Burning mouth syndrome: a review on diagnosis and treatment

PubMed Central

Coculescu, EC; Radu, A; Coculescu, BI

2014-01-01

Burning mouth syndrome (BMS) is defined as a chronic pain condition characterized by a burning sensation in the clinically healthy oral mucosa. It is difficult to diagnose BMS because there is a discrepancy between the severity, extensive objective pain felt by the patient and the absence of any clinical changes of the oral mucosa. This review presents some aspects of BMS, including its clinical diagnosis, classification, differential diagnosis, general treatment, evolution and prognosis. PMID:25713611

[EBOLA HEMORRHAGIC FEVER: DIAGNOSTICS, ETIOTROPIC AND PATHOGENETIC THERAPY, PREVENTION].

PubMed

Zhdanov, K V; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fisun, A Ya

2015-01-01

The data on diagnostics, etiotropic and pathogenetic therapy, prevention of Ebola hemorrhagic fever are presented including diagnostic algorithms for different clinical situations. Fundamentals of pathogenetic therapy are described. Various groups of medications used for antiviral therapy of conditions caused by Ebola virus are characterized. Experimental drugs at different stages of clinical studies are considered along with candidate vaccines being developed for the prevention of the disease.

Clinical, endoscopic and manometric features of the primary motor disorders of the esophagus.

PubMed

Martinez, Júlio César; Lima, Gustavo Rosa de Almeida; Silva, Diego Henrique; Duarte, Alexandre Ferreira; Novo, Neil Ferreira; da Silva, Ernesto Carlos; Pinto, Pérsio Campos Correia; Maia, Alexandre Moreira

2015-01-01

Significant incidence, diagnostic difficulties, clinical relevance and therapeutic efficacy associated with the small number of publications on the primary esophageal motor disorders, motivated the present study. To determine the manometric prevalence of these disorders and correlate them to the endoscopic and clinical findings. A retrospective study of 2614 patients, being 1529 (58.49%) women and 1085 (41.51%) men. From 299 manometric examinations diagnosed with primary esophageal motor disorder, were sought-clinical data (heartburn, regurgitation, dysphagia, odynophagia, non-cardiac chest pain, pharyngeal globe and extra-esophageal symptoms) and/or endoscopic (hiatal hernia, erosive esophagitis, food waste) that motivated the performance of manometry. Were found 49 cases of achalasia, 73 diffuse spasm, 89 nutcracker esophagus, 82 ineffective esophageal motility, and six lower esophageal sphincter hypertension. In relation to the correlations, it was observed that in 119 patients clinical conditions were associated with dysphagia, found in achalasia more than in other conditions; in relationship between endoscopic findings and clinical conditions there was no statistical significance between data. The clinical and endoscopic findings have little value in the characterization of the primary motor disorders of the esophagus, showing even more the need for manometry, particularly in the preoperative period of gastroesophageal reflux disease.

The genetic basis for survivorship in coronary artery disease

PubMed Central

Dungan, Jennifer R.; Hauser, Elizabeth R.; Qin, Xuejun; Kraus, William E.

2013-01-01

Survivorship is a trait characterized by endurance and virility in the face of hardship. It is largely considered a psychosocial attribute developed during fatal conditions, rather than a biological trait for robustness in the context of complex, age-dependent diseases like coronary artery disease (CAD). The purpose of this paper is to present the novel phenotype, survivorship in CAD as an observed survival advantage concurrent with clinically significant CAD. We present a model for characterizing survivorship in CAD and its relationships with overlapping time- and clinically-related phenotypes. We offer an optimal measurement interval for investigating survivorship in CAD. We hypothesize genetic contributions to this construct and review the literature for evidence of genetic contribution to overlapping phenotypes in support of our hypothesis. We also present preliminary evidence of genetic effects on survival in people with clinically significant CAD from a primary case-control study of symptomatic coronary disease. Identifying gene variants that confer improved survival in the context of clinically appreciable CAD may improve our understanding of cardioprotective mechanisms acting at the gene level and potentially impact patients clinically in the future. Further, characterizing other survival-variant genetic effects may improve signal-to-noise ratio in detecting gene associations for CAD. PMID:24143143

[WORKING CONDITIONS AND STATE OF HEALTH OF TBILISI SUBWAY EMPLOYEES].

PubMed

Khunashvili, N; Tsimakuridze, Mar; Bakradze, L; Khachapuridze, N; Tsimakuridze, Maya

2017-03-01

For the purpose of preventive events complex hygienic, clinical-functional, laboratory and biostatic researches are implemented on the basis of Tbilisi Subway. Conditions of work are characterized by complex of unfavorable factors of the working environment and the labor process. Working environment is characterized by combination of unfavorable state of physical factors and air pollution with dust and toxic substances. The levels of noise and vibration refer to the 3.4 class of harmfulness. The content of dust and toxic substances corresponds to 3.1-3.2 classes of working conditions harmfulness. In the indexes of health status, the leading diseases are pathology of cardiovascular, nervous and digestive systems. Cause-effect relationships between working conditions and individual health indicators have been already established, which served as the basis for the development of comprehensive preventive health measures.

Nutritional issues in heart transplant candidates and recipients.

PubMed

Amarelli, Cristiano; Buonocore, Marianna; Romano, Gianpaolo; Maiello, Ciro; De Santo, Luca Salvatore

2012-01-01

Heart transplant is the golden standard in the management of end-stage heart failure. Recent studies have pointed out the role of nutritional issues in patients evaluated for heart transplant listing. In particular, extremes in body habitus, cachexia and obesity, have been characterized and identified as independent prognostic factors and clinically relevant target for therapeutic interventions. Effects of such conditions exert a prognostic implication well beyond waiting time up to early post transplant setting. Changes in posttransplant clinical conditions and nutritional status have been recently described in their pattern of presentation and implications on weight gain, reversal of preoperative cachexia and early and late morbidity and mortality. New onset diabetes mellitus and metabolic syndrome have been disclosed as relevant clinical conditions in this setting. Implications for tailoring of immunosuppressive therapy and dietary prescription emerged as main stem of long term recipient management. All this issues have been reviewed focusing on the clinical relevance of this growing body of knowledge and emphasizing the role of a multidisciplinary approach for selection and management of heart transplant recipients.

Hamate-pisiform coalition: morphology, clinical significance, and a simplified classification scheme for carpal coalition.

PubMed

Burnett, Scott E

2011-03-01

Hamate-pisiform coalition is characterized by the abnormal union of the pisiform bone and hamulus of the hamate. Because most reported cases are isolated, and literature on the subject is sparse, relatively little is known about this condition and its clinical significance. The purpose of this report is to discuss the occurrence, morphology, and frequency of hamate-pisiform coalition identified in a skeletal sample of native South Africans, and to conduct a metaanalysis of all known cases in order to clarify the sex distribution, laterality, form, and clinical significance of this condition. Five new cases (three male, two female) of hamate-pisiform coalition were identified in 527 native South Africans. Results indicate that hamate-pisiform coalition is infrequent (0.76%) but may be more likely encountered in individuals of African ancestry. Morphologically, non-osseous examples ranged in appearance from minor expressions involving pitting of an expanded hamulus base, to a variably pitted articulation between an elongated pisiform and hamulus. Osseous union between the two bones tends to extend beyond the hamulus base to adjacent areas of the hamate. Cases involving osseous union appear predisposed to fracture while ulnar neuropathy is significantly more frequent in individuals exhibiting non-osseous coalition. As both non-osseous and osseous cases can have clinical significance, awareness of the variable manifestations of this condition is necessary for hand specialists. A simplified classification system is suggested to more consistently characterize carpal coalitions. Copyright © 2010 Wiley-Liss, Inc.

Clinically granulomatous cheilitis with plasma cells

PubMed Central

Sarkar, Somenath; Ghosh, Sarmistha; Sengupta, Dipayan

2016-01-01

Plasma cell cheilitis, also known as plasma cell orificial mucositis is a benign inflammatory condition clinically characterized by erythematous plaque on lips that may be ulcerated. Histopathologically it is characterized by dense plasma cell infiltrates in a band-like pattern in dermis, which corresponds to Zoon's plasma cell balanitis. On the other hand, granulomatous cheilitis, as a part of orofacial granulomatosis, manifests as sudden diffuse or nodular swelling involving lip and cheek. Initial swelling is soft to firm, but with recurrent episodes swelling gradually become firm rubbery in consistency. We hereby report a case of cheilitis in a 52-year-old man with diffuse swelling involving lower lip, which clinically resembles granulomatous cheilitis, but histopathological examination showed diffuse infiltrate of plasma cells predominantly in upper and mid-dermis. PMID:27057489

Stress-related Clinical Pain and Mood in Women with Chronic Pain: Moderating Effects of Depression and Positive Mood Induction

PubMed Central

Davis, Mary C.; Thummala, Kirti; Zautra, Alex J.

2014-01-01

Background Chronic pain with co-morbid depression is characterized by poor mood regulation and stress-related pain. Purpose Compare depressed and non-depressed pain patients in mood and pain stress reactivity and recovery, and test whether a post-stress positive mood induction moderates pain recovery. Methods Women with fibromyalgia and/or osteoarthritis (N=110) underwent interpersonal stress and were then randomly assigned by pain condition and depression status, assessed via the Center for Epidemiological Studies-Depression scale, to positive versus neutral mood induction. Results Depression did not predict stress-related reactivity in despondency, joviality, or clinical pain. However, depression X mood condition predicted recovery in joviality and clinical pain; depressed women recovered only in the positive mood condition, whereas non-depressed women recovered in both mood conditions. Conclusions Depression does not alter pain and mood stress reactivity, but does impair recovery. Boosting post-stress jovial mood ameliorates pain recovery deficits in depressed patients, a finding relevant to chronic pain interventions. PMID:24532393

Stress-related clinical pain and mood in women with chronic pain: moderating effects of depression and positive mood induction.

PubMed

Davis, Mary C; Thummala, Kirti; Zautra, Alex J

2014-08-01

Chronic pain with comorbid depression is characterized by poor mood regulation and stress-related pain. This study aims to compare depressed and non-depressed pain patients in mood and pain stress reactivity and recovery, and test whether a post-stress positive mood induction moderates pain recovery. Women with fibromyalgia and/or osteoarthritis (N = 110) underwent interpersonal stress and were then randomly assigned by pain condition and depression status, assessed via the Center for Epidemiological Studies-Depression scale, to positive versus neutral mood induction. Depression did not predict stress-related reactivity in despondency, joviality, or clinical pain. However, depression × mood condition predicted recovery in joviality and clinical pain; depressed women recovered only in the positive mood condition, whereas non-depressed women recovered in both mood conditions. Depression does not alter pain and mood stress reactivity, but does impair recovery. Boosting post-stress jovial mood ameliorates pain recovery deficits in depressed patients, a finding relevant to chronic pain interventions.

Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

PubMed

Malayandi, Rajkumar; Kondamudi, Phani Krishna; Ruby, P K; Aggarwal, Deepika

2014-04-01

Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

Dissecting Inflammatory Complications in Critically Injured Patients by Within-Patient Gene Expression Changes: A Longitudinal Clinical Genomics Study

PubMed Central

Leek, Jeffrey T.; Maier, Ronald V.; Tompkins, Ronald G.; Storey, John D.

2011-01-01

Background Trauma is the number one killer of individuals 1–44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition. Methods and Findings We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring ∼400 clinical variables and longitudinally profiling leukocyte gene expression with ∼800 microarrays. Marshall MOF (multiple organ failure) clinical score trajectories were first utilized to organize the patients into five categories of increasingly poor outcomes. We then developed an analysis framework modeling early within-patient expression changes to produce a robust characterization of the genomic response to trauma. A quarter of the genome shows early expression changes associated with longer-term post-injury complications, captured by at least five dynamic co-expression modules of functionally related genes. In particular, early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling pathway were found to strongly associate with longer-term post-injury complications, providing discrimination among patient outcomes from expression changes during the 40–80 h window post-injury. Conclusions The genomic characterization provided here substantially expands the scope by which the molecular response to trauma may be characterized and understood. These results may be instrumental in furthering our understanding of the disease process and identifying potential targets for therapeutic intervention. Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions. Trial Registration ClinicalTrials.gov NCT00257231 Please see later in the article for the Editors' Summary PMID:21931541

Peyronie's Disease: Still a Surgical Disease.

PubMed

Martinez, Daniel; Ercole, Cesar E; Hakky, Tariq S; Kramer, Andrew; Carrion, Rafael

2012-01-01

Peyronie's Disease (PD) remains a challenging and clinically significant morbid condition. Since its first description by François Gigot de la Peyronie, much of the treatment for PD remains nonstandardized. PD is characterized by the formation of fibrous plaques at the level of the tunica albuginea. Clinical manifestations include morphologic changes, such as curvatures and hourglass deformities. Here, we review the common surgical techniques for the management of patients with PD.

DETECTION,QUANTIFICATION AND CHARACTERIZATION OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS IN DRINKING WATER.

EPA Science Inventory

Bacteria belonging to the Mycobacterium avium complex (MAC), including Mycobacterium avium and M. intracellulare, are clinically relevant and cause a myriad of opportunistic infections. Children, the elderly, and persons with previous lung conditions or immune system dysfunction...

Childhood Disintegrative Disorder.

ERIC Educational Resources Information Center

Malhotra, Savita; Gupta, Nitin

1999-01-01

This article reviews what is known about childhood distintegrative disorder (CDD), a clinical syndrome characterized by disintegration of mental functions and regression of acquired language and intellectual functions after a period (usually 3-4 years) of normal development. It reviews the condition's epidemiology, onset and progression,…

Environmental enteric dysfunction is associated with altered bile acid metabolism

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED), a clinically asymptomatic condition characterized by inflammation of the small bowel mucosa, villous atrophy, and increased gut permeability, is common among children in developing countries. Because of abnormal gut mucosa and altered gut microbiome, EED coul...

Use of acute phase proteins for the clinical assessment and management of canine leishmaniosis: general recommendations.

PubMed

Ceron, J J; Pardo-Marin, L; Caldin, M; Furlanello, T; Solano-Gallego, L; Tecles, F; Bernal, L; Baneth, G; Martinez-Subiela, S

2018-06-20

Dogs with canine leishmaniosis (CanL) due to Leishmania infantum can show a wide spectrum of clinical and clinicopathological findings at the time of diagnosis. The aim of this paper is to describe the possible application of acute phase proteins (APPs) for the characterization and management of this disease, based on previously published information on the utility of APPs in CanL and the experience of the authors in using APPs as analytes in the profiling of canine diseases. Dogs diagnosed with L. infantum infection by serology, polymerase chain reaction, cytological or histopathological identification, can be divided into three groups based on their clinical condition at physical examination and their APPs concentrations: Group 1: dogs with no clinical signs on physical examination and APPs in reference range; Group 2: dogs with changes in APPs but no clinical signs on physical examination; Group 3: dogs with clinical signs and changes in APPs. This report describes the main characteristics of each group as well as its association with the clinical classification schemes of CanL. APPs concentration can be a useful clinical tool to characterize and manage CanL.

Stem Cell Sciences plc.

PubMed

Daniels, Sebnem

2006-09-01

Stem Cell Sciences' core objective is to develop safe and effective stem cell-based therapies for currently incurable diseases. In order to achieve this goal, Stem Cell Sciences recognizes the need for multiple technologies and a globally integrated stem cell initiative. The key challenges for the successful application of stem cells in the clinic is the need for a reproducible supply of pure, fully characterized stem cells that have been grown in suitable conditions for use in the clinic.

Peyronie's Disease: Still a Surgical Disease

PubMed Central

Martinez, Daniel; Ercole, Cesar E.; Hakky, Tariq S.; Kramer, Andrew; Carrion, Rafael

2012-01-01

Peyronie's Disease (PD) remains a challenging and clinically significant morbid condition. Since its first description by François Gigot de la Peyronie, much of the treatment for PD remains nonstandardized. PD is characterized by the formation of fibrous plaques at the level of the tunica albuginea. Clinical manifestations include morphologic changes, such as curvatures and hourglass deformities. Here, we review the common surgical techniques for the management of patients with PD. PMID:22956943

Advances in equine computed tomography and use of contrast media.

PubMed

Puchalski, Sarah M

2012-12-01

Advances in equine computed tomography have been made as a result of improvements in software and hardware and an increasing body of knowledge. Contrast media can be administered intravascularly or intrathecally. Contrast media is useful to differentiate between tissues of similar density. Equine computed tomography can be used for many different clinical conditions, including lameness diagnosis, fracture identification and characterization, preoperative planning, and characterization of skull diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

Brainstem encephalitis: etiologies, treatment, and predictors of outcome

PubMed Central

Tan, Ik Lin; Mowry, Ellen M.; Steele, Sonya U.; Pardo, Carlos A.; McArthur, Justin C.; Nath, Avindra

2016-01-01

Brainstem encephalitis (BE) is an uncommon condition. We sought to characterize clinical presentations, etiologies, response to treatment, and predictors of outcome. We performed a retrospective review of non–HIV infected patients diagnosed with BE at Johns Hopkins Hospital (January 1997–April 2010). We characterized clinical and paraclinical features, and used regression models to assess associations with poor outcome. BE was diagnosed in 81 patients. An etiology was identified in 58 of 81 (71.6 %) of cases, most of which were confirmed or probable inflammatory/autoimmune conditions. Of the remaining 23 cases in which a specific diagnosis remained undefined, clinical presentation, CSF, neuroimaging studies, and outcomes were similar to the inflammatory/autoimmune group. Brain biopsy identified a specific diagnosis in 7 of 14 patients (50 %). Fifteen patients (18.5 %) either died or had a poor outcome. In multivariate logistic regression models, a higher CSF protein (per 5 mg/dl, OR = 1.11, 95 % CI: 1.03–1.20), a higher CSF glucose (per 5 mg/dl, OR = 1.36, 95 % CI: 1.09–1.70), and higher serum glucose (per 5 mg/dl, OR = 1.27, 95 % CI: 1.06–1.52) were independently associated with increased odds of poor outcome. Inflammatory and non-infectious conditions accounted for most cases of BE. Higher CSF protein and glucose were independently associated with poor outcome. In immunocompetent patients with BE of undefined etiology despite extensive investigation, a trial of immunosuppressive treatment may be warranted, though deterioration clinically or on magnetic resonance imaging should prompt a brain biopsy. PMID:23749332

Chronobiology of chronic pain: focus on diurnal rhythmicity of neuropathic pain.

PubMed

Gilron, Ian; Ghasemlou, Nader

2014-12-01

Although circadian rhythmicity has long been recognized in various nociceptive pain conditions such as arthritis, diurnal pain patterns in neuropathic conditions have only recently been described. The purpose of this article is to review emerging evidence and discuss future research to further understand this phenomenon. Secondary analyses of neuropathic pain clinical trials demonstrate that pain intensity fluctuations exhibit a distinct diurnal pattern that contrasts that of nociceptive pain conditions. Ongoing preclinical investigations support the phenomenon of circadian pain fluctuations and provide the opportunity to better describe pain chronobiology and to elucidate underlying mechanisms of circadian pain rhythmicity. The observation of clinically relevant diurnal pain variability in neuropathic conditions has important implications for future research and treatment of pain. This is an immature research field, and further investigation is needed to better characterize these patterns in more detail, investigate contributory mechanisms, and to develop therapeutic strategies that exploit this phenomenon.

Automatic analysis of microscopic images of red blood cell aggregates

NASA Astrophysics Data System (ADS)

Menichini, Pablo A.; Larese, Mónica G.; Riquelme, Bibiana D.

2015-06-01

Red blood cell aggregation is one of the most important factors in blood viscosity at stasis or at very low rates of flow. The basic structure of aggregates is a linear array of cell commonly termed as rouleaux. Enhanced or abnormal aggregation is seen in clinical conditions, such as diabetes and hypertension, producing alterations in the microcirculation, some of which can be analyzed through the characterization of aggregated cells. Frequently, image processing and analysis for the characterization of RBC aggregation were done manually or semi-automatically using interactive tools. We propose a system that processes images of RBC aggregation and automatically obtains the characterization and quantification of the different types of RBC aggregates. Present technique could be interesting to perform the adaptation as a routine used in hemorheological and Clinical Biochemistry Laboratories because this automatic method is rapid, efficient and economical, and at the same time independent of the user performing the analysis (repeatability of the analysis).

Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism

DTIC Science & Technology

2012-08-01

system in relation to its evolution, structure and function . New York: CRC Press 1997 American Psychiatric Association. Diagnostic and statistical...Hesslow G, Yeo CH. The functional anatomy of skeletal conditioning. In: Moore JW, Editor. A neuroscientist’s guide to classical conditioning. New ...1995; Selkoe, 2001). Aβ is generated and detected in the endoplasmic reticulum/ Golgi apparatus and endosomal-lysosomal pathway (Cook D.G. et al., 1997

[Aplasia cutis congenita associated with epidermolysis bullosa].

