei is an opportunistic pathogen involved in various types of nosocomical infections. The species has been found to inhabit food and mammalian guts. However, its status as an enteropathogen, and whether the food-inhabiting strains could be a source of gastrointestinal infection remains obscure. In this report we present a draft genome of H. alvei strain FB1 isolated from fish paste meatball, a food popular among Malaysian and Chinese populations. The data was generated on the Illumina MiSeq platform. Results A comparative study was carried out on FB1 against two other previously sequenced H. alvei genomes. Several gene clusters putatively involved in survival and pathogenesis of H. alvei FB1 in food and gut environment were characterised in this study. These include the widespread colonisation island (WCI), the tad locus that is known to play an essential role in biofilm formation, a eut operon that might contribute to advantage in nutrient acquisition in gut environment, and genes responsible for siderophore production This features enable the bacteria to successful colonise in the host gut environment. Conclusion With the whole genome data of H. alvei FB1 presented in this study, we hope to provide an insight into future studies on this candidate of enteropathogen by looking into the possible mechanisms employed to survive stresses and gain advantage in competitions, which eventually leads to successful colonisation and pathogenesis. This is to serve as the basis for more effective clinical diagnosis and treatment. PMID:25075225

Systemic Lupus Erythematosus: Definitions, Contexts, Conflicts, Enigmas

PubMed Central

Rekvig, Ole Petter

2018-01-01

Systemic lupus erythematosus (SLE) is an inadequately defined syndrome. Etiology and pathogenesis remain largely unknown. SLE is on the other hand a seminal syndrome that has challenged immunologists, biologists, genetics, and clinicians to solve its nature. The syndrome is characterized by multiple, etiologically unlinked manifestations. Unexpectedly, they seem to occur in different stochastically linked clusters, although single gene defects may promote a smaller spectrum of symptoms/criteria typical for SLE. There is no known inner coherence of parameters (criteria) making up the disease. These parameters are, nevertheless, implemented in The American College of Rheumatology (ACR) and The Systemic Lupus Collaborating Clinics (SLICC) criteria to classify SLE. Still, SLE is an abstraction since the ACR or SLICC criteria allow us to define hundreds of different clinical SLE phenotypes. This is a major point of the present discussion and uses “The anti-dsDNA antibody” as an example related to the problematic search for biomarkers for SLE. The following discussion will show how problematic this is: the disease is defined through non-coherent classification criteria, its complexity is recognized and accepted, its pathogenesis is plural and poorly understood. Therapy is focused on dominant symptoms or organ manifestations, and not on the syndrome itself. From basic scientific evidences, we can add substantial amount of data that are not sufficiently considered in clinical medicine, which may change the paradigms linked to what “The Anti-DNA antibody” is—and is not—in context of the imperfectly defined syndrome SLE. PMID:29545801

Multiple myeloma and related disorders. Lessons from an animal model.

PubMed

Radl, J

1999-02-01

This short review of our own work presents two aspects of the studies on multiple myeloma (MM) in an animal model--the aging C57BL/KaLwRij mouse: 1. the immunological/biological aspect of the development of monoclonal B-cell proliferative disorders, the so-called monoclonal gammopathies (MG), and 2. the use of the mouse myeloma of the 5TMM lines for studies on the etiology/pathogenesis of MM and for developing new ways of treatment of this disease. Our research revealed that there are at least four major mechanisms in the development of MG. Many of the results were confirmed in clinical studies and lead to a new classification of MG according to their biology and possible pathogenesis. Most of MG can be classified into one of the following categories: 1. B-cell malignancies, 2. B-cell benign neoplasia, 3. MG due to an immunodeficiency with T/B cell imbalance, and 4. Antigen driven MG.

Endothelin type B (ETB) receptors: friend or foe in the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk?

PubMed

Mirabito Colafella, Katrina M

2018-01-16

In a recent issue of Clinical Science, Stanhewicz et al. investigated persistent microvascular dysfunction in women up to 16 months postpartum. The authors found sensitivity to the pressor effects of endothelin-1 (ET-1) was enhanced when compared with women who had a normotensive pregnancy. Importantly, the authors demonstrated that this effect was mediated via the endothelin type B (ET B ) receptors. Therefore, the present study highlights the possibility that alterations in the localization of the ET B receptor contributes to the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk. Currently, there is great interest in the role of the endothelin system in pre-eclampsia. Targetting the endothelin system, potentially by modulating upstream pathways to prevent ET B receptor dysfunction, may improve health outcomes for women and their offspring during pre-eclampsia and later life. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Pituitary carcinoma diagnosed on fine needle aspiration: Report of a case and review of pathogenesis

PubMed Central

Yakoushina, Tatiana V.; Lavi, Ehud; Hoda, R. S.

2010-01-01

Pituitary carcinoma (PC) is a very rare entity (0.2% of all pituitary tumors), with only about 140 cases reported in English literature. There are no reliable histological, immunohistochemical or ultrastructural features distinguishing pituitary adenoma (PA) from PC. By definition, a diagnosis of PC is made after a patient with PA develops non-contiguous central nervous system (CNS) or systemic metastases. To date, only three cases of PC have been reportedly diagnosed on fine needle aspiration (FNA). Two of the reported cases were diagnosed on FNA of the cervical lymph nodes and one on FNA of the vertebral bone lesion. Herein, we present a case of PC, diagnosed on FNA of the liver lesion. In this case, we describe cytologic features of PC and compare them to histologic features of the tumor in the pituitary. Clinical behavior of tumor, pathogenesis of metastasis and immunochemical and prognostic markers will also be described. PMID:20806088

G protein-coupled receptors as therapeutic targets for multiple sclerosis

PubMed Central

Du, Changsheng; Xie, Xin

2012-01-01

G protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants. They are considered as the most successful therapeutic targets for a broad spectrum of diseases. Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system (CNS). It is the leading cause of non-traumatic disability in young adults. Great progress has been made over the past few decades in understanding the pathogenesis of MS. Numerous data from animal and clinical studies indicate that many GPCRs are critically involved in various aspects of MS pathogenesis, including antigen presentation, cytokine production, T-cell differentiation, T-cell proliferation, T-cell invasion, etc. In this review, we summarize the recent findings regarding the expression or functional changes of GPCRs in MS patients or animal models, and the influences of GPCRs on disease severity upon genetic or pharmacological manipulations. Hopefully some of these findings will lead to the development of novel therapies for MS in the near future. PMID:22664908

Gastroparesis Updates on Pathogenesis and Management

PubMed Central

Liu, Nanlong; Abell, Thomas

2017-01-01

Gastroparesis (Gp) is a chronic disease that presents with clinical symptoms of early satiety, bloating, nausea, vomiting, and abdominal pain. Along with these symptoms, an objective finding of delayed gastric emptying, along with a documented absence of gastric outlet obstruction, are required for diagnosis. This article focuses on updates in the pathogenesis and management of Gp. Recent studies on full thickness biopsies of Gp patients have shed light on the complex interactions of the central, autonomic, and enteric nervous systems, which all play key roles in maintaining normal gut motility. The management of Gp has evolved beyond prokinetics and antiemetics with the use of gastric electrical stimulators (GES). In addition, this review aims to introduce the concept of gastroparesis-like syndrome (GLS). GLS helps groups of patients who have the cardinal symptoms of Gp but have a normal or rapid emptying test. Recent tests have shown that patients with Gp and GLS have similar pathophysiology, benefit greatly from GES placement, and likely should be treated in a similar manner. PMID:28535580

Molecular characterization of outer membrane vesicles released from Acinetobacter radioresistens and their potential roles in pathogenesis.

PubMed

Fulsundar, Shweta; Kulkarni, Heramb M; Jagannadham, Medicharla V; Nair, Rashmi; Keerthi, Sravani; Sant, Pooja; Pardesi, Karishma; Bellare, Jayesh; Chopade, Balu Ananda

2015-01-01

Acinetobacter radioresistens is an important member of genus Acinetobacter from a clinical point of view. In the present study, we report that a clinical isolate of A. radioresistens releases outer membrane vesicles (OMVs) under in vitro growth conditions. OMVs were released in distinctive size ranges with diameters from 10 to 150 nm as measured by the dynamic light scattering (DLS) technique. Additionally, proteins associated with or present into OMVs were identified using LC-ESI-MS/MS. A total of 71 proteins derived from cytosolic, cell membrane, periplasmic space, outer membrane (OM), extracellular and undetermined locations were found in OMVs. The initial characterization of the OMV proteome revealed a correlation of some proteins to biofilm, quorum sensing, oxidative stress tolerance, and cytotoxicity functions. Thus, the OMVs of A. radioresistens are suggested to play a role in biofilm augmentation and virulence possibly by inducing apoptosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Facial paralysis caused by metastasis of breast carcinoma to the temporal bone.

PubMed

Lan, Ming-Ying; Shiao, An-Suey; Li, Wing-Yin

2004-11-01

Metastatic tumors to the temporal bone are very rare. The most common sites of origin of temporal bone metastases are breast, lung, kidney, gastrointestinal tract, larynx, prostate gland, and thyroid gland. The pathogenesis of spread to the temporal bone is most commonly by the hematogenous route. The common otologic symptoms that manifest with facial nerve paralysis are often thought to be due to a mastoid infection. Here is a report on a case of breast carcinoma presenting with otalgia, otorrhea, and facial paralysis for 2 months. The patient was initially diagnosed as mastoiditis, and later the clinical impression was revised to metastatic breast carcinoma to temporal bone, based on the pathologic findings. Metastatic disease should be considered as a possible etiology in patients with a clinical history of malignant neoplasms presenting with common otologic or vestibular symptoms, especially with facial nerve paralysis.

Neurologic Involvement in Scleroderma en Coup de Sabre

PubMed Central

Amaral, Tiago Nardi; Marques Neto, João Francisco; Lapa, Aline Tamires; Peres, Fernando Augusto; Guirau, Caio Rodrigues; Appenzeller, Simone

2012-01-01

Localized scleroderma is a rare disease, characterized by sclerotic lesions. A variety of presentations have been described, with different clinical characteristics and specific prognosis. In scleroderma en coup de sabre (LScs) the atrophic lesion in frontoparietal area is the disease hallmark. Skin and subcutaneous are the mainly affected tissues, but case reports of muscle, cartilage, and bone involvement are frequent. These cases pose a difficult differential diagnosis with Parry-Romberg syndrome. Once considered an exclusive cutaneous disorder, the neurologic involvement present in LScs has been described in several case reports. Seizures are most frequently observed, but focal neurologic deficits, movement disorders, trigeminal neuralgia, and mimics of hemiplegic migraines have been reported. Computed tomography and magnetic resonance imaging have aided the characterization of central nervous system lesions, and cerebral angiograms have pointed to vasculitis as a part of disease pathogenesis. In this paper we describe the clinical and radiologic aspects of neurologic involvement in LScs. PMID:22319646

Comprehensive overview of prostatitis.

PubMed

Khan, Farhan Ullah; Ihsan, Awais Ullah; Khan, Hidayat Ullah; Jana, Ruby; Wazir, Junaid; Khongorzul, Puregmaa; Waqar, Muhammad; Zhou, Xiaohui

2017-10-01

Prostatitis is a common urinary tract syndrome that many doctors find problematic to treat effectively. It is the third most commonly found urinary tract disease in men after prostate cancer and Benign Prostate Hyperplasia (BPH). Prostatitis may account for 25% of all office visits made to the urological clinics complaining about the genital and urinary systems all over the world. In the present study, we classified prostatitis and comprehensively elaborated the etiology, pathogenesis, diagnosis, and treatment of acute bacterial prostatitis (category I), chronic bacterial prostatitis (category II), chronic pelvic pain syndrome (CPPS) (category III), and asymptomatic prostatitis (category IV). In addition, we also tried to get some insights about other types of prostatitis-like fungal, viral and gonococcal prostatitis. The aim of this review is to present the detail current perspective of prostatitis in a single review. To the best of our knowledge currently, there is not a single comprehensive review, which can completely elaborate this important topic in an effective way. Furthermore, this review will provide a solid platform to conduct future studies on different aspects such as risk factors, mechanism of pathogenesis, proper diagnosis, and rational treatment plans for fungal, viral, and gonococcal prostatitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Immunoglobulin G4-related acquired hemophilia: A case report

PubMed Central

Li, Xiaoyan; Duan, Wei; Zhu, Xiang; Xu, Jianying

2016-01-01

Acquired hemophilia A (AHA) is a relatively rare and life-threatening bleeding disorder whose pathogenesis is not completely understood. The present study reports a rare case of immunogubulin (IgG)4-related AHA with multisystemic involvement. A 55-year old male patient presented with symptoms of bronchial asthma and multiple subdermal hematomas. Chest computed tomography showed multiple diffuse nodular lesions with thickening of bronchovascular bundles, and scattered high-density spots in both lung lobes. Laboratory investigations showed increased activated partial prothrombin time (120.0 sec), a markedly decreased factor VIII (FVIII) activity (0.5%), a high-titer of FVIII inhibitor (27.2 Bethesda units/ml) and a marked increase in serum IgG4 (>4.03 g/l) level. Left inguinal lymph node biopsy revealed capsular thickening with marked lymphoplasmacytic infiltration, occlusive phlebitis and irregular fibrosis. Immunostaining revealed numerous IgG4-positive plasma cells (>100 cells/human plasma fibronectin) in the nodular lesions, with an IgG4/IgG ratio of >40%. The symptoms were markedly alleviated following corticosteroid therapy. The current study presents the first reported case of a rare IgG4-related AHA that presented with unusual clinical features and multisystemic involvement. The patient responded well to corticosteroid therapy. Documentation of such rare cases will help in characterizing the pathogenesis, and prompt recognition and timely treatment of this rare disorder. PMID:28105131

Ebola: Implications and Perspectives

PubMed Central

Del Rio, Carlos; Guarner, Jeannette

2015-01-01

The 2014 Ebola virus disease outbreak in West Africa has been the largest in recorded history. During this Ebola epidemic, the media has focused much attention to the magnitude of the problem in West Africa but has also overplayed the potential for an Ebola virus pandemic as patients have been transported for treatment to the United States and Europe causing panic and paranoia in the population. Knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and prevention of this infection will allow a better understanding of the disease and decrease irrational fear of spread. PMID:26330663

Birt-Hogg-Dubé Syndrome.

PubMed

Gupta, Nishant; Sunwoo, Bernie Y; Kotloff, Robert M

2016-09-01

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the Folliculin gene and is characterized by the formation of fibrofolliculomas, early onset renal cancers, pulmonary cysts, and spontaneous pneumothoraces. The exact pathogenesis of tumor and lung cyst formation in BHD remains unclear. There is great phenotypic variability in the clinical features of BHD, and patients can present with any combination of skin, pulmonary, or renal findings. More than 80% of adult patients with BHD have pulmonary cysts on high-resolution computed tomography scan of the chest. Published by Elsevier Inc.

Heart failure in a woman with SLE, anti-phospholipid syndrome and Fabry’s disease

PubMed Central

Nandagudi, A; Alonzi, D; Butters, TD; Hughes, S; Isenberg, DA

2013-01-01

We describe a female patient with systemic lupus erythematosus (SLE) also diagnosed with Fabry’s disease and anti-phospholipid antibody syndrome (APS). SLE and Fabry’s disease are both systemic diseases with variable clinical presentations. Recent studies have shown a relatively high incidence of late onset Fabry’s disease in female heterozygous individuals, suggesting that this condition could be under-diagnosed. We discuss a possible association between SLE and Fabry’s disease and consider the role of lipid abnormalities in the pathogenesis of SLE. PMID:23864039

Follicular Dowling Degos disease: a rare variant of an evolving dermatosis.

PubMed

Singh, Saurabh; Khandpur, Sujay; Verma, Parul; Singh, Manoj

2013-01-01

Dowling Degos disease is a rare, reticulate pigmentary disorder with variable phenotypic expression that manifests as hyperpigmented macules and reticulate pigmentary anomaly of the flexures. Many variants of this condition and its overlap with other reticulate pigmentary disorders have been reported in the literature. We present here two cases of DDD with follicular localization, both clinically and histologically. It was associated with ichthyosis vulgaris in one case. Follicular DDD is an uncommon variant of this evolving dermatosis. Our report supports the possible role for disordered follicular keratinisation in its pathogenesis.

[Ebola virus disease].

PubMed

Nazimek, Katarzyna; Bociaga-Jasik, Monika; Bryniarski, Krzysztof; Gałas, Aleksander; Garlicki, Aleksander; Gawda, Anna; Gawlik, Grzegorz; Gil, Krzysztof; Kosz-Vnenchak, Magdalena; Mrozek-Budzyn, Dorota; Olszanecki, Rafał; Piatek, Anna; Zawilińska, Barbara; Marcinkiewicz, Janusz

2014-01-01

Ebola is one of the most virulent zoonotic RNA viruses causing in humans haemorrhagic fever with fatality ratio reaching 90%. During the outbreak of 2014 the number of deaths exceeded 8.000. The "imported" cases reported in Western Europe and USA highlighted the extreme risk of Ebola virus spreading outside the African countries. Thus, haemorrhagic fever outbreak is an international epidemiological problem, also due to the lack of approved prevention and therapeutic strategies. The editorial review article briefly summarizes current knowledge on Ebola virus disease epidemiology, etiology, pathogenesis, clinical presentation, diagnosis as well as possible prevention and treatment.

Primary acquired cold urticaria.

PubMed

Lee, Chyh-Woei; Sheffer, Albert L

2003-01-01

Primary acquired cold urticaria (ACU) is the most common type of cold urticaria characterized by rapid onset of pruritic hives, swelling, and possible severe systemic reactions including hypotension and shock after cold exposure. Primary ACU is diagnosed by history of such symptoms, a positive immediate cold-contact stimulation test, and negative laboratory evaluation for underlying systemic disorders. Clinicians should be aware that patients with ACU may be susceptible to life-threatening systemic reactions especially during aquatic activities and that proper patient education is extremely important. This article reviews the clinical presentation, pathogenesis, diagnosis, and management of primary ACU.

Age-Related Macular Degeneration: Advances in Management and Diagnosis

PubMed Central

Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

2015-01-01

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

[A new hypothesis for the treatment of amblyopia: the flicker stimulator].

PubMed

Parrozzani, A; Fedriga, P; Ferrari, E; De Vincentiis, L

1984-01-01

A variety of cells are involved in the pathogenesis of amblyopia : ON, OFF, ON-OFF cells, postsynaptic cells, neurons of striate cortex and the select interest of the macula. The need for stimulation of these cells in treating amblyopia forms the theoretical basis of the Flicker stimulator with red monochromatic light (LED, 655 nm). The authors present a clinical investigation on 35 subjects with anisometropic or strabismic amblyopia, before extensive treatment with classic anti-amblyopic techniques without satisfactory improvement obtaining significant statistical results (p less than 0,001).

Aggressive periodontitis: case definition and diagnostic criteria.

PubMed

Albandar, Jasim M

2014-06-01

Aggressive periodontitis is a destructive disease characterized by the following: the involvement of multiple teeth with a distinctive pattern of periodontal tissue loss; a high rate of disease progression; an early age of onset; and the absence of systemic diseases. In some patients periodontal tissue loss may commence before puberty, whereas in most patients the age of onset is during or somewhat after the circumpubertal period. Besides infection with specific microorganisms, a host predisposition seems to play a key role in the pathogenesis of aggressive periodontitis, as evidenced by the familial aggregation of the disease. In this article we review the historical background of the diagnostic criteria of aggressive periodontitis, present a contemporary case definition and describe the clinical parameters of the disease. At present, the diagnosis of aggressive periodontitis is achieved using case history, clinical examination and radiographic evaluation. The data gathered using these methods are prone to relatively high measurement errors. Besides, this diagnostic approach measures past disease history and may not reliably measure existing disease activity or accurately predict future tissue loss. A diagnosis is often made years after the onset of the disease, partly because current assessment methods detect established disease more readily and reliably than they detect incipient or initial lesions where the tissue loss is minimal and usually below the detection threshold of present examination methods. Future advancements in understanding the pathogenesis of this disease may contribute to an earlier diagnosis. Insofar, future case definitions may involve the identification of key etiologic and risk factors, combined with high-precision methodologies that enable the early detection of initial lesions. This may significantly enhance the predictive value of these tests and detect cases of aggressive periodontitis before significant tissue loss develops. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Compound heterozygosity of SHOX-encompassing and downstream PAR1 deletions results in Langer mesomelic dysplasia (LMD).

PubMed

Campos-Barros, Angel; Benito-Sanz, Sara; Ross, Judith L; Zinn, Andrew R; Heath, Karen E

2007-05-01

We present the clinical and molecular characteristics of a multi-generation family in which the proband presented with clinical features of Langer mesomelic dysplasia (LMD) whilst different family members had a diagnosis of Léri-Weill dyschondrosteosis (LWD) and/or pseudoachondroplasia (PSACH). In the LMD proband two different deletions were identified in the pseudoautosomal 1 region (PAR1) of the X and Y chromosomes: a SHOX-encompassing deletion inherited from his father and a downstream PAR1 deletion, which did not include SHOX, inherited from his mother. The individuals with PSACH features presented the previously described G719D mutation in the C-terminal globular domain of the cartilage oligomeric matrix protein gene (COMP). The LMD proband described here represents the first LMD case due to compound heterozygosity for deletions of the two different PAR1 regions, SHOX-encompassing and downstream from SHOX, that have been shown to be implicated in the pathogenesis of LWD and LMD.

THE MOLECULAR PATHOLOGY OF MELANOMA: AN INTEGRATED TAXONOMY OF MELANOCYTIC NEOPLASIA

PubMed Central

Bastian, Boris C.

2016-01-01

Melanomas are comprised of multiple biologically distinct categories, which differ in cell of origin, age of onset, clinical and histologic presentation, pattern of metastasis, ethnic distribution, causative role of UV radiation, predisposing germ line alterations, mutational processes, and patterns of somatic mutations. Neoplasms are initiated by gain of function mutations in one of several primary oncogenes, typically leading to benign melanocytic nevi with characteristic histologic features. The progression of nevi is restrained by multiple tumor suppressive mechanisms. Secondary genetic alterations override these barriers and promote intermediate or overtly malignant tumors along distinct progression trajectories. The current knowledge about pathogenesis, clinical, histological and genetic features of primary melanocytic neoplasms is reviewed and integrated into a taxonomic framework. PMID:24460190

Anaerobic orbital cellulitis: a clinical and experimental study.

PubMed Central

Jedrzynski, M S; Bullock, J D; McGuire, T W; Elder, B L; Bullock, J D

1991-01-01

In this article we have reviewed the clinical and bacteriologic aspects of anaerobic orbital cellulitis and have presented six patients to illustrate these points. Physicians who treat patients with orbital cellulitis should have a high index of suspicion for possible instances involving anaerobes, so that appropriate management can be started early. To investigate this problem further, we created an animal model of anaerobic orbital cellulitis. This model may be useful in future studies of the pathogenesis and treatment of this serious and often devastating disease. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19 PMID:1808813

Parasitic diseases of the central nervous system: lessons for clinicians and policy makers

PubMed Central

Carpio, Arturo; Romo, Matthew L.; Parkhouse, R. M. E.; Short, Brooke; Dua, Tarun

2016-01-01

ABSTRACT Parasitic diseases of the central nervous system are associated with high mortality and morbidity, especially in resource-limited settings. The burden of these diseases is amplified as survivors are often left with neurologic sequelae affecting mobility, sensory organs, and cognitive functions, as well as seizures/epilepsy. These diseases inflict suffering by causing lifelong disabilities, reducing economic productivity, and causing social stigma. The complexity of parasitic life cycles and geographic specificities, as well as overlapping clinical manifestations in the host reflecting the diverse pathogenesis of parasites, can present diagnostic challenges. We herein provide an overview of these parasitic diseases and summarize clinical aspects, diagnosis, therapeutic strategies and recent milestones, and aspects related to prevention and control. PMID:26894629

Facial nerve hemangioma: a rare case involving the vertical segment.

PubMed

Ahmadi, Neda; Newkirk, Kenneth; Kim, H Jeffrey

2013-02-01

This case report and literature review reports on a rare case of facial nerve hemangioma (FNH) involving the vertical facial nerve (FN) segment, and discusses the clinical presentation, imaging, pathogenesis, and management of these rare lesions. A 53-year-old male presented with a 10-year history of right hemifacial twitching and progressive facial paresis (House-Brackmann grading score V/VI). The computed tomography and magnetic resonance imaging studies confirmed an expansile lesion along the vertical FN segment. Excision and histopathologic examination demonstrated FNH. FNHs involving the vertical FN segment are extremely rare. Despite being rare lesions, we believe that familiarity with the presentation and management of FNHs are imperative. Laryngoscope, 2012. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock

PubMed Central

Martillo, Miguel; Abed, Jean; Herman, Michael; Abed, Elie; Shi, Wenjing; Munot, Khushboo; Mankal, Pavan Kumar; Gurunathan, Rajan; Ionescu, Gabriel; Kotler, Donald P.

2015-01-01

Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration. PMID:26078733

Quantitative gene expression deregulation in mantle-cell lymphoma: correlation with clinical and biologic factors.

PubMed

Kienle, Dirk; Katzenberger, Tiemo; Ott, German; Saupe, Doreen; Benner, Axel; Kohlhammer, Holger; Barth, Thomas F E; Höller, Sylvia; Kalla, Jörg; Rosenwald, Andreas; Müller-Hermelink, Hans Konrad; Möller, Peter; Lichter, Peter; Döhner, Hartmut; Stilgenbauer, Stephan

2007-07-01

There is evidence for a direct role of quantitative gene expression deregulation in mantle-cell lymphoma (MCL) pathogenesis. Our aim was to investigate gene expression associations with other pathogenic factors and the significance of gene expression in a multivariate survival analysis. Quantitative expression of 20 genes of potential relevance for MCL prognosis and pathogenesis were analyzed using real-time reverse transcriptase polymerase chain reaction and correlated with clinical and genetic factors, tumor morphology, and Ki-67 index in 65 MCL samples. Genomic losses at the loci of TP53, RB1, and P16 were associated with reduced transcript levels of the respective genes, indicating a gene-dosage effect as the pathomechanism. Analysis of gene expression correlations between the candidate genes revealed a separation into two clusters, one dominated by proliferation activators, another by proliferation inhibitors and regulators of apoptosis. Whereas only weak associations were identified between gene expression and clinical parameters or blastoid morphology, several genes were correlated closely with the Ki-67 index, including the short CCND1 variant (positive correlation) and RB1, ATM, P27, and BMI (negative correlation). In multivariate survival analysis, expression levels of MYC, MDM2, EZH2, and CCND1 were the strongest prognostic factors independently of tumor proliferation and clinical factors. These results indicate a pathogenic contribution of several gene transcript levels to the biology and clinical course of MCL. Genes can be differentiated into factors contributing to proliferation deregulation, either by enhancement or loss of inhibition, and proliferation-independent factors potentially contributing to MCL pathogenesis by apoptosis impairment.

High-resolution copy number variation analysis of schizophrenia in Japan.

PubMed

Kushima, I; Aleksic, B; Nakatochi, M; Shimamura, T; Shiino, T; Yoshimi, A; Kimura, H; Takasaki, Y; Wang, C; Xing, J; Ishizuka, K; Oya-Ito, T; Nakamura, Y; Arioka, Y; Maeda, T; Yamamoto, M; Yoshida, M; Noma, H; Hamada, S; Morikawa, M; Uno, Y; Okada, T; Iidaka, T; Iritani, S; Yamamoto, T; Miyashita, M; Kobori, A; Arai, M; Itokawa, M; Cheng, M-C; Chuang, Y-A; Chen, C-H; Suzuki, M; Takahashi, T; Hashimoto, R; Yamamori, H; Yasuda, Y; Watanabe, Y; Nunokawa, A; Someya, T; Ikeda, M; Toyota, T; Yoshikawa, T; Numata, S; Ohmori, T; Kunimoto, S; Mori, D; Iwata, N; Ozaki, N

2017-03-01

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10 -9 , 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

Role of HLA-B27 in the pathogenesis of ankylosing spondylitis

PubMed Central

Chen, Bin; Li, Jia; He, Chongru; Li, Dahe; Tong, Wenwen; Zou, Yuming; Xu, Weidong

2017-01-01

The study of ankylosing spondylitis (AS) has made significant progress over the last decade. Genome-wide association studies have identified and further substantiated the role of susceptibility genes outside the major histocompatibility complex locus. However, human leukocyte antigen (HLA)-B27 has been suggested to be important in the pathogenesis of AS, contributing to ~20.1% of AS heritability. The current review will present the classical and non-classical forms of HLA-B27, as well as their pathogenic roles, and further discuss the hypotheses regarding the potential pathogenesis of AS. In addition, the association between the pathogenic role of HLA-B27 and inflammatory indexes, including the interleukin-23/−17 axis will be investigated to provide novel insights into the pathogenesis of AS. The aim of the present review is to provide an update of the current research into the pathogenesis of AS, and provide a comprehensive description of the pathogenic role of HLA-B27 in AS. PMID:28259985

Role of HLA-B27 in the pathogenesis of ankylosing spondylitis (Review).

PubMed

Chen, Bin; Li, Jia; He, Chongru; Li, Dahe; Tong, Wenwen; Zou, Yuming; Xu, Weidong

2017-04-01

The study of ankylosing spondylitis (AS) has made significant progress over the last decade. Genome-wide association studies have identified and further substantiated the role of susceptibility genes outside the major histocompatibility complex locus. However, human leukocyte antigen (HLA)‑B27 has been suggested to be important in the pathogenesis of AS, contributing to ~20.1% of AS heritability. The current review will present the classical and non‑classical forms of HLA-B27, as well as their pathogenic roles, and further discuss the hypotheses regarding the potential pathogenesis of AS. In addition, the association between the pathogenic role of HLA‑B27 and inflammatory indexes, including the interleukin-23/‑17 axis will be investigated to provide novel insights into the pathogenesis of AS. The aim of the present review is to provide an update of the current research into the pathogenesis of AS, and provide a comprehensive description of the pathogenic role of HLA-B27 in AS.

Red ear syndrome precipitated by a dietary trigger: a case report

PubMed Central

2014-01-01

Introduction Red ear syndrome is a rare condition characterized by episodic attacks of erythema of the ear accompanied by burning ear pain. Symptoms are brought on by touch, exertion, heat or cold, stress, neck movements and washing or brushing of hair. Diagnosis and treatment of this condition are challenging. The case we report here involves a woman whose symptoms were brought on by a dietary trigger: orange juice as well as stress, causing significant physical and psychological morbidity. Avoidance of triggers resulted in symptomatic improvement. Case presentation A 22-year-old Caucasian woman who was a student presented twice to our department with evolving symptoms, the first time with hyperacusis (abnormal sound sensitivity arising from within the auditory system to sounds of moderate volume), intermittent right tinnitus and subjective hearing difficulties. She presented five years later with highly distressing episodes of erythematous ears, which were associated with burning pain around the ear and temporal areas, and intolerance to noise. After keeping a symptom diary, she identified orange juice and stress as triggers of her symptoms. No local head and neck pathology was present. Investigations and imaging were negative. Avoidance of triggers led to great symptomatic improvement. To the best of our knowledge, dietary triggers have not previously been reported as a trigger for this syndrome. This case shows a direct temporal link to a dietary trigger and supports a primary pathogenesis. Recognition and management of primary headache disorder and simple dietary and lifestyle changes brought about symptomatic relief. Conclusion Red ear syndrome is a little-known clinical syndrome of unknown etiology and management. To the best of our knowledge, our present case report is the first to describe primary red ear syndrome triggered by orange juice. Clinical benefit derived from avoidance of this trigger, which is already known to precipitate migraines, gives some insight into the pathogenesis of red ear syndrome. PMID:25303997

Parkinson's disease--the debate on the clinical phenomenology, aetiology, pathology and pathogenesis.

PubMed

Jenner, Peter; Morris, Huw R; Robbins, Trevor W; Goedert, Michel; Hardy, John; Ben-Shlomo, Yoav; Bolam, Paul; Burn, David; Hindle, John V; Brooks, David

2013-01-01

The definition of Parkinson's disease (PD) is changing with the expansion of clinical phenomenology and improved understanding of environmental and genetic influences that impact on the pathogenesis of the disease at the cellular and molecular level. This had led to debate and discussion with as yet, no general acceptance of the direction that change should take either at the level of diagnosis or of what should and should not be sheltered under an umbrella of PD. This article is one contribution to this on-going discussion. There are two different themes running through the article--widening the definition of PD/LBD/synucleinopathies and the heterogeneity that exists within PD itself from a clinical, pathological and genetic perspective. The conclusion reached is that in the future, further diagnostic categories will need to be recognized. These are likely to include--Parkinson's syndrome, Parkinson's syndrome likely to be Lewy body PD, clinical PD (defined by QSBB criteria), Lewy body disease (PD, LBD, REM SBD) and synucleinopathies (including LBD, MSA).

Volvulus in term and preterm infants - clinical presentation and outcome.