PubMed

Muñoz-Guerrero, Félix; Muñoz-Solís, Adrián Antonio; Ornelas-Aguirre, José Manuel

2017-12-01

Aplasia cutis congenita (ACC) is a skin condition of rare presentation, this disease is characterized by absence of skin at birth and associated with facial, skin and bone skull deformities. The diagnosis is mainly clinical. Male 5 days after birth, unique product of primigravida mother and no family history of relevance. Physical examination revealed bilateral and symmetrical skin defects of both lower extremities, the disease is characterized by skin fragility, scabs, and coated pseudomembrane ulcers, decreased interdigital space between toes of the left foot, retraction of the foot and genu varum. It was handled with allograft of epidermis cultured in vitro, general wound care and clinical follow-up. ACC associated with epidermolysis bullosa is one of the rarer forms of presentation. It is necessary to rule out other skin diseases. Clinical management is recommended with biological or synthetic skin cover, infection prevention, early treatment of complications and clinical follow. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Identification and Clinical Characterization of Children with Benign Ethnic Neutropenia

PubMed Central

Ortiz, Michael V.; Meier, Emily R.; Hsieh, Matthew M.

2016-01-01

Benign ethnic neutropenia (BEN) is an asymptomatic condition reported in adults of African and Middle Eastern descent. The clinical description in children is currently lacking. In our urban outpatient pediatric hematology clinic, the median neutrophil count of children with BEN was lower than previous reports in adults at 893 × 106 cells/L, but increased with older age. There was an equal male to female ratio and 24% of our BEN children reported ethnicities other than African or Middle Eastern. Children with BEN had a clinical course comparable to other healthy children including otherwise normal blood counts, except for mild anemia. PMID:26925714

Overview of Classical Swine Fever (Hog Cholera, Classical Swine fever)

USDA-ARS?s Scientific Manuscript database

Classical swine fever is a contagious often fatal disease of pigs clinically characterized by high body temperature, lethargy, yellowish diarrhea, vomits and purple skin discoloration of ears, lower abdomen and legs. It was first described in the early 19th century in the USA. Later, a condition i...

Late Onset Presentation of Hori’s Nevus in and Elderly Caucasian Female

DTIC Science & Technology

2017-10-26

Acquired Bilateral Nevus of Ota-like Macules (Hori’s Nevus) are characterized clinically by bilateral blue-gray to gray-brown macules or patches most...melanocytoses, this condition is more common in Asians and is usually congenital or appears during childhood or adolescence.

Pathogenesis, imaging and clinical characteristics of CF and non-CF bronchiectasis.

PubMed

Schäfer, Jürgen; Griese, Matthias; Chandrasekaran, Ravishankar; Chotirmall, Sanjay H; Hartl, Dominik

2018-05-22

Bronchiectasis is a common feature of severe inherited and acquired pulmonary disease conditions. Among inherited diseases, cystic fibrosis (CF) is the major disorder associated with bronchiectasis, while acquired conditions frequently featuring bronchiectasis include post-infective bronchiectasis and chronic obstructive pulmonary disease (COPD). Mechanistically, bronchiectasis is driven by a complex interplay of inflammation and infection with neutrophilic inflammation playing a predominant role. The clinical characterization and management of bronchiectasis should involve a precise diagnostic workup, tailored therapeutic strategies and pulmonary imaging that has become an essential tool for the diagnosis and follow-up of bronchiectasis. Prospective future studies are required to optimize the diagnostic and therapeutic management of bronchiectasis, particularly in heterogeneous non-CF bronchiectasis populations.

Hypertrophic Osteoarthropathy: Clinical and Imaging Features.

PubMed

Yap, Felix Y; Skalski, Matthew R; Patel, Dakshesh B; Schein, Aaron J; White, Eric A; Tomasian, Anderanik; Masih, Sulabha; Matcuk, George R

2017-01-01

Hypertrophic osteoarthropathy (HOA) is a medical condition characterized by abnormal proliferation of skin and periosteal tissues involving the extremities and characterized by three clinical features: digital clubbing (also termed Hippocratic fingers), periostosis of tubular bones, and synovial effusions. HOA can be a primary entity, known as pachydermoperiostosis, or can be secondary to extraskeletal conditions, with different prognoses and management implications for each. There is a high association between secondary HOA and malignancy, especially non-small cell lung cancer. In such cases, it can be considered a form of paraneoplastic syndrome. The most prevalent secondary causes of HOA are pulmonary in origin, which is why this condition was formerly referred to as hypertrophic pulmonary osteoarthropathy. HOA can also be associated with pleural, mediastinal, and cardiovascular causes, as well as extrathoracic conditions such as gastrointestinal tumors and infections, cirrhosis, and inflammatory bowel disease. Although the skeletal manifestations of HOA are most commonly detected with radiography, abnormalities can also be identified with other modalities such as computed tomography, magnetic resonance imaging, and bone scintigraphy. The authors summarize the pathogenesis, classification, causes, and symptoms and signs of HOA, including the genetics underlying the primary form (pachydermoperiostosis); describe key findings of HOA found at various imaging modalities, with examples of underlying causative conditions; and discuss features differentiating HOA from other causes of multifocal periostitis, such as thyroid acropachy, hypervitaminosis A, chronic venous insufficiency, voriconazole-induced periostitis, progressive diaphyseal dysplasia, and neoplastic causes such as lymphoma. © RSNA, 2016.

Reticular telangiectatic erythema: case report and literature review.

PubMed

Beutler, Bryce D; Cohen, Philip R

2015-01-01

Reticular telangiectatic erythema is a benign cutaneous reaction that may occur in patients who have received a subcutaneous implantable cardioverter-defibrillator. Reticular telangiectatic erythema is characterized by asymptomatic telangiectasias, blanchable erythematous patches, or both overlying and/or adjacent to the subcutaneous implantable cardioverter-defibrillator. We describe a man who developed reticular telangiectatic erythema after receiving a subcutaneous implantable cardioverter-defibrillator and review the salient features of this condition. We also summarize the conditions that can mimic reticular telangiectatic erythema. The features of a man with reticular telangiectatic erythema are presented and the literature on reticular telangiectatic erythema is reviewed. Our patient developed reticular telangiectatic erythema within one month of subcutaneous implantable cardioverter-defibrillator insertion. The subcutaneous manifestations were asymptomatic. The patient concurred to have periodic clinical follow up and his condition will be monitored for any changes. Reticular telangiectatic erythema is a benign condition characterized by the development of erythema, telangiectasia, or both following insertion of a subcutaneous implantable cardioverter-defibrillator. Other subcutaneous implantable cardioverter-defibrillator-related side effects, such as pressure dermatitis and contact dermatitis, can mimic the condition. Reticular telangiectatic erythema can also be observed following insertion of other devices or, rarely, in the absence of inserted devices. Local microcirculatory changes and subcutaneous implantable cardioverter-defibrillator-related obstruction of blood flow have been suggested as possible mechanisms of pathogenesis. The diagnosis can usually be established by clinical presentation. Therefore, patch testing can usually be omitted. Reticular telangiectatic erythema is typically asymptomatic and thus removal of the device is not required.

Dry mouth as an initial sign of food-borne botulism: a case report and review of the literature.

PubMed

Manfredi, Maddalena; Scoditti, Umberto; Angelini, Monica; de Giampaulis, Piero; Borrini, Bianca Maria; Macaluso, Guido Maria; Pavesi, Giovanni; Vescovi, Paolo

2011-04-01

Botulism is a rare neuroparalytic disease caused by a potent neurotoxin produced by Clostridium botulinum. There are different clinical types of botulism. Early diagnosis of the condition is essential for effective treatment. We report a case of food-borne botulism in identical twins characterized by severe initial oral involvement and a review of the literature about the condition. Copyright © 2011 Mosby, Inc. All rights reserved.

Altered cerebral blood flow velocity features in fibromyalgia patients in resting-state conditions

PubMed Central

Rodríguez, Alejandro; Tembl, José; Mesa-Gresa, Patricia; Muñoz, Miguel Ángel; Montoya, Pedro

2017-01-01

The aim of this study is to characterize in resting-state conditions the cerebral blood flow velocity (CBFV) signals of fibromyalgia patients. The anterior and middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and 15 healthy women were monitored using Transcranial Doppler (TCD) during a 5-minute eyes-closed resting period. Several signal processing methods based on time, information theory, frequency and time-frequency analyses were used in order to extract different features to characterize the CBFV signals in the different vessels. Main results indicated that, in comparison with control subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV and a different distribution of the power spectral density. In addition, it has been observed that complexity and spectral features show correlations with clinical pain parameters and emotional factors. The characterization features were used in a lineal model to discriminate between fibromyalgia patients and healthy controls, providing a high accuracy. These findings indicate that CBFV signals, specifically their complexity and spectral characteristics, contain information that may be relevant for the assessment of fibromyalgia patients in resting-state conditions. PMID:28700720

Altered cerebral blood flow velocity features in fibromyalgia patients in resting-state conditions.

PubMed

Rodríguez, Alejandro; Tembl, José; Mesa-Gresa, Patricia; Muñoz, Miguel Ángel; Montoya, Pedro; Rey, Beatriz

2017-01-01

The aim of this study is to characterize in resting-state conditions the cerebral blood flow velocity (CBFV) signals of fibromyalgia patients. The anterior and middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and 15 healthy women were monitored using Transcranial Doppler (TCD) during a 5-minute eyes-closed resting period. Several signal processing methods based on time, information theory, frequency and time-frequency analyses were used in order to extract different features to characterize the CBFV signals in the different vessels. Main results indicated that, in comparison with control subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV and a different distribution of the power spectral density. In addition, it has been observed that complexity and spectral features show correlations with clinical pain parameters and emotional factors. The characterization features were used in a lineal model to discriminate between fibromyalgia patients and healthy controls, providing a high accuracy. These findings indicate that CBFV signals, specifically their complexity and spectral characteristics, contain information that may be relevant for the assessment of fibromyalgia patients in resting-state conditions.

Pediatric misophonia with comorbid obsessive-compulsive spectrum disorders.

PubMed

Webber, Troy A; Johnson, Patricia L; Storch, Eric A

2014-01-01

Misophonia is a potentially debilitating condition characterized by increased sensitivity to specific sounds, which cause subsequent behavioral and emotional responses. The nature, clinical phenomenology and etiology of misophonia remain unclear, and misophonic clinical presentations are not currently accounted for by existing psychiatric or audiological disorders. We present a case of pediatric misophonia in the context of comorbid obsessive-compulsive disorder and Tourette's syndrome. Given the interrelationships among obsessive-compulsive spectrum disorders and misophonia, these disorders may share underlying pathophysiology, particularly within the dopaminergic and serotonergic neural systems. Clinical (i.e., treatment) and theoretical implications are discussed. Published by Elsevier Inc.

Asthma and Fungus: Role in Allergic Bronchopulmonary Aspergillosis (ABPA) and Other Conditions.

PubMed

Singh, Meenu; Paul, Nandini; Singh, Shreya; Nayak, Gyan Ranjan

2018-03-17

Asthma is an allergic, respiratory disorder characterized by hyper responsiveness of the airway to external stimuli. Considerable research is currently being directed towards understanding the role of environmental and genetic factors contributing to the development of asthma and its severity. Recent years have seen a substantial rise in evidence linking fungi to asthma. Few major clinical conditions associated with fungal sensitization and hypersensitive immune response are Allergic bronchopulmonary aspergillosis (ABPA), Allergic fungal rhinosinusitis (AFRS) and Severe asthma with fungal sensitization (SAFS). The most common fungi implicated in these conditions belong to genus Aspergillus, although an association with several other fungi has been described. In this review authors discuss the varying clinical characteristics of fungus induced respiratory complications in individuals with asthma. They also highlight the epidemiology of these conditions including their prevalence in children and their fungal etiological profile. Laboratory diagnostic methods and clinical case definitions have also been discussed. Future studies evaluating the role of fungal exposure and susceptibility to asthma are required. Till date there are no guidelines for the diagnosis and treatment of ABPA in pediatric population, thus it is also imperative to establish validated clinical definitions of fungal allergic manifestations in pediatric patients with asthma to fully understand this complex interaction.

Comparative study of sickle cell anemia and hemoglobin SC disease: clinical characterization, laboratory biomarkers and genetic profiles.

PubMed

Aleluia, Milena Magalhães; Fonseca, Teresa Cristina Cardoso; Souza, Regiana Quinto; Neves, Fábia Idalina; da Guarda, Caroline Conceição; Santiago, Rayra Pereira; Cunha, Bruna Laís Almeida; Figueiredo, Camylla Villas Boas; Santana, Sânzio Silva; da Paz, Silvana Sousa; Ferreira, Júnia Raquel Dutra; Cerqueira, Bruno Antônio Veloso; Gonçalves, Marilda de Souza

2017-01-01

In this study, we evaluate the association of different clinical profiles, laboratory and genetic biomarkers in patients with sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in attempt to characterize the sickle cell disease (SCD) genotypes. We conducted a cross-sectional study from 2013 to 2014 in 200 SCD individuals (141 with SCA; 59 with HbSC) and analyzed demographic data to characterize the study population. In addition, we determined the association of hematological, biochemical and genetic markers including the β S -globin gene haplotypes and the 3.7 Kb deletion of α-thalassemia (-α 3.7Kb -thal), as well as the occurrence of clinical events in both SCD genotypes. Laboratory parameters showed a hemolytic profile associated with endothelial dysfunction in SCA individuals; however, the HbSC genotype was more associated with increased blood viscosity and inflammatory conditions. The BEN haplotype was the most frequently observed and was associated with elevated fetal hemoglobin (HbF) and low S hemoglobin (HbS). The -α 3.7Kb -thal prevalence was 0.09 (9%), and it was associated with elevated hemoglobin and hematocrit concentrations. Clinical events were more frequent in SCA patients. Our data emphasize the differences between SCA and HbSC patients based on laboratory parameters and the clinical and genetic profile of both genotypes.

Genetic disorders with heterotopic ossificans

PubMed Central

Sankar, Ruthiramurthy; Gowrishankar, Kalpana; Viswanathan, Saraswati

2015-01-01

Fibrodysplasia ossificans progressiva (FOP) and progressive ossific heteroplasia (POH) are rare genetic disorders characterized by heterotopic bone formation leading to progressive loss of mobility and function. We report three cases of these rare disorders (two cases of FOP and one case of POH), which were clinically diagnosed and underwent genetic analysis. The aim of this report is to highlight the clinical features and the differences between these two conditions. We would also like to emphasize on the morbidity that can arise from unnecessary invasive investigations for diagnostic purposes. PMID:26015640

[Non-autoimmune thyroiditis].

PubMed

Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D

2014-01-01

The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

Milestones of Lynch syndrome: 1895-2015.

PubMed

Lynch, Henry T; Snyder, Carrie L; Shaw, Trudy G; Heinen, Christopher D; Hitchins, Megan P

2015-03-01

Lynch syndrome, which is now recognized as the most common hereditary colorectal cancer condition, is characterized by the predisposition to a spectrum of cancers, primarily colorectal cancer and endometrial cancer. We chronicle over a century of discoveries that revolutionized the diagnosis and clinical management of Lynch syndrome, beginning in 1895 with Warthin's observations of familial cancer clusters, through the clinical era led by Lynch and the genetic era heralded by the discovery of causative mutations in mismatch repair (MMR) genes, to ongoing challenges.

Type I hereditary punctate keratoderma.

PubMed

Asadi, Arash K

2003-10-01

A 75-year-old man with a history of prostatic carcinoma and atypical fibroxanthoma reports a long-standing history of 1-2 mm depressed, hyperkeratotic papules on the palms. His mother suffered a similar condition. Histologically, the papules demonstrated hyperkeratosis, without columns of parakeratosis. A diagnosis of type I hereditary punctate keratoderma (Buschke-Fisher-Brauer disease) was made. This condition, which is classified as one of the three hereditary forms of punctate palmoplantar keratoderma, is an autosomal-dominant condition with variable penetrance. It is characterized clinically by multiple, tiny, punctate keratoses of the palms and soles. Affected individuals appear to be at increased risk of developing malignant conditions.

Exposure to Non-Extreme Solar UV Daylight: Spectral Characterization, Effects on Skin and Photoprotection

PubMed Central

Marionnet, Claire; Tricaud, Caroline; Bernerd, Françoise

2014-01-01

The link between chronic sun exposure of human skin and harmful clinical consequences such as photo-aging and skin cancers is now indisputable. These effects are mostly due to ultraviolet (UV) rays (UVA, 320–400 nm and UVB, 280–320 nm). The UVA/UVB ratio can vary with latitude, season, hour, meteorology and ozone layer, leading to different exposure conditions. Zenithal sun exposure (for example on a beach around noon under a clear sky) can rapidly induce visible and well-characterized clinical consequences such as sunburn, predominantly induced by UVB. However, a limited part of the global population is exposed daily to such intense irradiance and until recently little attention has been paid to solar exposure that does not induce any short term clinical impact. This paper will review different studies on non-extreme daily UV exposures with: (1) the characterization and the definition of the standard UV daylight and its simulation in the laboratory; (2) description of the biological and clinical effects of such UV exposure in an in vitro reconstructed human skin model and in human skin in vivo, emphasizing the contribution of UVA rays and (3) analysis of photoprotection approaches dedicated to prevent the harmful impact of such UV exposure. PMID:25546388

Exposure to non-extreme solar UV daylight: spectral characterization, effects on skin and photoprotection.

PubMed

Marionnet, Claire; Tricaud, Caroline; Bernerd, Françoise

2014-12-23

The link between chronic sun exposure of human skin and harmful clinical consequences such as photo-aging and skin cancers is now indisputable. These effects are mostly due to ultraviolet (UV) rays (UVA, 320-400 nm and UVB, 280-320 nm). The UVA/UVB ratio can vary with latitude, season, hour, meteorology and ozone layer, leading to different exposure conditions. Zenithal sun exposure (for example on a beach around noon under a clear sky) can rapidly induce visible and well-characterized clinical consequences such as sunburn, predominantly induced by UVB. However, a limited part of the global population is exposed daily to such intense irradiance and until recently little attention has been paid to solar exposure that does not induce any short term clinical impact. This paper will review different studies on non-extreme daily UV exposures with: (1) the characterization and the definition of the standard UV daylight and its simulation in the laboratory; (2) description of the biological and clinical effects of such UV exposure in an in vitro reconstructed human skin model and in human skin in vivo, emphasizing the contribution of UVA rays and (3) analysis of photoprotection approaches dedicated to prevent the harmful impact of such UV exposure.

Anterior ankle impingement syndromes.

PubMed

Umans, Hilary R; Cerezal, Luiz

2008-06-01

Ankle impingement syndromes are painful conditions that may complicate ankle trauma and are characterized by chronic, progressive pain, swelling, and limitation of movement. These disorders are subclassified according to anatomical location about the tibiotalar joint. This article reviews the various forms of anterior ankle impingement, detailing the unique clinical features, anatomical considerations, pathoetiology, and imaging findings for each.

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.

Quantitative characteristics of the foot-and-mouth disease carrier state under natural conditions in India

USDA-ARS?s Scientific Manuscript database

The goal of the current study was to characterize serological and virological parameters of the foot-and-mouth disease (FMD) carrier state at two farms in Nainital District, Uttarakhand State in northern India. Despite previous vaccination of cattle in these herds, clinical signs of FMD occurred in ...

Fibromyalgia and chronic fatigue syndrome in children.

PubMed

Itoh, Yasuhiko; Shigemori, Tomoko; Igarashi, Tohru; Fukunaga, Yoshitaka

2012-04-01

Fibromyalgia (FM) is characterized by widespread persistent pain and the presence of multiple discrete tender points. Chronic fatigue syndrome (CFS) is a syndrome characterized by debilitating fatigue associated with a variable number of non-specific complaints. Because neither condition had necessarily been recognized in children until recently, those patients have been treated as having school refusal without being diagnosed as having either syndrome. There is a considerable overlap of clinical symptoms between these two syndromes. It is therefore controversial as to whether these syndromes have the same pathogenesis or not. The aim of the present study was to clarify the relationship between these syndromes in children. Fifteen patients with FM and 21 patients with CFS were investigated both clinically and immunologically. Immunological assessments included thorough analysis of autoantibodies using several techniques. Anti-nuclear antibody titers were higher and the prevalence of anti-Sa antibody was far more frequent in CFS patients than in FM patients. CFS and FM are different from each other at least in childhood, from an immunological aspect, although some patients could have both conditions. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

β-Thalassemia intermedia: a comprehensive overview and novel approaches.