PubMed

Horsch, Sandra; Albayrak, Bilge; Tröbs, Ralf-Bodo; Roll, Claudia

2016-06-01

Our aim was to assess if term and preterm infants with volvulus showed different patterns with regard to pathogenesis, clinical presentation and outcome. We reviewed the medical records and imaging data of infants aged less than six months with volvulus treated in a single surgical referral centre from 2006-2013. Volvulus was diagnosed in 19 infants, with no anatomical anomaly in three of the 12 preterm infants and one of the seven term infants. Most cases (74%) presented during the first eight days of life. Later presentations occurred exclusively in preterm infants, with only one of the five having no anatomic anomalies. Bilious vomiting was the leading symptom in six of the seven term infants, while the symptoms in preterm infants were rather nonspecific. Intestinal necrosis, with the need for bowel resection, occurred in one term (14%) infant and nine (75%) preterm infants. The clinical presentation and outcome of volvulus differed between preterm and term infants, but the rate and distribution of underlying anomalies did not differ. Symptoms in preterm infants were often nonspecific and led to a delay in diagnosis. This might have contributed to the higher rate of intestinal necrosis in preterm infants. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture.

PubMed

Jiang, Hong; Du, Hong; Wang, Li M; Wang, Ping Z; Bai, Xue F

2016-01-01

Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China. The reservoir host of HTNV is field mouse (Apodemus agraricus). The main manifestation of HFRS, including acute kidney injury, increases vascular permeability, and coagulation abnormalities. In this paper, we review the current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors. Furthermore, the treatment and prevention will be discussed.

In brief: the (molecular) pathogenesis of Barrett's oesophagus.

PubMed

Aichler, Michaela; Walch, Axel

2014-03-01

Barrett's oesophagus is a metaplastic change, such that the normal squamous epithelial lining of the oesophagus is replaced by specialized columnar-lined epithelium. Barrett's oesophagus is clinically significant and has a high health economic impact as it is associated with heightened risk of progression to oesophageal adenocarcinoma. This review discusses the pathogenesis of Barrett's oesophagus with an emphasis on the underlying molecular events. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture

PubMed Central

Jiang, Hong; Du, Hong; Wang, Li M.; Wang, Ping Z.; Bai, Xue F.

2016-01-01

Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China. The reservoir host of HTNV is field mouse (Apodemus agraricus). The main manifestation of HFRS, including acute kidney injury, increases vascular permeability, and coagulation abnormalities. In this paper, we review the current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors. Furthermore, the treatment and prevention will be discussed. PMID:26870699

The Pathogenesis of Pulmonary Sarcoidosis and Implications for Treatment.

PubMed

Patterson, Karen C; Chen, Edward S

2018-06-01

Thoracic sarcoidosis is the most common form of sarcoidosis, encompassing a heterogeneous group of patients with a wide range of clinical features and associated outcomes. The distinction between isolated thoracic lymphadenopathy and pulmonary involvement matters. Morbidity is often higher, and long-term outcomes are worse for the latter. Although inflammatory infiltrates in pulmonary sarcoidosis may resolve, persistent disease activity is common and can result in lung fibrosis. Given the distinct clinical features and natural history of pulmonary sarcoidosis, its pathogenesis may differ in important ways from other sarcoidosis manifestations. This review highlights recent advances in the pathogenesis of pulmonary sarcoidosis, including the nature of the sarcoidosis antigen, the role of serum amyloid A and other host factors that contribute to alterations in innate immunity, factors that shape adaptive T-cell profiles in the lung, and how these mechanisms influence the maintenance of granulomatous inflammation in sarcoidosis. We discuss questions raised by recent findings, including the role of innate immunity in the pathogenesis, the meaning of immune cell exhaustion, and mechanisms that may contribute to lung fibrosis in sarcoidosis. We conclude with a reflection on when and how immunosuppressive therapies may be helpful for pulmonary sarcoidosis, a consideration of nonpharmacologic management strategies, and a survey of potential novel therapeutic targets for this vexing disease. Copyright © 2017 American College of Chest Physicians. All rights reserved.

Interleukin-1 or tumor necrosis factor-alpha augmented the cytotoxic effect of mycobacteria on human fibroblasts: application to evaluation of pathogenesis of clinical isolates of Mycobacterium tuberculosis and M. avium complex.

PubMed

Takii, T; Abe, C; Tamura, A; Ramayah, S; Belisle, J T; Brennan, P J; Onozaki, K

2001-03-01

Mycobacteria-induced in vitro events reflecting human tuberculosis can contribute to the evaluation of the pathogenesis of Mycobacterium tuberculosis (MTB). In this study, we propose such an in vitro method based on live mycobacteria-induced cytotoxicity to human cell lines. When human lung-derived normal fibroblast cell line MRC-5 was infected with various strains of mycobacteria (M. tuberculosis H(37)Rv and H(37) Ra, Mycobacterium avium 427S and 2151SmO, and Mycobacterium bovis BCG Pasteur and Tokyo), the fibroblasts were killed by mycobacteria according to the degree of virulence. Other human originated macrophage (U-937, THP-1), myeloid (HL-60), and epithelial carcinoma (A549) cell lines exhibited a similar cytotoxic response to virulent mycobacteria. MRC-5 was most susceptible to virulent mycobacteria among various human cell lines examined. The cytotoxicity was enhanced by the proinflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-alpha), which in the absence of mycobacteria stimulate the growth of normal human fibroblasts. This in vitro evaluation system was applied to clinical isolates of drug-sensitive MTB (DS-MTB), drug-resistant MTB (DR-MTB) including multidrug-resistant (MDR-MTB), and M. avium complex (MAC). MTB strains (n = 24) exhibited strong cytotoxic activity, but MAC strains (n = 5) had only weak activity. Furthermore, there was no significant difference in cytotoxicity between DS-MTB (n = 11) and DR-MTB (n = 13). Collectively, these results suggest that this new in vitro system is useful for evaluating the pathogenesis of mycobacteria and that there was no difference in the pathogenesis between drug-susceptible and drug-resistant clinical isolates.

Role of bacteria in the pathogenesis of recurrent uveitis in horses from the southeastern United States.

PubMed

Gilger, Brian C; Salmon, Jacklyn H; Yi, Na Y; Barden, Curtis A; Chandler, Heather L; Wendt, Jennifer A; Colitz, Carmen M H

2008-10-01

To determine the role of intraocular bacteria in the pathogenesis of equine recurrent uveitis (ERU) in horses from the southeastern United States by evaluating affected eyes of horses with ERU for bacterial DNA and intraocular production of antibodies against Leptospira spp. Aqueous humor, vitreous humor, and serum samples of 24 clinically normal horses, 52 horses with ERU, and 17 horses with ocular inflammation not associated with ERU (ie, non-ERU inflammation). Ribosomal RNA quantitative PCR (real-time PCR) assay was used to detect bacterial DNA in aqueous humor and vitreous humor from clinically normal horses (n = 12) and horses with chronic (> 3-month) ERU (28). Aqueous humor and serum were also evaluated for anti-Leptospira antibody titers from clinically normal horses (n = 12), horses with non-ERU inflammation (17), and horses with confirmed chronic ERU (24). Bacterial DNA was not detected in aqueous humor or vitreous humor of horses with ERU or clinically normal horses. No significant difference was found in titers of anti-Leptospira antibodies in serum or aqueous humor among these 3 groups. Only 2 horses, 1 horse with ERU and 1 horse with non-ERU inflammation, had definitive intraocular production of antibodies against Leptospira organisms. In horses from the southeastern United States, Leptospira organisms may have helped initiate ERU in some, but the continued presence of the organisms did not play a direct role in the pathogenesis of this recurrent disease.

Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses

PubMed Central

Muzny, Christina A.; Schwebke, Jane R.

2016-01-01

In April 2015, the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases hosted an experts technical consultation on bacterial vaginosis (BV), where data regarding controversies over the pathogenesis of BV were discussed. The discussion on the epidemiology and pathogenesis of BV is presented here, and several hypotheses on its pathogenesis are critiqued. Rigorous hypothesis-driven studies are needed to ultimately determine the cause of BV. This information is vital for the prevention and control of this important infection and its adverse public health consequences. PMID:27449868

Molecular biology, pathogenesis and pathology of mumps virus.

PubMed

Rubin, Steven; Eckhaus, Michael; Rennick, Linda J; Bamford, Connor G G; Duprex, W Paul

2015-01-01

Mumps is caused by the mumps virus (MuV), a member of the Paramyxoviridae family of enveloped, non-segmented, negative-sense RNA viruses. Mumps is characterized by painful inflammatory symptoms, such as parotitis and orchitis. The virus is highly neurotropic, with laboratory evidence of central nervous system (CNS) infection in approximately half of cases. Symptomatic CNS infection occurs less frequently; nonetheless, prior to the introduction of routine vaccination, MuV was a leading cause of aseptic meningitis and viral encephalitis in many developed countries. Despite being one of the oldest recognized diseases, with a worldwide distribution, surprisingly little attention has been given to its study. Cases of aseptic meningitis associated with some vaccine strains and a global resurgence of cases, including in highly vaccinated populations, has renewed interest in the virus, particularly in its pathogenesis and the need for development of clinically relevant models of disease. In this review we summarize the current state of knowledge on the virus, its pathogenesis and its clinical and pathological outcomes. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Rheumatoid Arthritis-Associated Interstitial Lung Disease: Current Concepts.

PubMed

Brito, Yoel; Glassberg, Marilyn K; Ascherman, Dana P

2017-11-09

Among the many extra-articular complications of rheumatoid arthritis (RA), interstitial lung disease (ILD) contributes significantly to morbidity and mortality. Prevalence estimates for RA-ILD vary widely depending on the specific clinical, radiographic, and functional criteria used to establish the diagnosis. A key unresolved issue is whether early, subclinical forms of RA-ILD represent a precursor to end stage, fibrotic lung disease. Based on uncertainties surrounding the natural history of RA-ILD, incomplete understanding of underlying disease pathogenesis, and lack of controlled clinical trials, evidence-based therapeutic strategies remain largely undefined. Correlative clinico-epidemiological studies have identified key risk factors for disease progression. Complementing these findings, the identification of specific molecular and serological markers of RA-ILD has improved our understanding of disease pathogenesis and established the foundation for predictive biomarker profiling. Experience from case series and cohort studies suggests that newer biological agents such as rituximab may be viable treatment options. RA-ILD continues to have a major impact on "disease intrinsic" morbidity and mortality. Increased understanding of disease pathogenesis and the natural history of subclinical RA-ILD will promote the development of more refined therapeutic strategies.

[Immunopathology of ulcerative colitis and granulomatous colitis (author's transl)].

PubMed

Bläker, F

1975-08-01

There is no convincing evidence as yet for a key role of immunological processes in the pathogenesis of unspecific colitis. However clinical findings as well as immunological data do support the hypothesis that immune reactions are involved primarily or secondarily in the pathogenesis and the clinical course of ulcerative colitis and granulomatous colitis. In such patients a specific adaptation of humoral and cell-bound immune reactions against antigenic material from the colon and other tissues has been found in peripheral blood, lymphatic tissue and bowel wall. In this context it seems to be especially noteworthy, that lymphocytes taken from patients with colitis lead to disintegration of colon epithelial cells in vitro. This cytotoxic effect of the lymphocytes is lost after colectomy or remission of the disease. Ulcerative and granulomatous colitis do have many clinical and immunological peculiarities in common. This makes one think, that possibly the same noxious factors induce differential local reactions because of different hereditary disposition.

Coagulation Abnormalities of Sickle Cell Disease: Relationship with Clinical Outcomes and the Effect of Disease Modifying Therapies

PubMed Central

Noubouossie, Denis; Key, Nigel S.; Ataga, Kenneth I.

2015-01-01

Sickle cell disease (SCD) is a hypercoagulable state. Patients exhibit increased platelet activation, high plasma levels of markers of thrombin generation, depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system, and increased tissue factor expression, even in the non-crisis “steady state.” Furthermore, SCD is characterized by an increased risk of thrombotic complications. The pathogenesis of coagulation activation in SCD appears to be multi-factorial, with contributions from ischemia-reperfusion injury and inflammation, hemolysis and nitric oxide deficiency, and increased sickle RBC phosphatidylserine expression. Recent studies in animal models suggest that activation of coagulation may contribute to the pathogenesis of SCD, but the data on the contribution of coagulation and platelet activation to SCD-related complications in humans are limited. Clinical trials of new generations of anticoagulants and antiplatelet agents, using a variety of clinical endpoints are warranted. PMID:26776344

Environmental Enteric Dysfunction: Pathogenesis, Diagnosis, and Clinical Consequences

PubMed Central

Keusch, Gerald T.; Denno, Donna M.; Black, Robert E.; Duggan, Christopher; Guerrant, Richard L.; Lavery, James V.; Nataro, James P.; Rosenberg, Irwin H.; Ryan, Edward T.; Tarr, Phillip I.; Ward, Honorine; Bhutta, Zulfiqar A.; Coovadia, Hoosen; Lima, Aldo; Ramakrishna, Balakrishnan; Zaidi, Anita K. M.; Hay Burgess, Deborah C.; Brewer, Thomas

2014-01-01

Stunting is common in young children in developing countries, and is associated with increased morbidity, developmental delays, and mortality. Its complex pathogenesis likely involves poor intrauterine and postnatal nutrition, exposure to microbes, and the metabolic consequences of repeated infections. Acquired enteropathy affecting both gut structure and function likely plays a significant role in this outcome, especially in the first few months of life, and serve as a precursor to later interactions of infection and malnutrition. However, the lack of validated clinical diagnostic criteria has limited the ability to study its role, identify causative factors, and determine cost-effective interventions. This review addresses these issues through a historical approach, and provides recommendations to define and validate a working clinical diagnosis and to guide critical research in this area to effectively proceed. Prevention of early gut functional changes and inflammation may preclude or mitigate the later adverse vicious cycle of malnutrition and infection. PMID:25305288

Clinical characteristics and thrombolysis in myocardial infarction frame counts in women with transient left ventricular apical ballooning syndrome.

PubMed

Bybee, Kevin A; Prasad, Abhiram; Barsness, Greg W; Lerman, Amir; Jaffe, Allan S; Murphy, Joseph G; Wright, R Scott; Rihal, Charanjit S

2004-08-01

The characteristics of 16 women with transient left ventricular (LV) apical ballooning syndrome in a United States population are presented. Additionally, Thrombolysis In Myocardial Infarction (TIMI) frame counts were evaluated during the acute period. Patients generally presented with anterior ST-elevation acute coronary syndrome in the absence of obstructive coronary disease. All patients had LV apical wall motion abnormalities. An acute emotional or physiologic stressor preceded most cases. TIMI frame counts were abnormal in all patients and often abnormal in all 3 major coronary vessels, suggesting that the diffuse impairment of coronary microcirculatory function may play a role in the pathogenesis of the syndrome.

Gender differences in clinicoepidemiological features of vitiligo: a cross-sectional analysis.

PubMed

Patil, Sharmila; Gautam, Manjyot; Nadkarni, Nitin; Saboo, Neha; Godse, Kiran; Setia, Maninder Singh

2014-01-01

Background. Vitiligo has important clinical and social consequences particularly in the pigmented skin. The present study was conducted to assess the differences in clinicoepidemiological presentation of vitiligo in males and females and to understand the factors associated with spread of vitiligo in them. Methods. This is a cross-sectional analysis of secondary clinical data of 168 vitiligo patients at a tertiary medical centre at Navi Mumbai. We used logistic regression models to estimate the association between gender and clinical characteristics of vitiligo and to evaluate the factors associated with spread of vitiligo. Results. There were no significant differences between the mean ages of males and females; however, males reported a longer duration of disease (6.9 (10.4) years) compared with females (4.9 (7.4) years). Males were significantly more likely to report a family history of vitiligo compared with females (adjusted OR (aOR): 16.87, 95% CI: 2.16 to 131.69). Even though females were more likely to report spread of lesions, the association was not statistically significant (OR: 1.21, 95% CI: 0.62 to 2.36). Discussion. The differences in the clinical presentations between genders highlight the need to understand the different factors (possibly genetic) that may play a part in the pathogenesis of this multifactorial disease in males and females.

Clinical and immunological studies of 49 cases of various types of intercellular IgA dermatosis and 13 cases of classical subcorneal pustular dermatosis examined at Kurume University.

PubMed

Hashimoto, T; Teye, K; Ishii, N

2017-01-01

Intercellular IgA dermatosis (IAD) is a subset of autoimmune bullous disease exclusively with IgA antikeratinocyte cell-surface antibodies. The classification and pathogenesis of this condition are still obscure. To classify IAD and study its pathogenesis. From our cohort of 5402 cases of autoimmune bullous disease, we selected 49 cases of various types of intercellular IgA dermatosis (IAD) and 13 cases of classical subcorneal pustular dermatosis (SPD), for which sera and information were available. We studied these cases clinically and immunologically. There were 17 SPD-type IAD, 12 intraepidermal neutrophilic IgA dermatosis (IEN)-type IAD, two IgA-pemphigus vegetans, four IgA-pemphigus foliaceus, six IgA-pemphigus vulgaris and eight unclassified IAD cases. There was no sex predominance, and the average age at disease onset was 45·9 years. Clinically, bullous and pustular skin lesions developed on various sites, particularly intertriginous areas. Histopathology showed intraepidermal blisters or pustules at the upper epidermis in the SPD-type and at the midepidermis in the IEN-type. Immunological studies revealed that direct immunofluorescence, indirect immunofluorescence of normal human skin and enzyme-linked immunosorbent assays (ELISAs) of recombinant proteins of desmogleins and desmocollins frequently showed positive results, although no antigens were detected in many cases. All cases of classical SPD, which showed no positive immunological results, were indistinguishable clinically and histopathologically from SPD-type IAD. The present study of the largest cohort of cases of IAD showed that the major subtypes are SPD and IEN, and that the combination of indirect immunofluorescence and ELISAs of desmogleins and desmocollins, in addition to direct immunofluorescence, was useful for the diagnosis of IAD and its subtypes. © 2016 British Association of Dermatologists.

Extensive genetic diversity, unique population structure and evidence of genetic exchange in the sexually transmitted parasite Trichomonas vaginalis.

PubMed

Conrad, Melissa D; Gorman, Andrew W; Schillinger, Julia A; Fiori, Pier Luigi; Arroyo, Rossana; Malla, Nancy; Dubey, Mohan Lal; Gonzalez, Jorge; Blank, Susan; Secor, William E; Carlton, Jane M

2012-01-01

Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection world-wide. Despite its prevalence, little is known about the genetic diversity and population structure of this haploid parasite due to the lack of appropriate tools. The development of a panel of microsatellite makers and SNPs from mining the parasite's genome sequence has paved the way to a global analysis of the genetic structure of the pathogen and association with clinical phenotypes. Here we utilize a panel of T. vaginalis-specific genetic markers to genotype 235 isolates from Mexico, Chile, India, Australia, Papua New Guinea, Italy, Africa and the United States, including 19 clinical isolates recently collected from 270 women attending New York City sexually transmitted disease clinics. Using population genetic analysis, we show that T. vaginalis is a genetically diverse parasite with a unique population structure consisting of two types present in equal proportions world-wide. Parasites belonging to the two types (type 1 and type 2) differ significantly in the rate at which they harbor the T. vaginalis virus, a dsRNA virus implicated in parasite pathogenesis, and in their sensitivity to the widely-used drug, metronidazole. We also uncover evidence of genetic exchange, indicating a sexual life-cycle of the parasite despite an absence of morphologically-distinct sexual stages. Our study represents the first robust and comprehensive evaluation of global T. vaginalis genetic diversity and population structure. Our identification of a unique two-type structure, and the clinically relevant phenotypes associated with them, provides a new dimension for understanding T. vaginalis pathogenesis. In addition, our demonstration of the possibility of genetic exchange in the parasite has important implications for genetic research and control of the disease.

Fibromyalgia Syndrome in Need of Effective Treatments

PubMed Central

Tsilioni, Irene; Arbetman, Lauren; Panagiotidou, Smaro; Stewart, Julia M.; Gleason, Rae M.; Russell, Irwin J.

2015-01-01

Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, nonarticular pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive dysfunction. The diagnostic criteria have changed repeatedly, and there is neither a definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment. PMID:26306765

A Dopamine Hypothesis of Autism Spectrum Disorder.

PubMed

Pavăl, Denis

2017-01-01

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. While several theories have emerged, the pathogenesis of ASD remains unknown. Although studies report dopamine signaling abnormalities in autistic patients, a coherent dopamine hypothesis which could link neurobiology to behavior in ASD is currently lacking. In this paper, we present such a hypothesis by proposing that autistic behavior arises from dysfunctions in the midbrain dopaminergic system. We hypothesize that a dysfunction of the mesocorticolimbic circuit leads to social deficits, while a dysfunction of the nigrostriatal circuit leads to stereotyped behaviors. Furthermore, we discuss 2 key predictions of our hypothesis, with emphasis on clinical and therapeutic aspects. First, we argue that dopaminergic dysfunctions in the same circuits should associate with autistic-like behavior in nonautistic subjects. Concerning this, we discuss the case of PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) which displays behaviors similar to those of ASD, presumed to arise from dopaminergic dysfunctions. Second, we argue that providing dopamine modulators to autistic subjects should lead to a behavioral improvement. Regarding this, we present clinical studies of dopamine antagonists which seem to have improving effects on autistic behavior. Furthermore, we explore the means of testing our hypothesis by using neuroreceptor imaging, which could provide comprehensive evidence for dopamine signaling dysfunctions in autistic subjects. Lastly, we discuss the limitations of our hypothesis. Along these lines, we aim to provide a dopaminergic model of ASD which might lead to a better understanding of the ASD pathogenesis. © 2017 S. Karger AG, Basel.

Genome-wide association studies on HIV susceptibility, pathogenesis and pharmacogenomics

PubMed Central

2012-01-01

Susceptibility to HIV-1 and the clinical course after infection show a substantial heterogeneity between individuals. Part of this variability can be attributed to host genetic variation. Initial candidate gene studies have revealed interesting host factors that influence HIV infection, replication and pathogenesis. Recently, genome-wide association studies (GWAS) were utilized for unbiased searches at a genome-wide level to discover novel genetic factors and pathways involved in HIV-1 infection. This review gives an overview of findings from the GWAS performed on HIV infection, within different cohorts, with variable patient and phenotype selection. Furthermore, novel techniques and strategies in research that might contribute to the complete understanding of virus-host interactions and its role on the pathogenesis of HIV infection are discussed. PMID:22920050

A Perspective on the Maillard Reaction and the Analysis of Protein Glycation by Mass Spectrometry: Probing the Pathogenesis of Chronic Disease

PubMed Central

Zhang, Qibin; Ames, Jennifer M.; Smith, Richard D.; Baynes, John W.; Metz, Thomas O.

2009-01-01

The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide an overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the analysis of glycated proteins by mass spectrometry. We propose that proteomics approaches, particularly bottom-up proteomics, will play a significant role in analyses of clinical samples leading to the identification of new markers of disease development and progression. PMID:19093874

A perspective on the Maillard reaction and the analysis of protein glycation by mass spectrometry: probing the pathogenesis of chronic disease.

PubMed

Zhang, Qibin; Ames, Jennifer M; Smith, Richard D; Baynes, John W; Metz, Thomas O

2009-02-01

The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide an overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the analysis of glycated proteins by mass spectrometry. We propose that proteomics approaches, particularly bottom-up proteomics, will play a significant role in analyses of clinical samples leading to the identification of new markers of disease development and progression.

An update on ocular complications of Ebola virus disease

PubMed Central

Shantha, Jessica G.; Crozier, Ian; Yeh, Steven

2018-01-01

Purpose of review This review provides a summary of our current understanding of the ophthalmic manifestations of Ebola virus disease (EVD), pathogenesis, treatment options and directions for future study. The individual, public health and global health implications of eye disease in EVD survivors are discussed. Recent findings The West Africa EVD outbreak was of unprecedented magnitude, leading to the largest survivor cohort since the first documented EVD outbreak in 1976. Because of the magnitude of the recent outbreak, thousands of survivors are at-risk of systemic and ophthalmic sequelae termed the ‘post Ebola virus disease syndrome’. Uveitis is the most common finding during EVD convalescence and may lead to severe vision impairment or blindness in 40% of affected individuals. Ocular complications leading to vision loss include cataract, retinal scarring, optic neuropathy, hypotony and phthisis bulbi. The pathogenesis of eye disease in EVD survivors likely involves Ebola virus persistence, severe inflammation and tissue edema, which present as acute, rapidly progressive disease or chronic, smoldering disease. Further studies into disease pathogenesis including mechanisms of viral persistence may provide guidance into therapies for uveitis secondary to EVD. Summary Uveitis is the most common ophthalmic finding in EVD survivors and can lead to vision loss. Further studies into the clinical manifestations and mechanisms of disease are needed to improve therapies for EVD survivors who often have limited access to ophthalmic medical and surgical care. PMID:28872492

Elevated interleukin-1β in peripheral blood mononuclear cells contributes to the pathogenesis of autoimmune thyroid diseases, especially of Hashimoto thyroiditis.

PubMed

Sun, Li; Zhang, Xiaoxu; Dai, Fang; Shen, Jijia; Ren, Cuiping; Zuo, Chunlin; Zhang, Qiu

2016-08-01

To explore the relationship between IL-1β expression and two common autoimmune thyroid diseases: Hashimoto thyroiditis (HT) and Graves' disease (GD). qRT-PCR, Quantiglo ELISA, and flow cytometry were used to evaluate the expression levels of IL-1β in serum, peripheral blood mononuclear cells (PBMCs), and thyroid tissue samples from patients with HT or GD. Local infiltration of monocytes was assessed by immunohistochemical study of patients' thyroid tissue samples. Although no significant differences in IL-1β levels were found between samples of serum from patients with HT or GD and normal controls, we found that IL-1β mRNA and protein levels in PBMCs of HT patients were significantly higher than those of patients with GD, which were in turn higher than the level in normal controls. In addition, IL-1β mRNA was also increased in thyroid gland tissue from patients with HT compared to those with GD, and this was accompanied by increased local infiltration of monocytes into thyroid tissues. Correlation analysis of the clinical samples validated the association of high IL-1β levels with the pathogenesis of HT. Our study suggests that IL-1β may be an active etiologic factor in the pathogenesis of HT and thus present a new target for novel diagnostics and treatment.

Pathogenesis and Immunobiology of Brucellosis

PubMed Central

de Figueiredo, Paul; Ficht, Thomas A.; Rice-Ficht, Allison; Rossetti, Carlos A.; Adams, L. Garry

2016-01-01

This review of Brucella–host interactions and immunobiology discusses recent discoveries as the basis for pathogenesis-informed rationales to prevent or treat brucellosis. Brucella spp., as animal pathogens, cause human brucellosis, a zoonosis that results in worldwide economic losses, human morbidity, and poverty. Although Brucella spp. infect humans as an incidental host, 500,000 new human infections occur annually, and no patient-friendly treatments or approved human vaccines are reported. Brucellae display strong tissue tropism for lymphoreticular and reproductive systems with an intracellular lifestyle that limits exposure to innate and adaptive immune responses, sequesters the organism from the effects of antibiotics, and drives clinical disease manifestations and pathology. Stealthy brucellae exploit strategies to establish infection, including i) evasion of intracellular destruction by restricting fusion of type IV secretion system-dependent Brucella-containing vacuoles with lysosomal compartments, ii) inhibition of apoptosis of infected mononuclear cells, and iii) prevention of dendritic cell maturation, antigen presentation, and activation of naive T cells, pathogenesis lessons that may be informative for other intracellular pathogens. Data sets of next-generation sequences of Brucella and host time-series global expression fused with proteomics and metabolomics data from in vitro and in vivo experiments now inform interactive cellular pathways and gene regulatory networks enabling full-scale systems biology analysis. The newly identified effector proteins of Brucella may represent targets for improved, safer brucellosis vaccines and therapeutics. PMID:25892682

Association of myasthenia gravis and Behçet's disease: A case report.

PubMed

Kisabay, Aysin; Sari, Ummu Serpil; Boyaci, Recep; Batum, Melike; Yilmaz, Hikmet; Selcuki, Deniz

2016-01-01

Myasthenia gravis is a disease of neuromuscular junction due to auto-immune destruction of the acetylcholine receptors. Behçet's disease, on the other hand, is a multisystemic vascular-inflammatory disease. Both conditions are not common in the general population although their association has not been reported in the literature. We wanted to present our patient who developed clinical course of myasthenia gravis following discontinuation of medications due to complications of corticosteroid for Behçet's disease. It was observed that clinical findings of myasthenia gravis recovered following restarting steroid treatment and he did not experience attacks of both conditions. Although Myasthenia gravis and Behçet's disease are distinct entities clinically as well as in terms of pathogenesis, they share common physiopathological features and their treatment is based on their common features. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Newer influenza antivirals, biotherapeutics and combinations.

PubMed

Hayden, Frederick G

2013-01-01

This summary provides an overview of investigational antiviral agents for influenza and of future directions for development of influenza therapeutics. While progress in developing clinically useful antiviral agents for influenza has been generally slow, especially with respect to seriously ill and high-risk patients, important clinical studies of intravenous neuraminidase inhibitors, antibodies and drug combinations are currently in progress. The current decade offers the promise of developing small molecular weight inhibitors with novel mechanisms of action, including host-directed therapies, new biotherapeutics and drug combinations, that should provide more effective antiviral therapies and help mitigate the problem of antiviral resistance. Immunomodulatory interventions also offer promise but need to be based on better understanding of influenza pathogenesis, particularly in seriously ill patients. The development of combination interventions, immunomodulators and host-directed therapies presents unique clinical trial design and regulatory hurdles that remain to be addressed. © 2012 Blackwell Publishing Ltd.

Current perspectives of herpesviral retinitis and choroiditis.

PubMed

Madhavan, H N; Priya, K; Biswas, J

2004-10-01

Vision-threatening viral retinitis are primarily caused by members of the herpesvirus family. The biology and molecular characterization of herpesviruses, clinical presentations of retinopathies, pathology and pathogenesis including the host responses, epidemiology and the laboratory methods of aetiological diagnosis of these diseases are described. Clinical syndromes are acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis, multifocal choroiditis and serpiginous choroiditis besides other viral retinopathies. Herpes simplex virus (HSV) retinitis is more common in immunocompetent persons while varicella zoster virus (VZV) affects both immunocompetent and immunosuppressed patients equally. CMV retinitis is most common among patients with AIDS. The currently employed laboratory methods of antigen detection, virus isolation and antibody detection by enzyme linked immuno-sorbent assay (ELISA) have low sensitivity. Polymerase chain reaction (PCR) has increased the value of diagnosis due to its high clinical sensitivity and absolute specificity in detection of herpesviruses in intraocular specimens.

An overview of occult hepatitis B virus infection

PubMed Central

Said, Zeinab Nabil Ahmed

2011-01-01

Occult hepatitis B virus (HBV) infection (OBI), alternatively defined as occult hepatitis B (OHB), is a challenging clinical entity. It is recognized by two main characteristics: absence of HBsAg, and low viral replication. The previous two decades have witnessed a remarkable progress in our understanding of OBI and its clinical implications. Appropriate diagnostic techniques must be adopted. Sensitive HBV DNA amplification assay is the gold standard assay for detection of OBI. Viral as well as host factors are implicated in the pathogenesis of OBI. However, published data reporting the infectivity of OBI by transfusion are limited. Several aspects including OBI transmission, infectivity and its relation to the development of chronic liver diseases and hepatocellular carcinoma have to be resolved. The aim of the present review is to highlight recent data on OBI with a focus on its virological diagnosis and clinical outcome. PMID:21528070

Atypical fibroxanthoma on a bald scalp.

PubMed

Nakai, Noriaki; Takenaka, Hideya; Kishimoto, Saburo

2005-10-01

We present the clinical, histopathological and immunohistochemical findings of an atypical fibroxanthoma (AFX) on the bald scalp of an 81-year-old French man who had worked at a private high school in Japan as a janitor for over 40 years. The patient had a history of basal cell carcinoma on the nape, and chronic solar radiation seemed to be a predisposing factor in the pathogenesis of this association. This case showed the typical clinical and histopathological characteristics of AFX, and the immunohistochemical results suggested differentiation of histiocytes and myofibroblasts. The AFX was completely resected, and the patient has not had tumor recurrence or metastasis for over four postoperative years. This case therefore provides further support to the theory that AFX displays a clinically benign course, even though it is essentially a malignant tumor histologically located in the dermis. Therefore, we must excise AFX completely with great care and perform regular physical examinations for several years after operation.

[Hernia surgery in urology. Part 2: parastomal, trocar and incisional hernias - fundamentals of clinical diagnostics and treatment].

PubMed

Franz, T; Schwalenberg, T; Dietrich, A; Müller, J; Stolzenburg, J-U

2013-06-01

Hernias are a common occurrence with a correspondingly huge clinical and economic impact on the healthcare system. Parastomal and trocar hernias are rare in routine urological work. The therapy of parastomal hernias remains problematic but basically the surgeon is able to use conventional techniques with suture repair or procedures with mesh implantation. The conventional parastomal hernia repair with mesh can be classified into sublay, onlay and intraperitoneal techniques. Furthermore, a relocation of the stoma is possible. Trocar hernias represent a rare but hazardous complication. Due to the increase in keyhole surgery there is also the danger of a rise in their occurrence. Incisional hernias occur frequently in patients who have undergone laparotomy and for repair different surgical techniques and types of meshes are available. This article presents an overview of the epidemiology, pathogenesis, clinical symptoms, diagnostic and therapy of parastomal, trocar and incisional hernias.