PubMed

Asadov, Chingiz; Alimirzoeva, Zohra; Mammadova, Tahira; Aliyeva, Gunay; Gafarova, Shahla; Mammadov, Jeyhun

2018-01-29

β-Thalassemia intermedia is a clinical condition of intermediate gravity between β-thalassemia minor, the asymptomatic carrier, and β-thalassemia major, the transfusion-dependent severe anemia. It is characterized by a significant clinical polymorphism, which is attributable to its genetic heterogeneity. Ineffective erythropoiesis, chronic anemia, and iron overload contribute to the clinical complications of thalassemia intermedia through stepwise pathophysiological mechanisms. These complications, including splenomegaly, extramedullary erythropoiesis, iron accumulation, leg ulcers, thrombophilia, and bone abnormalities can be managed via fetal hemoglobin induction, occasional transfusions, chelation, and in some cases, stem cell transplantation. Given its clinical diversity, thalassemia intermedia patients require tailored approaches to therapy. Here we present an overview and novel approaches to the genetic basis, pathophysiological mechanisms, clinical complications, and optimal management of thalassemia intermedia.

PubMed

Kelle, Bayram; Yıldız, Fatih; Paydas, Semra; Bagır, Emine Kılıc; Ergin, Melek; Kozanoglu, Erkan

2014-12-23

Hypertrophic osteoarthropathy (HOA) is a condition characterized by arthralgia/arthritis, clubbing, and periosteal reaction. Primary form of HOA is observed at early ages of life and is hereditary in nature. Secondary HOA is more frequently seen in clinical setting and occurs as a result of various disorders including inflammatory and malignant diseases. Regression in HOA may be seen after the treatment of underlying condition. In this report, we presented a case of HOA coexisted with myelofibrosis and reviewed the current literature. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Dyke-Davidoff-Masson syndrome: case report of fetal unilateral ventriculomegaly and hypoplastic left middle cerebral artery.

PubMed

Piro, Ettore; Piccione, Maria; Marrone, Gianluca; Giuffrè, Mario; Corsello, Giovanni

2013-05-14

Prenatal ultrasonographic detection of unilateral cerebral ventriculomegaly arises suspicion of pathological condition related to cerebrospinal fluid flow obstruction or cerebral parenchimal pathology. Dyke-Davidoff-Masson syndrome is a rare condition characterized by cerebral hemiatrophy, calvarial thickening, skull and facial asymmetry, contralateral hemiparesis, cognitive impairment and seizures. Congenital and acquired types are recognized and have been described, mainly in late childhood, adolescence and adult ages. We describe a female infant with prenatal diagnosis of unilateral left ventriculomegaly in which early brain MRI and contrast enhanced-MRI angiography, showed cerebral left hemiatrophy associated with reduced caliber of the left middle cerebral artery revealing the characteristic findings of the Dyke-Davidoff-Masson syndrome. Prenatal imaging, cerebral vascular anomaly responsible for the cerebral hemiatrophy and the early clinical evolution have never been described before in such a young child and complete the acquired clinical descriptions in older children. Differential diagnosis, genetic investigations, neurophysiologic assessments, short term clinical and developmental follow up are described. Dyke-Davidoff-Masson syndrome must be ruled out in differential diagnosis of fetal unilateral ventriculomegaly. Early clinical assessment, differential diagnosis and cerebral imaging including cerebral MRI angiography allow the clinicians to diagnose also in early infancy this rare condition.

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.

Papular, profuse, and precocious keratosis pilaris.

PubMed

Castela, Emeline; Chiaverini, Christine; Boralevi, Franck; Hugues, Rosalind; Lacour, Jean Philippe

2012-01-01

Keratosis pilaris (KP) is a frequent and benign condition in children characterized by the presence of rough, follicular papules and varying degrees of erythema. Different variants have been described, including simple KP and red KP. Between September 2007 and October 2010, 11 children with profuse and precocious KP seen at the department of pediatric dermatology were included. They defined an underemphasized clinical variant of childhood KP: the papular, profuse, and precocious KP characterized by early age of onset (<18 mos), extensive involvement of the limbs and cheeks, and papular nature of lesions. No clinical association has been found. The main complication was episodes of folliculitis. Diagnosis was delayed for all patients. Treatment is difficult, but association between emollient and keratolytic agents can provide some help. © 2011 Wiley Periodicals, Inc.

Plasma Cell Gingivitis: An Occasional Case Report.

PubMed

Mishra, M B; Sharma, Swati; Sharma, Alok

2015-01-01

Plasma cell gingivitis, an infrequently observed oral condition, has been clinically characterized by diffuse gingival enlargement, erythema and sometimes desquamation. These lesions are usually asymptomatic, but invariably the patient will complain of a burning sensation in the gingiva and bleeding from the mouth. The diagnosis requires hematological screening in addition to clinical and histopathological examinations. This case report outlines one such case of plasma cell gingivitis in a 15-year-old female caused by use of an herbal, homemade toothpowder. The case presented here highlights the adverse effects and irrational use of herbal agents in dentifrices. At the same time, it emphasizes the need for comprehensive history taking, careful clinical examination and appropriate diagnostic tests in order to arrive at a definitive diagnosis and treatment plan for gingival conditions that are refractory to conventional therapy and to exclude certain malignancies and oral manifestations of systemic diseases.

Depression-dementia medius: between depression and the manifestation of dementia symptoms.

PubMed

Kobayashi, Toshiyuki; Kato, Satoshi

2011-09-01

Depression and dementia, among the most common conditions in clinical practice, sometimes coexist, sometimes succeed each other, and often confuse clinicians. In the present paper, the clinical concept of 'depression-dementia medius' (which includes pseudodementia and depression in Alzheimer's disease as exemplars) is proposed, in reference to Janet's concept of psychological tension. Because psychosomatically complex human lives are always in a state of dynamic equilibrium, it seems sensible to propose that pseudodementia and depression in Alzheimer's disease are located within a spectrum extending from depression without dementia symptoms to dementia without depression. From the Janetian viewpoint, pseudodementia is regarded as uncovered latent dementia as a result of reduced psychological tension. Dementia is more than a fixed progressive condition under this view, and is a manifestation of dynamic mental activities. Characterizing these entities through perspectives such as psychological tension may yield deep insights in clinical practice. © 2011 The Authors. Psychogeriatrics © 2011 Japanese Psychogeriatric Society.

An overview of translationally informed treatments for PTSD: animal models of Pavlovian fear conditioning to human clinical trials

PubMed Central

Bowers, Mallory E.; Ressler, Kerry J.

2015-01-01

Posttraumatic stress disorder (PTSD) manifests after exposure to a traumatic event and is characterized by avoidance/numbing, intrusive symptoms and flashbacks, mood and cognitive disruptions, and hyperarousal/reactivity symptoms. These symptoms reflect dysregulation of the fear system likely caused by poor fear inhibition/extinction, increased generalization, and/or enhanced consolidation or acquisition of fear. These phenotypes can be modeled in animal subjects using Pavlovian fear conditioning, allowing investigation of the underlying neurobiology of normative and pathological fear. Pre-clinical studies reveal a number of neurotransmitter systems and circuits critical for aversive learning and memory, which have informed the development of therapies used in human clinical trials. In this review, we discuss the evidence for a number of established and emerging pharmacotherapies and device-based treatments for PTSD that have been developed via a bench to bedside translational model. PMID:26238379

Current research on pycnodysostosis.

PubMed

Turan, Serap

2014-08-01

Pycnodysostosis is a rare autosomal recessive disorder caused by an inactivating mutation in cathepsin K (CTSK) and characterized by dysmorphic facial features, a short stature, acroosteolysis, osteosclerosis with increased bone fragility, and delayed closure of cranial sutures. Patients usually present with short stature or dysmorphic features the Pediatric Endocrinology or Genetics clinics, with atypical fractures to the orthopedics clinics or hematological abnormalities to the hematology clinics. However, under-diagnosis or misdiagnosis of this condition is a major issue. Pycnodysostosis is not a life threatening condition, but craniosynostosis, frequent fractures, respiratory-sleep problems, and dental problems may cause significant morbidity. Although no specific treatment for this disorder has been described, patients should be followed for complications and treated accordingly. A specific treatment for the disorder must be established in the future to prevent complications and improve quality of life for patients in the current era of advanced molecular research.

Noonan syndrome: clinical features, diagnosis, and management guidelines.

PubMed

Romano, Alicia A; Allanson, Judith E; Dahlgren, Jovanna; Gelb, Bruce D; Hall, Bryan; Pierpont, Mary Ella; Roberts, Amy E; Robinson, Wanda; Takemoto, Clifford M; Noonan, Jacqueline A

2010-10-01

Noonan syndrome (NS) is a common, clinically and genetically heterogeneous condition characterized by distinctive facial features, short stature, chest deformity, congenital heart disease, and other comorbidities. Gene mutations identified in individuals with the NS phenotype are involved in the Ras/MAPK (mitogen-activated protein kinase) signal transduction pathway and currently explain ∼61% of NS cases. Thus, NS frequently remains a clinical diagnosis. Because of the variability in presentation and the need for multidisciplinary care, it is essential that the condition be identified and managed comprehensively. The Noonan Syndrome Support Group (NSSG) is a nonprofit organization committed to providing support, current information, and understanding to those affected by NS. The NSSG convened a conference of health care providers, all involved in various aspects of NS, to develop these guidelines for use by pediatricians in the diagnosis and management of individuals with NS and to provide updated genetic findings.

Torsion of Abdominal Organs in Sows: A Report of 36 Cases

PubMed Central

Morin, M.; Sauvageau, R.; Phaneuf, J.-B.; Teuscher, E.; Beauregard, M.; Lagacé, A.

1984-01-01

Necropsy records of 36 sows with torsion of abdominal organs involving individually the stomach, the spleen, a liver lobe or the intestine were reviewed for the years 1970 to 1983, and the age, the clinical signs and the gross lesions were recorded. These acute abdominal accidents were characterized clinically by sudden death. Dry sows from large breeding units were affected. Twenty-six cases were diagnosed between January 1981 and December 1983 while only ten cases had been seen between 1970 and 1980. Gastric torsion was the most common condition (40% of the cases) and the other three conditions were equally represented (20% each). Management practises that could be responsible for the apparent increase in occurrence of this problem are discussed. PMID:17422483

Effects of OEF/OIF-Related Physical and Emotional Co-Morbidities on Associative Learning: Concurrent Delay and Trace Eyeblink Classical Conditioning

PubMed Central

McGlinchey, Regina E.; Fortier, Catherine B.; Venne, Jonathan R.; Maksimovskiy, Arkadiy L.; Milberg, William P.

2014-01-01

This study examined the performance of veterans and active duty personnel who served in Operation Enduring Freedom and/or Operation Iraqi Freedom (OEF/OIF) on a basic associative learning task. Eighty-eight individuals participated in this study. All received a comprehensive clinical evaluation to determine the presence and severity of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI). The eyeblink conditioning task was composed of randomly intermixed delay and trace conditioned stimulus (CS) and unconditioned stimulus (US) pairs (acquisition) followed by a series of CS only trials (extinction). Results revealed that those with a clinical diagnosis of PTSD or a diagnosis of PTSD with comorbid mTBI acquired delay and trace conditioned responses (CRs) to levels and at rates similar to a deployed control group, thus suggesting intact basic associative learning. Differential extinction impairment was observed in the two clinical groups. Acquisition of CRs for both delay and trace conditioning, as well as extinction of trace CRs, was associated with alcoholic behavior across all participants. These findings help characterize the learning and memory function of individuals with PTSD and mTBI from OEF/OIF and raise the alarming possibility that the use of alcohol in this group may lead to more significant cognitive dysfunction. PMID:24625622

Profile of Travelers With Preexisting Medical Conditions Attending a Specialist Travel Medicine Clinic in Ireland.

PubMed

Han, Calvin Teo Jia; Flaherty, Gerard

2015-01-01

Patients with complex medical comorbidities travel for protracted periods to remote destinations, often with limited access to medical care. Few descriptions are available of their preexisting health burden. This study aimed to characterize preexisting medical conditions and medications of travelers seeking pre-travel health advice at a specialized travel medicine clinic. Records of travelers attending the Galway Tropical Medical Bureau clinic between 2008 and 2014 were examined and information relating to past medical history was entered into a database. Data were recorded only where the traveler had a documented medical history and/or was taking medications. Of the 4,817 records available, 56% had a documented medical history and 24% listed medications. The majority of travelers with preexisting conditions were female. The mean age of the cohort was 31.68 years. The mean period remaining before the planned trip was 40 days. Southeast Asia was the most popular single destination, and 17% of travelers with medical conditions were traveling alone. The most frequently reported conditions were allergies (20%), insect bite sensitivity (15%), asthma (11%), psychiatric conditions (4%), and hypertension (3%). Of the 30 diabetic travelers, 14 required insulin; 4.5% of travelers were taking immunosuppressant drugs, including corticosteroids. Half of the female travelers were taking the oral contraceptive pill while 11 travelers were pregnant at the time of their pre-travel consultation. This study provides an insight into the medical profile of travelers attending a travel health clinic. The diverse range of diseases reported highlights the importance of educating physicians and nurses about the specific travel health risks associated with particular conditions. Knowledge of the effects of travel on underlying medical conditions will inform the pre-travel health consultation. © 2015 International Society of Travel Medicine.

Mycobiome in the Lower Respiratory Tract – A Clinical Perspective

PubMed Central

Krause, Robert; Moissl-Eichinger, Christine; Halwachs, Bettina; Gorkiewicz, Gregor; Berg, Gabriele; Valentin, Thomas; Prattes, Jürgen; Högenauer, Christoph; Zollner-Schwetz, Ines

2017-01-01

Recently the paradigm that the healthy lung is sterile was challenged and it is now believed that the lungs harbor a diverse microbiota also contributing to the pathogenesis of various diseases. Most of the research studies targeting the respiratory microbiome have focused on bacteria and their impact on lung health and lung diseases. Recently, also the mycobiome has gained attention. Lower respiratory tract (LRT) diseases (e.g., cystic fibrosis) and other diseases or conditions (e.g., HIV infection, lung transplantation, and treatment at intensive care units) have been investigated with regard to possible involvement of mycobiome in development or progression of diseases. It has been shown that diversities of mycobiome in the LRT vary in different populations and conditions. It has been proposed that the mycobiome diversity associated with LRT can vary with different stages of diseases. Overall, Candida was the dominant fungal genus in LRT samples. In this review, we summarize the recent findings regarding the human LRT mycobiome from a clinical perspective focussing on characterization of investigated patient groups and healthy controls as well as sampling techniques. From these data, clinical implications for further studies or routine practice are drawn. To obtain clinically relevant answers efforts should be enhanced to collect well characterized and described patient groups as well as healthy individuals for comparative data analysis and to apply thorough sampling techniques. We need to proceed with elucidation of the role of mycobiota in healthy LRT and LRT diseases to hopefully improve patient care. PMID:28119685

Mycobiome in the Lower Respiratory Tract - A Clinical Perspective.

PubMed

Krause, Robert; Moissl-Eichinger, Christine; Halwachs, Bettina; Gorkiewicz, Gregor; Berg, Gabriele; Valentin, Thomas; Prattes, Jürgen; Högenauer, Christoph; Zollner-Schwetz, Ines

2016-01-01

Recently the paradigm that the healthy lung is sterile was challenged and it is now believed that the lungs harbor a diverse microbiota also contributing to the pathogenesis of various diseases. Most of the research studies targeting the respiratory microbiome have focused on bacteria and their impact on lung health and lung diseases. Recently, also the mycobiome has gained attention. Lower respiratory tract (LRT) diseases (e.g., cystic fibrosis) and other diseases or conditions (e.g., HIV infection, lung transplantation, and treatment at intensive care units) have been investigated with regard to possible involvement of mycobiome in development or progression of diseases. It has been shown that diversities of mycobiome in the LRT vary in different populations and conditions. It has been proposed that the mycobiome diversity associated with LRT can vary with different stages of diseases. Overall, Candida was the dominant fungal genus in LRT samples. In this review, we summarize the recent findings regarding the human LRT mycobiome from a clinical perspective focussing on characterization of investigated patient groups and healthy controls as well as sampling techniques. From these data, clinical implications for further studies or routine practice are drawn. To obtain clinically relevant answers efforts should be enhanced to collect well characterized and described patient groups as well as healthy individuals for comparative data analysis and to apply thorough sampling techniques. We need to proceed with elucidation of the role of mycobiota in healthy LRT and LRT diseases to hopefully improve patient care.

Characterization and management of exfoliative cheilitis: a single-center experience.

PubMed

Almazrooa, Soulafa A; Woo, Sook-Bin; Mawardi, Hani; Treister, Nathaniel

2013-12-01

Exfoliative cheilitis (EC) is a rare inflammatory condition affecting the vermilion of the lips and characterized by production of a thick keratin scale. Given the limited available data, the approach to optimal management of EC remains unclear. The objective of this retrospective study was to characterize the clinical features, management, and outcomes of a series of patients with EC. Fifteen patients with a median age of 59 years and a female-to-male ratio of 2:1 were diagnosed with EC from 2000 to 2010. Parafunctional lip licking (53%) and a history of psychiatric disorders (40%) were common. Ten patients (66%) returned for follow-up, with an overall response rate (partial or complete) of 80% at a median of 2 months, most frequently associated with the use of topical calcineurin inhibitors or moisturizing agents. Management of EC with topical calcineurin inhibitors and moisturizing agents is associated with clinical improvement, but prospective trials are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Reticular telangiectatic erythema: case report and literature review

PubMed Central

Beutler, Bryce D.; Cohen, Philip R.

2015-01-01

Background: Reticular telangiectatic erythema is a benign cutaneous reaction that may occur in patients who have received a subcutaneous implantable cardioverter-defibrillator. Reticular telangiectatic erythema is characterized by asymptomatic telangiectasias, blanchable erythematous patches, or both overlying and/or adjacent to the subcutaneous implantable cardioverter-defibrillator. Purpose: We describe a man who developed reticular telangiectatic erythema after receiving a subcutaneous implantable cardioverter-defibrillator and review the salient features of this condition. We also summarize the conditions that can mimic reticular telangiectatic erythema. Materials and methods: The features of a man with reticular telangiectatic erythema are presented and the literature on reticular telangiectatic erythema is reviewed. Results: Our patient developed reticular telangiectatic erythema within one month of subcutaneous implantable cardioverter-defibrillator insertion. The subcutaneous manifestations were asymptomatic. The patient concurred to have periodic clinical follow up and his condition will be monitored for any changes. Conclusion: Reticular telangiectatic erythema is a benign condition characterized by the development of erythema, telangiectasia, or both following insertion of a subcutaneous implantable cardioverter-defibrillator. Other subcutaneous implantable cardioverter-defibrillator-related side effects, such as pressure dermatitis and contact dermatitis, can mimic the condition. Reticular telangiectatic erythema can also be observed following insertion of other devices or, rarely, in the absence of inserted devices. Local microcirculatory changes and subcutaneous implantable cardioverter-defibrillator-related obstruction of blood flow have been suggested as possible mechanisms of pathogenesis. The diagnosis can usually be established by clinical presentation. Therefore, patch testing can usually be omitted. Reticular telangiectatic erythema is typically asymptomatic and thus removal of the device is not required. PMID:25692087

Blood pressure control in resistant hypertension: new therapeutic options.

PubMed

Grassi, Guido; Quarti-Trevano, Fosca; Brambilla, Gianmaria; Seravalle, Gino

2010-11-01

Resistant hypertension, namely the hypertensive state characterized by the inability of multiple antihypertensive drug interventions to lower blood pressure to goal levels, represents a condition frequently detected in clinical practice. Its main features are represented by its heterogeneous etiology as well as its very high cardiovascular risk. This latter peculiarity has implemented the research for new approaches to the treatment of the disease. This article will focus on two of them, namely carotid baroreceptor electric stimulation and the renal denervation procedure. Clinical studies and large-scale clinical trials are presently ongoing with the aim of defining the long-term efficacy and safety profile of the two interventions.

Combined Pulmonary Fibrosis and Emphysema Syndrome

PubMed Central

Rounds, Sharon I. S.

2012-01-01

There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome. PMID:22215830

Eosinophilic Endotype of Asthma.

PubMed

Aleman, Fernando; Lim, Hui Fang; Nair, Parameswaran

2016-08-01

Asthma is a heterogeneous disease that can be classified into different clinical endotypes, depending on the type of airway inflammation, clinical severity, and response to treatment. This article focuses on the eosinophilic endotype of asthma, which is defined by the central role that eosinophils play in the pathophysiology of the condition. It is characterized by elevated sputum and/or blood eosinophils on at least 2 occasions and by a significant response to treatments that suppress eosinophilia. Histopathologic demonstration of eosinophils in the airways provides the most direct diagnosis of eosinophilic asthma; but it is invasive, thus, impractical in clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

A Case of Atrophia Maculosa Varioliformis Cutis

PubMed Central

Kim, En Hyung

2008-01-01

Atrophia maculosa varioliformis cutis (AMVC) is a type of idiopathic noninflammatory macular atrophy that occurs in young individuals. It is clinically characterized by shallow, sharply demaracated depressions of various shapes. Considering that atrophia maculosa varioliformis cutis can be mistaken as scarring and artifact dermatitis, it is important for physicians to distinguish this condition and to diagnose it correctly. PMID:27303203

A Case of Atrophia Maculosa Varioliformis Cutis.