Modelling clinical systemic lupus erythematosus: similarities, differences and success stories

PubMed Central

Celhar, Teja

2017-01-01

Abstract Mouse models of SLE have been indispensable tools to study disease pathogenesis, to identify genetic susceptibility loci and targets for drug development, and for preclinical testing of novel therapeutics. Recent insights into immunological mechanisms of disease progression have boosted a revival in SLE drug development. Despite promising results in mouse studies, many novel drugs have failed to meet clinical end points. This is probably because of the complexity of the disease, which is driven by polygenic predisposition and diverse environmental factors, resulting in a heterogeneous clinical presentation. Each mouse model recapitulates limited aspects of lupus, especially in terms of the mechanism underlying disease progression. The main mouse models have been fairly successful for the evaluation of broad-acting immunosuppressants. However, the advent of targeted therapeutics calls for a selection of the most appropriate model(s) for testing and, ultimately, identification of patients who will be most likely to respond. PMID:28013204

Antibiotics and probiotics in treatment of inflammatory bowel disease

PubMed Central

Gionchetti, Paolo; Rizzello, Fernando; Lammers, Karen M; Morselli, Claudia; Sollazzi, Lucia; Davies, Samuel; Tambasco, Rosy; Calabrese, Carlo; Campieri, Massimo

2006-01-01

Many experimental and clinical observations suggest that intestinal microflora plays a potential role in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics or probiotics represents a potentially effective therapeutic option. The available studies do not support the use of antibiotics in ulcerative colitis (UC). Antibiotics are effective in treating septic complications of Crohn’s disease (CD) but their use as a primary therapy is more controversial, although this approach is frequently and successfully adopted in clinical practice. There is evidence that probiotic therapy may be effective in the prevention and treatment of mild to moderate UC. In contrast, a lack of successful study data at present precludes the widespread use of probiotics in the treatment of CD. Both antibiotics and probiotics appear to play a beneficial role in the treatment and prevention of pouchitis and further trials are warranted to fully quantify their clinical efficacy. PMID:16733845

[Short bowel syndrome].

PubMed

Parfenov, A I; Sabelnikova, E A; Kuzmina, T N

2017-01-01

The paper gives information on the classification, pathogenesis, and clinical manifestations of short bowel syndrome following after intestinal resection. It discusses the treatment and rehabilitation of patients with this condition.

Canine and Human Atopic Dermatitis: Two Faces of the Same Host-Microbe Interaction.

PubMed

Santoro, Domenico; Rodrigues Hoffmann, Aline

2016-06-01

Host-microbe interaction has been suggested to play a critical role in the pathogenesis of atopic dermatitis. The dog has been shown to be the best model to study both pathogenesis and microbiome modifications in atopic dermatitis. Bradley et al. show a significant correlation between microbiome diversity, clinical signs, and skin barrier function in atopic dogs before, during, and after antimicrobial therapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Targeting MicroRNAs with Small Molecules a Novel Approach to Treating Breast Cancer

DTIC Science & Technology

2011-10-01

pathogenesis of a disease. To date, the main RNA inhibition agents used in pre- clinical and clinical studies include antisense oligonucleotides, ribozymes ...antagomir Preclinical studies Ribozymes or DNAzymes A ribozyme , or RNA enzyme, is an RNA molecule that can catalyze a chemical reaction. A DNAzyme

Pre-Clinical and Clinical Investigation of the Impact of Obesity on Ovarian Cancer Pathogenesis

DTIC Science & Technology

2015-12-01

Atorvastatin on the Endometrium of Endometrial Cancer Patients: A Pre-Operative Window Study May 2015- April 2016 $50,000 (total and direct costs... atorvastatin in endometrial cancer patients American Cancer Society Research Scholar Grant – RSG CCE 128826 Obesity, Cation-Selective Transporters and

Mechanism of Flagellar Vaccine Protection Related to Pseudomonas Pathogenesis in Trauma Burns

DTIC Science & Technology

1989-01-19

differentiated by the indirect fluorescent-antibody and aglutination techniques 16). GNB. general clinical non-bum isolate; F. folliculitis isolate; CF...128.000(+ -, 256.000 - 5 12 000 n -s. GNB. general clinical non-burn isolate. F. folliculitis isolate. CF. ,:ystic fibrosis isolate. N R, not reactive

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fucharoen, S.; Rowley, P.T.; Paul, N.W.

This book contains papers divided among the following sections: molecular biology and pathogenesis; pathophysiology - molecular and cellular; clinical manifestations and hematologic changes; cardiopulmonary defects and platelet function; hormones and minerals; and infection and immunology.

Immunological pathogenesis of inflammatory bowel disease.

PubMed

Lee, Seung Hoon; Kwon, Jeong Eun; Cho, Mi-La

2018-01-01

Inflammatory bowel disease (IBD) is a chronic inflammatory state of the gastrointestinal tract and can be classified into 2 main clinical phenomena: Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD, including CD and UC, involves the presence of pathogenic factors such as abnormal gut microbiota, immune response dysregulation, environmental changes, and gene variants. Although many investigations have tried to identify novel pathogenic factors associated with IBD that are related to environmental, genetic, microbial, and immune response factors, a full understanding of IBD pathogenesis is unclear. Thus, IBD treatment is far from optimal, and patient outcomes can be unsatisfactory. As result of massive studying on IBD, T helper 17 (Th17) cells and innate lymphoid cells (ILCs) are investigated on their effects on IBD. A recent study of the plasticity of Th17 cells focused primarily on colitis. ILCs also emerging as novel cell family, which play a role in the pathogenesis of IBD. IBD immunopathogenesis is key to understanding the causes of IBD and can lead to the development of IBD therapies. The aim of this review is to explain the pathogenesis of IBD, with a focus on immunological factors and therapies.

DNA Hypomethylation Affects Cancer-Related Biological Functions and Genes Relevant in Neuroblastoma Pathogenesis

PubMed Central

Mayol, Gemma; Martín-Subero, José I.; Ríos, José; Queiros, Ana; Kulis, Marta; Suñol, Mariona; Esteller, Manel; Gómez, Soledad; Garcia, Idoia; de Torres, Carmen; Rodríguez, Eva; Galván, Patricia; Mora, Jaume; Lavarino, Cinzia

2012-01-01

Neuroblastoma (NB) pathogenesis has been reported to be closely associated with numerous genetic alterations. However, underlying DNA methylation patterns have not been extensively studied in this developmental malignancy. Here, we generated microarray-based DNA methylation profiles of primary neuroblastic tumors. Stringent supervised differential methylation analyses allowed us to identify epigenetic changes characteristic for NB tumors as well as for clinical and biological subtypes of NB. We observed that gene-specific loss of DNA methylation is more prevalent than promoter hypermethylation. Remarkably, such hypomethylation affected cancer-related biological functions and genes relevant to NB pathogenesis such as CCND1, SPRR3, BTC, EGF and FGF6. In particular, differential methylation in CCND1 affected mostly an evolutionary conserved functionally relevant 3′ untranslated region, suggesting that hypomethylation outside promoter regions may play a role in NB pathogenesis. Hypermethylation targeted genes involved in cell development and proliferation such as RASSF1A, POU2F2 or HOXD3, among others. The results derived from this study provide new candidate epigenetic biomarkers associated with NB as well as insights into the molecular pathogenesis of this tumor, which involves a marked gene-specific hypomethylation. PMID:23144874

Management of refractory pityriasis rubra pilaris: challenges and solutions

PubMed Central

Moretta, Gaia; De Luca, Erika V; Di Stefani, Alessandro

2017-01-01

Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory papulosquamous skin disease. Its clinical presentation and evolution is very variable. The most frequent clinical features are follicular papules, progressing to yellow-orange erythroderma with round small areas of normal skin and the well-demarcated palmoplantar keratoderma. Actually, six different types of PRP have been described based on clinical characteristics, age of onset, and prognosis. The pathogenesis is still unknown, and treatment can be challenging. Available treatments are mainly based on case reports or case series of clinical experience because no controlled randomized trials have never been performed because of the rarity of the condition. Traditional systemic treatment consists in retinoids, which are actually considered as first-line therapy, but refractory cases that do not respond or relapse after drug interruption do exist. In recent years, numerous reports have demonstrated the efficacy of new agents such as biological drugs. This article is an overview on available therapeutic options, in particular for refractory forms of PRP. PMID:29184428

Recent Advances in Understanding and Managing Autism Spectrum Disorders

PubMed Central

Germain, Blair; Eppinger, Melissa A.; Mostofsky, Stewart H.; DiCicco-Bloom, Emanuel; Maria, Bernard L.

2017-01-01

Autism spectrum disorder in children is a group of neurodevelopmental disorders characterized by difficulties with social communication and behavior. Growing scientific evidence in addition to clinical practice has led the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to categorize several disorders into the broader category of autism spectrum disorder. As more is learned about how autism spectrum disorder manifests, progress has been made toward better clinical management including earlier diagnosis, care, and when specific interventions are required. The 2014 Neurobiology of Disease in Children symposium, held in conjunction with the 43rd annual meeting of the Child Neurology Society, aimed to (1) describe the clinical concerns involving diagnosis and treatment, (2) review the current status of understanding in the pathogenesis of autism spectrum disorder, (3) discuss clinical management and therapies for autism spectrum disorder, and (4) define future directions of research. The article summarizes the presentations and includes an edited transcript of question-and-answer sessions. PMID:26336201

The complexities of malaria disease manifestations with a focus on asymptomatic malaria

PubMed Central

2012-01-01

Malaria is a serious parasitic disease in the developing world, causing high morbidity and mortality. The pathogenesis of malaria is complex, and the clinical presentation of disease ranges from severe and complicated, to mild and uncomplicated, to asymptomatic malaria. Despite a wealth of studies on the clinical severity of disease, asymptomatic malaria infections are still poorly understood. Asymptomatic malaria remains a challenge for malaria control programs as it significantly influences transmission dynamics. A thorough understanding of the interaction between hosts and parasites in the development of different clinical outcomes is required. In this review, the problems and obstacles to the study and control of asymptomatic malaria are discussed. The human and parasite factors associated with differential clinical outcomes are described and the management and treatment strategies for the control of the disease are outlined. Further, the crucial gaps in the knowledge of asymptomatic malaria that should be the focus of future research towards development of more effective malaria control strategies are highlighted. PMID:22289302

Painless thyroiditis complicating with hypercalcemic encephalopathy.

PubMed

Thewjitcharoen, Yotsapon; Lumlertgul, Nuttha

2012-01-01

Severe hypercalcemia has rarely been reported in patients with hyperthyroidism. Although the pathogenesis is not clear; it is believed to be due to activation of osteoclasts resulting in excessive bone resorption. To recognize the unusual cause of hypercalcemia from painless thyroiditis, which could manifest with transient hyperthyroidism in the early stage. A 70-year-old woman presented with watery diarrhea, nausea and vomiting and significant weight loss for two months. Initially, she was misdiagnosed as having Graves'disease from her clinical presentation and thyroid function tests. Oral propylthiouracil was given to treat hyperthyroidism. However two weeks after discharge, she developed altered consciousness due to severe hypercalcemia. After combined treatment of hypercalcemia and severe hyperthyroidism, her symptoms resolved quickly. Later on, her thyroid function tests switched to subclinical hypothyroid at two months after initial presentation. No concurrent pathological conditions could be found to explain the other causes of hypercalcemia. Therefore, painless thyroiditis complicated with severe hypercalcemia was subsequently diagnosed based on her clinical course. Hypercalcemic encephalopathy is an uncommon manifestation of hyperthyroidism that should be kept in mind in patients who demonstrated clinical pictures of hyperthyroidism and alteration of consciousness. Moreover the present case emphasizes the consideration of painless thyroiditis as a differential diagnosis of hyperthyroidism because anti-thyroid medications were not indicated in this condition.

The pathogenesis of iodide mumps: A case report.

PubMed

Zhang, Guilian; Li, Tao; Wang, Heying; Liu, Jiao

2017-11-01

Iodide mumps is an uncommon condition, induced by iodide-containing contrast, and is characterized by a rapid, painless enlargement of the bilateral or unilateral salivary gland. At present, the pathogenesis of iodide mumps is not yet clear. It may be related to an idiosyncratic reaction, a toxic accumulation of iodine in the gland duct, or renal function damage leading to an iodine excretion disorder. This paper reports the clinical manifestations and magnetic resonance imaging results of one case of iodide mumps, which occurred after digital subtraction angiography. A 66-year-old Chinese man presented to our department with a 1-month speech barrier and 1 day of vomiting. He had the history of high blood sugar, the history of high blood pressure and the history of Vitiligo. He had no history of allergies and had never previously received iodide-containing contrast. His renal function and other laboratory examinations were normal. During the digital subtraction angiography (DSA), the patient received approximately 130 mL of nonionic contrast agent (iodixanol). Five hours postsurgery, the patient experienced bilateral parotid enlargement with no other discomfort, such as pain, fever, skin redness, itching, hives, nausea, vomiting, or respiratory abnormalities. We thought the diagnosis was iodide mumps. Intravenous dexamethasone (5 mg) was administered. 20 hours post-DSA, after which the bilateral parotid shrunk. By 4 days postsurgery, the patient's bilateral parotid had recovered completely. We found no obvious abnormal sequence signal in diffusion magnetic resonance imaging or the corresponding apparent diffusion coefficient. Our findings suggest that vasogenic edema may play an important role in the pathogenesis of iodide mumps. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Pathogenesis of systemic inflammatory diseases in childhood: "Lessons from clinical trials of anti-cytokine monoclonal antibodies for Kawasaki disease, systemic onset juvenile idiopathic arthritis, and cryopyrin-associated periodic fever syndrome".

PubMed

Yokota, Shumpei; Kikuchi, Masako; Nozawa, Tomo; Kanetaka, Taichi; Sato, Tomomi; Yamazaki, Kazuko; Sakurai, Nodoka; Hara, Ryoki; Mori, Masaaki

2015-01-01

Inflammation has often been considered to be a nonspecific response and to play a bridging role in the activation of adaptive immunity. However, it is now accepted that inflammation is the product of an independent innate immune system closely linked to the adaptive immune system. The key mediators of inflammation are inflammatory cytokines, as determined by multiple lines of evidence both in vitro and in vivo. Due to the crucial role of inflammatory cytokines in the pathogenesis of autoimmune disorders, anti-cytokine treatment has been developed as a therapy for rheumatoid arthritis, juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases. We recently completed several clinical trials of anti-cytokine treatment for children with systemic inflammatory diseases: anti-IL-6 receptor monoclonal antibody (tocilizumab) for children with two subtypes of JIA (poly-JIA and systemic JIA), anti-TNF-α monoclonal antibody (infliximab) for children with Kawasaki disease, and anti-IL-1-β monoclonal antibody (canakinumab) for children with cryopyrin-associated periodic syndrome. This review summarizes the basis of inflammation in terms of innate immunity and adaptive immunity in these systemic inflammatory diseases, clinical efficacy, and tolerability of these biologic agents, and attempts to determine the roles of individual inflammatory cytokines in disease pathogenesis.

Emerging therapies in systemic lupus erythematous: from clinical trial to the real life.

PubMed

Zhang, Huza; Chambers, William; Sciascia, Savino; Cuadrado, Maria J

2016-01-01

Systemic lupus erythematous (SLE) is a chronic autoimmune disease characterised by multisystem involvement and a relapsing remitting course. SLE is a highly heterogeneous condition, with wide variations in both the presentation and severity of disease and the biological markers identified. The use of biologics in SLE has lagged behind that of other rheumatological conditions such as rheumatoid arthritis, in part due to the diverse clinical manifestations of SLE, making it difficult to design appropriate trials for novel treatments. As such, broad immunosuppressive treatment regimens are still widely used in SLE. Nevertheless, in recent years, elucidation of some aspects of SLE pathogenesis have allowed the development of therapies targeted at molecular mediators of SLE. This review provides an update of biological available therapies and those currently under development.

[The vertebral artery syndrome and patient management tactics].

PubMed

Panteleeva, E A

2012-01-01

The data of literature on vertebral artery syndrome, its clinical presentations, etiology and pathogenesis are summarized. Based on the own studies, the author considers possibilities for a pathogenetic treatment of this syndrome with sermion (nicergoline). Twenty-two patients, aged 21-71 years (a half of them were outpatients and another half were inpatients), were treated with sermion. Treatment duration ranged from 2 to 6 months. The positive effect of sermion on the most frequent clinical symptoms of the vertebral artery syndrome, including headache, vertigo and persistent or sudden increase in the blood pressure, was noted. The long-term treatment with sermion revealed a significant improvement in patient's quality of life measured with SF-36. The treatment was effective in any variant of vertebral artery syndrome regardless of its causes.

Detection of autoimmunity in early primary Epstein-Barr virus infection by Western blot analysis.

PubMed

Mascia, M T; Sandri, G; Guerzoni, C; Roncaglia, R; Mantovani, G; Ferri, C

2008-01-01

The Epstein-Barr virus (EBV) represents a potentially important factor in the pathogenesis of certain autoimmune disorders such as systemic lupus erythematosus (SLE), and Sjögren's syndrome, probably through a molecular mimicry mechanism. Several studies have focused on the relationship between previous EBV infection and clinically overt connective tissue diseases (CTDs), while the aim of this study was to investigate the immunological alterations during the early phase of primary acute EBV infection by means of ENA Western blotting (WB) analysis. This technique is able to detect a wide spectrum of anti-ENA autoantibodies, potentially directed against diverse epitopes of the same antigen. Sera from 54 subjects (F/M=24/30, mean age 17+/-6 SD years) with primary acute EBV infection were analysed using indirect immunofluorescence (IF) on Hep-2 cells for ANA, and both ELISA and WB for ENA. Only 8 ANA+ and no ENA+ were found by means of IF and ELISA techniques, respectively; however, one or more ENA autoantibodies were detected in 24/54 (44%) sera using WB. The autoantibodies were no longer present at the second evaluation. Subjects with immunological alterations had not developed any significant clinical manifestations at a 5-year follow-up. This study demonstrated the appearance of autoantibody production in a high proportion of individuals with primary acute EBV infection; interestingly, the observed serological subsets are quite similar to clinical SLE clusters. Moreover, the absence of immunological disorders during the follow-up reinforces the role of multiple genetic and/or environmental co-factors in the pathogenesis of CTDs.

R1 autonomic nervous system in acute kidney injury.

PubMed

Hering, Dagmara; Winklewski, Pawel J

2017-02-01

Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented. © 2016 John Wiley & Sons Australia, Ltd.

Autosomal-dominant non-autoimmune hyperthyroidism presenting with neuromuscular symptoms.

PubMed

Elgadi, Aziz; Arvidsson, C-G; Janson, Annika; Marcus, Claude; Costagliola, Sabine; Norgren, Svante

2005-08-01

Neuromuscular presentations are common in thyroid disease, although the mechanism is unclear. In the present study, we investigated the pathogenesis in a boy with autosomal-dominant hyperthyroidism presenting with neuromuscular symptoms. The TSHr gene was investigated by direct sequencing. Functional properties of the mutant TSHr were investigated during transient expression in COS-7 cells. Family members were investigated by clinical and biochemical examinations. Sequence analysis revealed a previously reported heterozygous missense mutation Glycine 431 for Serine in the first transmembrane segment, leading to an increased specific constitutive activity. Three additional affected family members carried the same mutation. There was no indication of autoimmune disorder. All symptoms disappeared upon treatment with thacapzol and L-thyroxine and subsequent subtotal thyroidectomy. The data imply that neuromuscular symptoms can be caused by excessive thyroid hormone levels rather than by autoimmunity.

Review of book vestibular crises

NASA Technical Reports Server (NTRS)

Blagoveshchenskaya, N. S.

1980-01-01

The etiology, pathogenesis, clinical practice, treatment and rehabilitation of patients with vestibular crises is discussed. Classifications for vestibular disorders are given. Information on the frequency of vestibular crises is given.

Managing toxic shock syndrome with antibiotics.

PubMed

Annane, Djillali; Clair, Bernard; Salomon, Jérôme

2004-08-01

Toxic shock syndrome (TSS) is a serious disorder with a worldwide prevalence of approximately 3/100,000 persons. TSS is mainly caused by Streptococcus pyogenes or Staphylococcus aureus. Thus, beta-lactam and lincosamides, such as clindamycin, are the first-line drugs. Yet, the mortality rate remains unacceptably high; highlighting the role of bacterial toxin-mediated activation of the inflammatory cascade in TSS pathogenesis. Further strategies should be targeted towards interfering with the interaction between bacterial toxins and host T cells. This paper aims to provide an overview of the epidemiology, pathomechanisms, and clinical presentation of TSS, and criteria for selecting drugs among available antibiotics.

Urinary Tract Infection and Asymptomatic Bacteriuria in Older Adults.

PubMed

Cortes-Penfield, Nicolas W; Trautner, Barbara W; Jump, Robin L P

2017-12-01

Urinary tract infections (UTIs) are a significant cause of morbidity among older adults. However, antibiotic prescriptions for clinically suspected UTIs are often inappropriate. Health care providers frequently struggle to differentiate UTI from asymptomatic bacteriuria, particularly in patients presenting with nonspecific symptoms. Patients with baseline cognitive impairments that limit history-taking can be particularly challenging. This article reviews the epidemiology and pathogenesis of UTI in older adults. It discusses an approach to diagnosis and treatment focused on recognizing patients who would likely benefit from antibiotic treatment and on identifying patients for whom empiric antibiotic therapy should not be given. Published by Elsevier Inc.

Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus.

PubMed

Rasmuson, J; Andersson, C; Norrman, E; Haney, M; Evander, M; Ahlm, C

2011-05-01

Hantaviruses have previously been recognised to cause two separate syndromes: hemorrhagic fever with renal syndrome in Eurasia, and hantavirus pulmonary syndrome (HPS) in the Americas. However, increasing evidence suggests that this dichotomy is no longer fruitful when recognising human hantavirus disease and understanding the pathogenesis. Herein are presented three cases of severe European Puumala hantavirus infection that meet the HPS case definition. The clinical and pathological findings were similar to those found in American hantavirus patients. Consequently, hantavirus infection should be considered as a cause of acute respiratory distress in all endemic areas worldwide.

Antioxidant vitamins and enzymatic and synthetic oxygen-derived free radical scavengers in the prevention and treatment of cardiovascular disease.

PubMed

Nayak, D U; Karmen, C; Frishman, W H; Vakili, B A

2001-01-01

Oxygen-derived free radical formation can lead to cellular injury and death. Under normal situations, the human body has a free radical scavenger system (catalase, superoxide dismutase) that can detoxify free radicals. Antioxidant vitamins and enzymatic and synthetic oxygen-derived free radical scavengers have been used clinically to prevent the formation of oxidized LDL and to prevent reperfusion injury, which is often caused by free radicals. In this article, the pathogenesis of free radical production and cell injury are discussed, and therapeutic approaches for disease prevention are presented.

Childhood inflammatory brain diseases: pathogenesis, diagnosis and therapy.

PubMed

Twilt, Marinka; Benseler, Susanne M

2014-08-01

Inflammatory brain diseases (IBrainDs) are a leading cause of devastating neurological deficits or neuropsychiatric syndromes in previously healthy children. The spectrum is expanding rapidly and new disease entities have been discovered in the last decade. IBrainD can occur as a primary disease or may occur secondary to an underlying cause. This review focuses on the clinical presentation, diagnostic features, pathology and histology characteristics and treatment of the primary childhood IBrainDs. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): two case reports.

PubMed

El Kohen, A; Planquart, X; Al Hamany, Z; Bienvenu, L; Kzadri, M; Herman, D

2001-12-01

Sinus histiocytosis with massive lymphadenopathy or Destombes-Rosai-Dorfman's syndrome is a rare benign disease of unknown etiology, usually seen in younger patients. The cases reported concerned a 15-month old Caucasian boy and an 8 year old black boy with unilateral cervical enlargement, occasional fever and without any extranodal involvement. Diagnosis was performed by superficial lymph node biopsy. No immunodeficiency was found. The patients received no therapy and a complete spontaneous resolution was seen after a few months in the two cases. The clinical presentation, histologic characteristics, pathogenesis and treatment of the Destombes-Rosai-Dorfman's syndrome are discussed.

Subacute constrictive pericarditis from Serratia marcescens bacteremia.

PubMed

Khan, M Y

1983-12-01

A case report of subacute constrictive pericarditis associated with disseminated Serratia marcescens infection and bacteremia in a patient with chronic tubulointerstitial nephritis and uremia is described. Although not substantiated by clinical history, the renal pathologic features were similar to those of ethylene glycol-induced tubulointerstitial nephritis. The patient did not have a history of heroin addiction. The importance of predisposing factors such as uremia, invasive vascular procedures, tracheal intubation, peritoneal dialysis, and pericardiocentesis in Serratia infection in susceptible persons is discussed, as are possible roles of uremia, pericardiocentesis, and pericardiotomy in the pathogenesis of constrictive pericarditis in the present case.

Self-healing juvenile cutaneous mucinosis: Clinical and histopathologic findings of 9 patients: The relevance of long-term follow-up.

PubMed

Luchsinger, Isabelle; Coulombe, Jérôme; Rongioletti, Franco; Haspeslagh, Marc; Dompmartin, Anne; Melki, Isabelle; Dagher, Rawane; Bader-Meunier, Brigitte; Fraitag, Sylvie; Bodemer, Christine

2018-06-01

Self-healing juvenile cutaneous mucinosis (SHJCM) is a rare disorder, and its pathogenesis and long-term prognosis are unknown. To elucidate the clinical and histopathologic characteristics, pathogenesis, and outcome in patients with SHJCM. Retrospective study of 9 patients with SHCJM. To complement initial findings, data collection forms were sent to the referring physicians. All patients had an acute onset of firm nodules. Of the 9 patients, 6 presented initially with waxy papules on the dorsum of the hands; 5 suffered from periorbital edema, and 6 had a febrile prodrome. Histopathologic assessment of the papules revealed dermal mucin deposition, whereas the nodules showed proliferative fasciitis-like features or nonspecific chronic lobular panniculitis. Laboratory studies elicited evidence of active viral infection in 2 patients (human herpes virus 6 and rotavirus). Seven cases had spontaneous resolution within 6 months, and 2 patients with incomplete resolution showed subsequent transition to fibroblastic rheumatism and an autoinflammatory rheumatologic disease, respectively. This was a retrospective study with incomplete data from referring physicians. Although spontaneous complete regression is expected, patients with SHJCM need long-term follow-up because of the possible development of dematorheumatolgic conditions. The pathogenetic role of microbial agents deserves further investigation. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

What causes alopecia areata?

PubMed Central

McElwee, K. J.; Gilhar, A.; Tobin, D. J.; Ramot, Y.; Sundberg, J. P.; Nakamura, M.; Bertolini, M.; Inui, S.; Tokura, Y.; Jr, L. E. King; Duque-Estrada, B.; Tosti, A; Keren, A.; Itami, S.; Shoenfeld, Y.; Zlotogorski, A.; Paus, R.

2014-01-01

The pathobiology of alopecia areata (AA), one of the most frequent autoimmune diseases and a major unsolved clinical problem, has intrigued dermatologists, hair biologists and immunologists for decades. Simultaneously, both affected patients and the physicians who take care of them are increasingly frustrated that there is still no fully satisfactory treatment. Much of this frustration results from the fact that the pathobiology of AA remains unclear, and no single AA pathogenesis concept can claim to be universally accepted. In fact, some investigators still harbour doubts whether this even is an autoimmune disease, and the relative importance of CD8+ T cells, CD4+ T cells and NKGD2+ NK or NKT cells and the exact role of genetic factors in AA pathogenesis remain bones of contention. Also, is AA one disease, a spectrum of distinct disease entities or only a response pattern of normal hair follicles to immunologically mediated damage? During the past decade, substantial progress has been made in basic AA-related research, in the development of new models for translationally relevant AA research and in the identification of new therapeutic agents and targets for future AA management. This calls for a re-evaluation and public debate of currently prevalent AA pathobiology concepts. The present Controversies feature takes on this challenge, hoping to attract more skin biologists, immunologists and professional autoimmunity experts to this biologically fascinating and clinically important model disease. PMID:23947678

Pulmonology meets rheumatology in sarcoidosis: a review on the therapeutic approach.

PubMed

Drent, Marjolein; Cremers, Johanna P; Jansen, Tim L

2014-05-01

Sarcoidosis is a systemic disease characterized by the formation of granulomas in various organs, mainly lungs and lymphatic system. Joint, muscle, and bone involvement is also rather common. Recent studies on its pathogenesis and therapeutic management are reviewed here. The pathogenesis of sarcoidosis is not fully elucidated. An exaggerated granulomatous reaction after exposure to unidentified antigens in genetically susceptible individuals evokes a clinical situation which we call sarcoidosis. No firm guidelines exist on whether, when, and how treatment should be started. Treatment is dependent on the presentation and the distribution, extensiveness and severity of sarcoidosis. Treatment of Löfgren's triad-related symptoms starts with NSAIDs; in other more extensive manifestations of sarcoidosis, the initiating dosage of glucocorticosteroids is approximately 20 mg daily. In terms of evidence-based treatment for sarcoidosis, only a few randomized controlled trials have been done. There is no cure for chronic sarcoidosis, and treatment only changes the granulomatous process and its clinical consequences. Identified associations of certain polymorphisms with severity of the disease and treatment response suggest future research questions as well as finding the cause(s) of sarcoidosis, and the elucidation of relevant biomarkers and new efficient treatments. Between 20 and 70% of patients need systemic therapy. The increased awareness of long-term side-effects of glucocorticosteroids and the emergence of new drugs have changed the treatment of sarcoidosis. Alternative or additional options to corticosteroids should be assessed.

Polypoidal Choroidal Vasculopathy: Definition, Pathogenesis, Diagnosis, and Management.

PubMed

Cheung, Chui Ming Gemmy; Lai, Timothy Y Y; Ruamviboonsuk, Paisan; Chen, Shih-Jen; Chen, Youxin; Freund, K Bailey; Gomi, Fomi; Koh, Adrian H; Lee, Won-Ki; Wong, Tien Yin

2018-05-01

Polypoidal choroidal vasculopathy (PCV) is an age-related macular degeneration (AMD) subtype and is seen particularly in Asians. Previous studies have suggested disparity in response to intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents between PCV and typical AMD, and thus, the preferred treatment for PCV has remained unclear. Recent research has provided novel insights into the pathogenesis of PCV, and imaging studies based on OCT suggest that PCV belongs to a spectrum of conditions characterized by pachychoroid, in which disturbance in the choroidal circulation seems to be central to its pathogenesis. Advances in imaging, including enhanced depth imaging, swept-source OCT, en face OCT, and OCT angiography, have facilitated the diagnosis of PCV. Importantly, 2 large, multicenter randomized clinical trials evaluating the safety and efficacy of anti-VEGF monotherapy and combination with photodynamic therapy (PDT) recently reported initial first-year outcomes, providing level I evidence to guide clinicians in choosing the most appropriate therapy for PCV. In this review, we summarize the latest updates in the epidemiologic features, pathogenesis, and advances in imaging and treatment trials, with a focus on the most recent key clinical trials. Finally, we propose current management guidelines and recommendations to help clinicians manage patients with PCV. Remaining gaps in current understanding of PCV, such as significance of polyp closure, high recurrence rate, and heterogeneity within PCV, are highlighted where further research is needed. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Advances in understanding the pathogenesis of CNS acute lymphoblastic leukaemia and potential for therapy.

PubMed

Frishman-Levy, Liron; Izraeli, Shai

2017-01-01

Central nervous system acute lymphoblastic leukaemia (CNS-ALL) is a major clinical problem. CNS-directed 'prophylactic' chemo- or radio - therapy is associated with significant early and long-term toxicity. Moreover, greater than a third of the relapses occur in the CNS. To design specific, more effective and less toxic therapy and for personalized precise adjustment of prophylactic therapy there is a need for better understanding of the biology of this disease. Specifically, the precise neurotropic mechanisms of ALL are currently unclear, as is the pathogenesis of CNS relapse. Here we review and contrast the recent findings with earlier studies of pathogenesis of CNS leukaemia. We also describe the challenges in research of this devastating complication of ALL. © 2016 John Wiley & Sons Ltd.

Theories on the pathogenesis of endometriosis.

PubMed

Sourial, Samer; Tempest, Nicola; Hapangama, Dharani K

2014-01-01

Endometriosis is a common, chronic inflammatory disease defined by the presence of extrauterine endometrial tissue. The aetiology of endometriosis is complex and multifactorial, where several not fully confirmed theories describe its pathogenesis. This review examines existing theories on the initiation and propagation of different types of endometriotic lesions, as well as critically appraises the myriad of biologically relevant evidence that support or oppose each of the proposed theories. The current literature suggests that stem cells, dysfunctional immune response, genetic predisposition, and aberrant peritoneal environment may all be involved in the establishment and propagation of endometriotic lesions. An orchestrated scientific and clinical effort is needed to consider all factors involved in the pathogenesis of this multifaceted disease and to propose novel therapeutic targets to reach effective treatments for this distressing condition.

Behavioral Contributions to the Pathogenesis of Type 2 Diabetes

PubMed Central

Spruijt-Metz, Donna; Cook, Lauren; O’Reilly, Gillian A.; Page, Kathleen A.; Quinn, Charlene

2014-01-01

Behavioral Contributions to the pathogenesis of prediabetes and Type 2 diabetes (T2D) include lifestyle behaviors including dietary intake, exercise, sedentariness, sleep, and stress. The purpose of this paper is to review evidence for the metabolic pathways by which the behavior is linked to T2D. Evidence for interventions which change each of the lifestyle behaviors is discussed. The article will close with a brief discussion on how new technologies may provide opportunities to better understand relationships between moment-to-moment fluctuations in behaviors and diabetes pathogenesis, as well as provide opportunities to personalize and adapt interventions to achieve successful behavior change and maintenance of that change. Especially promising are new technologies which assist in tracking lifestyle behaviors along with clinical and metabolic outcomes. PMID:24604714

Critical role of environmental factors in the pathogenesis of psoriasis.

PubMed

Zeng, Jinrong; Luo, Shuaihantian; Huang, Yumeng; Lu, Qianjin

2017-08-01

Psoriasis is a common cutaneous disease with multifactorial etiology including genetic and non-genetic factors, such as drugs, smoking, drinking, diet, infection and mental stress. Now, the role of the interaction between environmental factors and genetics are considered to be a main factor in the pathogenesis of psoriasis. However, it is a challenge to explore the mechanisms how the environmental factors break the body balance to affect the onset and development of psoriasis. In this article, we review the pathogenesis of psoriasis and summarize numerous clinical data to reveal the association between environmental factors and psoriasis. In addition, we focus on the mechanisms of environmental risk factors impact on psoriasis and provide a series of potential treatments against environmental risk factors. © 2017 Japanese Dermatological Association.

Theories on the Pathogenesis of Endometriosis

PubMed Central

Sourial, Samer; Hapangama, Dharani K.

2014-01-01

Endometriosis is a common, chronic inflammatory disease defined by the presence of extrauterine endometrial tissue. The aetiology of endometriosis is complex and multifactorial, where several not fully confirmed theories describe its pathogenesis. This review examines existing theories on the initiation and propagation of different types of endometriotic lesions, as well as critically appraises the myriad of biologically relevant evidence that support or oppose each of the proposed theories. The current literature suggests that stem cells, dysfunctional immune response, genetic predisposition, and aberrant peritoneal environment may all be involved in the establishment and propagation of endometriotic lesions. An orchestrated scientific and clinical effort is needed to consider all factors involved in the pathogenesis of this multifaceted disease and to propose novel therapeutic targets to reach effective treatments for this distressing condition. PMID:25763392

A Perspective on the Maillard Reaction and the Analysis of Protein Glycation by Mass Spectrometry: Probing the Pathogenesis of Chronic Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Qibin; Ames, Jennifer M.; Smith, Richard D.

2008-12-18

The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide on overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the analysis of glycated proteins by mass spectrometry. We propose that proteomics approaches, particularly bottom-up proteomics, will play a significant role in analyses of clinical samples leading to the identificationmore » of new markers of disease development and progression.« less

Animal Models of Zika Virus Infection, Pathogenesis, and Immunity

PubMed Central

2017-01-01

ABSTRACT Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis. PMID:28148798

Protection, pathogenesis and phenotypic plasticity in Plasmodium falciparum malaria.

PubMed

Roberts, D J; Biggs, B A; Brown, G; Newbold, C I

1993-08-01

Why does Plasmodium falciparum cause severe illness in some but not all infections? How is clinical immunity acquired? These questions have intrigued investigators since the clinical epidemiology of malaria was first described. The search for answers to both questions has highlighted the changes that take place at the surface of infected red blood cells during the last half of the erythrocytic cycle. These changes specify the antigenic and adhesive or cytoadherence phenotypes for the infected cell. Now the antigenic and adhesive phenotypes appear to be linked and together undergo clonal variation. In this article David Roberts, Beverley-Ann Biggs, Graham Brown and Christopher Newbold explain how clonal phenotypic variation and the linkage between adhesive and antigenic types contribute to our understanding of naturally acquired immunity and of pathogenesis of severe malaria.

Molecular genetics of chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia.

PubMed

Li, Bing; Gale, Robert Peter; Xiao, Zhijian

2014-12-12

According to the 2008 World Health Organization classification, chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia are rare diseases. The remarkable progress in our understanding of the molecular genetics of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms has made it clear that there are some specific genetic abnormalities in these 3 rare diseases. At the same time, there is considerable overlap among these disorders at the molecular level. The various combinations of genetic abnormalities indicate a multi-step pathogenesis, which likely contributes to the marked clinical heterogeneity of these disorders. This review focuses on the current knowledge and challenges related to the molecular pathogenesis of chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia and relationships between molecular findings, clinical features and prognosis.

[Chronic pancreatitis: new definition and perspectives.

PubMed

Conti Bellocchi, Maria Cristina; De Pretis, Nicolò; Amodio, Antonio; Zerbi, Alessandro; Frulloni, Luca

2018-01-01

Chronic pancreatitis has been considered over the past years as a single disease, alcohol-induced and different from acute pancreatitis, in terms of etiology and prognosis. Actually, the introduction of a new concept of chronic pancreatitis, now considered as a fibroinflammatory process caused by multiple factors (toxic-metabolic, genetic, immunologic, obstructive), allow to better understand the pathogenesis of this complex disease. Furthermore, the discover of peculiar forms of chronic pancreatitis (autoimmune, paraduodenal, associated to gene mutations), different in term of clinical aspects, findings at imaging, prognosis and therapy, radically changed the concept of the disease. In this brief review, we described the impact of this new concept in the comprehension of pathogenesis, in the definition of peculiar forms of chronic pancreatitis, and in the clinical and therapeutic approach of chronic pancreatitis.

Sensitization of TRPV1 receptors by TNF-α orchestrates the development of vincristine-induced pain.

PubMed

Wang, Ying; Feng, Chenyang; He, Haoying; He, Jinjin; Wang, Jun; Li, Xiaomin; Wang, Shasha; Li, Wei; Hou, Jiuzhou; Liu, Tong; Fang, Dong; Xie, Song-Qiang

2018-04-01

Vincristine is one of the most common anticancer drugs clinically employed in the treatment of various malignancies. A major side effect associated with vincristine is the development of neuropathic pain, which is not readily relieved by available analgesics. Although efforts have been made to identify the pathogenesis of vincristine-induced neuropathic pain, the mechanisms underlying its pathogenesis have not been fully elucidated. In the present study, a neuropathic pain model was established in Sprague-Dawley rats by intraperitoneal injection of vincristine sulfate. The results demonstrated that vincristine administration induced the upregulation of transient receptor potential cation channel subfamily V member 1 (TRPV1) protein expression and current density in dorsal root ganglion (DRG) nociceptive neurons. Consistently, inhibition of TRPV1 with capsazepine alleviated vincristine-induced mechanical allodynia and thermal hyperalgesia in rats. Furthermore, vincristine administration induced the upregulation of tumor necrosis factor (TNF)-α production in DRGs, and inhibition of TNF-α synthesis with thalidomide in vivo reversed TRPV1 protein expression, as well as pain hypersensitivity induced by vincristine in rats. The present results suggested that TNF-α could sensitize TRPV1 by promoting its expression, thus leading to mechanical allodynia and thermal hyperalgesia in vincristine-treated rats. Taken together, these findings may enhance our understanding of the pathophysiological mechanisms underlying vincristine-induced pain.

Parkinson’s Disease – the Debate on the Clinical Phenomenology, Aetiology, Pathology and Pathogenesis

PubMed Central

Jenner, Peter; Morris, Huw R.; Robbins, Trevor W.; Goedert, Michel; Hardy, John; Ben-Shlomo, Yoav; Bolam, Paul; Burn, David; Hindle, John V.; Brooks, David

2014-01-01

The definition of Parkinson’s disease (PD) is changing with the expansion of clinical phenomenology and improved understanding of environmental and genetic influences that impact on the pathogenesis of the disease at the cellular and molecular level. This had led to debate and discussion with as yet, no general acceptance of the direction that change should take either at the level of diagnosis or of what should and should not be sheltered under an umbrella of PD. This article is one contribution to this on-going discussion. There are two different themes running through the article - widening the definition of PD/LBD/synucleinopathies and the heterogeneity that exists within PD itself from a clinical, pathological and genetic per-spective. The conclusion reached is that in the future, further diagnostic categories will need to be recognized. These are likely to include - Parkinson’s syndrome, Parkinson’s syndrome likely to be Lewy body PD, clinical PD (defined by QSBB criteria), Lewy body disease (PD, LBD, REM SBD) and synucleinopathies (including LBD, MSA). PMID:23938306

How I treat Langerhans cell histiocytosis

PubMed Central

Allen, Carl E.; Ladisch, Stephan

2015-01-01

“Langerhans cell histiocytosis” (LCH) describes a spectrum of clinical presentations ranging from a single bone lesion or trivial skin rash to an explosive disseminated disease. Regardless of clinical severity, LCH lesions share the common histology of CD1a+/CD207+ dendritic cells with characteristic morphology among an inflammatory infiltrate. Despite historical uncertainty defining LCH as inflammatory vs neoplastic and incomplete understanding of mechanisms of pathogenesis, clinical outcomes have improved markedly over the past decades through cooperative randomized clinical trials based on empiric therapeutic strategies. Significant advances include recognition of high- and low-risk clinical groups defined by hematopoietic and/or hepatic involvement, and of the importance of optimal intensity and of duration of chemotherapy. Nevertheless, mortality of high-risk patients, disease recurrence, lack of robustly tested salvage strategies, and significant disease morbidity of both high- and low-risk patients remain challenges. Recent discovery of recurrent somatic mutations in mitogen-activated protein kinase pathway genes at critical stages of myeloid hematopoietic differentiation in LCH patients supports redefinition of the disease as a myeloproliferative disorder and provides opportunities to develop novel approaches to diagnosis and therapy. PMID:25827831

Funding agencies and disease organizations: resources and recommendations to facilitate ALS clinical research.

PubMed

Chad, David A; Bidichandani, Sanjay; Bruijn, Lucie; Capra, J Donald; Dickie, Brian; Ferguson, John; Figlewicz, Denise; Forsythe, Melissa; Kaufmann, Petra; Kirshner, Annette; Monti, William

2013-05-01

Ten groups presented their perspectives on facilitating clinical research in ALS including four federal agencies, four disease organizations, one foundation and one advocacy group. The federal agencies (National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, Office of Rare Diseases Research, Department of Defense) encourage fostering a team approach between pre-clinical and clinical research investigators, coordinating with patient groups in the early phases of clinical studies, enhancing private and public partnerships, and investigating the interplay between genetic susceptibility and environmental exposure. The disease organizations (Muscular Dystrophy Association, ALS Association, ALS Society of Canada, and the Motor Neurone Disease Association UK) support fellowship training programs to develop ALS clinician scientists, and encourage work on the epidemiology of ALS, on genetic and epigenetic mechanisms that are relevant to ALS pathogenesis, on developing ALS registries and biobanks, and building bridges of collaboration among study groups. The Foundation supports innovative projects, including stem-cell research, and Patient Advocacy is committed to supporting excellence in ALS research and patient care, and believes strongly in enhancing communication between patients and members of the research community.

MicroRNAs as biomarkers for graft-versus-host disease following allogeneic stem cell transplantation.

PubMed

Tomuleasa, Ciprian; Fuji, Shigeo; Cucuianu, Andrei; Kapp, Markus; Pileczki, Valentina; Petrushev, Bobe; Selicean, Sonia; Tanase, Alina; Dima, Delia; Berindan-Neagoe, Ioana; Irimie, Alexandru; Einsele, Hermann

2015-07-01

Allogeneic hematopoietic stem cell transplantation (HCT) is a well-established treatment for many malignant and non-malignant hematological disorders. As frequent complication in up to 50 % of all patients, graft-versus-host disease (GVHD) is still the main cause for morbidity and non-relapse mortality. Diagnosis of GVHD is usually done clinically, even though confirmation by pathology is often used to support the clinical findings. Effective treatment requires intensified immunosuppression as early as possible. Although several promising biomarkers have been proposed for an early diagnosis, no internationally recognized consensus has yet been established. Here, microRNAs (miRs) represent an interesting tool since miRs have been recently reported to be an important regulator of various cells, including immune cells such as T cells. Therefore, we could assume that miRs play a key role in the pathogenesis of acute GVHD, and their detection might be an interesting possibility in the early diagnosis and monitoring of acute GVHD. Recent studies additionally demonstrated the implication of miRs in the pathogenesis of acute GVHD. In this review, we aim to summarize the previous reports of miRs, focusing on the pathogenesis of acute GVHD and possible implications in diagnostic approaches.

Intestinal microbiota in primary sclerosing cholangitis.

PubMed

Hov, Johannes R; Kummen, Martin

2017-03-01

Alterations of the gut-liver axis have been linked to the pathogenesis of primary sclerosing cholangitis (PSC) since the disease was first described. The purpose of this review is to discuss multiple recent studies on the intestinal microbiota in human PSC and experimental models of this disease. Data are available from eight cross-sectional studies of human PSC, which include a variable number of patients (n = 11-85), material (mucosal or fecal), and microbiota profiling methodology. Despite the heterogeneity of the studies, a pattern of differences is observed that could represent a theme or signature of the PSC gut microbiota, characterized by low diversity and with alterations in multiple bacterial taxa. In experimental models of PSC, re-derivation of animals into germ-free facilities may either aggravate or attenuate the disease, depending on host genetics and putative disease mechanisms (e.g., fibrotic or immune-driven processes, respectively). The present data provide a strong rationale to explore the functional consequences of the observed gut microbial alterations and their influence on the pathogenesis in PSC. Studies of gut microbiota as biomarker and treatment target may potentially also lead to early translation into clinical practice.

Raman Spectroscopy: An Emerging Tool in Neurodegenerative Disease Research and Diagnosis.

PubMed

Devitt, George; Howard, Kelly; Mudher, Amrit; Mahajan, Sumeet

2018-03-21

The pathogenesis underlining many neurodegenerative diseases remains incompletely understood. The lack of effective biomarkers and disease preventative medicine demands the development of new techniques to efficiently probe the mechanisms of disease and to detect early biomarkers predictive of disease onset. Raman spectroscopy is an established technique that allows the label-free fingerprinting and imaging of molecules based on their chemical constitution and structure. While analysis of isolated biological molecules has been widespread in the chemical community, applications of Raman spectroscopy to study clinically relevant biological species, disease pathogenesis, and diagnosis have been rapidly increasing since the past decade. The growing number of biomedical applications has shown the potential of Raman spectroscopy for detection of novel biomarkers that could enable the rapid and accurate screening of disease susceptibility and onset. Here we provide an overview of Raman spectroscopy and related techniques and their application to neurodegenerative diseases. We further discuss their potential utility in research, biomarker detection, and diagnosis. Challenges to routine use of Raman spectroscopy in the context of neuroscience research are also presented.

Intestinal microbiota - a key to understanding the pathophysiology of anorexia nervosa?

PubMed

Karakuła-Juchnowicz, Hanna; Pankowicz, Hanna; Juchnowicz, Dariusz; Valverde Piedra, Jose Luis; Małecka-Massalska, Teresa

2017-10-29

Anorexia nervosa (AN) is a psychiatric disorder related to very serious consequences for physical and mental health of patients. Due to a complex clinical picture, which consists of anumber of somatic and mental symptoms, AN remains a serious problem of modern medicine and encourages the search for possible causes of the illness and new, more effective therapies. The recent reports emphasize the role of the intestinal microbiota in regulation of body weight. In this light, the hypothesis that in AN patients there is a significant imbalance of the intestinal microbiota, which contributes to the pathogenesis of the illness, seems interesting. The results of the latest research suggest that abnormal composition of the intestinal microbiota may be an important factor supporting cachexia of AN patients. Detailed analyzes of the composition of the microbiota characteristic for anorexia nervosa could be useful in developing new methods for monitoring and treatment of this illness. This paper aims to present the current state of the art about the role of the intestinal microbiota in the pathogenesis, course and treatment of AN.

Congenital portosystemic venous shunt.

PubMed

Papamichail, M; Pizanias, M; Heaton, N

2018-03-01

Congenital portosystemic venous shunts are rare developmental anomalies resulting in diversion of portal flow to the systemic circulation and have been divided into extra- and intrahepatic shunts. They occur during liver and systemic venous vascular embryogenesis and are associated with other congenital abnormalities. They carry a higher risk of benign and malignant liver tumors and, if left untreated, can result in significant medical complications including systemic encephalopathy and pulmonary hypertension. This article reviews the various types of congenital portosystemic shunts and their anatomy, pathogenesis, symptomatology, and timing and options of treatment. What is Known: • The natural history and basic management of this rare congenital anomaly are presented. What is New: • This paper is a comprehensive review; highlights important topics in pathogenesis, clinical symptomatology, and treatment options; and proposes an algorithm in the management of congenital portosystemic shunt disease in order to provide a clear idea to a pediatrician. An effort has been made to emphasize the indications for treatment in the children population and link to the adult group by discussing the consequences of lack of treatment or delayed diagnosis.

The Roles of T Helper 1, T Helper 17 and Regulatory T Cells in the Pathogenesis of Sarcoidosis.

PubMed

Mortaz, Esmaeil; Rezayat, Fatemeh; Amani, Davar; Kiani, Arda; Garssen, Johan; Adcock, Ian M; Velayati, Aliakbar

2016-08-01

Sarcoidosis is a systemic granulomatous disorder of unidentified etiology, with a heterogeneous clinical presentation. It is characterized by a reduced delayed-type hypersensitivity to tuberculin and common antigens. The balance between Th1, Th17 and Regulatory T(Treg) cells controls T-cell proliferation and activation.The Th17/Treg ratio in the peripheral blood and bronchoalveolar lavage fluidis increased in patients with active sarcoidosis. Amplified IL-17A expression in granulomas and the presence of IL-17A+, IL-17A+IL-4+ and IL-17A+IFN-γ+ memory T helper cells in the circulation and BAL indicate Th17 cell involvement in granuloma induction and/or maintenance in sarcoidosis. Sarcoidosis should therefore be considered as a Th1/Th17 multisystem disorder and anti-IL-17/Th17 approaches that control and reduce IL-17Amay be an option, therefore, for the treatment of sarcoidosis.Here we provide a short overview as to the role of Th17 cells as critical cells in the pathogenesis of sarcoidosis.

Hydrallantois in the mare--a report of five cases.

PubMed

Govaere, J L J; De Schauwer, C; Hoogewijs, M K; Chiers, K; Lefère, L; Catry, B; Roels, K; van Heerden, M; Broeckx, S; de Kruif, A

2013-02-01

Hydrallantois in the mare is a very rare condition, and clinical reports help to gather information to elucidate its pathogenesis, treatment options and prognosis. Five different cases of hydrallantois in the mare are reported in this article, all with the involvement of placentitis. The five mares were presented because of acute distention of the abdomen, dyspnoea, stiff gait and a lack of appetite. After a gradual release of the excessive amount of allantoic fluid, an abortion was induced in all five mares. The foals were either born dead or euthanized. The mares recovered quickly. One mare conceived within the same season, one remained barren despite several cycles of natural breeding, and no data were available on the other three mares. In this series, the condition is reported for the first time in two Shetland ponies, both pregnant with foals sharing a close genetic background. In both cases, the condition led to hyperlipidemia. The condition as it occurs in nulliparous mares is also discussed. Finally, the possible involvement of placentitis in the pathogenesis is emphasized. © 2012 Blackwell Verlag GmbH.

Subcutaneous phaeohyphomycosis caused by Cladophialophora bantiana.

PubMed

Hussey, Sean M; Gander, Rita; Southern, Paul; Hoang, Mai P

2005-06-01

Primary subcutaneous phaeohyphomycosis can rarely be caused by Cladophialophora bantiana, and we present the histologic and culture findings of such a case. A 32-year-old African American woman with systemic lupus erythematosus presented with a 2-year history of multiple, recurrent, tender, and ulcerated skin nodules with purulent drainage on her upper back. Histologic sections of the excision demonstrated features of phaeohyphomycosis. Culture findings were characteristic of C bantiana. Of interest, at age 10 she had sustained traumatic implantation of wood splinters into this area during a tornado, yet clinical symptoms of a subcutaneous infection did not manifest until she developed lupus erythematosus at age 27. Our case highlights the role of trauma and immunosuppression in the pathogenesis of subcutaneous phaeohyphomycosis.

Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus

PubMed Central

2015-01-01

Lactic acidosis occurs when lactate production exceeds its metabolism. There are many possible causes of lactic acidosis, and in any given patient, several causes may coexist. This Attending Rounds presents a case in point. Metformin’s role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. The treatment of lactic acidosis is controversial, except for the imperative to remedy its underlying cause. The use of sodium bicarbonate to treat the often alarming metabolic derangements may be quite efficacious in that regard but is of questionable benefit to patients. Renal replacement therapies (RRTs) have particular appeal in this setting for a variety of reasons, but their effect on clinical outcomes is untested. PMID:25762524

Multiple Sub-Epidermal Calcified Nodule Mimicking Eruptive Xanthoma: A Case Report and Review of the Literature

PubMed Central

Ozuguz, Pinar; Balta, Ilknur; Bozkurt, Ozlem; Unverdi, Hatice; Dostbil, Ahmet

2013-01-01

Sub-epidermal calcified nodule (SCN) is an uncommon form of idiopathic calcinosis. It usually occurs in children, particularly in the head and neck region, presenting as a solitary, painless, yellow-white nodule with papillomatous features. These lesions occur twice as common in males compared with females. The pathogenesis is uncertain, but the clinical and histological features of this lesion are distinctive. We report a case of 22-year-old man with multiple nodules bilaterally located on the dorsum of hands simulating eruptive xanthoma. Histopathological examination of one of the excised lesion confirmed the diagnosis showing epidermal and sub-epidermal deposition of calcium. This paper presents a review of the literature and adds a new case of SCN. PMID:24082201

Prevalence of growth hormone deficiency in adult polytransfused β-thalassemia patients and correlation with transfusional and chelation parameters.

PubMed

Poggi, M; Pascucci, C; Monti, S; Pugliese, P; Lauri, C; Amodeo, G; Girelli, G; Toscano, V

2010-09-01

Dysfunction of GH-IGF-I axis has been described in many patients affected by β-thalassemia major (TM), especially in children and in adolescents. Recent studies have demonstrated the necessity to evaluate adult patients affected by TM to establish the presence of this alteration which could be relevant in the pathogenesis of cardiac and bone disease, frequently present in this hematological condition. The pathogenesis of this alteration, correlated in the past with iron overload, is not yet completely understood. The aim of this paper is to evaluate GH-IGF-I axis in a group of adult polytransfused β-thalassemic patients (TM) and to correlate the results with transfusional and chelation parameters. We performed an arginine plus GHRH stimulation test in 28 adult TM patients. Ferritin, IGF-I, liver enzymes, and liver iron concentration, assessed by a superconducting quantum interference device (SQUID) susceptometer were also determined. Moreover, in each patient we evaluated the bone status by a dual-energy X-ray absorptiometry study. We found the presence of GH deficit in 9 patients (32.1%). There were no significant differences between the two groups regarding the value of ferritin, liver enzymes, and liver iron concentration, assessed by SQUID. The group affected by GH deficit showed a worse bone profile. This study confirms the necessity to screen the status of GH/IGF-I axis in this group of patients, even in adult age. The presence of GH deficiency does not seem to be correlated with the efficacy parameters of transfusional and chelation therapy. Other mechanisms, additional to iron overload, could therefore play a role in the pathogenesis of this clinical condition. The presence of GH deficit seems to be very important on clinical aspects, like bone disease, that are crucial for quality of life in these patients.

Ureteral endometriosis: A systematic literature review

PubMed Central

Palla, Viktoria-Varvara; Karaolanis, Georgios; Katafigiotis, Ioannis; Anastasiou, Ioannis

2017-01-01

Introduction: Ureteral endometriosis is a rare disease affecting women of childbearing age which presents with nonspecific symptoms and it may result in severe morbidity. The aim of this study was to review evidence about incidence, pathogenesis, clinical presentation, diagnosis, and management of ureteral endometriosis. Materials and Methods: PubMed Central database was searched to identify studies reporting cases of ureteral endometriosis. “Ureter” or “Ureteral” and “Endometriosis” were used as key words. Database was searched for articles published since 1996, in English without restrictions regarding the study design. Results: From 420 studies obtained through database search, 104 articles were finally included in this review, including a total of 1384 patients with ureteral endometriosis. Data regarding age, location, pathological findings, and interventions were extracted. Mean patients' age was 38.6 years, whereas the therapeutic arsenal included hormonal, endoscopic, and/or surgical treatment. Conclusions: Ureteral endometriosis represents a diagnostic and therapeutic challenge for the clinicians and high clinical suspicion is needed to identify it. PMID:29021650

Early-onset obsessive-compulsive disorder and personality disorders in adulthood.

PubMed

Maina, Giuseppe; Albert, Umberto; Salvi, Virginio; Pessina, Enrico; Bogetto, Filippo

2008-03-15

Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset (< or =10 years), and patients with a later onset (> or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.

[On classification of changes in necrotizing lesions of the midface].

PubMed

Szyfter, W; Wierzbicka, M

1996-01-01

Lethal midline granuloma syndrome (LMG) describes lesions of the midface and is characterized by a progressive and often fatal ulceration and destruction of the upper air way involving the nose, the paranasal sinuses, the palate and the soft tissues of the face. Under the term LMG we distinguish four entities: idiopathic midline destructive disease (IMDD), polymorphic reticulosis (PR), non Hodkin's lymphoma and Wegener's granulomatosis (WG). Review of the literature allows to present the differential diagnosis making use of latest technological achievements in clinical immunology and immunohistochemistry. First of all the LMG must be discriminated from localized WG occurring in the midface. The clinical, serological and histopathological findings in WG are described. Literature review is carried out and recent concepts of it's etiology and pathogenesis are presented. Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA) with specificity for proteinase 3 (PR 3) are valuable marker for differential diagnosis and specificity are discussed. We make a comparison between the "limited" or "non renal" WG and "classical" or "renal" form of the disease.

[Depression and epilepsy : Two clinical pictures with common causes?].

PubMed

Borgmann, M; Holtkamp, M; Adli, M; Behr, J

2016-07-01

Epilepsy and depressive disorders show a high rate of comorbidity. Thus, neurobiological similarities and a bidirectional relationship in terms of pathogenesis have been suggested. The aim of this article is to present the common neurobiological features of both disorders, to characterize the bidirectional relationship and to provide an overview of therapeutic consequences. A review of the current literature and evaluation of studies on the topics of depression and epilepsy are presented. Epilepsy and depression share common neurobiological features. In epileptic patients depression should be diagnosed early and reliably as the successful treatment has a great influence on the prognosis, quality of life and suicide risk in these individuals. In therapeutic doses, antidepressive medication with noradrenergic and specific serotonergic antidepressants (NaSSA) or selective serotonin reuptake inhibitors (SSRI) imparts no clinically relevant epileptogenic potential; however, it increases the quality of life and could have anticonvulsant effects in patients with epilepsy. Clomipramine, bupropion and maprotiline, however, should not be administered to patients with epilepsy as they are known to lower the seizure threshold.

Enterovirus and parechovirus infection in children: a brief overview.

PubMed

de Crom, S C M; Rossen, J W A; van Furth, A M; Obihara, C C

2016-08-01

Enterovirus and parechovirus are a frequent cause of infection in children. This review is an overview of what is known from enterovirus and parechovirus infection in children and contains information about the epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of enterovirus and parechovirus infection in children. EV and HPeV infections are a frequent cause of infection in childhood. The clinical presentation is diverse. RT-qPCR is the best way to detect an EV or HPeV. Cerebrospinal fluid, blood and feces have the highest sensitivity for detecting an EV or HPeV. There is no treatment for EV and HPeV infections. Two vaccines against EV 71 are just licensed in China and will be available on the private market. Little is known about the prognosis of EV and HPeV infections. •EV and HPeV are a frequent cause of infection in children. What is new: •This review gives a brief overview over EV and HPeV infection in children.

[Modern Views on Children's Interstitial Lung Disease].

PubMed

Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu

2015-01-01

Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article.

Smallpox: what every otolaryngologist should know.

PubMed

Tennyson, Heath C; Mair, Eric A

2004-03-01

In light of recent terrorist events and the potential threat of smallpox as a biological agent, we present information concerning smallpox to better inform the otolaryngologist concerning this disease and its prevention. We performed a review of the smallpox and smallpox vaccination literature over the past 200 years using MEDLINE, PREMEDLINE, Centers for Disease Control and Prevention Internet site, World Health Organization Internet site, and references found in previous publications not found in MEDLINE or PREMEDLINE. Our search focused on the pathogenesis, clinical presentation, course, unique manifestations in the head and neck, diagnosis, and treatment of smallpox, as well as the method of smallpox vaccination, vaccination contraindications, and complications. Smallpox is a viral disease with a high mortality rate. Its clinical course, manifestations, and methods of prevention are carefully analyzed in light of otolaryngology practice. Smallpox manifestations in the head and neck often presented as acute airway obstruction and also as long-term sequelae such as ectropion, nasal vestibular stenosis, conductive hearing loss, and blindness. Most chronic sequelae involve the head and neck. Smallpox vaccination is effective but not without potential serious risks.

What is new in systemic lupus erythematosus.

PubMed

Rúa-Figueroa Fernández de Larrinoa, Iñigo

2015-01-01

Systemic lupus erythematosus is a heterogeneous rheumatic systemic disease with extremely varied clinical manifestations and a diverse pathogenesis, as illustrated in this review on the most relevant new knowledge related to the disease. Topics such as anemia, pathogenesis, cardiovascular risk assessment, antiphospholipid syndrome, prediction of damage and recent advances in treatment, including tolerogenic and biological agents, are discussed. Relevant contributions regarding classical therapies such as corticosteroid and antimalarials and their optimal use, as well as the roll of vitamin D, are also referred. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

[Immunopathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)].

PubMed

Yamamura, Takashi; Ono, Hirohiko; Sato, Wakiro

2018-01-01

A recent study on the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has revealed an elevation of inflammatory and anti-inflammatory cytokines in the sera and cerebrospinal fluids of the patients and presence of autoantibodies in subgroups of ME/CFS patients. Furthermore, investigator-initiated clinical trials have proved the efficacy of anti-CD20 antibody (rituximab), that eliminate B cells, in the treatment of ME/CFS. Based on these findings, we hypothesize that immune abnormalities, such as enhanced autoimmune responses, may play an essential role in the neuroinflammatory pathogenesis of ME/CFS.

MicroRNAs as New Biomarkers for Diagnosis and Prognosis, and as Potential Therapeutic Targets in Acute Myeloid Leukemia

PubMed Central

Trino, Stefania; Caivano, Antonella; Laurenzana, Ilaria; Tagliaferri, Daniela; Falco, Geppino; Del Vecchio, Luigi; Musto, Pellegrino; De Luca, Luciana

2018-01-01

Acute myeloid leukemias (AML) are clonal disorders of hematopoietic progenitor cells which are characterized by relevant heterogeneity in terms of phenotypic, genotypic, and clinical features. Among the genetic aberrations that control disease development there are microRNAs (miRNAs). miRNAs are small non-coding RNAs that regulate, at post-transcriptional level, translation and stability of mRNAs. It is now established that deregulated miRNA expression is a prominent feature in AML. Functional studies have shown that miRNAs play an important role in AML pathogenesis and miRNA expression signatures are associated with chemotherapy response and clinical outcome. In this review we summarized miRNA signature in AML with different cytogenetic, molecular and clinical characteristics. Moreover, we reviewed the miRNA regulatory network in AML pathogenesis and we discussed the potential use of cellular and circulating miRNAs as biomarkers for diagnosis and prognosis and as therapeutic targets. PMID:29401684

Precursor Lesions of Urologic Malignancies.

PubMed

Khani, Francesca; Robinson, Brian D

2017-12-01

- Precursor lesions of urologic malignancies are established histopathologic entities, which are important not only to recognize for clinical purposes, but also to further investigate at the molecular level in order to gain a better understanding of the pathogenesis of these malignancies. - To provide a brief overview of precursor lesions to the most common malignancies that develop within the genitourinary tract with a focus on their clinical implications, histologic features, and molecular characteristics. - Literature review from PubMed, urologic pathology textbooks, and the 4th edition of the World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs. All photomicrographs were taken from cases seen at Weill Cornell Medicine or from the authors' personal slide collections. - The clinical importance and histologic criteria are well established for the known precursor lesions of the most common malignancies throughout the genitourinary tract, but further investigation is warranted at the molecular level to better understand the pathogenesis of these lesions. Such investigation may lead to better risk stratification of patients and potentially novel treatments.

Virology and Molecular Pathogenesis of Human Papillomavirus (HPV)-Associated Oropharyngeal Squamous Cell Carcinoma

PubMed Central

Miller, Daniel L.; Puricelli, Michael D.; Stack, M. Sharon

2012-01-01

Current literature fully supports HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) as a unique clinical entity. It affects an unambiguous patient population with defined risk factors, has a genetic expression pattern more similar to cervical squamous cell carcinoma than non-HPV-associated head and neck squamous cell carcinoma (HNSCC), and may warrant divergent clinical management compared to HNSCC associated with traditional risk factors. However, a detailed understanding of the molecular mechanisms driving these differences and the ability to exploit this knowledge to improve clinical management of OPSCC has not yet come to fruition. This review summarizes the etiology of HPV positive (HPV+) OPSCC and provides a detailed overview of HPV virology and molecular pathogenesis relevant to infection of oropharyngeal tissues. Methods of detection and differential gene expression analyses are also summarized. Future research into mechanisms that mediate tropism of HPV to oropharyngeal tissues, improved detection strategies, and the pathophysiologic significance of altered gene and microRNA expression profiles is warranted. PMID:22452816

Clinical characteristics and treatment of inflammatory bowel disease: A comparison of Eastern and Western perspectives

PubMed Central

Park, Soo Jung; Kim, Won Ho; Cheon, Jae Hee

2014-01-01

Inflammatory bowel disease (IBD) is a chronic, relapsing intestinal inflammatory disorder with unidentified causes. Both environmental factors and genetic aspects are believed to be crucial to the pathogenesis of IBD. The incidence and prevalence of IBD have recently been increasing throughout Asia, presumably secondary to environmental changes. This increasing trend in IBD epidemiology necessitates specific health care planning and education in Asia. To this end, we must gain a precise understanding of the distinctive clinical and therapeutic characteristics of Asian patients with IBD. The phenotypes of IBD reportedly differ considerably between Asians and Caucasians. Thus, use of the same management strategies for these different populations may not be appropriate. Moreover, investigation of the Asian-specific clinical aspects of IBD offers the possibility of identifying causative factors in the pathogenesis of IBD in this geographical area. Accordingly, this review summarizes current knowledge of the phenotypic manifestations and management practices of patients with IBD, with a special focus on a comparison of Eastern and Western perspectives. PMID:25206259

Circular RNA expression alterations are involved in OGD/R-induced neuron injury.