PubMed

Kim, En Hyung; Kang, Hee Young

2008-12-01

Atrophia maculosa varioliformis cutis (AMVC) is a type of idiopathic noninflammatory macular atrophy that occurs in young individuals. It is clinically characterized by shallow, sharply demaracated depressions of various shapes. Considering that atrophia maculosa varioliformis cutis can be mistaken as scarring and artifact dermatitis, it is important for physicians to distinguish this condition and to diagnose it correctly.

Demographics and co-occurring conditions in a clinic-based cohort with Down syndrome in the United Arab Emirates.

PubMed

Corder, Jennifer Price; Al Ahbabi, Fatima Jaber Sehmi; Al Dhaheri, Hind Saif; Chedid, Fares

2017-09-01

The majority of studies describing demographics and co-occurring conditions in cohorts with Down syndrome come from regions outside of the Middle East, mainly from Europe and North America. This paper describes demographics and co-occurring conditions in a hospital-based cohort of individuals with Down syndrome living in the Middle Eastern country of the United Arab Emirates (UAE). The first dedicated Down syndrome clinic in the UAE was established in 2012 at Tawam Hospital in Al Ain. This paper describes a clinic-based cohort of 221 participants over 4 years from the Gulf Down Syndrome Registry, a new Down syndrome database and contact registry created at Tawam Hospital. Key demographic findings include mean maternal age of 37 years, among the highest described in the literature. Sixty-two percent of mothers are >35 years. Over 90% of mothers received post-natal diagnosis of Down syndrome. High sex ratio, parental consanguinity, and large family size also characterize the group. The spectrum of many co-occurring conditions mirrors that of previously described populations, with some notable differences. Cardiovascular malformations are well represented, however, atrioventricular canal is not the most common. Genitourinary conditions are common, as evidenced by 12% of males with hypospadias and 15% with undescended testes. Glucose-6-phosphate dehydrogenase deficiency, alpha thalassemia trait, hypovitaminosis D, and dental caries are common in our cohort. This study describes a large hospital-based group with Down syndrome presenting to a new dedicated Down syndrome clinic in the UAE, highlighting unique demographic and co-occurring conditions found in that population. © 2017 Wiley Periodicals, Inc.

Nailfold video-capillaroscopy in systemic sclerosis.

PubMed

Cutolo, M; Pizzorni, C; Sulli, A

2004-12-01

The Raynaud's phenomenon (RP) is the most common and significant clinical condition supporting microvascular analysis as soon as possible. Microvascular involvement is a key feature of RP, and several rheumatic diseases are characterized by the presence of the RP. Nailfold capillary microscopy shows an impressive cost/effectiveness ratio: it is simple, noninvasive and inexpensive.Well-recognized videocapillaroscopic patterns (NVC) have been described mainly in scleroderma (SSc) patients complaining of a secondary RP. The peripheral microvascular damage in SSc is characterized by increasing structural alterations of the capillaries (giant capillaries and microhemorrhages) with progressive decrease of their density. The detection of the scleroderma NCV allows early differentiation between primary RP (functional, not disease associated), and secondary RP (disease associated). Other major NVC patterns have been described in the field of rheumatic diseases. Interestingly, correlations are evident between the NCV and the clinical symptoms, severity of the disease and the laboratory findings. Further clinical and epidemiological studies, as well as a standardized and computerized quantitation of the observed damages are required.

A Patient with Beta-Propeller Protein-Associated Neurodegeneration: Treatment with Iron Chelation Therapy.

PubMed

Lim, Shen-Yang; Tan, Ai Huey; Ahmad-Annuar, Azlina; Schneider, Susanne A; Bee, Ping Chong; Lim, Jia Lun; Ramli, Norlisah; Idris, Mohamad Imran

2018-05-01

We present a case of beta-propeller protein-associated neurodegeneration, a form of neurodegeneration with brain iron accumulation. The patient harbored a novel mutation in the WDR45 gene. A detailed video and description of her clinical condition are provided. Her movement disorder phenomenology was characterized primarily by limb stereotypies and gait dyspraxia. The patient's disability was advanced by the time iron-chelating therapy with deferiprone was initiated, and no clinical response in terms of cognitive function, behavior, speech, or movements were observed after one year of treatment.

Maternal and neonatal epidemiological features in clinical subtypes of preterm-birth

PubMed Central

Gimenez, Lucas G.; Krupitzki, Hugo B.; Momany, Allison M.; Gili, Juan A.; Poletta, Fernando A.; Campaña, Hebe; Cosentino, Viviana R.; Saleme, César; Pawluk, Mariela; Murray, Jeffrey C.; Castilla, Eduardo E.; Gadow, Enrique C.; Lopez-Camelo, Jorge S.

2016-01-01

Objective This study was designed to characterize and compare the maternal and newborn epidemiological characteristics through analysis of environmental factors, socio-demographic characteristics, and clinical characteristics between the different clinical subtypes of preterm birth (PTB): Idiopathic (PTB-I), premature rupture of the membranes (PTB-PPROM) and medically indicated (PTB-M). The two subtypes PTB-I and PTB-PPROM grouped are called spontaneous preterm births (PTB-S). Methods A retrospective, observational study was conducted in 1.291 preterm non-malformed singleton live-born children to nulliparous and multiparous mother’s in Tucumán-Argentina between 2005 and 2010. Over 50 maternal variables and ten newborn variables were compared between the different clinical subtypes. The comparisons were done to identify heterogeneity between subtypes of preterm birth: (PTB-S) vs. (PTB-M), and within spontaneous subtype: (PTB-I) vs. (PTB-PPROM). In the same way, two conditional logistic multivariate regressions were used to compare the odds ratio (OR) between PTB-S and PTB-M, as well as PTB-I and PTB-PPROM. We matched for maternal age when comparing maternal variables and gestational age when comparing infant variables. Results The PTB-I subtype was characterized by younger mothers of lower socioeconomic status, PTB-PPROM was characterized by environmental factors resulting from inflammatory processes, and PTB-M was characterized by increased maternal or fetal risk pregnancies. Conclusions The main risk factor for PTB-I and PTB-M was having had a prior preterm delivery, however previous spontaneous abortion was not a risk factor, suggesting a reproductive selection mechanism. PMID:26701680

Translational neuropathic pain research: A clinical perspective.

PubMed

Bouhassira, D; Attal, N

2016-12-03

Neuropathic pain encompasses a broad range of conditions associated with a lesion or disease of the peripheral or central somatosensory system and its prevalence in the general population may be as high as 7-8%. The interest in the pathophysiology of neuropathic pain has increased over the last two decades with an exponential increase in the number of experimental studies. However, despite the hopes raised by scientific discoveries, there has been no rational development of a truly new class of drugs. This situation revealing the limitations of certain experimental models, also results of limitations in clinical research. One of the reasons for the therapeutic difficulties in these patients is probably due to the fact that treatments are used in a uniform fashion whatever the clinical picture, while these syndromes are in fact highly heterogeneous. Clinical advances have recently been made in this field, following the validation of new specific clinical tools and the standardization of quantitative sensory testing paradigms facilitating improvements in the clinical characterization of these syndromes. It has been clearly demonstrated that neuropathic pain is a consistent clinical entity, but it is multidimensional in terms of its clinical expression, with different sensory profiles, potentially reflecting specific pathophysiological mechanisms. This new conceptualization of neuropathic pain should improve the characterization of the responder profiles in clinical trials and provide valuable information for the development of new and more clinically sound translational approaches in experimental models in animals. Copyright © 2016. Published by Elsevier Ltd.

Looking beyond historical patient outcomes to improve clinical models.

PubMed

Chia, Chih-Chun; Rubinfeld, Ilan; Scirica, Benjamin M; McMillan, Sean; Gurm, Hitinder S; Syed, Zeeshan

2012-04-25

Conventional algorithms for modeling clinical events focus on characterizing the differences between patients with varying outcomes in historical data sets used for the model derivation. For many clinical conditions with low prevalence and where small data sets are available, this approach to developing models is challenging due to the limited number of positive (that is, event) examples available for model training. Here, we investigate how the approach of developing clinical models might be improved across three distinct patient populations (patients with acute coronary syndrome enrolled in the DISPERSE2-TIMI33 and MERLIN-TIMI36 trials, patients undergoing inpatient surgery in the National Surgical Quality Improvement Program registry, and patients undergoing percutaneous coronary intervention in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium registry). For each of these cases, we supplement an incomplete characterization of patient outcomes in the derivation data set (uncensored view of the data) with an additional characterization of the extent to which patients differ from the statistical support of their clinical characteristics (censored view of the data). Our approach exploits the same training data within the derivation cohort in multiple ways to improve the accuracy of prediction. We position this approach within the context of traditional supervised (2-class) and unsupervised (1-class) learning methods and present a 1.5-class approach for clinical decision-making. We describe a 1.5-class support vector machine (SVM) classification algorithm that implements this approach, and report on its performance relative to logistic regression and 2-class SVM classification with cost-sensitive weighting and oversampling. The 1.5-class SVM algorithm improved prediction accuracy relative to other approaches and may have value in predicting clinical events both at the bedside and for risk-adjusted quality of care assessment.

Design of a pulsatile flow facility to evaluate thrombogenic potential of implantable cardiac devices.

PubMed

Arjunon, Sivakkumar; Ardana, Pablo Hidalgo; Saikrishnan, Neelakantan; Madhani, Shalv; Foster, Brent; Glezer, Ari; Yoganathan, Ajit P

2015-04-01

Due to expensive nature of clinical trials, implantable cardiac devices should first be extensively characterized in vitro. Prosthetic heart valves (PHVs), an important class of these devices, have been shown to be associated with thromboembolic complications. Although various in vitro systems have been designed to quantify blood-cell damage and platelet activation caused by nonphysiological hemodynamic shear stresses in these PHVs, very few systems attempt to characterize both blood damage and fluid dynamics aspects of PHVs in the same test system. Various numerical modeling methodologies are also evolving to simulate the structural mechanics, fluid mechanics, and blood damage aspects of these devices. This article presents a completely hemocompatible small-volume test-platform that can be used for thrombogenicity studies and experimental fluid mechanics characterization. Using a programmable piston pump to drive freshly drawn human blood inside a cylindrical column, the presented system can simulate various physiological and pathophysiological conditions in testing PHVs. The system includes a modular device-mounting chamber, and in this presented case, a 23 mm St. Jude Medical (SJM) Regents® mechanical heart valve (MHV) in aortic position was used as the test device. The system was validated for its capability to quantify blood damage by measuring blood damage induced by the tester itself (using freshly drawn whole human blood). Blood damage levels were ascertained through clinically relevant assays on human blood while fluid dynamics were characterized using time-resolved particle image velocimetry (PIV) using a blood-mimicking fluid. Blood damage induced by the tester itself, assessed through Thrombin-anti-Thrombin (TAT), Prothrombin factor 1.2 (PF1.2), and hemolysis (Drabkins assay), was within clinically accepted levels. The hydrodynamic performance of the tester showed consistent, repeatable physiological pressure and flow conditions. In addition, the system contains proximity sensors to accurately capture leaflet motion during the entire cardiac cycle. The PIV results showed skewing of the leakage jet, caused by the asymmetric closing of the two leaflets. All these results are critical to characterizing the blood damage and fluid dynamics characteristics of the SJM Regents® MHV, proving the utility of this tester as a precise system for assessing the hemodynamics and thrombogenicity for various PHVs.

Clinical and molecular features of Joubert syndrome and related disorders

PubMed Central

Parisi, Melissa A.

2009-01-01

Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other anomalies characterize Joubert syndrome and related disorders (JSRD), and may include retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis. The clinical course can be variable, but most children with this condition survive infancy to reach adulthood. At least 8 genes cause JSRD, with some genotype-phenotype correlations emerging, including the association between mutations in the MKS3 gene and hepatic fibrosis characteristic of the JSRD subtype known as COACH syndrome. Several of the causative genes for JSRD are implicated in other ciliary disorders, such as juvenile nephronophthisis and Meckel syndrome, illustrating the close association between these conditions and their overlapping clinical features that reflect a shared etiology involving the primary cilium. PMID:19876931

Thiamine Deficiency in Self-Induced Refeeding Syndrome, an Undetected and Potentially Lethal Condition

PubMed Central

Hershkowitz, Einat; Reshef, Alon; Munich, Olga; Yosefi, Bracha; Markel, Arie

2014-01-01

Rapid restoration of nutrients and electrolytes after prolonged starvation could result in a life threatening condition characterized by sensory and neurological dysfunction and severe metabolic imbalance that has been designated as refeeding syndrome. Its diagnosis is frequently missed resulting in severe complications and even death. We describe a 25-years-old female patient with mental disorders and severe malnutrition who developed severe clinical manifestations and biochemical abnormalities characteristic of the refeeding syndrome, after restarting oral feeding on her own. Schizophrenia was later diagnosed. Increased awareness of this condition and its complications is necessary to prevent its detrimental complications. PMID:25614745

Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer

PubMed Central

Carethers, John M; Stoffel, Elena M

2015-01-01

Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management. PMID:26309352

Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.

PubMed

Carethers, John M; Stoffel, Elena M

2015-08-21

Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.

Differences in clinical presentation and pregnancy outcomes in antepartum preeclampsia and new-onset postpartum preeclampsia: Are these the same disorder?

PubMed

Vilchez, Gustavo; Hoyos, Luis R; Leon-Peters, Jocelyn; Lagos, Moraima; Argoti, Pedro

2016-11-01

New-onset postpartum preeclampsia is a poorly defined condition that accounts for a significant percentage of eclampsia cases. It is unclear whether new-onset postpartum preeclampsia is a different disorder from or belongs to the same spectrum of classic antepartum preeclampsia. The objective of this study was to compare the clinical presentation and pregnancy outcomes of antepartum preeclampsia and new-onset postpartum preeclampsia. A retrospective study including 92 patients with antepartum preeclampsia and 92 patients with new-onset postpartum preeclampsia was performed. Clinical presentation and pregnancy outcomes were compared. Chi-square test was used to analyze categorical variables, and independent t -test and Mann-Whitney U -test for numerical variables. P -values of <0.05 were used to indicate statistical signifi cance. Patients with antepartum preeclampsia and new-onset postpartum preeclampsia differ significantly in profile, symptoms at presentation, laboratory markers and pregnancy outcomes. New-onset postpartum preeclampsia has a distinct patient profile and clinical presentation than antepartum preeclampsia, suggesting they may represent different disorders. Characterization of a patient profile with increased risk of developing this condition will help clinicians to identify patients at risk and provide early and targeted interventions to decrease the morbidity associated with this condition.

Aeromonas hydrophila as cause of hemorrhagic septicemia in a ground-hornbill (Bucorvus abyssinicus).

PubMed

Ocholi, R A; Kalejaiye, J O

1990-01-01

An acute hemorrhagic septicemia in a captive ground-hornbill (Bucorvus abyssinicus) is reported. Aeromonas hydrophila was isolated from lungs, liver, kidney, and intestines. Postmortem lesions were characterized by hemorrhages in the internal organs. Microscopically, necrotic lesions were found in the liver, lungs, and kidney. Factors that might have contributed to the clinical disease condition are discussed.

Characterizing Factors of Employment Status in Persons With Major Depressive Disorder.

PubMed

Chen, Fang-Pei; Samet, Sharon; Gorroochurn, Prakash; O'Hara, Kathleen M

2016-09-01

Employment is fundamental to mental health recovery. The aim of this study is to construct a parsimonious profile indicating employment potential of people with major depressive disorder (MDD) to facilitate clinical assessment on employment participation. Data were drawn from Waves 1 (2001-2002) and 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. We included participants who had MDD at Wave 1 and were interviewed in both waves (N = 2,864). We conducted Classification and Regression Tree (CART) analysis to identify key characterizing factors of Wave 2 employment among 32 Wave 1 risk and protective factors. The results show that 82.1% of those employed at Wave 1 were likely to be employed at Wave 2. Among those unemployed at Wave 1, 51% of those motivated to work, measured by work-seeking behavior in the prior year, were likely to be employed at Wave 2. Among those unemployed and motivated to work, better functional mental health was associated with employment (>25.3 vs. ≤25.3). Results highlight the importance of motivation to work, shown in active work seeking, in facilitating employment despite clinical conditions. © The Author(s) 2015.

The Ling 6(HL) test: typical pediatric performance data and clinical use evaluation.

PubMed

Glista, Danielle; Scollie, Susan; Moodie, Sheila; Easwar, Vijayalakshmi

2014-01-01

The Ling 6(HL) test offers a calibrated version of naturally produced speech sounds in dB HL for evaluation of detection thresholds. Aided performance has been previously characterized in adults. The purpose of this work was to evaluate and refine the Ling 6(HL) test for use in pediatric hearing aid outcome measurement. This work is presented across two studies incorporating an integrated knowledge translation approach in the characterization of normative and typical performance, and in the evaluation of clinical feasibility, utility, acceptability, and implementation. A total of 57 children, 28 normally hearing and 29 with binaural sensorineural hearing loss, were included in Study 1. Children wore their own hearing aids fitted using Desired Sensation Level v5.0. Nine clinicians from The Network of Pediatric Audiologists participated in Study 2. A CD-based test format was used in the collection of unaided and aided detection thresholds in laboratory and clinical settings; thresholds were measured clinically as part of routine clinical care. Confidence intervals were derived to characterize normal performance and typical aided performance according to hearing loss severity. Unaided-aided performance was analyzed using a repeated-measures analysis of variance. The audiologists completed an online questionnaire evaluating the quality, feasibility/executability, utility/comparative value/relative advantage, acceptability/applicability, and interpretability, in addition to recommendation and general comments sections. Ling 6(HL) thresholds were reliably measured with children 3-18 yr old. Normative and typical performance ranges were translated into a scoring tool for use in pediatric outcome measurement. In general, questionnaire respondents generally agreed that the Ling 6(HL) test was a high-quality outcome evaluation tool that can be implemented successfully in clinical settings. By actively collaborating with pediatric audiologists and using an integrated knowledge translation framework, this work supported the creation of an evidence-based clinical tool that has the potential to be implemented in, and useful to, clinical practice. More research is needed to characterize performance in alternative listening conditions to facilitate use with infants, for example. Future efforts focused on monitoring the use of the Ling 6(HL) test in daily clinical practice may help describe whether clinical use has been maintained across time and if any additional adaptations are necessary to facilitate clinical uptake. American Academy of Audiology.

On the nosology and pathogenesis of Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review.

PubMed

Zollino, Marcella; Murdolo, Marina; Marangi, Giuseppe; Pecile, Vanna; Galasso, Cinzia; Mazzanti, Laura; Neri, Giovanni

2008-11-15

Based on genotype-phenotype correlation analysis of 80 Wolf-Hirschhorn syndrome (WHS) patients, as well as on review of relevant literature, we add further insights to the following aspects of WHS: (1) clinical delineation and phenotypic categories; (2) characterization of the basic genomic defect, mechanisms of origin and familiarity; (3) identification of prognostic factors for mental retardation; (4) chromosome mapping of the distinctive clinical signs, in an effort to identify pathogenic genes. Clinically, we consider that minimal diagnostic criteria for WHS, defining a "core" phenotype, are typical facial appearance, mental retardation, growth delay and seizures (or EEG anomalies). Three different categories of the WHS phenotype were defined, generally correlating with the extent of the 4p deletion. The first one comprises a small deletion not exceeding 3.5 Mb, that is usually associated with a mild phenotype, lacking major malformations. This category is likely under-diagnosed. The second and by far the more frequent category is identified by large deletions, averaging between 5 and 18 Mb, and causes the widely recognizable WHS phenotype. The third clinical category results from a very large deletion exceeding 22-25 Mb causing a severe phenotype, that can hardly be defined as typical WHS. Genetically, de novo chromosome abnormalities in WHS include pure deletions but also complex rearrangements, mainly unbalanced translocations. With the exception of t(4p;8p), WHS-associated chromosome abnormalities are neither mediated by segmental duplications, nor associated with a parental inversion polymorphism on 4p16.3. Factors involved in prediction of prognosis include the extent of the deletion, the occurrence of complex chromosome anomalies, and the severity of seizures. We found that the core phenotype maps within the terminal 1.9 Mb region of chromosome 4p. Therefore, WHSCR-2 should be considered the critical region for this condition. We also confirmed that the pathogenesis of WHS is multigenic. Specific and independent chromosome regions were characterized for growth delay and seizures, as well as for the additional clinical signs that characterize this condition. With the exception of parental balanced translocations, familial recurrence is uncommon.

Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment

PubMed Central

Corante, Noemí

2016-01-01

Abstract Villafuerte, Francisco C., and Noemí Corante. Chronic mountain sickness: clinical aspects, etiology, management, and treatment. High Alt Med Biol. 17:61–69, 2016.—Millions of people worldwide live at a high altitude, and a significant number are at risk of developing Chronic Mountain Sickness (CMS), a progressive incapacitating syndrome caused by lifelong exposure to hypoxia. CMS is characterized by severe symptomatic excessive erythrocytosis (EE; Hb ≥19 g/dL for women and Hb ≥21 g/dL for men) and accentuated hypoxemia, which are frequently associated with pulmonary hypertension. In advanced cases, the condition may evolve to cor pulmonale and congestive heart failure. Current knowledge indicates a genetic predisposition to develop CMS. However, there are important risk factors and comorbidities that may trigger and aggravate the condition. Thus, appropriate medical information on CMS is necessary to provide adequate diagnosis and healthcare to high-altitude inhabitants. After reviewing basic clinical aspects of CMS, including its definition, diagnosis, and common clinical findings, we discuss aspects of its etiology, and address its epidemiology, risk factors, and treatment. PMID:27218284

A study on the characterization of Propionibacterium acnes isolated from ocular clinical specimens.

PubMed

Sowmiya, Murali; Malathi, Jambulingam; Swarnali, Sen; Priya, Jeyavel Padma; Therese, Kulandai Lily; Madhavan, Hajib N

2015-10-01

There are only a few reports available on characterization of Propionibacterium acnes isolated from various ocular clinical specimens. We undertook this study to evaluate the role of P. acnes in ocular infections and biofilm production, and also do the phylogenetic analysis of the bacilli. One hundred isolates of P. acnes collected prospectively from ocular clinical specimens at a tertiary care eye hospital between January 2010 and December 2011, were studied for their association with various ocular disease conditions. The isolates were also subjected to genotyping and phylogenetic analysis, and were also tested for their ability to produce biofilms. Among preoperative conjunctival swabs, P. acnes was a probably significant pathogen in one case; a possibly significant pathogen in two cases. In other clinical conditions, 13 per cent isolates were probably significant pathogens and 38 per cent as possibly significant pathogens. The analysis of 16S rRNA gene revealed four different phylogenies whereas analysis of recA gene showed two phylogenies confirming that recA gene was more reliable than 16S rRNA with less sequence variation. Results of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) had 100 per cent concordance with phylogenetic results. No association was seen between P. acnes subtypes and biofilm production. RecA gene phylogenetic studies revealed two different phylogenies. RFLP technique was found to be cost-effective with high sensitivity and specificity in phylogenetic analysis. No association between P. acnes subtypes and pathogenetic ability was observed. Biofilm producing isolates showed increased antibiotic resistance compared with non-biofilm producing isolates.

The Female Pattern Hair Loss: Review of Etiopathogenesis and Diagnosis

PubMed Central

Vujovic, Anja; Del Marmol, Véronique

2014-01-01

Female pattern hair loss (FPHL) is the most common hair loss disorder in women. Initial signs may develop during teenage years leading to a progressive hair loss with a characteristic pattern distribution. The condition is characterized by progressive replacement of terminal hair follicles over the frontal and vertex regions by miniaturized follicles, that leads progressively to a visible reduction in hair density. Women diagnosed with FPHL may undergo significant impairment of quality of life. FPHL diagnosis is mostly clinical. Depending on patient history and clinical evaluation, further diagnostic testing may be useful. The purpose of the paper is to review the current knowledge about epidemiology, pathogenesis, clinical manifestations, and diagnosis of FPHL. PMID:24812631

Weil’s disease in a 36 years old female: a case report

NASA Astrophysics Data System (ADS)

Rozalena, S.; Handayani, L.; Arman, A.; Permata, M.; Hudari, H.

2018-03-01

Leptospirosis is an acute zoonotic infection, itis caused by spirochetes of the genus Leptospira, has extensive vasculitis characterizes, can usually be transmitted indirectly, per contaminated water, rarely directly, and through contact with infected animals. Leptospira bacteria commonly enter the body through the damaged skin or mucous membranes. The clinical syndromes may vary from a subclinical infection and mild febrile condition to severe clinical symptoms with jaundice and renal failure. It is the case report from a woman 36 years old with leptospirosis (Weil’s disease) whose clinical manifestations included: icterus, renal failure, hemorrhagic syndrome and disturbances of consciousness. After the use of antibiotics, symptomatic and substitution therapy, all symptoms resolved completely.

Twinkling artifact on color Doppler ultrasound: an advantage or a pitfall?

PubMed

Ozan, Ebru; Atac, Gokce Kaan; Gundogdu, Sadi

2016-07-01

The twinkling artifact (TA) or color comet-tail artifact is characterized by a rapidly changing mixture of red and blue color Doppler signals. Even though many diseases and clinical conditions have been shown to produce this artifact, its source is not clearly understood yet. The TA may provide additional information to gray-scale ultrasound findings in several clinical situations. However, there may be pitfalls to keep in mind. We must first be aware of the TA to benefit from the advantages and avoid the pitfalls. In this review, we aim to give practicing radiologists an overview of the mechanisms and clinical applications of the TA by illustrating sample cases we have encountered.

Temporal characteristics of decisions in hospital encounters: a threshold for shared decision making? A qualitative study.

PubMed

Ofstad, Eirik H; Frich, Jan C; Schei, Edvin; Frankel, Richard M; Gulbrandsen, Pål

2014-11-01

To identify and characterize physicians' statements that contained evidence of clinically relevant decisions in encounters with patients in different hospital settings. Qualitative analysis of 50 videotaped encounters from wards, the emergency room (ER) and outpatient clinics in a department of internal medicine at a Norwegian university hospital. Clinical decisions could be grouped in a temporal order: decisions which had already been made, and were brought into the encounter by the physician (preformed decisions), decisions made in the present (here-and-now decisions), and decisions prescribing future actions given a certain course of events (conditional decisions). Preformed decisions were a hallmark in the ward and conditional decisions a main feature of ER encounters. Clinical decisions related to a patient-physician encounter spanned a time frame exceeding the duration of the encounter. While a distribution of decisions over time and space fosters sharing and dilution of responsibility between providers, it makes the decision making process hard to access for patients. In order to plan when and how to involve patients in decisions, physicians need increased awareness of when clinical decisions are made, who usually makes them, and who should make them. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Clinical effects of diet supplementation with DHA in pediatric patients suffering from cystic fibrosis.

PubMed

Leggieri, E; De Biase, R V; Savi, D; Zullo, S; Halili, I; Quattrucci, S

2013-08-01

Cystic fibrosis (CF) patients present an altered fatty acid (FA) metabolism characterized by imbalance in the arachidonic/docosohexasenoic acid (AA/DHA) ratio in favour of the former which can contribute to the increase in pulmonary inflammation. The present study aims to assess respiratory, nutritional, clinical and laboratory parameters, and inflammatory markers after six months of DHA supplementation in paediatric patients suffering from CF. A dose of 1 g/10 kg/die was administered to ten CF patients of paediatric age for the first month and 250 mg/10 kg/die for the remaining 5 months. We carried out follow-ups at T0 (baseline), T6 (after six months of the diet) and T12 (six months after supplementation was interrupted) during which respiratory, nutritional, clinical and laboratory parameters were assessed. After six months of DHA supplementation inflammatory marker levels had diminished: interleukin 8 (IL-8) and Tumour Necrosis Factor Alfa (TNF-α) in serum, and calprotectin in stools. In addition, auxometric parameters were improved as was the clinical condition of patients, who tolerated DHA well. Dietetic integration with DHA seems to improve clinical condition and the inflammatory pulmonary and intestinal state of pediatric patients suffering from CF.

The Leiden Family Lab study on Social Anxiety Disorder: A multiplex, multigenerational family study on neurocognitive endophenotypes

PubMed Central

Harrewijn, Anita; Tissier, Renaud L.M.; van der Molen, Melle J.W.; van Steenbergen, Henk; van Vliet, Irene M.; Reichart, Catrien G.; Houwing‐Duistermaat, Jeanine J.; Slagboom, P. Eline; van der Wee, Nic J.A.; Westenberg, P. Michiel

2018-01-01

abstract Objectives Social anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so‐called “endophenotypes”. These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety. Methods The LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD. Results The sample (n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self‐reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms. Conclusions By the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD. PMID:29700902

[The autoimmune rheumatic disease and laryngeal pathology].

PubMed

Osipenko, E V; Kotel'nikova, N M

Vocal disorders make up one of the autoimmune pathological conditions characterized by multiple organ system dysfunction. Laryngeal pathology in this condition has an autoimmune nature; it is highly diverse and poorly explored. The objective of the present work based on the analysis of the relevant literature publications was to study clinical manifestations of the autoimmune rheumatic disease affecting the larynx. 'Bamboo nodes' on the vocal folds is a rare manifestation of laryngeal autoimmune diseases. We found out references to 49 cases of this condition in the available literature. All the patients were women presenting with autoimmune diseases. The present review highlights the problems pertaining to etiology of 'bamboo nodes' on the vocal folds and the method for the treatment of this condition.

Obsessive–compulsive disorder: subclassification based on co-morbidity

PubMed Central

Nestadt, G.; Di, C. Z.; Riddle, M. A.; Grados, M. A.; Greenberg, B. D.; Fyer, A. J.; McCracken, J. T.; Rauch, S. L.; Murphy, D. L.; Rasmussen, S. A.; Cullen, B.; Pinto, A.; Knowles, J. A.; Piacentini, J.; Pauls, D. L.; Bienvenu, O. J.; Wang, Y.; Liang, K. Y.; Samuels, J. F.; Roche, K. Bandeen

2011-01-01

Background Obsessive–compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and co-morbid conditions to identify subtypes. Method Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions [generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD)]. The relationship of the derived classes to specific clinical characteristics was investigated. Results Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive disorder (MDD) is the most frequent additional disorder; (2) an OCD co-morbid tic-related class, in which tics are prominent and affective syndromes are considerably rarer; and (3) an OCD co-morbid affective-related class in which PD and affective syndromes are highly represented. The OCD co-morbid tic-related class is predominantly male and characterized by high conscientiousness. The OCD co-morbid affective-related class is predominantly female, has a young age at onset, obsessive–compulsive personality disorder (OCPD) features, high scores on the ‘taboo’ factor of OCD symptoms, and low conscientiousness. Conclusions OCD can be classified into three classes based on co-morbidity. Membership within a class is differentially associated with other clinical characteristics. These classes, if replicated, should have important implications for research and clinical endeavors. PMID:19046474

RNA-based analysis of two SMARCB1 mutations associated with familial schwannomatosis with meningiomas.

PubMed

Melean, German; Velasco, Ana; Hernández-Imaz, Elisabete; Rodríguez-Álvarez, Francisco Javier; Martín, Yolanda; Valero, Ana; Hernández-Chico, Concepción

2012-08-01

Germline mutations in the SMARCB1 gene cause familial schwannomatosis, a condition characterized by the presence of multiple schwannomas, although mutations in SMARCB1 have also been associated with rhadboid tumor predisposition syndrome 1 (RTPS1). Both schwannomatosis and RTPS1 are autosomal dominant conditions that predispose individuals to develop distinct types of tumors. We clinically and genetically characterized two families with schwannomatosis associated with SMARCB1 mutations. Eight affected members of these families developed different numbers of schwannomas and/or meningiomas at distinct ages, evidence that meningiomas are variably expressed in this condition. We identified two germline mutations in SMARCB1 associated with the familial disease, c.233-1G>A and the novel c.207_208dupTA mutation, which both proved to affect the main SMARCB1 isoforms at the RNA level distinctly. Interestingly, the c.207_208dupTA mutation had no effect on the coding sequence, pre-mRNA splicing or the level of expression of the SMARCB1 isoform 2. Furthermore, SMARCB1 isoforms harboring a premature termination codon were largely eliminated via the nonsense-mediated mRNA decay pathway. Our results highlight the importance of RNA-based studies to characterize SMARCB1 germline mutations in order to determine their impact on protein expression and gain further insight into the genetic basis of conditions associated with SMARCB1 mutations.

Regulation of immunotherapeutic products for cancer and FDA’s role in product development and clinical evaluation

PubMed Central

2013-01-01

Immunotherapeutics include drugs and biologics that render therapeutic benefit by harnessing the power of the immune system. The promise of immune-mediated therapies is target specificity with a consequent reduction in off-target side effects. Recent scientific advances have led to clinical trials of both active and passive immunotherapeutic products that have the potential to convert life-ending diseases into chronic but manageable conditions. Clinical trials investigating immunotherapeutics are ongoing with some trials at advanced stages of development. However, as with many products involving novel mechanisms of action, major regulatory and scientific issues arising with clinical use of immunotherapeutic products remain to be addressed. In this review, we address issues related to different immunotherapeutics and provide recommendations for the characterization and evaluation of these products during various stages of product and clinical development. PMID:24764535

High-intensity therapeutic ultrasound: metrological requirements versus clinical usage

NASA Astrophysics Data System (ADS)

Aubry, J.-F.

2012-10-01

High-intensity therapeutic ultrasound (HITU) is an appealing non-invasive, non-ionizing therapeutic modality with a wide range of tissue interactions ranging from transient permeabilization of cell membranes to thermal ablation. The ability to guide and monitor the treatment with an associated ultrasonic or magnetic resonance imaging device has resulted in a dramatic rise in the clinical use of therapeutic ultrasound in the past two decades. Nevertheless, the range of clinical applications and the number of patients treated has grown at a much higher pace than the definition of standards. In this paper the metrological requirements of the therapeutic beams are reviewed and are compared with the current clinical use of image-guided HITU mostly based on a practical approach. Liver therapy, a particularly challenging clinical application, is discussed to highlight the differences between some complex clinical situations and the experimental conditions of the metrological characterization of ultrasonic transducers.

Children With Medical Complexity: An Emerging Population for Clinical and Research Initiatives

PubMed Central

Kuo, Dennis Z.; Agrawal, Rishi; Berry, Jay G.; Bhagat, Santi K. M.; Simon, Tamara D.; Srivastava, Rajendu

2011-01-01

Children with medical complexity (CMC) have medical fragility and intensive care needs that are not easily met by existing health care models. CMC may have a congenital or acquired multisystem disease, a severe neurologic condition with marked functional impairment, and/or technology dependence for activities of daily living. Although these children are at risk of poor health and family outcomes, there are few well-characterized clinical initiatives and research efforts devoted to improving their care. In this article, we present a definitional framework of CMC that consists of substantial family-identified service needs, characteristic chronic and severe conditions, functional limitations, and high health care use. We explore the diversity of existing care models and apply the principles of the chronic care model to address the clinical needs of CMC. Finally, we suggest a research agenda that uses a uniform definition to accurately describe the population and to evaluate outcomes from the perspectives of the child, the family, and the broader health care system. PMID:21339266

Can Pharmacotherapists be Too Supportive? A Process Study of Active Medication and Placebo in the Treatment of Depression

PubMed Central

Strunk, Daniel R.; Stewart, Michael O.; Hollon, Steven D.; DeRubeis, Robert J.; Fawcett, Jan; Amsterdam, Jay D.; Shelton, Richard C.

2013-01-01

Background This study examined therapist-patient interactions during clinical management with anti-depressant medication and pill-placebo. Methods The sample consisted of 80 patients on active medication and 40 patients in a pill-placebo condition from a randomized controlled trial for moderate to severe depression. Pharmacotherapist-patient interactions were characterized using observer ratings of the therapeutic alliance, pharmacotherapist-offered facilitative conditions, pharmacotherapist adherence to clinical management treatment guidelines, and pharmacotherapist competence. Patients, therapists, and raters were blind to treatment condition and outcome. Results Provision of greater nonspecific support (facilitative conditions) in early sessions predicted less subsequent improvement in depressive symptoms for patients receiving pill-placebo but not those receiving active medications, for which none of the process ratings predicted subsequent change. Early symptom change predicted later alliance and adherence in both conditions and therapist competence in the active condition. Conclusions Higher levels of support in early sessions predict poorer subsequent response among placebo patients. It remains unclear whether patients who are likely to be refractory elicit greater nonspecific support or whether the provision of such support has a deleterious effect in unmedicated patients. Differences in treatment process variables between conditions late in treatment are likely to be largely a consequence of symptom relief produced by active medications. PMID:19891806

Periodontal conditions in vegetarians: a clinical study.

PubMed

Staufenbiel, I; Weinspach, K; Förster, G; Geurtsen, W; Günay, H

2013-08-01

Investigations about possible correlations between vegetarian diet and periodontal conditions are rare and characterized by small case numbers. The aim of this clinical study was to investigate the influence of a vegetarian diet on periodontal parameters with an appropriate sample size. A total of 200 patients, 100 vegetarians and 100 non-vegetarians, were included in the study. All patients were examined including a full mouth assessment of the periodontal and dental conditions. In addition, a questionnaire was handed out to ask for patients' oral hygiene habits and level of education. For statistical analysis the Mann-Whitney Test (χ(2) for analysis of the questionnaire) was applied (level of significance: P<0.05). Well known periodontal risk factors like age, gender and smoking habits were equally distributed within each group (71 females, 29 males, respectively and 10 smokers in each group; mean age: 41.45 years vegetarians versus 41.72 years non-vegetarians). Vegetarians had significantly lower probing pocket depths (P=0.039), bleeding on probing (P=0.001), periodontal screening index (P=0.012), a better hygiene index (P<0.001) and less mobile teeth (P=0.013). Dental examinations revealed significantly less missing teeth (P=0.018) but also more decayed (P=0.001) and eroded (P=0.026) teeth in vegetarians. Furthermore, vegetarians had a higher level of education (P<0.001), but visited dentists significantly less frequent. Vegetarians revealed better periodontal conditions (less inflammation signs, less periodontal damage and a better dental home care). However, it should be considered that vegetarians are not only avoiding meat in their nutrition but are also characterized by an overall healthier life style.

Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses.

PubMed

Ungerechts, Guy; Bossow, Sascha; Leuchs, Barbara; Holm, Per S; Rommelaere, Jean; Coffey, Matt; Coffin, Rob; Bell, John; Nettelbeck, Dirk M

2016-01-01

Oncolytic viruses (OVs) are unique anticancer agents based on their pleotropic modes of action, which include, besides viral tumor cell lysis, activation of antitumor immunity. A panel of diverse viruses, often genetically engineered, has advanced to clinical investigation, including phase 3 studies. This diversity of virotherapeutics not only offers interesting opportunities for the implementation of different therapeutic regimens but also poses challenges for clinical translation. Thus, manufacturing processes and regulatory approval paths need to be established for each OV individually. This review provides an overview of clinical-grade manufacturing procedures for OVs using six virus families as examples, and key challenges are discussed individually. For example, different virus features with respect to particle size, presence/absence of an envelope, and host species imply specific requirements for measures to ensure sterility, for handling, and for determination of appropriate animal models for toxicity testing, respectively. On the other hand, optimization of serum-free culture conditions, increasing virus yields, development of scalable purification strategies, and formulations guaranteeing long-term stability are challenges common to several if not all OVs. In light of the recent marketing approval of the first OV in the Western world, strategies for further upscaling OV manufacturing and optimizing product characterization will receive increasing attention.

Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses

PubMed Central

Ungerechts, Guy; Bossow, Sascha; Leuchs, Barbara; Holm, Per S; Rommelaere, Jean; Coffey, Matt; Coffin, Rob; Bell, John; Nettelbeck, Dirk M

2016-01-01

Oncolytic viruses (OVs) are unique anticancer agents based on their pleotropic modes of action, which include, besides viral tumor cell lysis, activation of antitumor immunity. A panel of diverse viruses, often genetically engineered, has advanced to clinical investigation, including phase 3 studies. This diversity of virotherapeutics not only offers interesting opportunities for the implementation of different therapeutic regimens but also poses challenges for clinical translation. Thus, manufacturing processes and regulatory approval paths need to be established for each OV individually. This review provides an overview of clinical-grade manufacturing procedures for OVs using six virus families as examples, and key challenges are discussed individually. For example, different virus features with respect to particle size, presence/absence of an envelope, and host species imply specific requirements for measures to ensure sterility, for handling, and for determination of appropriate animal models for toxicity testing, respectively. On the other hand, optimization of serum-free culture conditions, increasing virus yields, development of scalable purification strategies, and formulations guaranteeing long-term stability are challenges common to several if not all OVs. In light of the recent marketing approval of the first OV in the Western world, strategies for further upscaling OV manufacturing and optimizing product characterization will receive increasing attention. PMID:27088104

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.

Ferroptosis and Cell Death Analysis by Flow Cytometry.

PubMed

Chen, Daishi; Eyupoglu, Ilker Y; Savaskan, Nicolai

2017-01-01

Cell death and its recently discovered regulated form ferroptosis are characterized by distinct morphological, electrophysiological, and pharmacological features. In particular ferroptosis can be induced by experimental compounds and clinical drugs (i.e., erastin, sulfasalazine, sorafenib, and artesunate) in various cell types and cancer cells. Pharmacologically, this cell death process can be inhibited by iron chelators and lipid peroxidation inhibitors. Relevance of this specific cell death form has been found in different pathological conditions such as cancer, neurotoxicity, neurodegeneration, and ischemia. Distinguishing cell viability and cell death is essential for experimental and clinical applications and a key component in flow cytometry experiments. Dead cells can compromise the integrity of the data by nonspecific binding of antibodies and dyes. Therefore it is essential that dead cells are robustly and reproducibly identified and characterized by means of cytometry application. Here we describe a procedure to detect and quantify cell death and its specific form ferroptosis based on standard flow cytometry techniques.