PubMed

Lin, Shao-Peng; Ye, Shan; Long, Youming; Fan, Yongxiang; Mao, Hai-Feng; Chen, Mei-Ting; Ma, Qiu-Jie

2016-02-26

Cerebral ischemia-reperfusion injury (IRI) is a common clinical pathological process, and it is a key step in causing further ischemic organ damage. The mechanism of cerebral IRI is still not fully understood, leading to a lack of effective treatment. It has been demonstrated that circular RNAs (circRNAs) can act as miRNA sponges and play an important role in regulating gene expression through a circRNA-miRNA-gene pathway. The specific role of circRNAs in the pathogenesis of cerebral IRI, however, is still unclear. Thus, in the present study, we investigated circRNA expression differences in HT22 cells with oxygen-glucose deprivation/reoxygenation (OGD/R) versus normal controls. The results from circRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model (p < 0.05) compared with the control group. Among them, 3 were significantly up-regulated, and the other 12 were down-regulated. Furthermore, the up-regulated expression of mmu-circRNA-015947 was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analysis revealed that up-regulated expression of mmu-circRNA-015947 could interact with miRNAs (mmu-miR-188-3p, mmu-miR-329-5p, mmu-miR-3057-3p, mmu-miR-5098 and mmu-miR-683) and thereby enhance target gene expression. KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in apoptosis-related, metabolism-related and immune-related pathways, which are known to be involved in the pathogenesis of IRI. This research suggests that the overlapping expression of mmu-circRNA-015947 might be involved in the process of cerebral IRI and presents a novel molecular target for clinical therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Streptococcal pyrogenic exotoxin G gene in blood and pharyngeal isolates of Streptococcus dysgalactiae subspecies equisimilis has a limited role in pathogenesis.

PubMed

Korem, Maya; Hidalgo-Grass, Carlos; Michael-Gayego, Ayelet; Nir-Paz, Ran; Salameh, Shaden; Moses, Allon E

2014-08-01

Streptococcus dysgalactiae subspecies equisimilis (SE) causes human infections that clinically resemble infections due to Streptococcus pyogenes (SP). SE expresses several virulence determinants initially identified in SP, including genes encoding streptococcal pyrogenic exotoxins. SE isolates from patients with toxic shock syndrome were found to harbor a gene designated spegg, which is similar to the SP pyrogenic exotoxin-G gene, termed speG. Other streptococcal pyrogenic exotoxins known to exist in SP were not detected. To determine the prevalence of the superantigen gene, spegg, we examined 65 invasive SE from patients presenting from 1989 to 2008 with bacteremia secondary to a variety of illnesses including two patients who fulfilled the criteria for toxic shock syndrome, in comparison with 46 noninvasive pharyngeal isolates. All isolates were tested for the presence of spegg by polymerase chain reaction. Forty-four of the 65 blood isolates were also characterized by emm typing. spegg was identified in 49.2% and 69.5% of the blood and pharyngeal isolates, respectively. emm typing revealed the presence of 13 distinct types. There was no association between clinical presentation and the presence of spegg. We found an association between the presence of spegg and the emm type (p < 0.001). The emm types stG485 and stG840 were more frequent among spegg positive isolates, and stG4222, stG6, and stG166b were associated with spegg negative isolates. We found a high prevalence of spegg in invasive and noninvasive SE isolates, associated with specific emm types. Our finding suggests that this gene does not have a role in the pathogenesis of bacteremia. Copyright © 2012. Published by Elsevier B.V.

Clinical spectrum of microsporidial keratoconjunctivitis.

PubMed

Tham, Alex Chengyao; Sanjay, Srinivasan

2012-07-01

The purpose of this paper was to analyse the causes, pathogenesis, diagnostic modalities and treatment outcomes of microsporidial keratoconjunctivitis (MKC). Microsporidia are increasingly recognized as opportunistic infectious pathogens in immunocompromized patients causing keratoconjunctivitis. In the recent years, there has been a surge in reports of MKC in immunocompetent individuals presenting with stromal keratitis. A detailed literature search was done using Medline, OVID, Cochrane Library, UptoDate and Google Scholar databases with the terms microsporidia, keratitis, conjunctivitis, immunocompromized and immunocompetent. The articles were reviewed to determine the spectrum of clinical presentation, disease course, investigations, treatment modalities and outcome. Thirty-six publications were reviewed, and 151 cases of MKC were included for this review. The main presenting features included pain, redness, photophobia, epiphora and blurring of vision. Duration of the symptoms lasted between 4 days and 18 months. Light microscopy with modified trichrome stain was most commonly used to diagnose MKC. Resolution of symptoms was most commonly achieved with oral albendazole and/or topical fumidil B. Topical fluoroquinolones are also effective as a monotherapy as suggested by recent studies. Clinical outcome was good (visual acuity ≤ 6/12) for the patients who presented earlier (≤1 month) (75% of cases with documented final best-corrected visual acuity). MKC occurs more commonly in immunocompetent individuals than expected and can be diagnosed in earlier stages. From our review, we conclude that the patients, who were diagnosed early and treated, had complete resolution of symptoms with a better clinical outcome. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

Pathogenesis and immunobiology of brucellosis: review of Brucella-host interactions.

PubMed

de Figueiredo, Paul; Ficht, Thomas A; Rice-Ficht, Allison; Rossetti, Carlos A; Adams, L Garry

2015-06-01

This review of Brucella-host interactions and immunobiology discusses recent discoveries as the basis for pathogenesis-informed rationales to prevent or treat brucellosis. Brucella spp., as animal pathogens, cause human brucellosis, a zoonosis that results in worldwide economic losses, human morbidity, and poverty. Although Brucella spp. infect humans as an incidental host, 500,000 new human infections occur annually, and no patient-friendly treatments or approved human vaccines are reported. Brucellae display strong tissue tropism for lymphoreticular and reproductive systems with an intracellular lifestyle that limits exposure to innate and adaptive immune responses, sequesters the organism from the effects of antibiotics, and drives clinical disease manifestations and pathology. Stealthy brucellae exploit strategies to establish infection, including i) evasion of intracellular destruction by restricting fusion of type IV secretion system-dependent Brucella-containing vacuoles with lysosomal compartments, ii) inhibition of apoptosis of infected mononuclear cells, and iii) prevention of dendritic cell maturation, antigen presentation, and activation of naive T cells, pathogenesis lessons that may be informative for other intracellular pathogens. Data sets of next-generation sequences of Brucella and host time-series global expression fused with proteomics and metabolomics data from in vitro and in vivo experiments now inform interactive cellular pathways and gene regulatory networks enabling full-scale systems biology analysis. The newly identified effector proteins of Brucella may represent targets for improved, safer brucellosis vaccines and therapeutics. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

[Pathogenesis and management of Grave's ophthalmopathy].

PubMed

Wierzbowska, Joanna; Stankiewicz, Andrzej

2002-01-01

The most recent hypothesis on pathogenesis of Graves' Ophthalmopathy (GO) and short characteristics of the disease was presented. Emphasis was placed on the necessity of coordinated treatment of the thyroid dysfunction and ophthalmopathy. Management of hyperthyroidism and Graves' ophthalmopathy, including the latest methods was described.

Evidence for the Role of B Cells and Immunoglobulins in the Pathogenesis of Multiple Sclerosis

PubMed Central

Wootla, Bharath; Denic, Aleksandar; Keegan, B. Mark; Winters, Jeffrey L.; Astapenko, David; Warrington, Arthur E.; Bieber, Allan J.; Rodriguez, Moses

2011-01-01

The pathogenesis of multiple sclerosis (MS) remains elusive. Recent reports advocate greater involvement of B cells and immunoglobulins in the initiation and propagation of MS lesions at different stages of their ontogeny. The key role of B cells and immunoglobulins in pathogenesis was initially identified by studies in which patients whose fulminant attacks of demyelination did not respond to steroids experienced remarkable functional improvement following plasma exchange. The positive response to Rituximab in Phase II clinical trials of relapsing-remitting MS confirms the role of B cells. The critical question is how B cells contribute to MS. In this paper, we discuss both the deleterious and the beneficial roles of B cells and immunoglobulins in MS lesions. We provide alternative hypotheses to explain both damaging and protective antibody responses. PMID:21961063

Animal Models of Zika Virus Infection, Pathogenesis, and Immunity.

PubMed

Morrison, Thomas E; Diamond, Michael S

2017-04-15

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis. Copyright © 2017 American Society for Microbiology.

Oxidative Stress, Nitric Oxide, and Diabetes

PubMed Central

Pitocco, Dario; Zaccardi, Francesco; Di Stasio, Enrico; Romitelli, Federica; Santini, Stefano A.; Zuppi, Cecilia; Ghirlanda, Giovanni

2010-01-01

In the recent decades, oxidative stress has become focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence from research on several diseases show that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on this research, the emerging concept is that oxidative stress is the “final common pathway”, through which risk factors of several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell-cell homeostasis. In this review, we discuss the role of oxidative stress in the pathogenesis of insulin resistance and beta-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes, and in the pathogenesis of diabetic vascular complications, the leading cause of death in diabetic patients. PMID:20703435

The spectrum of renal thrombotic microangiopathy in lupus nephritis

PubMed Central

2013-01-01

Introduction Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China. Methods Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed. Results In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with the non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09 ± 4.64 vs. 4.75 ± 3.13 g/24h, P = 0.007) and serum creatinine (159, 86 to 215 vs. 81, 68 to 112 μmol/l, P <0.001), higher scores of total activity indices (AI) (P <0.001), endocapillary hypercellularity (P <0.001), subendothelial hyaline deposits (P = 0.003), interstitial inflammation (P = 0.005), glomerular leukocyte infiltration (P = 0.006), total chronicity indices (CI) (P = 0.033), tubular atrophy (P = 0.004) and interstitial fibrosis (P = 0.018). Patients with renal TMA presented with poorer renal outcome (P = 0.005) compared with the non-TMA group. Renal TMA (hazard ratio (HR): 2.772, 95% confidence interval: 1.009 to 7.617, P = 0.048) was an independent risk factor for renal outcome in patients with lupus nephritis. The renal outcome was poorer for those with both C4d deposition and decreased serum complement factor H in the TMA group (P = 0.007). Conclusions There were various causes of renal TMA in lupus nephritis. Complement over-activation via both classical and alternative pathways might play an important role in the pathogenesis of renal TMA in lupus nephritis. PMID:23320601

Bordetellosis

USDA-ARS?s Scientific Manuscript database

This chapter, entitled "Bordetellosis", will be included in the 11th Edition of Diseases of Swine, and reviews the etiology, public health significance, epidemiology, pathogenesis, clinical signs, lesions, diagnosis, immunity, and prevention and control of diseases caused by Bordetella bronchiseptic...

Perivascular epithelioid cell neoplasms: pathology and pathogenesis.

PubMed

Folpe, Andrew L; Kwiatkowski, David J

2010-01-01

This review article summarizes our current understanding of the clinical, pathologic, immunohistochemical, and genetic aspects of perivascular epithelioid cell neoplasms, a rare group of related tumors defined by both morphologic and immunophenotypic criteria.

Diverticular Disease: An Update on Pathogenesis and Management

PubMed Central

Rezapour, Mona; Ali, Saima

2018-01-01

Diverticular disease is one of the most common conditions in the Western world and one of the most common findings identified at colonoscopy. Recently, there has been a significant paradigm shift in our understanding of diverticular disease and its management. The pathogenesis of diverticular disease is thought to be multifactorial and include both environmental and genetic factors in addition to the historically accepted etiology of dietary fiber deficiency. Symptomatic uncomplicated diverticular disease (SUDD) is currently considered a type of chronic diverticulosis that is perhaps akin to irritable bowel syndrome. Mesalamine, rifaximin and probiotics may achieve symptomatic relief in some patients with SUDD, although their role(s) in preventing complications remain unclear. Antibiotic use for acute diverticulitis and elective prophylactic resection surgery are considered more individualized treatment modalities that take into account the clinical status, comorbidities and lifestyle of the patient. Our understanding of the pathogenesis of diverticular disease continues to evolve and is likely to be diverse and multifactorial. Paradigm shifts in several areas of the pathogenesis and management of diverticular disease are explored in this review. PMID:28494576

Neurofibromatoses.

PubMed

Uhlmann, Erik J; Plotkin, Scott R

2012-01-01

The studies of familial tumor predisposition syndromes have contributed immensely to our understanding of oncogenesis. Neurofibromatosis 1, neurofibromatosis 2 and schwannomatosis are inherited autosomal dominant neurocutaneous disorders with complete penetrance. They are clinically and genetically distinct and considerable knowledge has been gathered about their pathogenesis. In this chapter, the genetics, molecular mechanism of disease, as well as clinical features, diagnosis and treatment are discussed.

Crohn’s disease complicated by strictures: a systematic review

PubMed Central

Rieder, Florian; Zimmermann, Ellen M; Remzi, Feza H; Sandborn, William J

2016-01-01

The occurrence of strictures as a complication of Crohn’s disease is a significant clinical problem. No specific antifibrotic therapies are available. This systematic review comprehensively addresses the pathogenesis, epidemiology, prediction, diagnosis and therapy of this disease complication. We also provide specific recommendations for clinical practice and summarise areas that require future investigation. PMID:23626373

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

PubMed Central

Magyari, Lili; Varszegi, Dalma; Kovesdi, Erzsebet; Sarlos, Patricia; Farago, Bernadett; Javorhazy, Andras; Sumegi, Katalin; Banfai, Zsolt; Melegh, Bela

2014-01-01

Rheumatoid arthritis (RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice patient care generates many questions about diagnosis, prognosis, and treatment. It is challenging for health care specialists to keep up to date with the medical literature. This review summarizes the pathogenesis, the polymorphisms of interleukin and interleukin genes and the standard available and possible future immunologic targets for RA treatment. The identification of disease-associated interleukin and interleukin receptor genes can provide precious insight into the genetic variations prior to disease onset in order to identify the pathways important for RA pathogenesis. The knowledge of the complex genetic background may prove useful for developing novel therapies and making personalized medicine based on the individual’s genetics. PMID:25232528

Update on Merkel Cell Carcinoma: Epidemiology, Etiopathogenesis, Clinical Features, Diagnosis, and Staging.

PubMed

Llombart, B; Requena, C; Cruz, J

2017-03-01

Merkel cell carcinoma (MCC) is a rare, highly aggressive tumor, and local or regional disease recurrence is common, as is metastasis. MCC usually develops in sun-exposed skin in patients of advanced age. Its incidence has risen 4-fold in recent decades as the population has aged and immunohistochemical techniques have led to more diagnoses. The pathogenesis of MCC remains unclear but UV radiation, immunosuppression, and the presence of Merkel cell polyomavirus in the tumor genome seem to play key roles. This review seeks to update our understanding of the epidemiology, etiology, pathogenesis, and clinical features of MCC. We also review histologic and immunohistochemical features required for diagnosis. MCC staging is discussed, given its great importance in establishing a prognosis for these patients. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection

PubMed Central

Sun, Xingmin; Hirota, Simon A.

2014-01-01

Clostridium difficile (C. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. The clinical manifestation of Clostridium difficile infection (CDI) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. Furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. C. difficile expresses two key virulence factors; the exotoxins, toxin A (TcdA) and toxin B (TcdB), which are glucosyltransferases that target host-cell monomeric GTPases. In addition, some hypervirulent strains produce a third toxin, binary toxin or C. difficile transferase (CDT), which may contribute to the pathogenesis of CDI. More recently, other factors such as surface layer proteins (SLPs) and flagellin have also been linked to the inflammatory responses observed in CDI. Although the adaptive immune response can influence the severity of CDI, the innate immune responses to C. difficile and its toxins play crucial roles in CDI onset, progression, and overall prognosis. Despite this, the innate immune responses in CDI have drawn relatively little attention from clinical researchers. Targeting these responses may prove useful clinically as adjuvant therapies, especially in refractory and/or recurrent CDI. This review will focus on recent advances in our understanding of how C. difficile and its toxins modulate innate immune responses that contribute to CDI pathogenesis. PMID:25242213

The cystic dilation of ventriculus terminalis with neurological symptoms: Three case reports and a literature review.

PubMed

Lotfinia, Iraj; Mahdkhah, Ata

2018-05-23

The ventriculus terminalis (VT) is a very small ependymal-lined residual lumen in the conus medullaris. It is normally present in all subjects during fetal development. VT in adults appears as an unusual pathology with an uncertain pathogenesis. In this paper, we described three case reports of symptomatic fifth ventricle cystic dilations. All of them were female and their mean age was 59 years. We treated them surgically and all three patients were improved based on clinical and imaging assessments. Our cases suggested that surgical decompression was a safe and effective treatment in symptomatic patients and the neurosurgeons should be aware of such rare situations. A complete list of differential diagnosis about other cystic dilations of the conus medullaris should be emphasized to select the correct clinical approach.

Appendicitis-like clinical image elicited by Enterobius vermicularis: case report and review of the literature.

PubMed

Vleeschouwers, W; Hofman, Ph; Gillardin, J P; Meert, V; Van Slycke, S

2013-01-01

A 17-year-old female patient presented with the clinical features of an acute appendicitis. During laparoscopic exploration a macroscopically normal appendix was found. Since there were no intra-abdominal abnormalities found, the appendix was resected. Anatomopathology demonstrated Enterobius vermicularis, a pinworm infecting only humans, and mostly living in the caecum. This parasite is responsible for possibly the most common helminthic infection in the developed world. Its role in the pathogenesis of acute appendicitis is controversial, but more recent studies indicate a stronger association between enterobiasis and appendicitis. Often, enterobius mimics appendicitis by obstructing the lumen of the appendix, thereby causing appendiceal colic. This case report stresses the importance of microscopic examination of all appendectomy resection specimens. In case of enterobius infestation, systemic therapy of patient and family is necessary.

Urticarial vasculitis.

PubMed

Chang, Suyoung; Carr, Warner

2007-01-01

A case of urticarial vasculitis (UV) is presented. The pathogenesis, clinical characteristics, diagnosis, and management of this disease are reviewed, followed by clinical pearls and pitfalls for the practicing allergist (Venzor J, et al., Urticarial vasculitis, Clin Rev Allergy Immunol 23:201-216, 2002). The lesions in UV typically lasts > 24 hours in a fixed location, resolves with residual hyperpigmentation, and may or may not be pruritic. In contrast, standard urticaria lesions persist < 24 hours, leave no trace, and is always pruritic (Black AK, Urticarial vasculitis, Clin Dermatol 17:565-569, 1999). Since urticarial vasculitis is characterized by a variety of cutaneous, systemic, and serological features, different names of this disorder exist in the literature (Wisnieski JJ, Urticarial vasculitis, Curr Opin Rheumatol 12:24-31, 2000). A biopsy of an active lesion remains the gold standard for the diagnosis of urticarial vasculitis.

The KATP channel in migraine pathophysiology: a novel therapeutic target for migraine.

PubMed

Al-Karagholi, Mohammad Al-Mahdi; Hansen, Jakob Møller; Severinsen, Johanne; Jansen-Olesen, Inger; Ashina, Messoud

2017-08-23

To review the distribution and function of K ATP channels, describe the use of K ATP channels openers in clinical trials and make the case that these channels may play a role in headache and migraine. K ATP channels are widely present in the trigeminovascular system and play an important role in the regulation of tone in cerebral and meningeal arteries. Clinical trials using synthetic K ATP channel openers report headache as a prevalent-side effect in non-migraine sufferers, indicating that K ATP channel opening may cause headache, possibly due to vascular mechanisms. Whether K ATP channel openers can provoke migraine in migraine sufferers is not known. We suggest that K ATP channels may play an important role in migraine pathogenesis and could be a potential novel therapeutic anti-migraine target.

Immunotherapy in the management of sepsis.

PubMed

Sikora, Janusz Piotr

2002-01-01

This work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so-called "respiratory burst" of neutrophils and the antioxidant mechanisms of the host are also discussed. The work focuses on possible approaches to the management of sepsis connected with immunotherapy. Neutralization of endotoxin lipopolysaccharide (LPS), anti-tumor necrosis factor alpha (TNF-alpha) therapy with monoclonal antibodies or pentoxifylline (PTXF), as well as soluble recombinant cytokine agonists and antagonists used in clinical trials are taken into consideration. In addition, cytokine manipulation therapy, anti-adhesion techniques, glucocorticoides and antioxidant barrier interference are also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts an aggressive examination of the immune system aimed at affecting its function.

Implementing targeted region capture sequencing for the clinical detection of Alagille syndrome: An efficient and cost‑effective method.

PubMed

Huang, Tianhong; Yang, Guilin; Dang, Xiao; Ao, Feijian; Li, Jiankang; He, Yizhou; Tang, Qiyuan; He, Qing

2017-11-01

Alagille syndrome (AGS) is a highly variable, autosomal dominant disease that affects multiple structures including the liver, heart, eyes, bones and face. Targeted region capture sequencing focuses on a panel of known pathogenic genes and provides a rapid, cost‑effective and accurate method for molecular diagnosis. In a Chinese family, this method was used on the proband and Sanger sequencing was applied to validate the candidate mutation. A de novo heterozygous mutation (c.3254_3255insT p.Leu1085PhefsX24) of the jagged 1 gene was identified as the potential disease‑causing gene mutation. In conclusion, the present study suggested that target region capture sequencing is an efficient, reliable and accurate approach for the clinical diagnosis of AGS. Furthermore, these results expand on the understanding of the pathogenesis of AGS.

German guidelines for the diagnosis and therapy of localized scleroderma.

PubMed

Kreuter, Alexander; Krieg, Thomas; Worm, Margitta; Wenzel, Jörg; Moinzadeh, Pia; Kuhn, Annegret; Aberer, Elisabeth; Scharffetter-Kochanek, Karin; Horneff, Gerd; Reil, Emma; Weberschock, Tobias; Hunzelmann, Nicolas

2016-02-01

Localized scleroderma designates a heterogeneous group of sclerotic skin disorders. Depending on the subtype, severity, and site affected, adjacent structures such as adipose tissue, muscles, joints, and bones may be involved. This is an update of the existing German AWMF (Association of the Scientific Medical Societies in Germany) guidelines (classification: S2k). These guidelines provide an overview of the definition, epidemiology, classification, pathogenesis, laboratory workup, histopathology, clinical scoring systems, as well as imaging and device-based workup of localized scleroderma. Moreover, consensus-based recommendations are given on the management of localized scleroderma depending on its clinical subtype. Treatment recommendations are presented in a therapeutic algorithm. No financial support was given by any pharmaceutical company. The guidelines are valid until July 2019. © 2016 The Authors | Journal compilation © Blackwell Verlag GmbH, Berlin.

Osteogenesis imperfecta types I-XI: implications for the neonatal nurse.

PubMed

Womack, Jody

2014-10-01

Osteogenesis imperfecta (OI), also called "brittle bone disease," is a rare heterozygous connective tissue disorder that is caused by mutations of genes that affect collagen. Osteogenesis imperfecta is characterized by decreased bone mass, bone fragility, and skin hyperlaxity. The phenotype present is determined according to the mutation on the affected gene as well as the type and location of the mutation. Osteogenesis imperfecta is neither preventable nor treatable. Osteogenesis imperfecta is classified into 11 types to date, on the basis of their clinical symptoms and genetic components. This article discusses the definition of the disease, the classifications on the basis of its clinical features, incidence, etiology, and pathogenesis. In addition, phenotype, natural history, diagnosis and management of this disease, recurrence risk, and, most importantly, the implications for the neonatal nurse and management for the family are discussed.

Peripheral cemento-ossifying fibroma: A case report with review of literature

PubMed Central

Mishra, Amit Kumar; Maru, Rahul; Dhodapkar, Shrikant Vishnuprasad; Jaiswal, Gagan; Kumar, Rajesh; Punjabi, Heena

2013-01-01

Peripheral cemento-ossifying fibroma (PCOF) is a rare osteogenic neoplasm that ordinarily presents as an epulis-like growth. This is of a reactive rather than neoplastic nature and its pathogenesis is uncertain. PCOF predominantly affects adolescent and young adults with greatest prevalence around 28 years. We report here a rare clinical case of PCOF of the mandible, 1 cm mesiodistally and 1.5 cm occluso-gingivally in diameter, which caused difficulty in eating and speech, in a 42-year-old female patient. She was asymptomatic for 1 year and on follow-up for 6 mo post surgically showed gingival health and normal radioopacity of bone without any recurrence. Clinical, radiographic and histological characteristics are discussed and recommendations regarding differential diagnosis, treatment and follow up are provided. The controversial varied nomenclature and possible etiopathogenesis of PCOF are emphasized. PMID:24303483

Peripheral cemento-ossifying fibroma: A case report with review of literature.

PubMed

Mishra, Amit Kumar; Maru, Rahul; Dhodapkar, Shrikant Vishnuprasad; Jaiswal, Gagan; Kumar, Rajesh; Punjabi, Heena

2013-06-16

Peripheral cemento-ossifying fibroma (PCOF) is a rare osteogenic neoplasm that ordinarily presents as an epulis-like growth. This is of a reactive rather than neoplastic nature and its pathogenesis is uncertain. PCOF predominantly affects adolescent and young adults with greatest prevalence around 28 years. We report here a rare clinical case of PCOF of the mandible, 1 cm mesiodistally and 1.5 cm occluso-gingivally in diameter, which caused difficulty in eating and speech, in a 42-year-old female patient. She was asymptomatic for 1 year and on follow-up for 6 mo post surgically showed gingival health and normal radioopacity of bone without any recurrence. Clinical, radiographic and histological characteristics are discussed and recommendations regarding differential diagnosis, treatment and follow up are provided. The controversial varied nomenclature and possible etiopathogenesis of PCOF are emphasized.

Anterior Inferior Iliac Spine (AIIS) and Subspine Hip Impingement.

PubMed

Carton, Patrick; Filan, David

2016-01-01

Abnormal morphology of the anterior inferior iliac spine (AIIS) and the subspine region of the acetabular rim are increasingly being recognised as a source of symptomatic extra-articular hip impingement. This review article aims to highlight important differences in the pathogenesis, clinical presentation and management of extra-articular hip impingement from both the AIIS and subspine bony regions, and the outcome following surgical intervention. A literature review was undertaken to examine the supporting evidence for AIIS and subspine hip impingement. A narrative account of the Author's professional experience in this area, including operative technique for arthroscopic correction, is also presented. Abnormal morphology of the AIIS and subspine region has been classified using cadaveric, radiological and arthroscopic means; the clinical presentation and operative treatment has been documented in several case series studies. Dual pathology is often present - recognition and treatment of both intra- and extra-articular components are necessary for good postoperative outcome. AIIS and sub-spine hip impingement should be considered as distinct pathological entities, which may also co-exist. Symptom relief can be expected following arthroscopic deformity correction with the treatment of concomitant intra-articular pathology. Failure to recognise and treat the extra-articular component may affect postoperative outcome. V.

Current challenges to overcome in the management of type 2 diabetes mellitus and associated neurological disorders.

PubMed

Khan, Nazir M; Ahmad, Ausaf; Tiwari, Rajesh K; Kamal, Mohammad A; Mushtaq, Gohar; Ashraf, Ghulam M

2014-01-01

The increasing worldwide prevalence of type 2 diabetes mellitus (T2DM) and associated neurological disorders (NDs), such as Alzheimer disease and Parkinson's disease, have raised concerns about increasing health care and financial burden. Due to the overwhelming growth rate of T2DM and its strong association with NDs, there is an ever-growing and an urgent need to improve the diagnosis and management of the disease. Major hurdles in the management of T2DM comprise of striving for glycemic targets, polypharmacy, patient adherence and clinical inertia. The challenges occurring in the treatment of T2DM are mainly attributed to the complex heterogeneous nature of the disease and its close association with a wide variety of neurological, metabolic and cardiovascular disorders. To overcome these challenges, authors propose to focus on the treatment strategies that employ shared pathogenesis and common molecular denominators involved in the aetiology of T2DM and associated NDs. Impaired insulin signalling (as a result of perturbed redox status), insulin resistance and mitochondrial dysfunction are key molecular events that may lead to the pathogenesis of T2DM and associated NDs. However, effective management of these therapeutic strategies requires holistic experimental evidence from animal as well as clinical human studies. Therefore, a shift in the treatment paradigm from single point glycemic control to shared pathogenesis control would be an ideal approach to combat the alarming progression of diabetes and associated NDs. Therapeutic interventions focused on shared molecular pathogenesis, along with effective glycemic control, may provide protection from associated NDs.

Fournier's Gangrene: Literature Review and Clinical Cases.

PubMed

Chernyadyev, Sergey A; Ufimtseva, Marina A; Vishnevskaya, Irina F; Bochkarev, Yuri M; Ushakov, Alexey A; Beresneva, Tatiana A; Galimzyanov, Farid V; Khodakov, Valery V

2018-06-27

Fornier gangrene is an extremely rare disease of the genitals. This disease is a result of the urogenital tract, anorectal area, and genital skin infections, appearing usually in immunocompromised patients with diabetes, obesity, and malignant neoplasms. The basic treatment of Fournier gangrene includes an emergency surgical intervention combined with antibiotic therapy and detoxification. A review of recent papers comprising studies and reviews published in 2005-2016 was performed. The clinical cases were studied at the Department of Purulent Surgery Central Clinical Hospital No. 1, where 7 patients were diagnosed and treated. The etiology, pathogenesis, clinical and laboratory presentation, diagnosis, treatment, and prognosis of Fournier gangrene are described in this article. The authors have described several clinical cases of patients with Fournier gangrene and with necrotic cellulitis and fasciomyositis of anterior abdominal wall, which is a manifestation of Fournier gangrene. Making allowance for the unfavorable epidemiological situation of syphilis in Russia, the increase in the incidence of complicated, atypical chancre, and therefore, the need for differentiation of Fournier gangrene with such manifestations of syphilis as necrotizing, esthiomenous chancre, indurative edema, the appropriate clinical examples are well explained in this article. © 2018 The Author(s) Published by S. Karger AG, Basel.

Alcohol and high fat induced chronic pancreatitis: TRPV4 antagonist reduces hypersensitivity.

PubMed

Zhang, L P; Kline, R H; Deevska, G; Ma, F; Nikolova-Karakashian, M; Westlund, K N

2015-12-17

The pathogenesis of pain in chronic pancreatitis is poorly understood, and its treatment can be a major clinical challenge. Surgical and other invasive methods have variable outcomes that can be unsatisfactory. Therefore, there is a great need for further discovery of the pathogenesis of pancreatitis pain and new therapeutic targets. Human and animal studies indicate a critical role for oxidative stress and activation of transient receptor potential (TRP) cation channel subfamily members TRPV1 and TRPA1 on pancreatic nociceptors in sensitization mechanisms that result in pain. However, the in vivo role of transient receptor potential cation channel subfamily V member 4 (TRPV4) in chronic pancreatitis needs further evaluation. The present study characterized a rat alcohol/high fat diet (AHF)-induced chronic pancreatitis model with hypersensitivity, fibrotic pathology, and fat vacuolization consistent with the clinical syndrome. The rats with AHF-induced pancreatitis develop referred visceral pain-like behaviors, i.e. decreased hindpaw mechanical thresholds and shortened abdominal and hindpaw withdrawal latency to heat. In this study, oxidative stress was characterized as well as the role of TRPV4 in chronic visceral hypersensitivity. Lipid peroxidase and oxidative stress were indicated by increased plasma thiobarbituric acid reactive substances (TBARS) and diminished pancreatic manganese superoxide dismutase (MnSOD). The secondary sensitization associated with AHF-induced pancreatitis was effectively alleviated by the TRPV4 antagonist, HC 067047. Similarity of the results to those with the peripherally restricted μ-opiate receptor agonist, loperamide, suggested TRPV4 channel activated peripheral sensitization. This study using a reliable model that provides pre-clinical correlates of human chronic pancreatitis provides further evidence that TRPV4 channel is a potential therapeutic target for treatment of pancreatitis pain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

The stereotypical molecular cascade in neovascular age-related macular degeneration: the role of dynamic reciprocity.