Surgical treatment of bumblefoot in a captive golden eagle (Aquila chrysaetos)

PubMed Central

Poorbaghi, Seyedeh Leila; Javdani, Moosa; Nazifi, Saeed

2012-01-01

The golden eagle is one of the world's largest living birds. Footpad dermatitis, also known as plantar pododermatitis or bumblefoot, is a condition characterized by lesions due to contact with unhealthy "perching" conditions, such as plastic perches, sharp-cornered perches on the ventral footpad of birds. A young female golden eagle (Aquila chrysaetos) in Fars province of Iran was presented to veterinary clinics of Shiraz University with clinical signs of lameness. The bird was examined clinically and a variety of complementary diagnostic procedures such as blood analysis, X-ray and bacteriological culture were performed. Then a surgical method was pick out for removing of scab, pus and necrotic tissues from abscess on the plantar aspect of bird's feet and healing the skin of area. After surgery, specific bandage, systemic antibiotics and vitamins were used. Corynebacterium, a gram negative bacterium, was isolated in the pus from the abscess. After the surgical operation, swelling in the digital pad reduced, the skin of pad healed and the signs of lameness vanished. To prevent developing bumblefoot, good bedding for proper "perching" conditions is necessary. Additionally, vitamin therapy to promote a healthy integument is advised. PMID:25653750

Misophonia: current perspectives

PubMed Central

Cavanna, Andrea E; Seri, Stefano

2015-01-01

Misophonia is characterized by a negative reaction to a sound with a specific pattern and meaning to a given individual. In this paper, we review the clinical features of this relatively common yet underinvestigated condition, with focus on co-occurring neurodevelopmental disorders. Currently available data on the putative pathophysiology of the condition can inform our understanding and guide the diagnostic process and treatment approach. Tinnitus retraining therapy and cognitive behavior therapy have been proposed as the most effective treatment strategies for reducing symptoms; however, current treatment algorithms should be validated in large population studies. At the present stage, competing paradigms see misophonia as a physiological state potentially inducible in any subject, an idiopathic condition (which can present with comorbid psychiatric disorders), or a symptomatic manifestation of an underlying psychiatric disorder. Agreement on the use of standardized diagnostic criteria would be an important step forward in terms of both clinical practice and scientific inquiry. Areas for future research include phenomenology, epidemiology, modulating factors, neurophysiological underpinnings, and treatment trials. PMID:26316758

Misophonia: current perspectives.

PubMed

Cavanna, Andrea E; Seri, Stefano

2015-01-01

Misophonia is characterized by a negative reaction to a sound with a specific pattern and meaning to a given individual. In this paper, we review the clinical features of this relatively common yet underinvestigated condition, with focus on co-occurring neurodevelopmental disorders. Currently available data on the putative pathophysiology of the condition can inform our understanding and guide the diagnostic process and treatment approach. Tinnitus retraining therapy and cognitive behavior therapy have been proposed as the most effective treatment strategies for reducing symptoms; however, current treatment algorithms should be validated in large population studies. At the present stage, competing paradigms see misophonia as a physiological state potentially inducible in any subject, an idiopathic condition (which can present with comorbid psychiatric disorders), or a symptomatic manifestation of an underlying psychiatric disorder. Agreement on the use of standardized diagnostic criteria would be an important step forward in terms of both clinical practice and scientific inquiry. Areas for future research include phenomenology, epidemiology, modulating factors, neurophysiological underpinnings, and treatment trials.

Clinical Impact and Cellular Mechanisms of Iron Overload-Associated Bone Loss

PubMed Central

Jeney, Viktória

2017-01-01

Diseases/conditions with diverse etiology, such as hemoglobinopathies, hereditary hemochromatosis and menopause, could lead to chronic iron accumulation. This condition is frequently associated with a bone phenotype; characterized by low bone mass, osteoporosis/osteopenia, altered microarchitecture and biomechanics, and increased incidence of fractures. Osteoporotic bone phenotype constitutes a major complication in patients with iron overload. The purpose of this review is to summarize what we have learnt about iron overload-associated bone loss from clinical studies and animal models. Bone is a metabolically active tissue that undergoes continuous remodeling with the involvement of osteoclasts that resorb mineralized bone, and osteoblasts that form new bone. Growing evidence suggests that both increased bone resorption and decreased bone formation are involved in the pathological bone-loss in iron overload conditions. We will discuss the cellular and molecular mechanisms that are involved in this detrimental process. Fuller understanding of this complex mechanism may lead to the development of improved therapeutics meant to interrupt the pathologic effects of excess iron on bone. PMID:28270766

Diagnosis and Management of Systemic Sclerosis: A Practical Approach.

PubMed

Lee, Jason J; Pope, Janet E

2016-02-01

Systemic sclerosis is a devastating multisystem rheumatologic condition that is characterized by autoimmunity, tissue fibrosis, obliterative vasculopathy and inflammation. Clinical presentation and course of the condition vary greatly, which complicates both diagnosis and corresponding treatment. In this regard, recent advances in disease understanding, both clinically and biochemically, have led to newer classification criteria for systemic sclerosis that are more inclusive than ever before. Still, significant disease modifying therapies do not yet exist for most patients. Therefore, organ-based management strategies are employed and research has been directed within this paradigm focusing on either the most debilitating symptoms, such as Raynaud's phenomenon, digital ulcers and cutaneous sclerosis, or life-threatening organ involvement such as interstitial lung disease and pulmonary arterial hypertension. The current trends in systemic sclerosis diagnosis, evidence-based treatment recommendations and potential future directions in systemic sclerosis treatment are discussed.

Impulse Control Disorders: Updated Review of Clinical Characteristics and Pharmacological Management

PubMed Central

Schreiber, Liana; Odlaug, Brian L.; Grant, Jon E.

2011-01-01

Impulse control disorders (ICDs) are characterized by urges and behaviors that are excessive and/or harmful to oneself or others and cause significant impairment in social and occupational functioning, as well as legal and financial difficulties. ICDs are relatively common psychiatric conditions, yet are poorly understood by the general public, clinicians, and individuals struggling with the disorder. Although ICD treatment research is limited, studies have shown ICDs may respond well to pharmacological treatment. This article presents a brief overview about the clinical characteristics of ICDs and pharmacological treatment options for individuals with ICDs. PMID:21556272

Clinical presentation of Churg–Strauss syndrome in children

PubMed Central

Razenberg, Femke G.E.M.; Heynens, Jan W.C.M.; Jan de Vries, Geeuwke; Duijts, Liesbeth; de Jongste, Johan C.; de Blic, Jacques; Rosias, Philippe P.R.

2012-01-01

Churg–Strauss syndrome is an uncommon multisystem disorder characterized by asthma, eosinophilia and vasculitis. We report on a 12-year-old boy with asthma and deterioration of his general condition, who was eventually diagnosed with an ANCA-negative Churg–Strauss syndrome. The propositus included, 50 cases of childhood Churg–Strauss syndrome have been reported. The patient characteristics and clinical characteristics of these children are summarized. The respiratory tract is most frequently involved with pulmonary infiltrates, asthma and sinusitis. Early recognition of childhood Churg–Strauss syndrome is important as delayed diagnosis can lead to severe organ involvement, and possible fatal outcome. PMID:26029598

Testicular feminization in the Finnish racoon dog (Nyctereutes procyonoides).

PubMed

Smith, A; Nes, N; Berg, K A; Valtonen, M; Mäkinen, A; Lukola, A

1983-12-01

The clinical features of testicular feminization in the racoon dog (Nyctereutes procyonoides) are reported. The condition is characterized by a normal male karyotype, but a mixed phenotype consisting of vulva, enlarged clitoris and scrotal testes. Partial spermatogenesis with a relative arrest at the first meiotic division was observed. The likely underlying genetic defect and mode of inheritance are discussed, together with implications for breeding programmes.

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine.

PubMed

Samsonraj, Rebekah M; Raghunath, Michael; Nurcombe, Victor; Hui, James H; van Wijnen, Andre J; Cool, Simon M

2017-12-01

Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self-renewal and differentiation into tissue-specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age-related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone-forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical-grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173-2185. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Novel mutations in the genes TGM1 and ALOXE3 underlying autosomal recessive congenital ichthyosis

PubMed Central

Ullah, Rahim; Ansar, Muhammad; Durrani, Zaka Ullah; Lee, Kwanghyuk; Santos-Cortez, Regie Lyn P.; Muhammad, Dost; Ali, Mahboob; Zia, Muhammad; Ayub, Muhammad; Khan, Suliman; Smith, Josh D.; Nickerson, Deborah A.; Shendure, Jay; Bamshad, Michael; Leal, Suzanne M.; Ahmad, Wasim

2016-01-01

Background Ichthyoses are clinically characterized by scaling or hyperkeratosis of the skin or both. It can be an isolated condition limited to the skin or appear secondarily with involvement of other cutaneous or systemic abnormalities. Methods The present study investigated clinical and molecular characterization of three consanguineous families (A, B, C) segregating two different forms of autosomal recessive congenital ichthyosis (ARCI). Linkage in three consanguineous families (A, B, C) segregating two different forms of ARCI was searched by typing microsatellite and single nucleotide polymorphism marker analysis. Sequencing of the two genes TGM1 and ALOXE3 was performed by the dideoxy chain termination method. Results Genome-wide linkage analysis established linkage in family A to TGM1 gene on chromosome 14q11 and in families B and C to ALOXE3 gene on chromosome 17p13. Subsequently, sequencing of these genes using samples from affected family members led to the identification of three novel mutations: a missense variant p.Trp455Arg in TGM1 (family A); a nonsense variant p.Arg140* in ALOXE3 (family B); and a complex rearrangement in ALOXE3 (family C). Conclusion The present study further extends the spectrum of mutations in the two genes involved in causing ARCI. Characterizing the clinical spectrum resulting from mutations in the TGM1 and ALOXE3 genes will improve diagnosis and may direct clinical care of the family members. PMID:26578203

Photoacoustic tomography: applications for atherosclerosis imaging

NASA Astrophysics Data System (ADS)

Sangha, Gurneet S.; Goergen, Craig J.

2016-08-01

Atherosclerosis is a debilitating condition that increases a patient’s risk for intermittent claudication, limb amputation, myocardial infarction, and stroke, thereby causing approximately 50% of deaths in the western world. Current diagnostic imaging techniques, such as ultrasound, digital subtraction angiography, computed tomography angiography, magnetic resonance angiography, and optical imaging remain suboptimal for detecting development of early stage plaques. This is largely due to the lack of compositional information, penetration depth, and/or clinical efficiency of these traditional imaging techniques. Photoacoustic imaging has emerged as a promising modality that could address some of these limitations to improve the diagnosis and characterization of atherosclerosis-related diseases. Photoacoustic imaging uses near-infrared light to induce acoustic waves, which can be used to recreate compositional images of tissue. Recent developments in photoacoustic techniques show its potential in noninvasively characterizing atherosclerotic plaques deeper than traditional optical imaging approaches. In this review, we discuss the significance and development of atherosclerosis, current and novel clinical diagnostic methods, and recent works that highlight the potential of photoacoustic imaging for both experimental and clinical studies of atherosclerosis.

Melorheostosis: report of two cases affecting the jaw.

PubMed

Parashar, Pallavi; Musella, Anthony; Novak, Timothy; Greer, Robert O

2007-10-01

Melorheostosis is a rare sclerosing bone dysplasia that is characterized by a localized, diffuse thickening of the cortical bone. This condition usually affects the appendicular skeleton and associated soft tissue and rarely affects the craniofacial complex. The etiology of this condition is obscure. Diagnosis of melorheostosis relies on clinical, radiographic, and histological correlation. Only 8 cases of melorheostosis involving the craniofacial complex have been reported. We report 2 new cases of isolated melorheostosis involving the maxilla and mandible, together with differential diagnostic considerations. To our knowledge, involvement of the maxilla only has not been previously reported.

Advanced Diagnostic Techniques in Autoimmune Bullous Diseases

PubMed Central

Jindal, Anuradha; Rao, Raghavendra; Bhogal, Balbir S

2017-01-01

Autoimmune blistering diseases are diverse group of conditions characterized by blisters in the skin with or without mucosal lesions. There may be great degree of clinical and histopathological overlap; hence, advanced immunological tests may be necessary for more precise diagnosis of these conditions. Direct immunofluorescence microscopy is the gold standard tests to demonstrate the tissue-bound antibodies and should be done in all cases. Magnitude of antibody level in patient’ serum can be assessed by indirect immunofluorescence and enzyme linked immunosorbent assay. In this article we have reviewed the various techniques that are available in the diagnosis of autoimmune blistering diseases. PMID:28584369

Noneczematous Contact Dermatitis

PubMed Central

Foti, Caterina; Vestita, Michelangelo; Angelini, Gianni

2013-01-01

Irritant or allergic contact dermatitis usually presents as an eczematous process, clinically characterized by erythematoedematovesicous lesions with intense itching in the acute phase. Such manifestations become erythematous-scaly as the condition progresses to the subacute phase and papular-hyperkeratotic in the chronic phase. Not infrequently, however, contact dermatitis presents with noneczematous features. The reasons underlying this clinical polymorphism lie in the different noxae and contact modalities, as well as in the individual susceptibility and the various targeted cutaneous structures. The most represented forms of non-eczematous contact dermatitis include the erythema multiforme-like, the purpuric, the lichenoid, and the pigmented kinds. These clinical entities must obviously be discerned from the corresponding “pure” dermatitis, which are not associated with contact with exogenous agents. PMID:24109520

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.

Burning mouth syndrome: an enigmatic disorder.

PubMed

Javali, M A

2013-01-01

Burning mouth syndrome (BMS) is a chronic oral pain or burning sensation affecting the oral mucosa, often unaccompanied by mucosal lesions or other evident clinical signs. It is observed principally in middle-aged patients and postmenopausal women and may be accompanied by xerostomia and altered taste. Burning mouth syndrome is characterized by an intense burning or stinging sensation, preferably on the tongue or in other areas of mouth. This disorder is one of the most common, encountered in the clinical practice. This condition is probably of multifactorial origin; however the exact underlying etiology remains uncertain. This article discusses several aspects of BMS, updates current knowledge about the etiopathogenesis and describes the clinical features as well as the diagnosis and management of BMS patients.

The prognostic significance of atrial fibrillation in heart failure with preserved ejection function: insights from KaRen, a prospective and multicenter study.

PubMed

Bosseau, Christian; Donal, Erwan; Lund, Lars H; Oger, Emmanuel; Hage, Camilla; Mulak, Geneviève; Daubert, Jean-Claude; Linde, Cecilia

2017-06-01

The prognostic value of atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFPEF) remains controversial. We sought to study the prognostic value of AF in a prospective cohort and to characterize the HFPEF patients with AF. KaRen was a prospective, multicenter, international, observational study intended to characterize HFPEF; 538 patients presenting with an acute decompensated cardiac failure and a left ventricular EF > 45% were included. EKG and echocardiogram performed 4-8 week following the index hospitalization were analyzed in core centers. Clinical and echocardiographic characteristics of patients in sinus rhythm vs. with documented AF at enrolment (decompensated HF), upon their 4-8-week visit (in presumed stable clinical condition) and according to patients' cardiac history, were compared. The primary study endpoint was death from any cause or first hospitalization for decompensated heart failure (HF). A total of 413 patients (32% in AF) were analyzed, with a mean follow-up period of 28 months. The patients were primarily elderly individuals (mean age: 76.2 years), with a slight female predominance and a high prevalence of non-cardiovascular comorbidities. The baseline echocardiographic characteristics and the natriuretic peptide levels were indicative of a more severe heart condition among the patients with AF. However, the patients with AF exhibited a similar survival-free interval compared with the patients in sinus rhythm. In this elderly HFPEF population with a high prevalence of non-cardiovascular comorbidities, the presence of AF was not associated with a worse prognosis despite impaired clinical and echocardiographic features.ClinicalTrials.gov: NCT00774709.

An evaluation of the processing conditions, structure, and properties (biaxial flexural strength and antibacterial efficacy) of sintered strontium-zinc-silicate glass ceramics.

PubMed

Looney, Mark; Shea, Helen O'; Gunn, Lynda; Crowley, Dolores; Boyd, Daniel

2013-05-01

The use of artificial bone grafts has increased in order to satisfy a growing demand for bone replacement materials. Initial mechanical stability of synthetic bone grafts is very advantageous for certain clinical applications. Coupled with the advantage of mechanical strength, a material with inherent antibacterial properties would be very beneficial. A series of strontium-doped zinc silicate (Ca-Sr-Na-Zn-Si) glass ceramics have been characterized in terms of their crystalline structure, biaxial flexural strength and antibacterial efficacy based on the identification of optimum sintering conditions. All three glass ceramics, namely, BT110, BT111, and BT112 were found to be fully crystalline, with BT111 and BT112 comprising of biocompatible crystalline phases. The biaxial flexural strengths of the three glass ceramics ranged from 70 to 149 MPa and were shown to be superior to those of clinically established ceramics in dry conditions and following incubation in simulated physiological conditions. The bacteriostatic effect for each glass ceramic was also established, where BT112 showed an inhibitory effect against three of the most common bacteria found at implantation sites, namely, Enterococcus faecalis, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa. The results of the evaluation suggest that the materials studied offer advantages over current clinical materials and indicate the potential suitability of the glass ceramics as therapeutic bone grafts.

Axillary hyperhidrosis: a focused review.

PubMed

Sammons, Jason E; Khachemoune, Amor

2017-11-01

Axillary hyperhidrosis is characterized by an increased amount of sweat production, localized to the armpits, to compensate for environmental conditions and to control thermoregulation. It affects about 3.12% of the US population. It has a significant effect on one's psychological and physical health, as well as one's occupational life. The objective of this paper is to review the epidemiology, clinical presentation, pathophysiology, histology, genetics, and management and treatment of axillary hyperhidrosis.

In vivo native fluorescence spectroscopy and nicotinamide adinine dinucleotide/flavin adenine dinucleotide reduction and oxidation states of oral submucous fibrosis for chemopreventive drug monitoring

NASA Astrophysics Data System (ADS)

Sivabalan, Shanmugam; Vedeswari, C. Ponranjini; Jayachandran, Sadaksharam; Koteeswaran, Dornadula; Pravda, Chidambaranathan; Aruna, Prakasa Rao; Ganesan, Singaravelu

2010-01-01

Native fluorescence spectroscopy has shown potential to characterize and diagnose oral malignancy. We aim at extending the native fluorescence spectroscopy technique to characterize normal and oral submucous fibrosis (OSF) patients under pre- and post-treated conditions, and verify whether this method could also be considered in the monitoring of therapeutic prognosis noninvasively. In this study, 28 normal subjects and 28 clinically proven cases of OSF in the age group of 20 to 40 years are diagnosed using native fluorescence spectroscopy. The OSF patients are given dexamethasone sodium phosphate and hyaluronidase twice a week for 6 weeks, and the therapeutic response is monitored using fluorescence spectroscopy. The fluorescence emission spectra of normal and OSF cases of both pre- and post-treated conditions are recorded in the wavelength region of 350 to 600 nm at an excitation wavelength of 330 nm. The statistical significance is verified using discriminant analysis. The oxidation-reduction ratio of the tissue is also calculated using the fluorescence emission intensities of flavin adenine dinucleotide and nicotinamide adinine dinucleotide at 530 and 440 nm, respectively, and they are compared with conventional physical clinical examinations. This study suggests that native fluorescence spectroscopy could also be extended to OSF diagnosis and therapeutic prognosis.

Behavioral and language variants of frontotemporal dementia: a review of key symptoms.

PubMed

Laforce, Robert

2013-12-01

While recent advances in the development of neuroimaging and molecular biomarkers for studying neurodegenerative conditions have revolutionized the field, dementia remains a clinical diagnosis. No component of the diagnostic process is more crucial than obtaining a good history. Getting to know the first manifestations of the disease, tracking their evolution and functional impact, combined with a targeted neurological examination, further guides differential diagnosis. This paper summarizes the key symptoms of the behavioral and language variants of frontotemporal dementia. The behavioral variant of frontotemporal dementia (bvFTD) is characterized by severe changes in behavior and personality such as disinhibition, apathy, loss of empathy, or stereotypic behavior, leading to a loss of social competence. Executive functions are impaired, while memory and visuospatial skills are relatively better preserved. By contrast, the language variants or primary progressive aphasias (PPAs) are marked by prominent language disturbances that can be subclassified into a non-fluent/agrammatic variant (naPPA), a semantic variant (svPPA), and a logopenic variant (lvPPA). Although combined characterization of clinical, imaging, biological and genetic biomarkers is essential to establish a detailed diagnosis of such heterogeneous conditions, the author emphasizes the importance of accurate recognition of key symptoms that can lead to better identification of underlying neuropathology and appropriate treatment approaches.