PubMed

Kent, D

2015-11-01

This review summarises our current understanding of the molecular basis of subretinal neovascularisation (SRNV) in age-related macular degeneration (AMD). The term neovascular AMD (NVAMD) is derived from the dominant early clinical features of haemorrhage, fluid, and lipid in the subretinal space (SRS) and the historical role of fluorescein angiography in detecting the presence of NV tissue. However, at the cellular level, SRNV resembles an aberrant but stereotypical tissue repair response that incorporates both an early inflammatory phase and a late fibrotic phase in addition to the neovascular (NV) component that dominates the early clinical presentation. This review will seek not only to highlight the important molecules involved in each of these components but to demonstrate that the development of SRNV has its origins in the earliest events in non-NV AMD pathogenesis. Current evidence suggests that this early-stage pathogenesis is characterised by complement-mediated immune dysregulation, leading to a state of chronic inflammation in the retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. These initial events can be seamlessly and inextricably linked to late-stage development of SRNV in AMD by the process of dynamic reciprocity (DyR), the ongoing bidirectional communication between cells, and their surrounding matrix. Moreover, this correlation between disease onset and eventual outcome is reflected in the temporal and spatial correlation between chronic inflammation, NV, and fibrosis within the reparative microenvironment of the SRS. In summary, the downstream consequences of the earliest dysfunctional molecular events in AMD can result in the late-stage entity we recognize clinically as SRNV and is characterized by a spectrum of predictable, related, and stereotypical processes referred to as DyR.

Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection.

PubMed

Tincati, Camilla; Douek, Daniel C; Marchetti, Giulia

2016-01-01

Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies. Results from studies addressing the pathogenesis of microbial translocation have improved our knowledge of the damage of the gastrointestinal epithelial barrier occurring in HIV infection. However, the extent to which mucosal impairment translates directly to increased gastrointestinal permeability remains an open issue. In this respect, novel work has established a role for IL-17 and IL-22-secreting T cell populations in limiting microbial translocation and systemic T-cell activation/inflammation, thus representing a possible target of immune-therapeutic interventions shown to be promising in the animal model. Further, recent reports have not only confirmed the presence of a dysbiotic intestinal community in the course of HIV infection but have also shown that it may be linked to mucosal damage, microbial translocation and peripheral immune activation. Importantly, technical advances have also shed light on the metabolic activity of gut microbes, highlighting the need for novel therapeutic approaches to correct the function, as well as the composition, of the gastrointestinal microbiota.

[Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Contribution of two new cases].

PubMed

Fernández Fernández, F J; de la Fuente Aguado, J; Pérez Fernández, S; Sopeña Pérez-Argüelles, B; Nodar Germiñas, A; Butrón Vila, M

2005-03-01

The autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome is characterized for clinical, biochemical, immunological, and histological features overlapping those of AIH and PBC, whose pathogenesis and more appropriate treatment are unknown at present. We describe two new patients of this entity, which made debut with cholestasic acute hepatitis accompanied of hypergammaglobulinemia. In the first patient was demonstrated the presence of AMA, ASMA, and anti-LKM1 autoantibodies; and ANA in the second one. The histological findings showed changes suggestive of AIH and PBC. After the start of immunosuppressive treatment, associated to ursodeoxycholic acid in one patient, a successful outcome was observed.

An Overview of Internal and External Fixation Methods for the Diabetic Charcot Foot and Ankle.

PubMed

Ramanujam, Crystal L; Zgonis, Thomas

2017-01-01

Diabetic Charcot neuroarthropathy (DCN) of the foot and ankle is a challenging disease with regard to clinical presentation, pathogenesis, and prognosis. Its surgical management is equally difficult to interpret based on the wide array of options available. In the presence of an ulceration or concomitant osteomyelitis, internal fixation by means of screws, plates, or intramedullary nailing needs to be avoided when feasible. External fixation becomes a great surgical tool when managing DCN with concomitant osteomyelitis. This article describes internal and external fixation methods along with available literature to enlighten surgeons faced with treating this complex condition. Copyright © 2016 Elsevier Inc. All rights reserved.

Interaction between endodontics and periodontics.

PubMed

Rotstein, Ilan

2017-06-01

Endodontic-periodontal lesions present challenges to the clinician regarding diagnosis, treatment planning and prognosis. Etiologic factors, such as bacteria and viruses, as well as contributing factors, such as trauma, root resorptions, perforations, cracks and dental malformations, play an important role in the development and progression of such lesions. Treatment and prognosis of endodontic-periodontal lesions vary, depending on the etiology, pathogenesis and correct diagnosis of each specific condition. This chapter will appraise the interrelationship between endodontic and periodontal lesions and provide biological and clinical evidence for diagnosis, prognosis and decision-making in the treatment of these conditions. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Urinary Tract Infection and Asymptomatic Bacteriuria in Older Adults

PubMed Central

Cortes-Penfield, Nicolas W.; Trautner, Barbara W.; Jump, Robin

2018-01-01

Synopsis Urinary tract infections (UTIs) are a significant cause of morbidity among older adults; however, antibiotic prescriptions for clinically suspected UTIs are often inappropriate. Healthcare providers frequently struggle to differentiate UTI from asymptomatic bacteriuria, particularly in patients presenting with nonspecific symptoms. Patients with baseline cognitive impairments that limit history-taking can be particularly challenging. Here, we review the epidemiology and pathogenesis of UTI in older adults. We also discuss an approach to the diagnosis and treatment of UTIs, focusing on recognizing patients who would likely benefit from antibiotic treatment and on identifying patients for whom empiric antibiotic therapy should not be given. PMID:29079155

TRPV1 as a key determinant in ciguatera and neurotoxic shellfish poisoning

PubMed Central

Cuypers, Eva; Yanagihara, Angel; Rainier, Jon D.; Tytgat, Jan

2007-01-01

Ciguatera fish poisoning and neurotoxic shellfish poisoning are distinct clinical entities characterized by gastrointestinal and neurological disturbances, following the consumption of certain reef fish and shellfish containing toxic polyether compounds sporadically present in certain toxic marine dinoflagellates. The biotransformation and bioaccumulation of gambierol and brevetoxin, and their congeners, are believed to be involved in the pathogenesis of these “food-chain diseases”, for which no effective treatments are available. Here, we describe for the first time the potent effect of gambierol and brevetoxin on TRPV1 channels, a key player in thermal and pain sensation. Our findings may lead to promising new therapeutic interventions. PMID:17659256

Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats

PubMed Central

Diesel, Alison

2017-01-01

Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly “feline atopic syndrome” when compared to dogs or people. This article aims to review what is currently known in regards to allergic skin disease in the feline patient, with focus on non-flea, non-food hypersensitivity dermatitis. PMID:29056684

Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats.

PubMed

Diesel, Alison

2017-05-09

Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly "feline atopic syndrome" when compared to dogs or people. This article aims to review what is currently known in regards to allergic skin disease in the feline patient, with focus on non-flea, non-food hypersensitivity dermatitis.

Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension.

PubMed

Rabinovitch, Marlene; Guignabert, Christophe; Humbert, Marc; Nicolls, Mark R

2014-06-20

This review summarizes an expanding body of knowledge indicating that failure to resolve inflammation and altered immune processes underlie the development of pulmonary arterial hypertension. The chemokines and cytokines implicated in pulmonary arterial hypertension that could form a biomarker platform are discussed. Pre-clinical studies that provide the basis for dysregulated immunity in animal models of the disease are reviewed. In addition, we present therapies that target inflammatory/immune mechanisms that are currently enrolling patients, and discuss others in development. We show how genetic and metabolic abnormalities are inextricably linked to dysregulated immunity and adverse remodeling in the pulmonary arteries. © 2014 American Heart Association, Inc.

Pernicious Anemia: Fundamental and Practical Aspects in Diagnosis.

PubMed

Tun, Aung Myint; Thein, Kyaw Zin; Myint, Zin War; Oo, Thein Hlaing

2017-11-08

Pernicious Anemia (PA), the most common cause of cobalamin deficiency anemia worldwide, is an autoimmune disease of multifactorial etiologies involving complex environmental and immunological factors. Although it was first reported by Addison in 1849 with subsequent advances in understanding of pathogenesis and molecular biology, diagnosis of PA is still challenging for clinicians because of its complexity and diverse clinical presentations. Herein, we provide an overview of PA, mainly focusing on its scientific and practical aspects in diagnosis. We also discuss the limitations of currently available diagnostic tools for the evaluation of cobalamin deficiency and PA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Radiological manifestations of radiation-induced injury to the normal upper gastrointestinal tract

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldstein, H.M.; Rogers, L.F.; Fletcher, G.H.

1975-10-01

Radiation-induced injury to the normal esophagus, stomach, and duodenum in patients with advanced cervical carcinoma who received high para-aortic lymph- node irradiation to an average tumor dose of 5,000 rads is discussed. Radiation esophagitis is usually the result of mediastinal irradiation for bronchogenic carcinoma. The most consistent radiological finding is abnormal motility, with esophageal stricture and/or ulceration occurring less frequently. Radiation gastritis is usually present as pyloric ulceration or irregular contractions of the antrum, simulating gastric carcinoma. Postbulbar duodenal mucosal thickening, ulceration, and strictures may occur. Pertinent clinical features, pathogenesis, and pathological correlations are discussed. (auth)

Hypothyroid myopathy: A peculiar clinical presentation of thyroid failure. Review of the literature.

PubMed

Sindoni, Alessandro; Rodolico, Carmelo; Pappalardo, Maria Angela; Portaro, Simona; Benvenga, Salvatore

2016-12-01

Abnormalities in thyroid function are common endocrine disorders that affect 5-10 % of the general population, with hypothyroidism occurring more frequently than hyperthyroidism. Clinical symptoms and signs are often nonspecific, particularly in hypothyroidism. Muscular symptoms (stiffness, myalgias, cramps, easy fatigability) are mentioned by the majority of patients with frank hypothyroidism. Often underestimated is the fact that muscle symptoms may represent the predominant or the only clinical manifestation of hypothyroidism, raising the issue of a differential diagnosis with other causes of myopathy, which sometimes can be difficult. Elevated serum creatine kinase, which not necessarily correlates with the severity of the myopathic symptoms, is certainly suggestive of muscle impairment, though it does not explain the cause. Rare muscular manifestations, associated with hypothyroidism, are rhabdomyolysis, acute compartment syndrome, Hoffman's syndrome and Kocher-Debré-Sémélaigne syndrome. Though the pathogenesis of hypothyroid myopathy is not entirely known, proposed mechanisms include altered glycogenolytic and oxidative metabolism, altered expression of contractile proteins, and neuro-mediated damage. Correlation studies of haplotype, muscle gene expression and protein characterization, could help understanding the pathophysiological mechanisms of this myopathic presentation of hypothyroidism.

Frontal fibrosing alopecia: a multicenter review of 355 patients.

PubMed

Vañó-Galván, Sergio; Molina-Ruiz, Ana M; Serrano-Falcón, Cristina; Arias-Santiago, Salvador; Rodrigues-Barata, Ana R; Garnacho-Saucedo, Gloria; Martorell-Calatayud, Antonio; Fernández-Crehuet, Pablo; Grimalt, Ramón; Aranegui, Beatriz; Grillo, Emiliano; Diaz-Ley, Blanca; Salido, Rafael; Pérez-Gala, Sivia; Serrano, Salvio; Moreno, Jose Carlos; Jaén, Pedro; Camacho, Francisco M

2014-04-01

To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. We sought to describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. In all, 355 patients (343 women [49 premenopausal] and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). The retrospective design is a limitation. Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Diagnostic Value of Vaginal Discharge, Wet Mount and Vaginal pH – An Update on the Basics of Gynecologic Infectiology

PubMed Central

Frobenius, W.; Bogdan, C.

2015-01-01

The majority of uncomplicated vulvovaginal complaints (e.g. bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis) can be detected with uncomplicated basic infectiological tests and can usually be treated effectively without requiring further diagnostic procedures. Tests include measurement of vaginal pH, preparation and assessment of wet mount slides prepared from vaginal or cervical discharge, and the correct clinical and microbiological classification of findings. In Germany, at least in recent years, this has not been sufficiently taught or practiced. As new regulations on specialist gynecologic training in Germany are currently being drawn up, this overview provides basic information on gynecologic infectiology and summarizes clinically relevant aspects of recent microbiological findings on the physiology and pathology of vaginal flora. The clinical signs and symptoms of aerobic vaginitis, the pathogenesis of which is still not completely understood, are also reviewed. Finally, the symptoms, indications and risk factors for pelvic inflammatory disease (PID) are presented. In contrast to the above-listed infections, PID requires immediate culture of the pathogen from samples (e.g. obtained by laparoscopy) with microbiological diagnostic procedures carried out by specialist laboratories. A schematic summary of all pathologies discussed here is presented. PMID:26028693

Idiopathic pulmonary fibrosis may be a disease of recurrent, tractional injury to the periphery of the aging lung: a unifying hypothesis regarding etiology and pathogenesis.

PubMed

Leslie, Kevin O

2012-06-01

Idiopathic pulmonary fibrosis is a progressive, fatal lung disease occurring in older individuals. Despite 50 years of accrued data about the disease, little progress has been made in slowing functional loss or in decreasing patient mortality. To present a novel hypothesis on the etiology and pathogenesis of idiopathic pulmonary fibrosis. Published data are reviewed regarding the epidemiology, clinical presentation, natural history, radiologic findings, and pathologic findings in patients with idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis may be predisposed genetically to tractional injury to the peripheral lung. The result is recurrent damage to the epithelial-mesenchymal interface, preferentially at the outer edges of the basilar lung lobules where tractional stress is high during inspiration, compliance is relatively low, and there is a greater tendency for alveolar collapse at end-expiration. A distinctive "reticular network of injury" (the fibroblast focus) forms, attended by a prolonged phase of wound repair (tear and slow repair). Discrete areas of alveolar collapse are observed in scar at the periphery of the lung lobules. The cycle repeats over many years resulting in progressive fibrous remodeling and replacement of the alveoli in a lobule by bronchiolar cysts surrounded by scar (honeycomb lung). Abnormalities in surfactant function are proposed as a potential mechanism of initial lung damage. Age of onset may be a function of a required threshold of environmental exposures (eg, cigarette smoking) or other comorbid injury to the aging lung. Evidence supporting this hypothesis is presented and potential mechanisms are discussed. A potential role for contributing cofactors is presented.

The Evolving Classification of Pulmonary Hypertension.

PubMed

Foshat, Michelle; Boroumand, Nahal

2017-05-01

- An explosion of information on pulmonary hypertension has occurred during the past few decades. The perception of this disease has shifted from purely clinical to incorporate new knowledge of the underlying pathology. This transfer has occurred in light of advancements in pathophysiology, histology, and molecular medical diagnostics. - To update readers about the evolving understanding of the etiology and pathogenesis of pulmonary hypertension and to demonstrate how pathology has shaped the current classification. - Information presented at the 5 World Symposia on pulmonary hypertension held since 1973, with the last meeting occurring in 2013, was used in this review. - Pulmonary hypertension represents a heterogeneous group of disorders that are differentiated based on differences in clinical, hemodynamic, and histopathologic features. Early concepts of pulmonary hypertension were largely influenced by pharmacotherapy, hemodynamic function, and clinical presentation of the disease. The initial nomenclature for pulmonary hypertension segregated the clinical classifications from pathologic subtypes. Major restructuring of this disease classification occurred between the first and second symposia, which was the first to unite clinical and pathologic information in the categorization scheme. Additional changes were introduced in subsequent meetings, particularly between the third and fourth World Symposia meetings, when additional pathophysiologic information was gained. Discoveries in molecular diagnostics significantly progressed the understanding of idiopathic pulmonary arterial hypertension. Continued advancements in imaging modalities, mechanistic pathogenicity, and molecular biomarkers will enable physicians to define pulmonary hypertension phenotypes based on the pathobiology and allow for treatment customization.

Newer influenza antivirals, biotherapeutics and combinations

PubMed Central

Hayden, Frederick G.

2012-01-01

Please cite this paper as: Hayden FG. (2012) Newer Influenza Antivirals, Biotherapeutics and Combinations. Influenza and Other Respiratory Viruses 7(Suppl. 1), 63–75. This summary provides an overview of investigational antiviral agents for influenza and of future directions for development of influenza therapeutics. While progress in developing clinically useful antiviral agents for influenza has been generally slow, especially with respect to seriously ill and high‐risk patients, important clinical studies of intravenous neuraminidase inhibitors, antibodies and drug combinations are currently in progress. The current decade offers the promise of developing small molecular weight inhibitors with novel mechanisms of action, including host‐directed therapies, new biotherapeutics and drug combinations, that should provide more effective antiviral therapies and help mitigate the problem of antiviral resistance. Immunomodulatory interventions also offer promise but need to be based on better understanding of influenza pathogenesis, particularly in seriously ill patients. The development of combination interventions, immunomodulators and host‐directed therapies presents unique clinical trial design and regulatory hurdles that remain to be addressed. PMID:23279899

Phosphodiesterase type 5 and cancers: progress and challenges

PubMed Central

Barone, Ines; Giordano, Cinzia; Bonofiglio, Daniela; Andò, Sebastiano; Catalano, Stefania

2017-01-01

Cancers are an extraordinarily heterogeneous collection of diseases with distinct genetic profiles and biological features that directly influence response patterns to various treatment strategies as well as clinical outcomes. Nevertheless, our growing understanding of cancer cell biology and tumor progression is gradually leading towards rational, tailored medical treatments designed to destroy cancer cells by exploiting the unique cellular pathways that distinguish them from normal healthy counterparts. Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a promising approach to restore normal intracellular cyclic guanosine monophosphate (cGMP) signalling, and thereby resulting into the activation of various downstream molecules to inhibit proliferation, motility and invasion of certain cancer cells. In this review, we present an overview of the experimental and clinical evidences highlighting the role of PDE5 in the pathogenesis and prevention of various malignancies. Current data are still not sufficient to draw conclusive statements for cancer patient management, but could provide further rational for testing PDE5-targeting drugs as anticancer agents in clinical settings. PMID:29228762

Leprosy: review of the epidemiological, clinical, and etiopathogenic aspects - Part 1*

PubMed Central

Lastória, Joel Carlos; de Abreu, Marilda Aparecida Milanez Morgado

2014-01-01

Leprosy is caused by Mycobacterium leprae and has been known since biblical times. It is still endemic in many regions of the world and a public health problem in Brazil. The prevalence rate in 2011 reached 1.54 cases per 10,000 inhabitants in Brazil. The mechanism of transmission of leprosy consists of prolonged close contact between susceptible and genetically predisposed individuals and untreated multibacillary patients. Transmission occurs through inhalation of bacilli present in upper airway secretion. The nasal mucosa is the main entry or exit route of M. leprae. The deeper understanding of the structural and biological characteristics of M. leprae, the sequencing of its genome, along with the advances in understanding the mechanisms of host immune response against the bacilli, dependent on genetic susceptibility, have contributed to the understanding of the pathogenesis, variations in the clinical characteristics, and progression of the disease. This article aims to update dermatologist on epidemiological, clinical, and etiopathogenic leprosy aspects. PMID:24770495

Present status of yellow fever: memorandum from a PAHO meeting.

PubMed

1986-01-01

An international seminar on the treatment and laboratory diagnosis of yellow fever, sponsored by the Pan American Health Organization (PAHO) and held in 1984, differed from previous meetings on yellow fever because of its emphasis on the care and management of patients and because the participants included specialists from several branches of medicine, such as hepatology, haematology, cardiology, infectious diseases, pathology and nephrology. The meeting reviewed the current status of yellow fever and problems associated with case-finding and notification; features of yellow fever in individual countries of Latin America; health services and facilities for medical care as they relate to diagnosis and management of cases; prevention strategies for and current status of immunization programmes; clinical and pathological aspects of yellow fever in humans; pathogenesis and pathophysiology of yellow fever in experimental animal models; clinical and specific laboratory diagnosis; treatment of the disease and of complications in the functioning of individual organ systems; prognosis and prognostic indicators; and directions for future clinical and experimental research on pathophysiology and treatment.

Idiopathic Noncirrhotic Portal Hypertension: An Appraisal

PubMed Central

Lee, Hwajeong; Rehman, Aseeb Ur; Fiel, M. Isabel

2016-01-01

Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity. PMID:26563701

Celiac disease: Prevalence, diagnosis, pathogenesis and treatment

PubMed Central

Gujral, Naiyana; Freeman, Hugh J; Thomson, Alan BR

2012-01-01

Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either “typical” or “atypical”. In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture. PMID:23155333

Clinical improvement following therapy for periodontitis: Association with a decrease in IL-1 and IL-6

PubMed Central

REIS, CÁTIA; DA COSTA, ALEXANDRA VIANA; GUIMARÃES, JOÃO TIAGO; TUNA, DIANA; BRAGA, ANA CRISTINA; PACHECO, JOSÉ JULIO; AROSA, FERNANDO A.; SALAZAR, FILOMENA; CARDOSO, ELSA MARIA

2014-01-01

Although a number of inflammatory cytokines have been shown to be associated with periodontal pathogenesis, it is important to investigate further whether these biomarkers are associated with the degree of success in nonsurgical treatment of chronic periodontitis. The aim of the present study was to quantify the total levels of interleukin (IL)-1α, -1β, -6, -10 and tumour necrosis factor (TNF)-α in gingival crevicular fluid (GCF) of chronic periodontitis patients prior to and following nonsurgical periodontal therapy. In total, 52 GCF samples from disease sites of patients with chronic periodontitis, prior to and following periodontal therapy, and ten non-disease sites from non-periodontitis subjects, were collected and cytokine concentrations were determined using a multiplex method. Periodontal parameters, including bleeding on probing, probing pocket depth and the clinical attachment level, in all the sites were recorded. Untreated disease sites exhibited higher cytokine levels in the GCF when compared with the non-disease sites. Nonsurgical periodontal therapy resulted in a statistically significant decrease in the total levels of IL-1α, -1β and -6 in the GCF, but not in IL-10 or TNF-α. The results support the hypothesis that proinflammatory cytokines, including IL-1α, IL-1β and IL-6, are likely to be involved in the pathogenesis of periodontitis and are good markers to evaluate the success of nonsurgical therapy in disease sites of patients with periodontitis. PMID:24944641

Clinical improvement following therapy for periodontitis: Association with a decrease in IL-1 and IL-6.

PubMed

Reis, Cátia; DA Costa, Alexandra Viana; Guimarães, João Tiago; Tuna, Diana; Braga, Ana Cristina; Pacheco, José Julio; Arosa, Fernando A; Salazar, Filomena; Cardoso, Elsa Maria

2014-07-01

Although a number of inflammatory cytokines have been shown to be associated with periodontal pathogenesis, it is important to investigate further whether these biomarkers are associated with the degree of success in nonsurgical treatment of chronic periodontitis. The aim of the present study was to quantify the total levels of interleukin (IL)-1α, -1β, -6, -10 and tumour necrosis factor (TNF)-α in gingival crevicular fluid (GCF) of chronic periodontitis patients prior to and following nonsurgical periodontal therapy. In total, 52 GCF samples from disease sites of patients with chronic periodontitis, prior to and following periodontal therapy, and ten non-disease sites from non-periodontitis subjects, were collected and cytokine concentrations were determined using a multiplex method. Periodontal parameters, including bleeding on probing, probing pocket depth and the clinical attachment level, in all the sites were recorded. Untreated disease sites exhibited higher cytokine levels in the GCF when compared with the non-disease sites. Nonsurgical periodontal therapy resulted in a statistically significant decrease in the total levels of IL-1α, -1β and -6 in the GCF, but not in IL-10 or TNF-α. The results support the hypothesis that proinflammatory cytokines, including IL-1α, IL-1β and IL-6, are likely to be involved in the pathogenesis of periodontitis and are good markers to evaluate the success of nonsurgical therapy in disease sites of patients with periodontitis.

Unilateral severe chronic periodontitis associated with ipsilateral surgical resection of cranial nerves V, VI, and VII.

PubMed

Zavarella, Matthew M; Leblebicioglu, Binnaz; Claman, Lewis J; Tatakis, Dimitris N

2006-01-01

The central and peripheral nervous systems participate in several local physiological and pathological processes. There is experimental evidence that the inflammatory, local immune, and wound healing responses of a tissue can be modulated by its innervation. The aim of this clinical report is to present a case of unilateral severe periodontitis associated with ipsilateral surgical resection of the fifth, sixth, and seventh cranial nerves and to discuss the possible contribution of the nervous system to periodontal pathogenesis. A 39-year-old female patient with a history of a cerebrovascular accident caused by a right pontine arteriovenous malformation and destruction of the right fifth, sixth, and seventh cranial nerves was diagnosed with severe chronic periodontitis affecting only the right maxillary and mandibular quadrants. The patient's oral hygiene was similar for right and left sides of the mouth. Percentages of tooth surfaces carrying dental plaque were 41% and 36% for right and left sides, respectively. Non-surgical and surgical periodontal therapy was performed, and the patient was placed on a regular periodontal maintenance schedule. Healing following initial periodontal therapy and osseous periodontal surgery occurred without complications. Follow-up clinical findings at 1 year revealed stable periodontal health. This case report suggests that periodontal innervation may contribute to the regulation of local processes involved in periodontitis pathogenesis. It also suggests that periodontal therapy can be performed successfully at sites and in patients affected by paralysis.

Virulence and pathogenesis of the MSW and MSD strains of Californian myxoma virus in European rabbits with genetic resistance to myxomatosis compared to rabbits with no genetic resistance.

PubMed

Silvers, L; Inglis, B; Labudovic, A; Janssens, P A; van Leeuwen, B H; Kerr, P J

2006-04-25

The pathogenesis of two Californian strains of myxoma virus (MSW and MSD) was examined in European rabbits (Oryctolagus cuniculus) that were either susceptible to myxomatosis (laboratory rabbits) or had undergone natural selection for genetic resistance to myxomatosis (Australian wild rabbits). MSW was highly lethal for both types of rabbits with average survival times of 7.3 and 9.4 days, respectively, and 100% mortality. Classical clinical signs of myxomatosis were not present except in one rabbit that survived for 13 days following infection. Previously described clinical signs of trembling and shaking were observed in laboratory but not wild rabbits. Despite the high resistance of wild rabbits to myxomatosis caused by South American strains of myxoma virus, the MSW strain was of such high virulence that it was able to overcome resistance. The acute nature of the infection, relatively low viral titers in the tissues and destruction of lymphoid tissues, suggested that death was probably due to an acute and overwhelming immunopathological response to the virus. No virus was found in the brain. The MSD strain was attenuated compared to previously published descriptions and therefore was only characterized in laboratory rabbits. It is concluded that Californian MSW strain of myxoma virus is at the extreme end of a continuum of myxoma virus virulence but that the basic pathophysiology of the disease induced is not broadly different to other strains of myxoma virus.

The Global Nonalcoholic Fatty Liver Disease Epidemic: What a Radiologist Needs to Know

PubMed Central

Pereira, Keith; Salsamendi, Jason; Casillas, Javier

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disorders from a benign steatosis to hepatocellular carcinoma (HCC). Metabolic syndrome, mainly obesity, plays an important role, both as an independent risk factor and in the pathogenesis of NAFLD. With the progressive epidemics of obesity and diabetes mellitus, the prevalence of NAFLD and its associated complications is expected to increase dramatically. Therapeutic strategies for treating NAFLD and metabolic syndrome, particularly obesity, are continuously being refined. Their goal is the prevention of NAFLD by the management of risk factors, prevention of progression of the disease, as well as management of complications, ultimately preventing morbidity and mortality. Optimal management of NAFLD and metabolic syndrome requires a multidisciplinary collaboration between the government as well as the health system including the nutritionist, primary care physician, radiologist, hepatologist, oncologist, and transplant surgeon. An awareness of the clinical presentation, risk factors, pathogenesis, diagnosis, and management is of paramount importance to a radiologist, both from the clinical perspective as well as from the imaging standpoint. With expertise in imaging modalities as well as minimally invasive percutaneous endovascular therapies, radiologists play an essential role in the comprehensive management, which is highlighted in this article, with cases from our practice. We also briefly discuss transarterial embolization of the left gastric artery (LGA), a novel method that promises to have an enormous potential in the minimally invasive management of obesity, with details of a case from our practice. PMID:26167390

[Prevalence of Dog circovirus in healthy and diarrhoeic dogs].

PubMed

Gentil, Michaela; Gruber, Achim D; Müller, Elisabeth

2017-04-19

In 2012, a Dog circovirus (DogCV) was discovered in the USA, which was followed by further descriptions of the virus in the USA, Italy and Germany. The present study is the first to examine the prevalence of DogCV in faeces of dogs from Germany and other European countries. Faecal samples from 184 dogs with diarrhoea and from 82 clinically healthy dogs (control group) were analysed for the presence of DogCV by PCR. Furthermore, the detection of parvovirus, coronavirus, Giardia and Cryptosporidium was performed in all samples. In the group of dogs with diarrhoea the prevalence of DogCV was 20.1% (37/184), in the healthy control group it was 7.3% (6/82). Therefore, the virus could be detected significantly more frequently in dogs with diarrhoea. The detection frequency of DogCV is comparable with those of the other tested pathogens. In approximately 50% of the DogCV-positive dogs, infections with other enteropathogenic organisms were diagnosed. The role of co-infection in the pathogenesis of the disease remains unclear, but there appears to be an association between co-infection and disease severity. Evidence of DogCV in clinically healthy dogs appears important for the epidemiology and raises questions about its pathogenicity. Further studies are needed to clarify questions regarding the pathogenesis, causal relevance and possible interference by other diarrhoeal pathogens. Nevertheless, the results of this study are an important indication that DogCV should be considered as a differential diagnosis in dogs with diarrhoea.

Equine deep stromal abscesses (51 cases - 2004-2009)--Part 1: the clinical aspects with attention to the duration of the corneal disease, treatment history, clinical appearance, and microbiology results.

PubMed

de Linde Henriksen, Michala; Andersen, Pia H; Thomsen, Preben D; Plummer, Caryn E; Mangan, Brendan; Heegaard, Steffen; Toft, Nils; Brooks, Dennis E

2014-07-01

To study the equine deep stromal abscesses (DSA) with focus on the duration of the corneal disease, medical treatment, season of presentation, clinical appearance, and the degree of corneal vascularization. Equine DSA diagnosed, biopsied, and surgically treated at the University of Florida Veterinary Medical Center (UFVMC) from 2004 to 2009 were identified. The medical record, clinical photographic images, and microbiology results for each case were evaluated. Frequency and prevalence calculation as well as qualitative data analysis was performed for clinical and microbiological data. Fifty-one equine DSA were included in the study. Spring (March, April, May; 33.4%) and winter (December, January, February; 31.4%) were the most common seasons for DSA presentation. The 51 cases were divided into four categories of focal opacity from their clinical appearance: focal yellow (45.2%), focal white (23.5%), diffuse yellow/white (23.5%), and focal pink (7.8%). 5.9% of the DSA (n = 3) were culture positive for fungal growth, whereas 17.6% were positive for bacterial growth (n = 9). No association between short-/long-term systemically administered NSAID treatment and the corneal vascular response to the corneal lesion could be appreciated. Equine DSA most often present in the spring and winter in the subtropical environment of the state of Florida (USA). The clinical appearance may have a connection with the etiology and pathogenesis of the equine DSA. No connection between short- or long-term systemically administered NSAID and the degree of corneal vascularization of the DSA was noted. © 2013 American College of Veterinary Ophthalmologists.

Current status and clinical association of beta-catenin with juvenile nasopharyngeal angiofibroma.

PubMed

Mishra, A; Singh, V; Verma, V; Pandey, S; Trivedi, R; Singh, H P; Kumar, S; Dwivedi, R C; Mishra, S C

2016-10-01

A possible role of the APC/beta-catenin pathway in the pathogenesis of sporadic juvenile nasopharyngeal angiofibroma has been suggested. This paper presents its current status and clinical association in our patients. A prospective observational study was conducted at King George Medical University and Central Drug Research Institute, in Lucknow, India. Western blot analysis was undertaken in 16 cases to examine beta-catenin expression. The clinical details were recorded along with follow up observations, to determine associations. Up-regulation of beta-catenin expression was seen in 69 per cent of cases. The clinical variables did not reveal significant differences between patients with extremes of expression (extreme under- vs over-expression). However, absent expression was shown exclusively in young adults aged over 18 years, while enhanced expression was associated with an altered facial profile. Although a beta-catenin association was seen in a subset of our sporadic juvenile nasopharyngeal angiofibroma cases, its expression was not homogeneous. This is in contrast to the Western literature that suggests a universal (homogenous) enhanced expression in the majority. Hence, further research is required to better define its molecular cascade.

Quantitative analysis of hepatitis C virus activity in vivo in different groups of untreated patients.

PubMed

Manzin, A; Solforosi, L; Giostra, F; Bianchi, F B; Bruno, S; Rossi, S; Gabrielli, A; Candela, M; Petrelli, E; Clementi, M

1997-01-01

Highly sensitive competitive PCR (cPCR) and competitive reverse transcription PCR (cRT-PCR) methodologies were recently developed and applied for quantifying viral DNA and RNA species (including HCV RNA) present in clinical samples at low concentration. In this study, we used cRT-PCR to compare the viral load of 118 untreated patients with HCV infection and different clinical conditions (80 patients with chronic hepatitis, 18 infected subjects with persistently normal ALT levels and various degrees of liver injury, 10 HCV infected subjects that tested positive for anti-LKM1 antibodies, and 10 patients with HCV infection and cryoglobulinemia). The results indicate that while great individual variability of HCV viremia is detectable even among patients with similar clinical conditions, the mean HCV RNA copy number in samples from patients with different clinical conditions was similar in all groups with the single exception of patients that tested positive for anti-liver-kidney microsomal auto-antibodies type 1 (anti-LKM1); interestingly, lower HCV viremia levels were revealed in these anti-LKM1-positive cases with liver disease of uncertain pathogenesis.

Milk and Soy Allergy

PubMed Central

Kattan, Jacob D.; Cocco, Renata R.; Järvinen, Kirsi M.