Respiratory manifestations in 38 patients with Alström syndrome.

PubMed

Boerwinkle, Caroline; Marshall, Jan D; Bryant, Joy; Gahl, William A; Olivier, Kenneth N; Gunay-Aygun, Meral

2017-04-01

Alström syndrome (AS) is a rare, multi-system condition characterized by retinal degeneration, sensorineural hearing loss, obesity, insulin-resistant diabetes, hypertriglyceridemia, cardiomyopathy, hepatorenal disease, and recurrent respiratory infections. It belongs to a group of genetic disorders known as primary ciliopathies, which includes autosomal dominant and recessive polycystic kidney diseases, as well as Joubert and Bardet-Biedl syndromes. Prior studies have suggested phenotypic overlap between primary ciliopathies affecting the non-motile, sensory cilia, and primary ciliary dyskinesia (PCD), a motile ciliopathy characterized by respiratory tract disease. We describe the burden of oto-sino-pulmonary disease in 38 individuals with AS and examines the degree of clinical overlap between PCD and AS. Evaluation at the NIH Clinical Center included clinical examination, chest imaging, and clinical history surveys, as well as measurement of nasal nitric oxide (nNO) in nine patients. Recurrent otitis media was ubiquitous in the AS cohort (92%) with 50% requiring pressure equalization tube placement. A history of bronchitis/pneumonia and sinusitis was reported in 61% and 50% of individuals, respectively. PCD-characterizing symptoms (laterality defects, unexplained neonatal respiratory distress, year-round nasal congestion, and wet cough) were far less prevalent in the AS cohort compared to PCD, and the average nNO production in the AS cohort was 232 ± 57.1 nl/min compared to a cut-off of <77 nl/min for PCD. These data suggest that the oto-sino-respiratory complications in AS are prominent enough to warrant increased clinical attention, but significantly impaired respiratory cilia function as seen in PCD is unlikely in AS. (www.clinicaltrials.gov, trial NCT00068224) Pediatr Pulmonol. 2017;52:487-493. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fetal phenotypes in otopalatodigital spectrum disorders.

PubMed

Naudion, S; Moutton, S; Coupry, I; Sole, G; Deforges, J; Guerineau, E; Hubert, C; Deves, S; Pilliod, J; Rooryck, C; Abel, C; Le Breton, F; Collardeau-Frachon, S; Cordier, M P; Delezoide, A L; Goldenberg, A; Loget, P; Melki, J; Odent, S; Patrier, S; Verloes, A; Viot, G; Blesson, S; Bessières, B; Lacombe, D; Arveiler, B; Goizet, C; Fergelot, P

2016-03-01

Otopalatodigital spectrum disorders (OPDSD) include OPD syndromes types 1 and type 2 (OPD1, OPD2), Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). These conditions are clinically characterized by variable skeletal dysplasia associated in males, with extra-skeletal features including brain malformations, cleft palate, cardiac anomalies, omphalocele and obstructive uropathy. Mutations in the FLNA gene have been reported in most FMD and OPD2 cases and in all instances of typical OPD1 and MNS. Here, we report a series of 10 fetuses and a neonatally deceased newborn displaying a multiple congenital anomalies syndrome suggestive of OPDSD and in whom we performed FLNA analysis. We found a global mutation rate of 44%. This series allows expanding the clinical and FLNA mutational spectrum in OPDSD. However, we emphasize difficulties to correctly discriminate OPDSD based on clinical criteria in fetuses due to the major overlap between these conditions. Molecular analyses may help pathologists to refine clinical diagnosis according to the type and the location of FLNA mutations. Discriminating the type of OPDSD is of importance in order to improve the genetic counseling to provide to families. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical Features, Etiologic Factors, Associated Disorders, and Treatment of Palmoplantar Pustulosis: The Mayo Clinic Experience, 1996-2013.

PubMed

Olazagasti, Jeannette M; Ma, Janice E; Wetter, David A

2017-09-01

To further characterize clinical characteristics, etiologic factors, associated disorders, and treatment of palmoplantar pustulosis (PPP). We conducted a retrospective review of patients with PPP at Mayo Clinic between January 1, 1996, and December 31, 2013. Of 215 patients with PPP identified, 179 (83%) were female, and the mean age at onset was 45.3 years. Most patients (n=165, 77%) were current or former smokers. At diagnosis, 15 patients (7%) had an anxiety diagnosis and 9 (4%) had an infection. Nineteen cases (9%) were drug induced. Comorbid conditions included thyroid disease in 18 patients (8%), gluten sensitivity in 3 (1%), and type 2 diabetes mellitus in 21 (10%). In all, 194 patients (90%) received topical corticosteroids, 55 (26%) received phototherapy, and 54 (25%) received systemic agents. More than three-fourths of the patients in this study had a history of smoking, which is considered a triggering or aggravating factor for PPP. Regarding comorbid conditions, gluten sensitivity and thyroid disease were found less frequently than previously reported in the literature. Treatment regimens and responses in this cohort varied considerably. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Early vascular ageing in translation: from laboratory investigations to clinical applications in cardiovascular prevention.

PubMed

Nilsson, Peter M; Boutouyrie, Pierre; Cunha, Pedro; Kotsis, Vasilios; Narkiewicz, Krzysztof; Parati, Gianfranco; Rietzschel, Ernst; Scuteri, Angelo; Laurent, Stephane

2013-08-01

The ageing of the vascular tree is a fundamental reflection of biological ageing in general and a determinant of organ function. In the arterial wall this is characterized by a reduction in the elastin content, as well as by an increased content of collagen and its cross-linkages, leading to increased arterial stiffness and elevated central as well as brachial blood pressure, accompanied by increased SBP variability. In recent years a better understanding of these processes have led to the proposal of a condition named early vascular ageing (EVA) in patients with increased arterial stiffness for their age and sex. This is a condition that could increase cardiovascular risk and is associated with various degrees of cognitive dysfunction, as well as other features of biological ageing. This brief review aims to give an update on EVA and how the concept can be used in clinical practice.

Clinical and genetic diversity of SMN1-negative proximal spinal muscular atrophies

PubMed Central

Jordanova, Albena

2014-01-01

Hereditary spinal muscular atrophy is a motor neuron disorder characterized by muscle weakness and atrophy due to degeneration of the anterior horn cells of the spinal cord. Initially, the disease was considered purely as an autosomal recessive condition caused by loss-of-function SMN1 mutations on 5q13. Recent developments in next generation sequencing technologies, however, have unveiled a growing number of clinical conditions designated as non-5q forms of spinal muscular atrophy. At present, 16 different genes and one unresolved locus are associated with proximal non-5q forms, having high phenotypic variability and diverse inheritance patterns. This review provides an overview of the current knowledge regarding the phenotypes, causative genes, and disease mechanisms associated with proximal SMN1-negative spinal muscular atrophies. We describe the molecular and cellular functions enriched among causative genes, and discuss the challenges in the post-genomics era of spinal muscular atrophy research. PMID:24970098

Catatonia Update.

PubMed

Brar, Kanwarjeet; Kaushik, Sachin S; Lippmann, Steven

2017-10-26

Catatonia is a neuropsychiatric condition characterized by physical presentations ranging from profound immobility to excessive motor activity. Emotional aspects of catatonia vary clinically between psychomotor retardation and extreme excitability. In the past, catatonia was considered to be a variant of schizophrenia. However, the disorder actually occurs as a clinical expression of many different psychiatric, neurologic, or medical diagnoses. A prompt diagnostic evaluation should identify any underlying diseases with consideration of somatic pathologies, especially those affecting central nervous system function. The workup focuses on a range of metabolic, traumatic, infectious, degenerative, autoimmune, drug-related, or other possible conditions, including psychiatric etiologies. Appropriate interventions should be instituted as quickly as possible to avoid complications like dehydration or deep vein thromboses. Symptomatic treatment commonly includes various pharmaceuticals or electroconvulsive therapy. Benzodiazepine drugs are, and have long been, the most preferred pharmacotherapy. These medications are usually fast acting and effective, are safe, and remain the catatonia treatment of choice. © Copyright 2017 Physicians Postgraduate Press, Inc.

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

PubMed Central

Samsonraj, Rebekah M.; Raghunath, Michael; Nurcombe, Victor; Hui, James H.

2017-01-01

Abstract Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self‐renewal and differentiation into tissue‐specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age‐related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone‐forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical‐grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173–2185 PMID:29076267

The Leiden Family Lab study on Social Anxiety Disorder: A multiplex, multigenerational family study on neurocognitive endophenotypes.

PubMed

Bas-Hoogendam, Janna Marie; Harrewijn, Anita; Tissier, Renaud L M; van der Molen, Melle J W; van Steenbergen, Henk; van Vliet, Irene M; Reichart, Catrien G; Houwing-Duistermaat, Jeanine J; Slagboom, P Eline; van der Wee, Nic J A; Westenberg, P Michiel

2018-06-01

Social anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so-called "endophenotypes". These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety. The LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD. The sample (n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self-reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms. By the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD. © 2018 The Authors International Journal of Methods in Psychiatric Research Published by John Wiley & Sons Ltd.

Molecular and cytogenetic characterization of a de novo partial trisomy 3p case with review

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

Conte, R.A.; Pitter, J.; Verma, R.S.

A one-year-old male infant was found to have a de novo unbalanced translocation resulting in partial trisomy for 3p, i.e. 46,XY,der(7)t(3;7)(p24.2;p22). Major clinical features included: dysmorphic ears, decreased muscle tone and episodes of seizures associated with fever. GTG- and QFQ-banding revealed additional material suggestive of chromosome 3p that was translocated to the terminal 7p. The FISH technique with two-color specific DNA probes for whole chromosomes 3 and 7 verified this finding. Other probands with the same amount of trisomic 3p2 segments as the present case had additional clinical abnormalities. Previously, identification of this so-called trisomy 3p2 syndrome was invariably basedmore » on the analysis of GTG-banded metaphase chromosomes. A review of 37 earlier cases revealed that the clinical manifestations varied with the amount of 3p2 material in the trisomic state, demonstrating increased anomalies with increased 3p2 sub-band trisomy. Phenotype to genotype correlation is best understood under conditions that can achieve respective characterization with a high degree of certainty. Presently, the FISH technique fulfills this requirement and the employment of loci probes that span 3p, when available, will ultimately increase the characterization resolution to the gene level.« less

Follicular cyst of the jaw developing into a keratocyst in a patient with unrecognized Gorlin-Goltz syndrome.

PubMed

Longobardi, Gianluigi; Diana, Giovanni; Poddi, Valentina; Pagano, Immacolata

2010-05-01

Gorlin-Goltz (GG) syndrome is an inherited autosomal dominant condition. Its diagnosis may be clinically confirmed by checking either major or minor signs that define the diagnostic criteria. It may occur that, although GG syndrome is a well-known condition, only the specific symptom could be observed by different specialists. Therefore, the patient cannot be placed into an always complex clinical panel. We introduce an example in this report. Throughout a 20-year clinical history characterized by the lack of proper diagnosis and missed follow-up operations, a patient with GG syndrome underwent partial amputation of the jaw after severe complications. A 52-year-old man required an implant-prosthetic rehabilitation since becoming edentulous after a partial resection of the jaw due to a keratocyst, which was later reconstructed through a free fibula flap. The observation of a typical phenotype and various symptoms that succeeded for longer than 20 years, with anamnestic evaluation and clinical examination, led us to suspect a complex pathologic condition such as GG syndrome, which was not previously considered, although the patient had undergone several polyspecialistic evaluations. Diagnosis has been eventually confirmed by a genetic study, which was always mandatory. The simultaneous presence of muscular and skeletal malformations, basocellular nevi, and multiple cysts of the jaw can represent signs linking to a condition such as GG syndrome. There are many syndromes involving the head and neck region, and specialists are supposed to be alerted when faced with similar typical expressions associated with a characteristic soma so as to avoid delays in diagnosing the syndrome.

An interesting case of straight back syndrome and review of the literature.

PubMed

Soleti, Pavan; Wilson, Bivin; Vijayakumar, Arani Rajabathar; Chakravarthi, Paulraj Ignatius Sudhakar; Reddy, Chilakala Gopinath

2016-01-01

Straight back syndrome is characterized by loss of the normal upper thoracic kyphosis, leading to a reduced anteroposterior diameter and squashing of the heart. Most patients are asymptomatic; if symptomatic, chest pain and palpitations are most common. On examination, the abnormal clinical findings simulate organic heart disease that needs to be ruled out by echocardiography and cardiac catheterization. A lateral chest radiograph is diagnostic. This condition is commonly associated with mitral valve prolapse and bicuspid aortic valve. We describe an interesting case of straight back syndrome with all the classic and rarely reported clinical findings. © The Author(s) 2014.

Ectodermal Dysplasia: A Clinical Overview for the Dental Practitioner.

PubMed

Halai, Tina; Stevens, Claire

2015-10-01

The term ectodermal dysplasia (ED) is used to describe a group of rare congenital disorders characterized by abnormalities of two or more ectodermal structures such as the skin, hair, nails, teeth and sweat glands. This paper will give an overview of the aetiology of ED and describe the manifestations and dental management of this condition. In particular, the important role of the dental practitioner in the identification and management of patients with ED will be highlighted. CPD/Clinical Relevance: Dental practitioners should be aware of the oral features of ectodermal dysplasia and be able to make timely referrals and provide appropriate continuing care for these patients.

CARs: Synthetic Immunoreceptors for Cancer Therapy and Beyond

PubMed Central

Chang, ZeNan L.; Chen, Yvonne Y.

2017-01-01

Chimeric antigen receptors (CARs) are versatile synthetic receptors that provide T cells with engineered specificity. Clinical success in treating B-cell malignancies has demonstrated the therapeutic potential of CAR-T cells against cancer, and efforts are underway to expand the use of engineered T cells to the treatment of diverse medical conditions, including infections and autoimmune diseases. Here, we review current understanding of the molecular properties of CARs, how this knowledge informs the rational design and characterization of novel receptors, successes and shortcomings of CAR-T cells in the clinic, and emerging solutions for the continued improvement of CAR-T cell therapy. PMID:28416139

Clinical presentation of Churg-Strauss syndrome in children: A 12-year-old-boy with ANCA-negative Churg-Strauss syndrome.

PubMed

Razenberg, Femke G E M; Heynens, Jan W C M; Jan de Vries, Geeuwke; Duijts, Liesbeth; de Jongste, Johan C; de Blic, Jacques; Rosias, Philippe P R

2012-01-01

Churg-Strauss syndrome is an uncommon multisystem disorder characterized by asthma, eosinophilia and vasculitis. We report on a 12-year-old boy with asthma and deterioration of his general condition, who was eventually diagnosed with an ANCA-negative Churg-Strauss syndrome. The propositus included, 50 cases of childhood Churg-Strauss syndrome have been reported. The patient characteristics and clinical characteristics of these children are summarized. The respiratory tract is most frequently involved with pulmonary infiltrates, asthma and sinusitis. Early recognition of childhood Churg-Strauss syndrome is important as delayed diagnosis can lead to severe organ involvement, and possible fatal outcome.

Quadriplegia due to celiac crisis with hypokalemia as initial presentation of celiac disease: a case report.

PubMed

Bhattacharya, Malobika; Kapoor, Seema

2012-02-01

Celiac crisis is a rare, life-threatening complication of celiac disease characterized by worsening of clinical symptoms, multiple metabolic derangements and shock. We report an 8-year-old girl with previously undiagnosed celiac disease who presented with flaccid quadriparesis secondary to severe hypokalemia associated with celiac crisis. Diagnosis was expedited by an elevated anti-tissue transglutaminase antibody titer. The patient improved with correction of hypokalemia, corticosteroids and gluten-free diet. In tropical countries such as India, where both acute flaccid paresis and diarrhea are usually of infective etiologies, this rare clinical condition should also be considered in the differential diagnosis of both.

Novel targeted therapies for eosinophilic disorders

PubMed Central

Wechsler, Michael E.; Fulkerson, Patricia C.; Bochner, Bruce S.; Gauvreau, Gail M.; Gleich, Gerald J.; Henkel, Tim; Kolbeck, Roland; Mathur, Sameer K.; Ortega, Hector; Patel, Jatin; Prussin, Calman; Renzi, Paolo; Rothenberg, Marc E.; Roufosse, Florence; Simon, Dagmar; Simon, Hans-Uwe; Wardlaw, Andrew; Weller, Peter F.; Klion, Amy D.

2013-01-01

Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. HESs are chronic disorders with significant morbidity and mortality. Although the availability of targeted chemotherapeutic agents, including imatinib, has improved quality of life and survival in some patients with HESs, additional agents with increased efficacy and decreased toxicity are sorely needed. The purpose of this review is to provide an overview of eosinophil biology with an emphasis on potential targets of pharmacotherapy and to provide a summary of potential eosinophil-targeting agents, including those in development, in clinical trials, or approved for other disorders. PMID:22935585

Biosimilars: Here and Now.

PubMed

Lemery, Steven J; Esteva, Francisco J; Weise, Martina

2016-01-01

Congress passed the Biologics Price Competition and Innovation Act (BPCI Act) as part of the Affordable Care Act on March 23, 2010. The BPCI Act authorized an approval pathway for biosimilar and interchangeable products. It defines biosimilarity to mean "that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components" and that "there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency of the product." The biosimilar pathway has the potential to facilitate access to biologic products through increased competition, in the same manner as biosimilars have done for almost 10 years in Europe. The goal of a biosimilar program is not to independently establish safety and effectiveness for each condition of use. Rather, the goal is to demonstrate biosimilarity through an extensive analytical characterization and a targeted clinical program designed to assess for clinically meaningful differences, if they exist. The regulatory approaches in both the United States and Europe involve a totality-of-the-evidence approach to demonstrate biosimilarity. Importantly, the biosimilar pathway allows for extrapolation of data across indications so that a sponsor, with adequate scientific justification, need not conduct clinical studies in each intended condition of use. Without extrapolation, development may not be feasible for many products, and patients and resources could be diverted from clinical studies of newer agents for cancer.

Secondary Conditions Among Males With Duchenne or Becker Muscular Dystrophy.

PubMed

Latimer, Rebecca; Street, Natalie; Conway, Kristin Caspers; James, Kathy; Cunniff, Christopher; Oleszek, Joyce; Fox, Deborah; Ciafaloni, Emma; Westfield, Christina; Paramsothy, Pangaja

2017-06-01

Duchenne and Becker muscular dystrophy are X-linked neuromuscular disorders characterized by progressive muscle degeneration. Despite the involvement of multiple systems, secondary conditions among affected males have not been comprehensively described. Two hundred nine caregivers of affected males (aged 3-31 years) identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network completed a mailed survey that included questions about secondary conditions impacting multiple body functions. The 5 most commonly reported conditions in males with Duchenne were cognitive deficits (38.4%), constipation (31.7%), anxiety (29.3%), depression (27.4%), and obesity (19.5%). Higher frequencies of anxiety, depression, and kidney stones were found among nonambulatory males compared to ambulatory males. Attention-deficit hyperactivity disorder (ADHD) was more common in ambulatory than nonambulatory males. These data support clinical care recommendations for monitoring of patients with Duchenne or Becker muscular dystrophy by a multidisciplinary team to prevent and treat conditions that may be secondary to the diagnosis.

Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients.

PubMed

Domínguez, Raúl O; Marschoff, Enrique R; González, Silvia E; Repetto, Marisa G; Serra, Jorge A

2012-10-01

To evaluate the cognitive performance of a homogeneous population of Alzheimer's disease (AD), non-demented Type 2 Diabetes Mellitus (DIAB), demented with concomitant diseases (AD+DIAB) and healthy control subjects. AD is a progressive dementia disorder characterized clinically by impairment of memory, cognition and behavior. Recently, a major research interest in AD has been placed on early evaluation. Diabetes is one of the clinical conditions that represent the greatest risk of developing oxidative stress and dementia. Glucose overload, leading to the development of impaired-induced insulin secretion in DIAB and has been suggested to slow or deter AD pathogenesis. The degree of cognitive impairment was determined on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) and the Folstein's Mini Mental State Examination (MMSE); the severity of dementia was quantified applying the Clinical Dementia Rating (CDR) test; the Hamilton test was employed to evaluate depressive conditions; the final population studied was 101 subjects. The cognitive deterioration is statistically significantly lower (p<0.05) in AD+DIAB patients as compared with AD patients. In this longitudinal study the superimposed diabetic condition was associated with a lower rate of cognitive decline, while diabetic non-demented patients and controls present normal scores. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hypopituitarism in the elderly: a narrative review on clinical management of hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes dysfunction.