2011-01-01

SYNOPSIS Cow’s milk allergy (CMA) affects 2% to 3% of young children and presents with a wide range of immunoglobulin E (IgE-) and non-IgE-mediated clinical syndromes, which have a significant economic and lifestyle impact. Definitive diagnosis is based on a supervised oral food challenge (OFC), but convincing clinical history, skin prick testing, and measurement of cow’s milk (CM)-specific IgE can aid in the diagnosis of IgE-mediated CMA and occasionally eliminate the need for OFCs. It is logical that a review of CMA would be linked to a review of soy allergy, as soy formula is often an alternative source of nutrition for infants who do not tolerate cow’s milk. The close resemblance between the proteins from soy and other related plants like peanut, and the resulting cross-reactivity and lack of predictive values for clinical reactivity, often make the diagnosis of soy allergy far more challenging. This review examines the epidemiology, pathogenesis, clinical features, natural history and diagnosis of cow’s milk and soy allergy. Cross-reactivity and management of milk allergy are also discussed. PMID:21453810

[TORCH syndrome: Rational approach of pre and post natal diagnosis and treatment. Recommendations of the Advisory Committee on Neonatal Infections Sociedad Chilena de Infectología, 2016].

PubMed

Cofre, Fernanda; Delpiano, Luis; Labraña, Yenis; Reyes, Alejandra; Sandoval, Alejandra; Izquierdo, Giannina

2016-04-01

There is a lot of bacterial, viral or parasite infections who are able to be transmitted vertically from the mother to the fetus or newborn which implicates an enormous risk for it. The TORCH acronym is used universally to refer to a fetus or newborn which presents clinical features compatible with a vertically acquired infection and allows a rational diagnostic and therapeutic approach. The traditional "TORCH test" is nowadays considered not appropriate and it has been replaced for specific test for specific pathogens under well defined circumstances. The present document reviews the general characteristics, epidemiology, pathogenesis, diagnostic and therapeutic options for the most frequently involved pathogens in the fetus or newborn with TORCH suspicion.

Celiac disease: From pathophysiology to treatment

PubMed Central

Parzanese, Ilaria; Qehajaj, Dorina; Patrinicola, Federica; Aralica, Merica; Chiriva-Internati, Maurizio; Stifter, Sanja; Elli, Luca; Grizzi, Fabio

2017-01-01

Celiac disease, also known as “celiac sprue”, is a chronic inflammatory disorder of the small intestine, produced by the ingestion of dietary gluten products in susceptible people. It is a multifactorial disease, including genetic and environmental factors. Environmental trigger is represented by gluten while the genetic predisposition has been identified in the major histocompatibility complex region. Celiac disease is not a rare disorder like previously thought, with a global prevalence around 1%. The reason of its under-recognition is mainly referable to the fact that about half of affected people do not have the classic gastrointestinal symptoms, but they present nonspecific manifestations of nutritional deficiency or have no symptoms at all. Here we review the most recent data concerning epidemiology, pathogenesis, clinical presentation, available diagnostic tests and therapeutic management of celiac disease. PMID:28573065

Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus.

PubMed

Weisberg, Lawrence S

2015-08-07

Lactic acidosis occurs when lactate production exceeds its metabolism. There are many possible causes of lactic acidosis, and in any given patient, several causes may coexist. This Attending Rounds presents a case in point. Metformin's role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. The treatment of lactic acidosis is controversial, except for the imperative to remedy its underlying cause. The use of sodium bicarbonate to treat the often alarming metabolic derangements may be quite efficacious in that regard but is of questionable benefit to patients. Renal replacement therapies (RRTs) have particular appeal in this setting for a variety of reasons, but their effect on clinical outcomes is untested. Copyright © 2015 by the American Society of Nephrology.

Diprosopus: a unique case and review of the literature.

PubMed

Wu, June; Staffenberg, David A; Mulliken, John B; Shanske, Alan L

2002-12-01

We present a case of partial facial duplication in a male infant. The clinical, radiological, and laboratory findings for this patient are described, followed by a review of the literature. Craniofacial duplication is a rare form of conjoined twinning and presents in a wide spectrum, from dicephalus to diprosopus to partial facial duplication. Many of these cases can be diagnosed prenatally. Prenatal assessment of our patient revealed only agenesis of the corpus callosum. The pathogenesis is believed to involve duplication of the notochord. Where there are more severe associated anomalies, the prognosis is poor. Partial facial duplication, as in our case, is associated with fewer anomalies, and the prognosis is better. Symmetry and an excess of tissue, rather than deficiency, favor a positive result. Copyright 2002 Wiley-Liss, Inc.

Oral Chronic Graft-versus-Host Disease: Current Pathogenesis, Therapy, and Research

PubMed Central

Mays, JW; Fassil, H; Edwards, DA; Pavletic, SZ; Bassim, CW

2012-01-01

Optimal management of complex autoimmune diseases requires a multidisciplinary medical team including dentists to care for lesions of the oral cavity. In this review, we discuss the presentation, prevalence, diagnosis and treatment of oral manifestations in chronic Graft-versus-Host Disease (cGVHD) which is a major late complication in patients treated by allogeneic hematopoietic stem cell transplantation. We assess current general knowledge of systemic and oral cGVHD, and present general treatment recommendations based on literature review and our clinical experience. Additionally, we review areas where the understanding of oral cGVHD could be improved by further research, and address tools with which to accomplish the long-term goal of providing better health and quality-of-life to patients with cGVHD. PMID:23107104

[Intestinal polyp of the umbilical cord].

PubMed

Guschmann, M; Janda, J; Wenzelides, K; Vogel, M

2002-02-01

The morphology, pathogenesis, complications and differential diagnosis of an intestinal polyp of the umbilical cord are presented. The polyp were detected postnatal on the umbilical cord in an healthy male newborn. The presents of intestinal tissue upon the umbilical cord ist possible about the persistence from remnants of the ductus omphalomesentericus with prolapse and differentiation of the intestinal cells. The ductus omphalomesentericus is a tubular structure, a communication between the developing embryonic gut and the yolk sac, forming during the early embryonic life. Obliteration of the omphalomesenteric duct is usually complete by the 10(th) week of gestation. Various portions of the duct may persist, however, giving rise to polyps, fistulas or cysts of the umbilical cord with potentially dangerous clinical consequences. Other tumors of the umbilical cord are myxoma, angioma and teratoma are differential diagnosis.

New approaches for Helicobacter vaccine development--difficulties and progress.

PubMed

Jagusztyn-Krynicka, Elzbieta K; Godlewska, Renata

2008-01-01

Despite the enormous progress in understanding the process of bacterial pathogenesis and interactions of pathogens with eucaryotic cells the infectious diseases still remain the main cause of human premature deaths. It is now recognized that Helicobacter pylori infects about half of the world's population. Based on results of clinical studies the World Health Organization has assigned H. pylori as a class I carcinogen. The review presents new achievements aimed at construction efficient and safe anti-Helicobacter vaccine. We discuss the new global technologies such as immunoproteomics employed for selecting new candidates for vaccine construction as well as new vaccine delivery systems. The review presents also our knowledge concerning H. pylori interaction with immune system which might facilitate modulation of the host immune system by specific adjuvant included into vaccine.

Congenital cardiac disease in the newborn infant: past, present, and future.

PubMed

Sadowski, Sharyl L

2009-03-01

Congenital heart defects are the most common of all congenital malformations, with a review of the literature reporting the incidence at 6 to 8 per 1000 live births. The Centers for Disease Control reports cyanotic heart defects occurred in 56.9 per 100,000 live births in the United States in 2005, with higher rates noted when maternal age exceeded 40 years. The incidence of congenital heart disease in premature infants is 12.5 per 1000 live births, excluding isolated patent ductus arteriosus and atrial septal defect. Despite advances in detection and treatment, congenital heart disease accounts for 3% of all infant deaths and 46% of death from congenital malformations. This article discusses the embryology, pathogenesis, clinical presentation, incidence, classifications, and management of congenital heart diseases.

Polycystic Kidney Disease: Pathogenesis and Potential Therapies

PubMed Central

Takiar, Vinita; Caplan, Michael J.

2011-01-01

Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent, inherited condition for which there is currently no effective specific clinical therapy. The disease is characterized by the progressive development of fluid-filled cysts derived from renal tubular epithelial cells which gradually compress the parenchyma and compromise renal function. Current interests in the field focus on understanding and exploiting signaling mechanisms underlying disease pathogenesis as well as delineating the role of the primary cilium in cystogenesis. This review highlights the pathogenetic pathways underlying renal cyst formation as well as novel therapeutic targets for the treatment of PKD. PMID:21146605

Role of endogenous opioid peptides in the pathogenesis of motion sickness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yasnetsov, V.V.; Il'ina, S.L.; Karsanova, S.K.

1986-01-01

This paper examines the pathogenesis of motion sickness and the role of the various neurochemical systems of the body in the genesis of the condition. It has been shown that the endogenous opioid system participates in the genesis of several pathological processes; this was the motivation for the study. The plasma beta-endorphin level was determined in samples from 19 clinically healthy males. Considering the positive prophylactic and therapeutic effect of naloxone against motion sickness it can be postulated that endogenous opioid peptides participate in the genesis of the vestibulo-autonomic disorders in motion sickness.

Molecular pathogenesis and mechanisms of thyroid cancer

PubMed Central

Xing, Mingzhao

2013-01-01

Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. PMID:23429735

Of the Phrensy: an update on the epidemiology and pathogenesis of bacterial meningitis in the pediatric population.

PubMed

Janowski, Andrew; Newland, Jason

2017-01-01

In the past century, advances in antibiotics and vaccination have dramatically altered the incidence and clinical outcomes of bacterial meningitis. We review the shifting epidemiology of meningitis in children, including after the implementation of vaccines that target common meningitic pathogens and the introduction of intrapartum antibiotic prophylaxis offered to mothers colonized with Streptococcus agalactiae . We also discuss what is currently known about the pathogenesis of meningitis. Recent studies of the human microbiome have illustrated dynamic relationships of bacterial and viral populations with the host, which may potentiate the risk of bacterial meningitis.

Familial ALS

PubMed Central

Boylan, Kevin

2015-01-01

Synopsis Genes linked to ALS susceptibility are being identified at an increasing rate owing to advances in molecular genetic technology. Genetic mechanisms in ALS pathogenesis appear to exert major effects in ~10% of patients, but genetic factors at some level may be important components of disease risk in most ALS patients. Identification of gene variants associated with ALS has informed concepts of the pathogenesis of ALS, aided the identification of therapeutic targets, facilitated research to develop new ALS biomarkers, and supported the establishment of clinical diagnostic tests for ALS-linked genes. Translation of this knowledge to ALS therapy development is ongoing. PMID:26515623

Pre-clinical and Clinical Investigation of the Impact of Obesity on Ovarian Cancer Pathogenesis

DTIC Science & Technology

2013-10-01

Cancer. 2006;107(7):1520-4. PubMed PMID: 16941453. 3. Olsen CM, Green AC, Whiteman DC, Sadeghi S, Kolahdooz F, Webb PM. Obesity and the risk of...PMC3317899. 18. Engeland A, Bjorge T, Selmer RM, Tverdal A. Height and body mass index in relation to total mortality. Epidemiology. 2003;14(3):293

Singular PCV2a or PCV2b infection results in apoptosis of hepatocytes in clinically affected gnotobiotic pigs

USDA-ARS?s Scientific Manuscript database

Porcine circovirus type 2 (PCV2) which can be further subdivide into two main genotypes, PCV2a and PCV2b, is often clinically associated with respiratory signs, failure-to-thrive, and diarrhea. The precise pathogenesis of PCV2, and in particular its involvement in apoptosis, is controversial. The ob...

[A modern look at benign stenosing lesions. Etiology and pathogenesis of diagnostic capabilities. A systematic review].

PubMed

Pakhabova, E Iu; Belova, G V

2012-01-01

The problem of nonneoplastic stenosis of major duodenal papilla is on joint of gastroenterology and surgery and present a challenge for physicians. This article reviews what is known about the pathogenesis, epidemiology and diagnostics of papillostenosis and sphincter of Oddi dysfunction.

Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance

PubMed Central

Vural, Atay; Doppler, Kathrin; Meinl, Edgar

2018-01-01

Discovery of disease-associated autoantibodies has transformed the clinical management of a variety of neurological disorders. Detection of autoantibodies aids diagnosis and allows patient stratification resulting in treatment optimization. In the last years, a set of autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies target neurofascin, contactin1, or contactin-associated protein 1, and we propose to name CIDP patients with these antibodies collectively as seropositive. They have unique clinical characteristics that differ from seronegative CIDP. Moreover, there is compelling evidence that autoantibodies are relevant for the pathogenesis. In this article, we review the current knowledge on the characteristics of autoantibodies against the node of Ranvier proteins and their clinical relevance in CIDP. We start with a description of the structure of the node of Ranvier followed by a summary of assays used to identify seropositive patients; and then, we describe clinical features and characteristics linked to seropositivity. We review knowledge on the role of these autoantibodies for the pathogenesis with relevance for the emerging concept of nodopathy/paranodopathy and summarize the treatment implications. PMID:29867996

Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance.

PubMed

Vural, Atay; Doppler, Kathrin; Meinl, Edgar

2018-01-01

Discovery of disease-associated autoantibodies has transformed the clinical management of a variety of neurological disorders. Detection of autoantibodies aids diagnosis and allows patient stratification resulting in treatment optimization. In the last years, a set of autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies target neurofascin, contactin1, or contactin-associated protein 1, and we propose to name CIDP patients with these antibodies collectively as seropositive. They have unique clinical characteristics that differ from seronegative CIDP. Moreover, there is compelling evidence that autoantibodies are relevant for the pathogenesis. In this article, we review the current knowledge on the characteristics of autoantibodies against the node of Ranvier proteins and their clinical relevance in CIDP. We start with a description of the structure of the node of Ranvier followed by a summary of assays used to identify seropositive patients; and then, we describe clinical features and characteristics linked to seropositivity. We review knowledge on the role of these autoantibodies for the pathogenesis with relevance for the emerging concept of nodopathy/paranodopathy and summarize the treatment implications.

The clinical maze of mitochondrial neurology

PubMed Central

DiMauro, Salvatore; Schon, Eric A.; Carelli, Valerio; Hirano, Michio

2014-01-01

Mitochondrial diseases involve the respiratory chain, which is under the dual control of nuclear and mitochondrial DNA (mtDNA). The complexity of mitochondrial genetics provides one explanation for the clinical heterogeneity of mitochondrial diseases, but our understanding of disease pathogenesis remains limited. Classification of Mendelian mitochondrial encephalomyopathies has been laborious, but whole-exome sequencing studies have revealed unexpected molecular aetiologies for both typical and atypical mitochondrial disease phenotypes. Mendelian mitochondrial defects can affect five components of mitochondrial biology: subunits of respiratory chain complexes (direct hits); mitochondrial assembly proteins; mtDNA translation; phospholipid composition of the inner mitochondrial membrane; or mitochondrial dynamics. A sixth category—defects of mtDNA maintenance—combines features of Mendelian and mitochondrial genetics. Genetic defects in mitochondrial dynamics are especially important in neurology as they cause optic atrophy, hereditary spastic paraplegia, and Charcot–Marie–Tooth disease. Therapy is inadequate and mostly palliative, but promising new avenues are being identified. Here, we review current knowledge on the genetics and pathogenesis of the six categories of mitochondrial disorders outlined above, focusing on their salient clinical manifestations and highlighting novel clinical entities. An outline of diagnostic clues for the various forms of mitochondrial disease, as well as potential therapeutic strategies, is also discussed. PMID:23835535

Vedolizumab: A novel anti-integrin drug for treatment of inflammatory bowel disease

PubMed Central

Singh, Harmanjit; Grewal, Nipunjot; Arora, Ekta; Kumar, Harish; Kakkar, Ashish Kumar

2016-01-01

Inflammatory bowel disease (IBD) is the chronic inflammatory disorder of gastrointestinal tract consisting of two subtypes: Ulcerative colitis and Crohn's disease. IBD occurs due to infiltration of leukocytes in intestinal mucosa and derangements in intestinal barrier function. One of the most important steps in pathogenesis of IBD is the interactions between integrins on the surface of leukocyte. The α4β7 integrin expressing T-cell is an important leukocyte involved in pathogenesis and represents a new drug target for the treatment of IBD. Vedolizumab is a humanized monoclonal antibody, which acts against α4β7 integrin heterodimer and blocks the interaction of α4β7 integrin with MAdCAM-1. It prevents leukocyte binding to endothelial surface and its extravasation into affected tissue. The efficacy and safety of the vedolizumab have been established in many clinical studies. It has shown promising results in various clinical studies where a greater percentage of patients as compared to a placebo achieved and maintained clinical response, clinical remission, and corticosteroid-free clinical remission. Vedolizumab has been shown to be well tolerated with slightly higher risk of infections, headache, naspharyngitis as compared to placebo. This review focuses on the potential role of vedolizumab for the treatment of IBD. PMID:27003961

[Discussion on six errors of formulas corresponding to syndromes in using the classic formulas].

PubMed

Bao, Yan-ju; Hua, Bao-jin

2012-12-01

The theory of formulas corresponding to syndromes is one of the characteristics of Treatise on Cold Damage and Miscellaneous Diseases (Shanghan Zabing Lun) and one of the main principles in applying classic prescriptions. It is important to take effect by following the principle of formulas corresponding to syndromes. However, some medical practitioners always feel that the actual clinical effect is far less than expected. Six errors in the use of classic prescriptions as well as the theory of formulas corresponding to syndromes are the most important causes to be considered, i.e. paying attention only to the local syndromes while neglecting the whole, paying attention only to formulas corresponding to syndromes while neglecting the pathogenesis, paying attention only to syndromes while neglecting the pulse diagnosis, paying attention only to unilateral prescription but neglecting the combined prescriptions, paying attention only to classic prescriptions while neglecting the modern formulas, and paying attention only to the formulas but neglecting the drug dosage. Therefore, not only the patients' clinical syndromes, but also the combination of main syndrome and pathogenesis simultaneously is necessary in the clinical applications of classic prescriptions and the theory of prescription corresponding to syndrome. In addition, comprehensive syndrome differentiation, modern formulas, current prescriptions, combined prescriptions, and drug dosage all contribute to avoid clinical errors and improve clinical effects.

Advances in mechanisms of systemic lupus erythematosus.

PubMed

Dema, Barbara; Charles, Nicolas

2014-05-01

Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with hormonal, environmental, and genetic factors and linked to the tolerance breakdown of B and T cells to self-antigens. SLE is characterized by the presence in patient serum of autoantibodies raised against nuclear components. Association of these antibodies to self-antigens, complement factors, DNA, and particular proteins will form circulating immune complexes (CIC) which can deposit in several organs, causing tissue damage and clinical manifestations. Historically, SLE is considered as an adaptive immune system disorder. Over the past decade, advances in the understanding of SLE pathogenesis placed the innate immune system as a key player in perpetuating and amplifying this systemic disease. In this review, we summarize some recent key advances in understanding the SLE immune-pathogenesis with a particular focus on newly discovered key factors from the innate immune system and how they influence the pathogenic adaptive immune system: neutrophils and neutrophil extracellular traps (NETs), plasmacytoid dendritic cells (pDCs) and type I interferons, basophils and autoreactive IgE, monocytes/macrophages and the inflammasome. Recent advances on B and T cell involvement in the SLE pathogenesis mechanisms are also discussed. Although the disease is clinically, genetically, and immunologically heterogeneous between affected individuals, the latest discoveries are offering new promising therapeutic strategies.

Nociceptive transmission and modulation via P2X receptors in central pain syndrome.

PubMed

Kuan, Yung-Hui; Shyu, Bai-Chuang

2016-05-26

Painful sensations are some of the most frequent complaints of patients who are admitted to local medical clinics. Persistent pain varies according to its causes, often resulting from local tissue damage or inflammation. Central somatosensory pathway lesions that are not adequately relieved can consequently cause central pain syndrome or central neuropathic pain. Research on the molecular mechanisms that underlie this pathogenesis is important for treating such pain. To date, evidence suggests the involvement of ion channels, including adenosine triphosphate (ATP)-gated cation channel P2X receptors, in central nervous system pain transmission and persistent modulation upon and following the occurrence of neuropathic pain. Several P2X receptor subtypes, including P2X2, P2X3, P2X4, and P2X7, have been shown to play diverse roles in the pathogenesis of central pain including the mediation of fast transmission in the peripheral nervous system and modulation of neuronal activity in the central nervous system. This review article highlights the role of the P2X family of ATP receptors in the pathogenesis of central neuropathic pain and pain transmission. We discuss basic research that may be translated to clinical application, suggesting that P2X receptors may be treatment targets for central pain syndrome.

Update on mucormycosis pathogenesis.

PubMed

Ibrahim, Ashraf S; Kontoyiannis, Dimitrios P

2013-12-01

Mucormycosis is an increasingly common fungal infection with unacceptably high mortality. The recent sequencing genome projects of Mucorales and the development of gene manipulation have enabled significant advances in understanding the pathogenesis of mucormycosis. Therefore, we review the pathogenesis of mucormycosis and highlight potential development of novel diagnostic and therapeutic modalities against this lethal disease. Much of the work has been focused on the role of iron uptake in the virulence of Mucorales. Additionally, host receptors and fungal ligands involved in the process of tissue invasion as well as sporangiospore size and sex loci and their contribution to virulence of Mucorales are discussed. Finally, the role of innate and adaptive immunity in protection against Mucorales and new evidence about drug-induced apoptosis in these fungi are discussed. Recent discoveries introduce several potentially novel diagnostic and therapeutic modalities, which are likely to improve management and outcome for mucormycosis. Future preclinical and clinical research is warranted to develop these diagnostic and therapeutic strategies.

Advances in MR imaging for cervical spondylotic myelopathy.

PubMed

Ellingson, Benjamin M; Salamon, Noriko; Holly, Langston T

2015-04-01

To outline the pathogenesis of cervical spondylotic myelopathy (CSM), the correlative abnormalities observed on standard magnetic resonance imaging (MRI), the biological implications and current status of diffusion tensor imaging (DTI), and MR spectroscopy (MRS) as clinical tools, and future directions of MR technology in the management of CSM patients. A systematic review of the pathogenesis and current state-of-the-art in MR imaging technology for CSM was performed. CSM is caused by progressive, degenerative, vertebral column abnormalities that result in spinal cord damage related to both primary mechanical and secondary biological injuries. The T2 signal change on conventional MRI is most commonly associated with neurological deficits, but tends not to be a sensitive predictor of recovery of function. DTI and MRS show altered microstructure and biochemistry that reflect patient-specific pathogenesis. Advanced imaging techniques, including DTI and MRS, show higher sensitivity to microstructural and biochemical changes within the cord, and may aid in management of CSM patients.

Extensive Genetic Diversity, Unique Population Structure and Evidence of Genetic Exchange in the Sexually Transmitted Parasite Trichomonas vaginalis

PubMed Central

Conrad, Melissa D.; Gorman, Andrew W.; Schillinger, Julia A.; Fiori, Pier Luigi; Arroyo, Rossana; Malla, Nancy; Dubey, Mohan Lal; Gonzalez, Jorge; Blank, Susan; Secor, William E.; Carlton, Jane M.

2012-01-01

Background Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection world-wide. Despite its prevalence, little is known about the genetic diversity and population structure of this haploid parasite due to the lack of appropriate tools. The development of a panel of microsatellite makers and SNPs from mining the parasite's genome sequence has paved the way to a global analysis of the genetic structure of the pathogen and association with clinical phenotypes. Methodology/Principal Findings Here we utilize a panel of T. vaginalis-specific genetic markers to genotype 235 isolates from Mexico, Chile, India, Australia, Papua New Guinea, Italy, Africa and the United States, including 19 clinical isolates recently collected from 270 women attending New York City sexually transmitted disease clinics. Using population genetic analysis, we show that T. vaginalis is a genetically diverse parasite with a unique population structure consisting of two types present in equal proportions world-wide. Parasites belonging to the two types (type 1 and type 2) differ significantly in the rate at which they harbor the T. vaginalis virus, a dsRNA virus implicated in parasite pathogenesis, and in their sensitivity to the widely-used drug, metronidazole. We also uncover evidence of genetic exchange, indicating a sexual life-cycle of the parasite despite an absence of morphologically-distinct sexual stages. Conclusions/Significance Our study represents the first robust and comprehensive evaluation of global T. vaginalis genetic diversity and population structure. Our identification of a unique two-type structure, and the clinically relevant phenotypes associated with them, provides a new dimension for understanding T. vaginalis pathogenesis. In addition, our demonstration of the possibility of genetic exchange in the parasite has important implications for genetic research and control of the disease. PMID:22479659

The role of MicroRNA molecules and MicroRNA-regulating machinery in the pathogenesis and progression of epithelial ovarian cancer.

PubMed

Wang, Xiyin; Ivan, Mircea; Hawkins, Shannon M

2017-11-01

MicroRNA molecules are small, single-stranded RNA molecules that function to regulate networks of genes. They play important roles in normal female reproductive tract biology, as well as in the pathogenesis and progression of epithelial ovarian cancer. DROSHA, DICER, and Argonaute proteins are components of the microRNA-regulatory machinery and mediate microRNA production and function. This review discusses aberrant expression of microRNA molecules and microRNA-regulating machinery associated with clinical features of epithelial ovarian cancer. Understanding the regulation of microRNA molecule production and function may facilitate the development of novel diagnostic and therapeutic strategies to improve the prognosis of women with epithelial ovarian cancer. Additionally, understanding microRNA molecules and microRNA-regulatory machinery associations with clinical features may influence prevention and early detection efforts. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic variation in IBD: progress, clues to pathogenesis and possible clinical utility

PubMed Central

Ye, Byong Duk; McGovern, Dermot P.B.

2016-01-01

Epidemiological and clinical studies have suggested that the pathogenesis of inflammatory bowel disease (IBD) is strongly influenced by genetic predisposition. Beyond the limitations of linkage analysis, multiple genome-wide association studies, their meta-analyses, and targeted genotyping array techniques have broadened our understanding of the genetic architecture of IBD. Currently, over 200 single nucleotide polymorphisms are known to be associated with susceptibility to IBD and through functional analysis of genes and loci, a substantial proportion of pathophysiologic mechanisms have been revealed. However, because only a modest fraction of predicted heritability can be explained by known genes/loci, additional strategies are needed including the identification of rare variants with large effect sizes to help explain the missing heritability. Considerable progress is also being made on applying outcomes of genetic research in diagnostics, classification, prognostics, and the development of new therapeutics of IBD. PMID:27156530

Pregnancy-related group a streptococcal infections: temporal relationships between bacterial acquisition, infection onset, clinical findings, and outcome.

PubMed

Hamilton, Stephanie M; Stevens, Dennis L; Bryant, Amy E

2013-09-01

Puerperal sepsis caused by group A Streptococcus (GAS) remains an important cause of maternal and infant mortality worldwide, including countries with modern antibiotic regimens, intensive care measures and infection control practices. To provide insights into the genesis of modern GAS puerperal sepsis, we reviewed the published cases and case series from 1974 to 2009, specifically seeking relationships between the likely source of pathogen acquisition, clinical signs, and symptoms at infection onset and patient outcomes that could provide clues for early diagnosis. Results suggest that the pathogenesis of pregnancy-related GAS infections in modern times is complex and not simply the result of exposure to GAS in the hospital setting. Additional research is needed to further explore the source of GAS, the specific M types involved, and the pathogenesis of these pregnancy-related infections to generate novel preventative and therapeutic strategies.

Hypersensitivity pneumonitis: an immunopathology review.

PubMed

Woda, Bruce A

2008-02-01

Hypersensitivity pneumonitis (HSP) is an immunologically mediated alveolar and interstitial lung disease caused by repeated inhalation of organic dusts and some occupational agents. The pathogenesis of HSP is uncertain. A number of unexplained features of HSP remain, namely (1) why do so few exposed individuals develop clinical HSP, (2) what triggers an acute episode after prolonged periods of previous sensitization, and (3) what leads to disease progression. This article considers these issues and aims to discuss and clarify current concepts in pathogenesis. Pertinent literature review in conjunction with the author's personal interpretive opinion. Current data suggest that individuals with a T(H)1 dominant response are likely to develop clinical disease. There is also some evidence that genetic factors such as polymorphisms in the major histocompatibility complex, tumor necrosis factor alpha, and tissue inhibitor of metalloproteinase 3 are associated with the development of or resistance to the disease.

Tibetan medicine "RNSP" in treatment of Alzheimer disease.

PubMed

Shi, Jing-Ming; He, Xue; Lian, Hui-Juan; Yuan, Dong-Ya; Hu, Qun-Ying; Sun, Zheng-Qi; Li, Yan-Song; Zeng, Yu-Wen

2015-01-01

Alzheimer disease (Alzheimer Disease, AD) is one of the most common type in senile dementia. Its main pathological features were that a large number of senile plaques gathered in brain extracellular and tangles fibrosis appeared in nerve cells. Currently, the pathogenesis of AD is still uncertain, and scale investigation and combined brain CT, MRI data were analyzed mainly for clinical diagnosis. Mitigation and improvement of the nervous system activity to interfere with the subsequent behavior of the patients are the main methods for treatment. In clinical no drug can really prevent and cure AD. From the view point of Tibetan medicine studies, Tibetan medicine RNSP has effect on improving memory and repairing the neurons in the brain. In this study, we combined the characteristics of AD pathology, pathogenesis, diagnosis and treatment methods to explore the feasibility of Tibetan medicine RNSP for the treatment of AD to provide new ideas for the diagnosis and treatment of AD.

Amyloidosis: Insights from Proteomics.

PubMed

Dogan, Ahmet

2017-01-24

Amyloidoses are a spectrum of disorders caused by abnormal folding and extracellular deposition of proteins. The deposits lead to tissue damage and organ dysfunction, particularly in the heart, kidneys, and nerves. There are at least 30 different proteins that can cause amyloidosis. The clinical management depends entirely on the type of protein deposited, and thus on the underlying pathogenesis, and often requires high-risk therapeutic intervention. Application of mass spectrometry-based proteomic technologies for analysis of amyloid plaques has transformed the way amyloidosis is diagnosed and classified. Proteomic assays have been extensively used for clinical management of patients with amyloidosis, providing unprecedented diagnostic and biological information. They have shed light on the pathogenesis of different amyloid types and have led to identification of numerous new amyloid types, including ALECT2 amyloidosis, which is now recognized as one of the most common causes of systemic amyloidosis in North America.

Pregnancy-Related Group A Streptococcal Infections: Temporal Relationships Between Bacterial Acquisition, Infection Onset, Clinical Findings, and Outcome

PubMed Central

Hamilton, Stephanie M.; Stevens, Dennis L.; Bryant, Amy E.

2013-01-01

Puerperal sepsis caused by group A Streptococcus (GAS) remains an important cause of maternal and infant mortality worldwide, including countries with modern antibiotic regimens, intensive care measures and infection control practices. To provide insights into the genesis of modern GAS puerperal sepsis, we reviewed the published cases and case series from 1974 to 2009, specifically seeking relationships between the likely source of pathogen acquisition, clinical signs, and symptoms at infection onset and patient outcomes that could provide clues for early diagnosis. Results suggest that the pathogenesis of pregnancy-related GAS infections in modern times is complex and not simply the result of exposure to GAS in the hospital setting. Additional research is needed to further explore the source of GAS, the specific M types involved, and the pathogenesis of these pregnancy-related infections to generate novel preventative and therapeutic strategies. PMID:23645851

Improved understanding of the pathophysiology of atrial fibrillation through the lens of discrete pathological pathways

PubMed Central

Balouch, Muhammad A.; Kolek, Matthew J.; Darbar, Dawood

2014-01-01

Atrial fibrillation (AF) is a common disorder with a complex and incompletely understood pathophysiology. Genetic approaches to understanding the pathophysiology of AF have led to the identification of several biological pathways important in the pathogenesis of the arrhythmia. These include pathways important for cardiac development, generation and propagation of atrial electrical impulses, and atrial remodeling and fibrosis. While common and rare genetic variants in these pathways are associated with increased susceptibility to AF, they differ substantially among patients with lone versus typical AF. Furthermore, how these pathways converge to a final common clinical phenotype of AF is unclear and might also vary among different patient populations. Here, we review the contemporary knowledge of AF pathogenesis and discuss how derangement in cardiac development, ion channel dysfunction, and promotion of atrial fibrosis may contribute to this common and important clinical disorder. PMID:25054116

Adverse Effects of Plasma Transfusion

PubMed Central

Pandey, Suchitra; Vyas, Girish N.

2012-01-01

Plasma utilization has increased over the last two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions following infusion of fresh frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: (1) transfusion related acute lung injury; (2) transfusion associated circulatory overload, and (3) allergic/anaphylactic reactions. Other less common risks include (1) transmission of infections, (2) febrile non-hemolytic transfusion reactions, (3) RBC allo-immunization, and (4) hemolytic transfusion reactions. The affect of pathogen inactivation/reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice. PMID:22578374

A model for dental hygiene education concerning the relationship between periodontal health and systemic health.

PubMed

Bush, Barbara Crafton; Donley, Timothy G

2002-01-01

To develop a format for educating the appropriate health care professionals as to the relationships between periodontal inflammation and increased risks for poor diabetes control, cardiovascular disease, cerebrovascular disease, pre-term low birth weight, pneumonia and gastric ulcer reinfection. Dental hygiene students in the Advanced Periodontology curriculum were instructed to review current literature regarding the increased risk for systemic health problems when periodontal inflammation is present. Abstracts of the reviewed material were then presented in group setting to all course participants. For each systemic entity (diabetes, cardio/cerebrovascular disease, adverse pregnancy outcome, pneumonia, gastric ulcer) literature-based evidence of periodontal disease's association, affect, pathogenesis, validity and clinical significance was determined. Consensus statements for each entity were developed and used as a basis for clinical interpretation. Following this, patient health-history materials were developed to obtain the necessary information from patients while educating them about the increased risk for systemic health problems when periodontal inflammation is present. Lastly, correspondence materials were developed to alert managing physicians and medical auxiliaries about the increased risk for systemic problems in their patients who may present with periodontal inflammation. A methodology which medical personnel can use to quickly screen for the presence of periodontal inflammation in at-risk patients was also developed in these correspondences. An educational model and clinical materials were developed which are aimed at alerting patients, dental and medical personnel to the increased risk for systemic health problems when inflammatory periodontal disease is present.

10TH International Workshop on Campylobacter, Helicobacter & Related Organisms.

DTIC Science & Technology

2000-01-01

food safety , and human and animal ecology; 2) present overviews and updates in these diverse areas by keynote speakers who are experts in their fields both inside the field and leading figures in pathogenesis; 3) present the latest results from investigators in these diverse areas in poster sessions and short invited talks; and 4) foster new collaborative multi disciplinary interactions to address pressing questions of prevention, pathogenesis, and treatment of disease due to Campylobacter and

Pathogenesis of post-traumatic ankylosis of the temporomandibular joint: a critical review.

PubMed

Arakeri, Gururaj; Kusanale, Atul; Zaki, Graeme A; Brennan, Peter A

2012-01-01

Many factors have been implicated in the development of bony ankylosis following trauma to the temporomandibular joint (TMJ) or ankylosis that recurs after surgical treatment for the condition. Although many reports have been published, to our knowledge very little has been written about the pathogenesis of the process and there are few scientific studies. Over the last 70 years various treatments have been described. Different methods have been used with perceived favourable outcomes although recurrence remains a problem in many cases, and ankylosis presents a major therapeutic challenge. We present a critical review of published papers and discuss the various hypotheses regarding the pathogenesis of the condition. Copyright © 2010 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Pathogenesis and prevention of rheumatic disease: focus on preclinical RA and SLE

PubMed Central

and, Kevin D. Deane; El-Gabalawy, Hani

2014-01-01

Established and emerging data demonstrate that a ‘preclinical’ period of disease precedes the onset of clinical rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), as well as other autoimmune rheumatic diseases (ARDs).This preclinical stage of development of disease is characterized by abnormalities in disease-related biomarkers before the onset of the clinically apparent signs and symptoms. Numerous genetic and environmental risk factors for ARDs have also been identified, and many of these factors are likely to act before the clinical appearance of tissue injury to initiate and/or propagate autoimmunity and autoimmune disease. Thus, biomarkers representative of these autoimmune processes could potentially be used in conjunction with other clinical parameters during the preclinical period of ARDs to predict the future development of clinically apparent disease. This Review focuses on the preclinical stages of RA and SLE, as our current understanding of these diseases can be used to present an overall model of the development of ARDs that might ultimately be used to develop screening programmes and preventive strategies. Important considerations for the future development of such approaches, in particular, the issues that require additional research and how they might be addressed, are also discussed. PMID:24514912

Alzheimer disease therapy--moving from amyloid-β to tau.

PubMed

Giacobini, Ezio; Gold, Gabriel

2013-12-01

Disease-modifying treatments for Alzheimer disease (AD) have focused mainly on reducing levels of amyloid-β (Aβ) in the brain. Some compounds have achieved this goal, but none has produced clinically meaningful results. Several methodological issues relating to clinical trials of these agents might explain this failure; an additional consideration is that the amyloid cascade hypothesis--which places amyloid plaques at the heart of AD pathogenesis--does not fully integrate a large body of data relevant to the emergence of clinical AD. Importantly, amyloid deposition is not strongly correlated with cognition in multivariate analyses, unlike hyperphosphorylated tau, neurofibrillary tangles, and synaptic and neuronal loss, which are closely associated with memory deficits. Targeting tau pathology, therefore, might be more clinically effective than Aβ-directed therapies. Furthermore, numerous immunization studies in animal models indicate that reduction of intracellular levels of tau and phosphorylated tau is possible, and is associated with improved cognitive performance. Several tau-related vaccines are in advanced preclinical stages and will soon enter clinical trials. In this article, we present a critical analysis of the failure of Aβ-directed therapies, discuss limitations of the amyloid cascade hypothesis, and suggest the potential value of tau-targeted therapy for AD.

Epileptic activity in Alzheimer’s disease: causes and clinical relevance

PubMed Central

Vossel, Keith A; Tartaglia, Maria C; Nygaard, Haakon B; Zeman, Adam Z; Miller, Bruce L

2018-01-01

Epileptic activity is frequently associated with Alzheimer’s disease; this association has therapeutic implications, because epileptic activity can occur at early disease stages and might contribute to pathogenesis. In clinical practice, seizures in patients with Alzheimer’s disease can easily go unrecognised because they usually present as non-motor seizures, and can overlap with other symptoms of the disease. In patients with Alzheimer’s disease, seizures can hasten cognitive decline, highlighting the clinical relevance of early recognition and treatment. Some evidence indicates that subclinical epileptiform activity in patients with Alzheimer’s disease, detected by extended neurophysiological monitoring, can also lead to accelerated cognitive decline. Treatment of clinical seizures in patients with Alzheimer’s disease with select antiepileptic drugs (AEDs), in low doses, is usually well tolerated and efficacious. Moreover, studies in mouse models of Alzheimer’s disease suggest that certain classes of AEDs that reduce network hyperexcitability have disease-modifying properties. These AEDs target mechanisms of epileptogenesis involving amyloid β and tau. Clinical trials targeting network hyperexcitability in patients with Alzheimer’s disease will identify whether AEDs or related strategies could improve their cognitive symptoms or slow decline. PMID:28327340

Reversible splenial lesion syndrome associated with lobar pneumonia

PubMed Central

Li, Chunrong; Wu, Xiujuan; Qi, Hehe; Cheng, Yanwei; Zhang, Bing; Zhou, Hongwei; Lv, Xiaohong; Liu, Kangding; Zhang, Hong-Liang

2016-01-01

Abstract Background: Reversible splenial lesion syndrome (RESLES) is a rare clinico-radiological disorder with unclear pathophysiology. Clinically, RESLES is defined as reversible isolated splenial lesions in the corpus callosum, which can be readily identified by magnetic resonance imaging (MRI) and usually resolve completely over a period of time. RESLES could be typically triggered by infection, antiepileptic drugs (AEDs), poisoning, etc. More factors are increasingly recognized. Methods and results: We reported herein an 18-year-old female patient with lobar pneumonia who developed mental abnormalities during hospitalization. An isolated splenial lesion in the corpus callosum was found by head MRI and the lesion disappeared 15 days later. Based on her clinical manifestations and radiological findings, she was diagnosed with lobar pneumonia associated RESLES. We further summarize the up-to-date knowledge about the etiology, possible pathogenesis, clinical manifestations, radiological features, treatment, and prognosis of RESLES. Conclusion: This report contributes to the clinical understanding of RESLES which may present with mental abnormalities after infection. The characteristic imaging of reversible isolated splenial lesions in the corpus callosum was confirmed in this report. The clinical manifestations and lesions on MRI could disappear naturally after 1 month without special treatment. PMID:27684805

Bilateral nevus comedonicus of the eyelids.

PubMed

Mendoza, Pia R; Jakobiec, Frederick A; Townsend, Daniel J

2013-01-01

Nevus comedonicus is a rare developmental abnormality of the infundibulum of the hair follicle. It is usually unilateral and commonly presents at birth or during childhood. A rare case of late-onset, bilateral nevus comedonicus of the eyelids is reported. A 79-year-old man presented with asymptomatic but disfiguring eyelid lesions noted several months earlier. On physical examination, multiple papules resembling comedones were present bilaterally in the eyelids, canthi, temple regions, and bridge of the nose. Microscopically, there were deep invaginations of the follicular canals forming focal tunnels or pseudosinus tracts with poral openings to the surface. These variably cystic structures were lined by keratinizing and nonkeratinizing squamous epithelium, contained concentric lamellae of keratin in their lumens, and some were acutely or chronically inflamed. The diagnosis of a nevus comedonicus was made. The clinical and histopathologic characteristics, pathogenesis, differential diagnosis, and management of nevus comedonicus are briefly discussed.

Bioterrorism for the respiratory physician.

PubMed

Waterer, Grant W; Robertson, Hannah

2009-01-01

Terrorist attacks by definition are designed to cause fear and panic. There is no question that a terrorist attack using biological agents would present a grave threat to stability of the society in which they were released. Early recognition of such a bioterrorist attack is crucial to containing the damage they could cause. As many of the most likely bioterrorism agents present with pulmonary disease, respiratory physicians may be crucial in the initial recognition and diagnosis phase, and certainly would be drawn into treatment of affected individuals. This review focuses on the biological agents thought most likely to be used by terrorists that have predominantly respiratory presentations. The primary focus of this review is on anthrax, plague, tularaemia, ricin, and Staphylococcal enterotoxin B. The pathogenesis, clinical manifestations and treatment of these agents will be discussed as well as historical examples of their use. Other potential bioterrorism agents with respiratory manifestations will also be discussed briefly.

Exploring the Crosstalk between Adipose Tissue and the Cardiovascular System.

PubMed

Akoumianakis, Ioannis; Akawi, Nadia; Antoniades, Charalambos

2017-09-01

Obesity is a clinical entity critically involved in the development and progression of cardiovascular disease (CVD), which is characterised by variable expansion of adipose tissue (AT) mass across the body as well as by phenotypic alterations in AT. AT is able to secrete a diverse spectrum of biologically active substances called adipocytokines, which reach the cardiovascular system via both endocrine and paracrine routes, potentially regulating a variety of physiological and pathophysiological responses in the vasculature and heart. Such responses include regulation of inflammation and oxidative stress as well as cell proliferation, migration and hypertrophy. Furthermore, clinical observations such as the "obesity paradox," namely the fact that moderately obese patients with CVD have favourable clinical outcome, strongly indicate that the biological "quality" of AT may be far more crucial than its overall mass in the regulation of CVD pathogenesis. In this work, we describe the anatomical and biological diversity of AT in health and metabolic disease; we next explore its association with CVD and, importantly, novel evidence for its dynamic crosstalk with the cardiovascular system, which could regulate CVD pathogenesis.

Exploring the Crosstalk between Adipose Tissue and the Cardiovascular System

PubMed Central

2017-01-01

Obesity is a clinical entity critically involved in the development and progression of cardiovascular disease (CVD), which is characterised by variable expansion of adipose tissue (AT) mass across the body as well as by phenotypic alterations in AT. AT is able to secrete a diverse spectrum of biologically active substances called adipocytokines, which reach the cardiovascular system via both endocrine and paracrine routes, potentially regulating a variety of physiological and pathophysiological responses in the vasculature and heart. Such responses include regulation of inflammation and oxidative stress as well as cell proliferation, migration and hypertrophy. Furthermore, clinical observations such as the “obesity paradox,” namely the fact that moderately obese patients with CVD have favourable clinical outcome, strongly indicate that the biological “quality” of AT may be far more crucial than its overall mass in the regulation of CVD pathogenesis. In this work, we describe the anatomical and biological diversity of AT in health and metabolic disease; we next explore its association with CVD and, importantly, novel evidence for its dynamic crosstalk with the cardiovascular system, which could regulate CVD pathogenesis. PMID:28955384

Phenotypes and enviromental factors: their influence in PCOS.

PubMed

Diamanti-Kandarakis, Evanthia; Christakou, Charikleia; Marinakis, Evangelos

2012-01-01

Polycystic ovary syndrome (PCOS) is a complex syndrome of unclear etiopathogenesis characterized by heterogeneity in phenotypic manifestations. The clinical phenotype of PCOS includes reproductive and hormonal aberrations, namely anovulation and hyperandrogenism, which coexist with metabolic disturbances. Reflecting the crosstalk between the reproductive system and metabolic tissues, obesity not only deteriorates the metabolic profile but also aggravates ovulatory dysfunction and hyperandrogenism. Although the pathogenesis of PCOS remains unclear, the syndrome appears to involve environmental and genetic components. Starting from early life and extending throughout lifecycle, environmental insults may affect susceptible women who finally demonstrate the clinical phenotype of PCOS. Diet emerges as the major environmental determinant of PCOS. Overnutrition leading to obesity is widely recognized to have an aggravating impact, while another detrimental dietary factor may be the high content of food in advanced glycated end products (AGEs). Environmental exposure to industrial products, particularly Bisphenol A (BPA), may also exacerbate the clinical course of PCOS. AGEs and BPA may act as endocrine disruptors in the pathogenesis of the syndrome. PCOS appears to mirror the harmful influence of the modern environment on the reproductive and metabolic balance of inherently predisposed individuals.

Localized scleroderma.

PubMed

Kreuter, Alexander

2012-01-01

Localized scleroderma (also called morphea) is a term encompassing a spectrum of sclerotic autoimmune diseases that primarily affect the skin, but also might involve underlying structures such as the fat, fascia, muscle, and bones. Its exact pathogenesis is still unknown, but several trigger factors in genetically predisposed individuals might initially lead to an immunologically triggered release of pro-inflammatory cytokines, resulting in a profound dysregulation of the connective tissue metabolism and ultimately to induction of fibrosis. To date, there are no specific serological markers available for localized scleroderma. Within the last years, several validated clinical scores have been introduced as potential outcome measures for the disease. Given the rarity of localized scleroderma, only few evidence-based therapeutical treatment options exist. So far, the most robust data is available for ultraviolet A1 phototherapy in disease that is restricted to the skin, and methotrexate alone or in combination with systemic corticosteroids in more severe disease that additionally affects extracutaneous structures. This practical review summarizes relevant information on the epidemiology, pathogenesis, clinical subtypes and classifications, differential diagnoses, clinical scores and outcome measures, and current treatment strategies of localized scleroderma. © 2012 Wiley Periodicals, Inc.

New Concepts in the Pathogenesis, Diagnosis and Control of Diseases Caused by the Bovine Viral Diarrhea Virus

PubMed Central

Radostits, Otto M.; Littlejohns, Ian R.

1988-01-01

The new information on the pathogenesis and epidemiology of mucosal disease of cattle is reviewed. It is now known that clinical mucosal disease occurs only in cattle which were infected with a pestivirus in early gestation and were born with persistent viral infection and specific immunotolerance. These animals may be clinically normal at birth but may develop fatal mucosal disease, perhaps following superinfection with another pestivirus, usually between 6 and 24 months of age. They may also remain clinically normal indefinitely and breed successfully. The progeny from persistently infected females will similarly be persistently viremic, and maternal families of such animals may be established. Congenital defects may occur when infection of the fetus occurs in mid-gestation. Although fetuses may be infected in utero in late gestation, the infections do not persist, the fetuses develop antibodies, and they appear to suffer no ill-effects. Postnatal infection can result in subclinical disease (bovine viral diarrhea) with a normal immune response; the virus may also be responsible for enhanced susceptibility to other infections, diarrhea in newborn calves, and reproductive failure. Prevention of the economically important diseases caused by the virus is dependent upon the identification and elimination of persistently viremic animals, which are reservoirs of infection, and the vaccination of immunocompetent females at least three weeks before breeding. However, because of serotypic differences between strains, there is some doubt whether vaccination will reliably provide protection against the transplacental fetal infections that are important in the pathogenesis of this disease. There is no substantial evidence to warrant the vaccination of feedlot cattle. PMID:17423063

Pathogenesis of highly virulent African swine fever virus in domestic pigs exposed via intraoropharyngeal, intranasopharyngeal, and intramuscular inoculation, and by direct contact with infected pigs.

PubMed

Howey, Erin B; O'Donnell, Vivian; de Carvalho Ferreira, Helena C; Borca, Manuel V; Arzt, Jonathan

2013-12-26

To investigate the pathogenesis of African swine fever virus (ASFV), domestic pigs (n=18) were challenged with a range (10(2)-10(6) 50% hemadsorbing doses (HAD50)) of the highly virulent ASFV-Malawi strain by inoculation via the intraoropharyngeal (IOP), intranasopharyngeal (INP), or intramuscular (IM) routes. A subsequent contact challenge experiment was performed in which six IOP-inoculated donor pigs were allowed to have direct contact (DC) with six naïve pigs for exposure times that varied from 24 to 72 h. All challenge routes resulted in clinical progression and postmortem lesions similar to those previously described in experimental and natural infection. The onset of clinical signs occurred between 1 and 7 days post inoculation (dpi) and included pyrexia with variable progression to obtundation, hematochezia, melena, moribundity and death with a duration of 4-11 days. Viremia was first detected between 4 and 5 dpi in all inoculation groups whereas ASFV shedding from the nasal cavity and tonsil was first detected at 3-9 dpi. IM and DC were the most consistent modes of infection, with 12/12 (100%) of pigs challenged by these routes becoming infected. Several clinical and virological parameters were significantly different between IM and DC groups indicating dissimilarity between these modes of infection. Amongst the simulated natural routes, INP inoculation resulted in the most consistent progression of disease across the widest range of doses whilst preserving simulation of natural exposure and therefore may provide a superior system for pathogenesis and vaccine efficacy investigation. Published by Elsevier B.V.

Calciphylaxis: diagnosis and clinical features.

PubMed

Hayashi, Matsuhiko

2013-08-01

Calciphylaxis is a relatively rare disease, observed mainly in patients on dialysis, associated with high mortality rates, and characterized by painful skin ulceration. The pathogenesis of calciphylaxis is virtually unknown, although several risk factors, including warfarin therapy, hypoalbuminemia, and disturbances in calcium-phosphate metabolism, have been reported. The prevalence of calciphylaxis in Japan is likely to be less than 1:10,000 dialysis patients per year based on our nationwide survey in 2009. However, the results of the survey also showed that about 60 % of nephrologists in Japan are not familiar with the disease itself and it is highly likely that calciphylaxis is being overlooked. To facilitate recognition of calciphylaxis, we have proposed diagnostic criteria. At present, there is no specific therapy for calciphylaxis and general supportive measures, especially antibiotics for the accompanying infection and wound care, are important. Recently, sodium thiosulfate has been increasingly used to treat calciphylaxis and its efficacy should be evaluated by large clinical trials.

Leprosy. An update: definition, pathogenesis, classification, diagnosis, and treatment.

PubMed

Eichelmann, K; González González, S E; Salas-Alanis, J C; Ocampo-Candiani, J

2013-09-01

Leprosy is a chronic granulomatous disease caused by the bacillus Mycobacterium leprae. It primarily affects the skin and peripheral nerves and is still endemic in various regions of the world. Clinical presentation depends on the patient's immune status at the time of infection and during the course of the disease. Leprosy is associated with disability and marginalization. Diagnosis is clinical and is made when the patient has at least 1 of the following cardinal signs specified by the World Health Organization: hypopigmented or erythematous macules with sensory loss; thickened peripheral nerves; or positive acid-fast skin smear or skin biopsy with loss of adnexa at affected sites. Leprosy is treated with a multidrug combination of rifampicin, clofazimine, and dapsone. Two main regimens are used depending on whether the patient has paucibacillary or multibacillary disease. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

Traumatic bone cyst suggestive of large apical periodontitis.

PubMed

Rodrigues, Cleomar Donizeth; Estrela, Carlos

2008-04-01

This case report shows the importance of establishing the correct diagnosis to provide the appropriate treatment options The traumatic bone cyst is a pseudocyst, usually asymptomatic and found by a routine radiographic examination. Unicystic radiolucency is almost always observed, which can involve the periradicular area of teeth, simulating an inflammatory lesion of endodontic origin. Differential diagnosis should include other pathologies, such as odontogenic keratocyst, central giant cell granuloma, and unicystic ameloblastoma. Its etiology and pathogenesis are not yet definitely established. In the present study, after review of the medical and dental histories and clinical and radiographic examination of teeth #24-27 (pulpal vitality test showed positive), the primary diagnosis was traumatic bone cyst. The planning was excisional biopsy. After surgical exploration, only one small blood clot was observed in the intraosseous socket, which was carefully curetted and filled with blood. A clinical and radiographic examination after 6 months showed apical formation and pulpal vitality preserved.

Dry eye disease as an inflammatory disorder.

PubMed

Calonge, Margarita; Enríquez-de-Salamanca, Amalia; Diebold, Yolanda; González-García, María J; Reinoso, Roberto; Herreras, José M; Corell, Alfredo

2010-08-01

Dry eye disease (DED) is a prevalent inflammatory disorder of the lacrimal functional unit of multifactorial origin leading to chronic ocular surface disease, impaired quality of vision, and a wide range of complications, eventually causing a reduction in quality of life. It still is a frustrating disease because of the present scarcity of therapies that can reverse, or at least stop, its progression. A comprehensive literature survey of English-written scientific publications on the role of inflammation in DED. New investigations have demonstrated that a chronic inflammatory response plays a key role in the pathogenesis of human DED. Additionally, correlations between inflammatory molecules and clinical data suggest that inflammation can be responsible for some of the clinical symptoms and signs. Research efforts to clarify its pathophysiology are leading to a better understanding of DED, demonstrating that inflammation, in addition to many other factors, plays a relevant role.

Hereditary nonpolyposis colorectal cancer: Review of clinical, molecular genetics, and counseling aspects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bellacosa, A.; Genuardi, M.; Anti, M.

Lynch syndrome, or hereditary nonpolyposis colon cancer (HNPCC), is an autosomal dominant disease accounting for approximately 1-5% of all colorectal cancer cases. Due to the lack of pathognomonic morphological or biomolecular markers, HNPCC has traditionally posed unique problems to clinicians and geneticists alike, both in terms of diagnosis and clinical management. Recently, novel insight into the pathogenesis of this syndrome has been provided by the identification of its molecular basis. In HNPCC families, germline mutations in any of four genes encoding proteins of a specialized DNA repair system, the mismatch repair, predispose to cancer development. Mutations in mismatch repair genesmore » lead to an overall increase of the mutation rate and are associated with a phenotype of length instability of microsatellite loci. The present report summarizes the clinicopathological aspects of HNPCC and reviews the most recent molecular and biochemical findings. 115 refs., 2 figs., 3 tabs.« less

Understanding the biology of melanoma and therapeutic implications

PubMed Central

Sullivan, Ryan J; Fisher, David E

2014-01-01

From 1976 – 2010, the US FDA approved only two medications for the treatment of metastatic melanoma, dacarbazine and high-dose interleukin 2. Between 2011–13, four agents were approved (ipilimumab, vemurafenib, dabrafenib, trametinib) and other therapies have shown great promise in clinical trials. This startling progress has been made possible by the groundbreaking efforts of basic scientists and the vision and innovation of translational and clinical investigators. Fundamental discoveries such as the identification of oncogenic mutations in the majority melanomas, the elucidation of the molecular signaling resultant from these mutations, and the revelation that a number of cell surface molecules serve as regulators of immune activation, have all been instrumental to this progress. This chapter provides a summary of the molecular pathogenesis of melanoma by reviewing the relevant melanocyte biology and molecular signaling used by melanoma, describes the current efforts to target oncogene driven signaling, and presents the rationale for combining immune and molecular targeting. PMID:24880940

Autophagy as a Therapeutic Target in Cardiovascular Disease

PubMed Central

Nemchenko, Andriy; Chiong, Mario; Turer, Aslan; Lavandero, Sergio; Hill, Joseph A.

2011-01-01

The epidemic of heart failure continues apace, and development of novel therapies with clinical efficacy has lagged. Now, important insights into the molecular circuitry of cardiovascular autophagy have raised the prospect that this cellular pathway of protein quality control may be a target of clinical relevance. Whereas basal levels of autophagy are required for cell survival, excessive levels – or perhaps distinct forms of autophagic flux – contribute to disease pathogenesis. Our challenge will be to distinguish mechanisms that drive adaptive versus maladaptive autophagy and to manipulate those pathways for therapeutic gain. Recent evidence suggests this may be possible. Here, we review the fundamental biology of autophagy and its role in a variety of forms of cardiovascular disease. We discuss ways in which this evolutionarily conserved catabolic mechanism can be manipulated, discuss studies presently underway in heart disease, and provide our perspective on where this exciting field may lead in the future. PMID:21723289

[Treatment of multiple sclerosis symptoms and exacerbations].

PubMed

Prieto González, José María

2014-12-01

In the last few years, there has been an explosion of new drugs acting on the clinical course of multiple sclerosis (MS) but less attention has been paid to better knowledge of the symptoms of this disease and their pathogenesis and treatment, which is essential to improve patients' quality of life. Because many patients have numerous concurrent symptoms during their clinical course, their management is complex and consequently it is important to know which symptoms are a direct result of the degenerative lesions of MS. The present article describes all the therapeutic options available for spasticity and its associated pain, paroxystic symptoms, fatigue, genitourinary disorders and sexual dysfunction, tremor, ataxia, gait disorder and cognitive impairment, with special emphasis on novel treatments. The article also defines exacerbations, how to recognize them and the available treatments, mainly oral administration of high-dose methylprednisolone and plasmapheresis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome

PubMed Central

Muscatello, Maria Rosaria A; Bruno, Antonio; Scimeca, Giuseppe; Pandolfo, Gianluca; Zoccali, Rocco A

2014-01-01

Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting. PMID:24976697

Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome.

PubMed

Muscatello, Maria Rosaria A; Bruno, Antonio; Scimeca, Giuseppe; Pandolfo, Gianluca; Zoccali, Rocco A

2014-06-28

Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting.

Role of the adrenal cortex and sodium in the pathogenesis of human hypertension.

PubMed Central

Genest, J.; Nowaczynski, W.; Boucher, R.; Kuchel, O.

1978-01-01

After 30 years of continuous research into the mechanisms of human hypertension, we summarize the results obtained by the members of the multidisciplinary research group on hypertension of the Clinical Research Institute of Montreal on the disturbances of minerlocorticoid activity in a rigorously selected group of patients with early, mild essential hypertension. We attempt to integrate these findings with those of many other groups working on other aspects of hypertensive cardiovascular diseases. On the assumption that the increased peripheral resistance responsible for hypertension results from an imbalance or a disturbance of the equilibrium between the sympathetic nervous system and norepinephrine on one hand, and the vascular tone, sensitivity and responsiveness of the arterial smooth muscle to norepinephrine and to angiotensin II on the other hand, three models that fit the experimental and clinical facts as known at present are described. PMID:343905

Clinical Perspectives on Lupus Genetics: Advances and Opportunities

PubMed Central

James, Judith A.

2014-01-01

Synopsis In recent years, genome wide association studies have led to an explosion in the identification of regions containing confirmed genetic risk variants within complex human diseases, for example in systemic lupus erythematosus (SLE). Many of these strongest SLE genetic associations can be divided into groups based upon their potential roles in different processes implicated in lupus pathogenesis, including ubiquitination (a process of marking proteins for degradation), DNA degradation, innate immunity, cellular immunity (B cell, T cell, neutrophil, monocytes), lymphocyte development, and antigen presentation. Recent advances have also demonstrated several genetic associations with SLE subphenotypes and subcriteria, such as autoantibody production, lupus nephritis, serositis, and arthritis. Despite the broad range of lupus genetic studies to date, many areas for further exploration remain to move lupus genetic studies toward clinically informative endpoints, such as identifying individuals at the greatest risk of end-organ damage, early mortality or poor response to a specific therapeutic regimen. PMID:25034154

Nonpuerperal mastitis and subareolar abscess of the breast.

PubMed

Kasales, Claudia J; Han, Bing; Smith, J Stanley; Chetlen, Alison L; Kaneda, Heather J; Shereef, Serene

2014-02-01

The purpose of this article is to show radiologists how to readily recognize nonpuerperal subareolar abscess and its complications in order to help reduce the time to definitive therapy and improve patient care. To achieve this purpose, the various theories of pathogenesis and the associated histopathologic features are reviewed; the typical clinical characteristics are detailed in contrast to those seen in lactational abscess and inflammatory breast cancer; the common imaging findings are described with emphasis on the sonographic features; correlative pathologic findings are presented to reinforce the imaging findings as they pertain to disease origins; and the various treatment options are reviewed. Nonpuerperal subareolar mastitis and abscess is a benign breast entity often associated with prolonged morbidity. Through better understanding of the underlying disease process the imaging, physical, and clinical findings of this rare process can be more readily recognized and treatment options expedited, improving patient care.

Overtraining Syndrome

PubMed Central

Kreher, Jeffrey B.; Schwartz, Jennifer B.

2012-01-01

Context: Fatigue and underperformance are common in athletes. Understanding overtraining syndrome (OTS) is helpful in the evaluation, management, and education of athletes. Evidence Acquisition: Relevant articles in English were searched with OVID (1948-2011) and PubMed using the following keywords: overtraining syndrome, overtraining, overreaching, unexplained underperformance, staleness, pathophysiology, management, treatment, evaluation. Bibliographies were reviewed for additional resources. Results: OTS appears to be a maladapted response to excessive exercise without adequate rest, resulting in perturbations of multiple body systems (neurologic, endocrinologic, immunologic) coupled with mood changes. Many hypotheses of OTS pathogenesis are reviewed, and a clinical approach to athletes with possible OTS (including history, testing, and prevention) is presented. Conclusions: OTS remains a clinical diagnosis with arbitrary definitions per the European College of Sports Science’s position statement. History and, in most situations, limited serologies are helpful. However, much remains to be learned given that most past research has been on athletes with overreaching rather than OTS. PMID:23016079

Time for a change: is idiopathic pulmonary fibrosis still idiopathic and only fibrotic?

PubMed Central

Wolters, Paul J; Blackwell, Timothy S; Eickelberg, Oliver; Loyd, James E; Kaminski, Naftali; Jenkins, Gisli; Maher, Toby M; Molina-Molina, Maria; Noble, Paul W; Raghu, Ganesh; Richeldi, Luca; Schwarz, Marvin I; Selman, Moises; Wuyts, Wim A; Schwartz, David A

2018-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and typically fatal lung disease characterised by subpleural fibrosis, subepithelial fibroblast foci, and microscopic honeycombing. Although understanding of the pathogenic mechanisms continues to evolve, evidence indicates that distal airway and alveolar epithelial cells are central drivers of the disease. In this Viewpoint, we review the history of naming and classifications used to define the disease now referred to as IPF, in the context of understanding the clinical presentation, causes, and pathogenesis of the disease. We aim to generate discussion on whether, given the substantial progress made in understanding the clinical, genetic, cellular, and molecular mechanisms involved in the development of IPF, a change of name should be considered. To initiate this discussion, we offer new suggestions to update the name of this disease and new approaches to classify all forms of pulmonary fibrosis. PMID:29413083

Necroptosis in acute kidney injury: a shedding light

PubMed Central

Wang, S; Zhang, C; Hu, L; Yang, C

2016-01-01

Acute kidney injury (AKI) is a common and severe clinical condition with a heavy healthy burden around the world. In spite of supportive therapies, the mortality associated with AKI remains high. Our limited understanding of the complex cell death mechanism in the process of AKI impedes the development of desirable therapeutics. Necroptosis is a recently identified novel form of cell death contributing to numerable diseases and tissue damages. Increasing evidence has suggested that necroptosis has an important role in the pathogenesis of various types of AKI. Therefore, we present here the signaling pathways and main regulators of necroptosis that are potential candidate for therapeutic strategies. Moreover, we emphasize on the potential role and corresponding mechanisms of necroptosis in AKI based on recent advances, and also discuss the possible therapeutic regimens based on manipulating necroptosis. Taken together, the progress in this field sheds new light into the prevention and management of AKI in clinical practice. PMID:26938298

Gray Matter Is Targeted in First-Attack Multiple Sclerosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schutzer, Steven E.; Angel, Thomas E.; Liu, Tao

The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We foundmore » that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.« less

Breast cancer subtype distribution is different in normal weight, overweight, and obese women.

PubMed

Gershuni, Victoria; Li, Yun R; Williams, Austin D; So, Alycia; Steel, Laura; Carrigan, Elena; Tchou, Julia

2017-06-01

Obesity is associated with tumor promoting pathways related to insulin resistance and chronic low-grade inflammation which have been linked to various disease states, including cancer. Many studies have focused on the relationship between obesity and increased estrogen production, which contributes to the pathogenesis of estrogen receptor-positive breast cancers. The link between obesity and other breast cancer subtypes, such as triple-negative breast cancer (TNBC) and Her2/neu+ (Her2+) breast cancer, is less clear. We hypothesize that obesity may be associated with the pathogenesis of specific breast cancer subtypes resulting in a different subtype distribution than normal weight women. A single-institution, retrospective analysis of tumor characteristics of 848 patients diagnosed with primary operable breast cancer between 2000 and 2013 was performed to evaluate the association between BMI and clinical outcome. Patients were grouped based on their BMI at time of diagnosis stratified into three subgroups: normal weight (BMI = 18-24.9), overweight (BMI = 25-29.9), and obese (BMI > 30). The distribution of breast cancer subtypes across the three BMI subgroups was compared. Obese and overweight women were more likely to present with TNBC and normal weight women with Her2+ breast cancer (p = 0.008). We demonstrated, for the first time, that breast cancer subtype distribution varied significantly according to BMI status. Our results suggested that obesity might activate molecular pathways other than the well-known obesity/estrogen circuit in the pathogenesis of breast cancer. Future studies are needed to understand the molecular mechanisms that drive the variation in subtype distribution across BMI subgroups.