PubMed

Curtò, L; Trimarchi, F

2016-10-01

Hypopituitarism is an uncommon and under-investigated endocrine disorder in old age since signs and symptoms are unspecific and, at least in part, can be attributed to the physiological effects of aging and related co-morbidities. Clinical presentation is often insidious being characterized by non-specific manifestations, such as weight gain, fatigue, low muscle strength, bradipsychism, hypotension or intolerance to cold. In these circumstances, hypopituitarism is a rarely life-threatening condition, but evolution may be more dramatic as a result of pituitary apoplexy, or when a serious condition of adrenal insufficiency suddenly occurs. Clinical presentation depends on the effects that each pituitary deficit can cause, and on their mutual relationship, but also, inevitably, it depends on the severity and duration of the deficit itself, as well as on the general condition of the patient. Indeed, indications and methods of hormone replacement therapy must include the need to normalize the endocrine profile without contributing to the worsening of intercurrent diseases, such as those of glucose and bone metabolism, and the cardiovascular system, or to the increasing cancer risk. Hormonal requirements of elderly patients are reduced compared to young adults, but a prompt diagnosis and appropriate treatment of pituitary deficiencies are strongly recommended, also in this age range.

The Spectrum of Differences between Childhood and Adulthood Celiac Disease

PubMed Central

Ciccocioppo, Rachele; Kruzliak, Peter; Cangemi, Giuseppina C.; Pohanka, Miroslav; Betti, Elena; Lauret, Eugenia; Rodrigo, Luis

2015-01-01

An old saying states that ‘’children are not little adults” and this certainly holds true for celiac disease, as there are many peculiar aspects regarding its epidemiology, diagnosis, clinical presentations, associated diseases, and response to treatment in pediatric compared to adult populations, to such an extent that it merits a description of its own. In fact, contrary to the past when it was thought that celiac disease was a disorder predominantly affecting childhood and characterized by a malabsorption syndrome, nowadays it is well recognized that it affects also adult and elderly people with an impressive variability of clinical presentation. In general, the clinical guidelines for diagnosis recommend starting with specific serologic testing in all suspected subjects, including those suffering from extraintestinal related conditions, and performing upper endoscopy with appropriate biopsy sampling of duodenal mucosa in case of positivity. The latter may be omitted in young patients showing high titers of anti-transglutaminase antibodies. The subsequent management of a celiac patient differs substantially depending on the age at diagnosis and should be based on the important consideration that this is a lifelong condition. PMID:26506381

Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation

PubMed Central

Thomson, Angus W.; Zahorchak, Alan F.; Ezzelarab, Mohamed B.; Butterfield, Lisa H.; Lakkis, Fadi G.; Metes, Diana M.

2016-01-01

Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients’ dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail. PMID:26858719

Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation.

PubMed

Thomson, Angus W; Zahorchak, Alan F; Ezzelarab, Mohamed B; Butterfield, Lisa H; Lakkis, Fadi G; Metes, Diana M

2016-01-01

Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients' dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail.

Late outcomes of adult survivors of childhood non-Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study.

PubMed

Ehrhardt, Matthew J; Sandlund, John T; Zhang, Nan; Liu, Wei; Ness, Kirsten K; Bhakta, Nickhill; Chemaitilly, Wassim; Krull, Kevin R; Brinkman, Tara M; Crom, Deborah B; Kun, Larry; Kaste, Sue C; Armstrong, Gregory T; Green, Daniel M; Srivastava, Kumar; Robison, Leslie L; Hudson, Melissa M; Mulrooney, Daniel A

2017-06-01

Survivors of childhood non-Hodgkin lymphoma (NHL) are at increased risk for chronic health conditions. The objective of this study was to characterize health conditions, neurocognitive function, and physical performance among a clinically evaluated cohort of 200 childhood NHL survivors. Chronic health and neurocognitive conditions were graded as per a modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and impaired physical function defined as performance < 10th percentile of normative data. Multivariable regression was used to investigate associations between sociodemographic characteristics, therapeutic exposures, and outcomes. Survivors were a median age of 10 years (range 1-19) at diagnosis and 34 years (range 20-58) at evaluation. Eighty-eight (44%) received radiation, 46 (23%) cranial radiation, and 69 (35%) high-dose methotrexate. Most prevalent CTCAE Grades 3-4 (severe life-threatening) conditions were obesity (35%), hypertension (9%), and impairment of executive function (13%), attention (9%), and memory (4%). Many had impaired strength (48%), flexibility (39%), muscular endurance (36%), and mobility (36%). Demographic and treatment-related factors were associated with the development of individual chronic diseases and functional deficits. Clinical evaluation identified a high prevalence of chronic health conditions, neurocognitive deficits, and performance limitations in childhood NHL survivors. © 2016 Wiley Periodicals, Inc.

Quantitative characterization of mechanically indented in vivo human skin in adults and infants using optical coherence tomography

NASA Astrophysics Data System (ADS)

Huang, Pin-Chieh; Pande, Paritosh; Shelton, Ryan L.; Joa, Frank; Moore, Dave; Gillman, Elisa; Kidd, Kimberly; Nolan, Ryan M.; Odio, Mauricio; Carr, Andrew; Boppart, Stephen A.

2017-03-01

Influenced by both the intrinsic viscoelasticity of the tissue constituents and the time-evolved redistribution of fluid within the tissue, the biomechanical response of skin can reflect not only localized pathology but also systemic physiology of an individual. While clinical diagnosis of skin pathologies typically relies on visual inspection and manual palpation, a more objective and quantitative approach for tissue characterization is highly desirable. Optical coherence tomography (OCT) is an interferometry-based imaging modality that enables in vivo assessment of cross-sectional tissue morphology with micron-scale resolution, which surpasses those of most standard clinical imaging tools, such as ultrasound imaging and magnetic resonance imaging. This pilot study investigates the feasibility of characterizing the biomechanical response of in vivo human skin using OCT. OCT-based quantitative metrics were developed and demonstrated on the human subject data, where a significant difference between deformed and nondeformed skin was revealed. Additionally, the quantified postindentation recovery results revealed differences between aged (adult) and young (infant) skin. These suggest that OCT has the potential to quantitatively assess the mechanically perturbed skin as well as distinguish different physiological conditions of the skin, such as changes with age or disease.

Physical frailty and sarcopenia (PF&S): a point of view from the industry.

PubMed

Del Signore, Susanna; Roubenoff, Ronenn

2017-02-01

We have observed over the last 15 years a wide debate both in the medical scientific community and in the public health arena on the definition and operationalization of frailty, typically a geriatric condition, and in particular of physical frailty linked to sarcopenia. Because physical frailty in its initial phase can still be reversed, fighting sarcopenia in elderly persons has the potential to slow or halt progressive decline towards disability and dependency. Quite recently, regulators focused attention on frailty as an indicator of biological age to be measured to characterize elderly patients before their inclusion in clinical trials. A European guidance regarding most adapted evaluation instruments of frailty is currently under public consultation. Does the regulatory initiative imply we should now consider frailty, and particularly physical frailty, primarily as an important risk factor for adverse events and poor response, or mainly as a clinical tool helping the physician to opt for one therapeutic pathway or another? Or is physical frailty above all a specific geriatric condition deserving an effective and innovative therapeutic approach with the objective to curb the incidence of its most common result, e.g., mobility disability? Pharmaceutical industry developers consider both faces of the coin very relevant. We agree with regulators that better characterization of subpopulations, not only in elderly patients, can improve the benefit risk ratio of medicines. At the same time, we believe it is in the public health interest to develop novel drugs indicated for specific geriatric conditions, like osteoporosis in the 1990s and sarcopenia today. We consider it an important therapeutic goal to effectively delay mobility disability and to extend the active, independent, and healthy life years of aging people. The "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) collaborative project under IMI is paving the way for adapted methodologies to study the change of physical frailty and sarcopenia in at-risk older persons and to adequately characterize the population that needs to be treated.

Magnesium in the gynecological practice: a literature review.

PubMed

Parazzini, Fabio; Di Martino, Mirella; Pellegrino, Paolo

2017-02-01

A growing amount of evidence suggests that magnesium deficiency may play an important role in several clinical conditions concerning women health such as premenstrual syndrome, dysmenorrhea, and postmenopausal symptoms. A number of studies highlighted a positive correlation between magnesium administration and relief or prevention of these symptoms, thus suggesting that magnesium supplementation may represent a viable treatment for these conditions. Despite this amount of evidence describing the efficacy of magnesium, few and un-systematize data are available about the pharmacological mechanism of this ion for these conditions. Herein, we review and systematize the available evidence about the use of oral magnesium supplementation in several gynecological conditions and discuss the pharmacological mechanisms that characterize these interventions. The picture that emerges indicates that magnesium supplementation is effective in the prevention of dysmenorrhea, premenstrual syndrome, and menstrual migraine and in the prevention of climacteric symptoms.

Understanding Bartter syndrome and Gitelman syndrome.

PubMed

Fremont, Oliver T; Chan, James C M

2012-02-01

We aim to review the clinical features of two renal tubular disorders characterized by sodium and potassium wasting: Bartter syndrome and Gitelman syndrome. Selected key references concerning these syndromes were analyzed, together with a PubMed search of the literature from 2000 to 2011. The clinical features common to both conditions and those which are distinct to each syndrome were presented. The new findings on the genetics of the five types of Bartter syndrome and the discrete mutations in Gitelman syndrome were reviewed, together with the diagnostic workup and treatment for each condition. Patients with Bartter syndrome types 1, 2 and 4 present at a younger age than classic Bartter syndrome type 3. They present with symptoms, often quite severe in the neonatal period. Patients with classic Bartter syndrome type 3 present later in life and may be sporadically asymptomatic or mildly symptomatic. The severe, steady-state hypokalemia in Bartter syndrome and Gitelman syndrome may abruptly become life-threatening under certain aggravating conditions. Clinicians need to be cognizant of such renal tubular disorders, and promptly treat at-risk patients.

Patient-Specific Simulations of Reactivity in Models of the Pulmonary Vasculature: A 3-D Numerical Study with Fluid-Structure Interaction

NASA Astrophysics Data System (ADS)

Hunter, Kendall; Zhang, Yanhang; Lanning, Craig

2005-11-01

Insight into the progression of pulmonary hypertension may be obtained from thorough study of vascular flow during reactivity testing, an invasive diagnostic procedure which can dramatically alter vascular hemodynamics. Diagnostic imaging methods, however, are limited in their ability to provide extensive data. Here we present detailed flow and wall deformation results from simulations of pulmonary arteries undergoing this procedure. Patient-specific 3-D geometric reconstructions of the first four branches of the pulmonary vasculature were obtained clinically and meshed for use with computational software. Transient simulations in normal and reactive states were obtained from four such models were completed with patient-specific velocity inlet conditions and flow impedance exit conditions. A microstructurally based orthotropic hyperelastic model that simulates pulmonary artery mechanics under normotensive and hypoxic hypertensive conditions treated wall constitutive changes due to pressure reactivity and arterial remodeling. Pressure gradients, velocity fields, arterial deformation, and complete topography of shear stress were obtained. These models provide richer detail of hemodynamics than can be obtained from current imaging techniques, and should allow maximum characterization of vascular function in the clinical situation.

Proctalgia fugax: a clinical enigma.

PubMed

Peery, W H

1988-05-01

Proctalgia fugax is a benign condition characterized by paroxysms of anorectal pain in the absence of identifiable anorectal lesions. The cause is unknown but may involve spasm of smooth or striated muscle. Surveys indicate the disorder is common in the general population, with only a minority of victims seeking medical attention. There is no universally accepted treatment for proctalgia fugax. The diagnosis is established by the typical history and the exclusion of other pelvic and anorectal abnormality.

Epidemiological and etiological aspects of burning mouth syndrome.

PubMed

Coculescu, E C; Tovaru, S; Coculescu, B I

2014-09-15

Burning mouth syndrome (BMS) is defined as a chronic pain condition characterized by a burning sensation in clinically healthy oral mucosa. Incidence BMS diagnosed in the Department of Oral Medicine - Oral Pathology Dental Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy Bucharest is 16,23%. The etiology of BMS remains far less known. This article makes an overview of the latest theories about possible etiopathogenic factors involved in the occurrence of BMS.

[Tall stature: some classical syndromes].

PubMed

Gusbin, N; Verloes, A; Daly, A; Beckers, A

2006-01-01

We describe the findings of XYY syndrome in the setting of encountering an individual with this particular condition in the endocrinology clinic. XYY syndrome is a relatively frequent if unfamiliar condition, which is characterized by taller than average height. The extra Y chromosome may play a role in determining the height of these individuals. From this case, a differential diagnosis of tall stature is outlined, in addition to a description of the principal syndromes associated with gigantism. These primarily include Klinefelter syndrome, Marfan syndrome, androgen resistance and growth hormone excess. These various entities are described from the point of view of their symptomatology, biology, pathophysiology and therapeutic characteristics.

Occurrence of killer Candida glabrata clinical isolates

PubMed Central

Arroyo-Helguera, O; Penas Alejandro, De Las; Irene, Castaño

2012-01-01

In this work we characterized the occurrence of killer activity in 64 Candida glabrata clinical isolates under different conditions. We found that only 6.25 % of the clinical isolates tested were positive for killer activity against a Saccharomyces cerevisiae W303 sensitive strain. Sensitivity of killer activity to different values of pH and temperatures was analyzed. We found that the killer activity presented by all isolates was resistant to every pH and temperature tested, although optimal activity was found at a range of pH values from 4 to 7 and at 37°C. We did not observe extrachromosomal genetic elements associated with killer activity in any of the positive C. glabrata isolates. The killer effect was due to a decrease in viability and DNA fragmentation in sensitive yeast. PMID:24031902

Quantitative CT characterization of pediatric lung development using routine clinical imaging

PubMed Central

Stein, Jill M.; Walkup, Laura L.; Brody, Alan S.; Fleck, Robert J.

2016-01-01

Background The use of quantitative CT analysis in children is limited by lack of normal values of lung parenchymal attenuation. These characteristics are important because normal lung development yields significant parenchymal attenuation changes as children age. Objective To perform quantitative characterization of normal pediatric lung parenchymal X-ray CT attenuation under routine clinical conditions in order to establish a baseline comparison to that seen in pathological lung conditions. Materials and methods We conducted a retrospective query of normal CT chest examinations in children ages 0–7 years from 2004 to 2014 using standard clinical protocol. During these examinations semi-automated lung parenchymal segmentation was performed to measure lung volume and mean lung attenuation. Results We analyzed 42 CT examinations in 39 children, ages 3 days to 83 months (mean ± standard deviation [SD] = 42±27 months). Lung volume ranged 0.10–1.72 liters (L). Mean lung attenuation was much higher in children younger than 12 months, with values as high as −380 Hounsfield units (HU) in neonates (lung volume 0.10 L). Lung volume decreased to approximately −650 HU by age 2 years (lung volume 0.47 L), with subsequently slower exponential decrease toward a relatively constant value of −860 HU as age and lung volume increased. Conclusion Normal lung parenchymal X-ray CT attenuation decreases with increasing lung volume and age; lung attenuation decreases rapidly in the first 2 years of age and more slowly thereafter. This change in normal lung attenuation should be taken into account as quantitative CT methods are translated to pediatric pulmonary imaging. PMID:27576458

Numerical analysis for characterization of the gold nanorod mediated-plasmonic heating with temporary NIR laser radiation for superficial breast cancer therapy

NASA Astrophysics Data System (ADS)

Bae, Ji Yong; Nam, Ki-Hwan; Jeong, Chan Bae; Kim, Geon-hee; Chang, Ki Soo

2016-09-01

Over the last decade, plasmonic photothermal therapy (PPTT) has received significant attention as the new therapeutic strategy for the cancer therapy due to unique characteristics of the gold-nanoparticles. The characterization of the spatiotemporal heating potential for the gold nanorods (GNR) through mimicking PPTT process on the various conditions can help more quantitative approaches to treatment planning. The purpose of this study was to clearly understand the optical-thermal interactions between the laser, GNRs, and bio-tissues, and provide the information in clinical applications to implement the concept of heterogeneity, which can enable the optimization of treatment parameters for superficial breast cancer treatment.

Tissue slide-based microRNA characterization of tumors: how detailed could diagnosis become for cancer medicine?

PubMed Central

Sempere, Lorenzo F

2014-01-01

miRNAs are short, non-coding, regulatory RNAs that exert cell type-dependent, context-dependent, transcriptome-wide gene expression control under physiological and pathological conditions. Tissue slide-based assays provide qualitative (tumor compartment) and semi-quantitative (expression levels) information about altered miRNA expression at single-cell resolution in clinical tumor specimens. Reviewed here are key technological advances in the last 5 years that have led to implementation of fully automated, robust and reproducible tissue slide-based assays for in situ miRNA detection on US FDA-approved instruments; recent tissue slide-based discovery studies that suggest potential clinical applications of specific miRNAs in cancer medicine are highlighted; and the challenges in bringing tissue slide-based miRNA assays into the clinic are discussed, including clinical validation, biomarker performance, biomarker space and integration with other biomarkers. PMID:25090088

Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis☆

PubMed Central

Pangrazio, Alessandra; Puddu, Alessandro; Oppo, Manuela; Valentini, Maria; Zammataro, Luca; Vellodi, Ashok; Gener, Blanca; Llano-Rivas, Isabel; Raza, Jamal; Atta, Irum; Vezzoni, Paolo; Superti-Furga, Andrea; Villa, Anna; Sobacchi, Cristina

2014-01-01

Autosomal Recessive Osteopetrosis is a genetic disorder characterized by increased bone density due to lack of resorption by the osteoclasts. Genetic studies have widely unraveled the molecular basis of the most severe forms, while cases of intermediate severity are more difficult to characterize, probably because of a large heterogeneity. Here, we describe the use of exome sequencing in the molecular diagnosis of 2 siblings initially thought to be affected by “intermediate osteopetrosis”, which identified a homozygous mutation in the CTSK gene. Prompted by this finding, we tested by Sanger sequencing 25 additional patients addressed to us for recessive osteopetrosis and found CTSK mutations in 4 of them. In retrospect, their clinical and radiographic features were found to be compatible with, but not typical for, Pycnodysostosis. We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative. In conclusion, we underline the difficulties of differential diagnosis in some patients whose clinical appearance does not fit the classical malignant or benign picture and recommend that CTSK gene be included in the molecular diagnosis of high bone density conditions. PMID:24269275

Systemic mastocytosis--a systematic review.

PubMed

Andersen, Christen Lykkegaard; Kristensen, Thomas Kielsgaard; Severinsen, Marianne Tang; Møller, Michael Boe; Vestergaard, Hanne; Bergmann, Olav J; Hasselbalch, Hans Carl; Bjerrum, Ole Weis

2012-03-01

The mast cell lives a hidden life, but it is implicated in several physiological reactions. Its ability to react to different stimuli impacts a variety of conditions such as asthma, atopic dermatitis, urticaria and anaphylaxis. It is not until recent decades that the evolution of the cell has been described and its fascinating biology has only recently been depicted. We here give a review of systemic mastocytosis in regards to cell biology, diagnostic approaches and clinical practice. A search was made in PubMed in August 2011 entering the keywords: mastocytosis, (systemic, cutaneous, aggressive), mast cell leukaemia, mast cell sarcoma, chromosome, mutation, haematology and treatment. Mastocytosis is characterized by an abnormal proliferation of mast cells, which accumulate in one or several organ systems, primarily the skin and bone marrow. The disease is clinically heterogeneous and varies from a relatively benign condition with isolated cutaneous lesions to a very aggressive systemic condition with a grave prognosis. The condition affects men and women equally. Children are especially affected by the cutaneous form. In most children, the condition will improve or remit spontaneously before adulthood. Mastocytosis in adults, however, is more often systemic and tends to persist. Patients with mastocytosis represent a heterogeneous group in terms of clinical presentation, management and prognosis. Furthermore, a range of medical specialties serve as the primary entrance to health services, which can be a challenge in respect of achieving uniform management. In order to improve diagnostics and management of systemic mastocytosis, the European Competence Network on Mastocytosis has been established. Patients under suspicion of systemic mastocytosis should be conferred with or referred to a haematological and a dermatological/allergological department.

The use of current source density as electrophysiological correlates in neuropsychiatric disorders: a review of human studies

PubMed Central

Kamarajan, Chella; Pandey, Ashwini K.; Chorlian, David B.; Porjesz, Bernice

2014-01-01

The use of current source density (CSD), the Laplacian of the scalp surface voltage, to map the electrical activity of the brain is a powerful method in studies of cognitive and affective phenomena. During the last few decades, mapping of CSD has been successfully applied to characterize several neuropsychiatric conditions such as alcoholism, schizophrenia, depression, anxiety disorders, childhood/developmental disorders, and neurological conditions (i.e., epilepsy and brain lesions) using electrophysiological data from resting state and during cognitive performance. Use of CSD and Laplacian measures has proven effective in elucidating topographic and activation differences between groups: i) patients with a specific diagnosis vs. healthy controls, ii) subjects at high risk for a specific diagnosis vs. low risk or normal controls, and iii) patients with specific symptom(s) vs. patients without these symptom(s). The present review outlines and summarizes the studies that have employed CSD measures in investigating several neuropsychiatric conditions. The advantages and potential of CSD-based methods in clinical and research applications along with some of the limitations inherent in the CSD-based methods are discussed in the review, as well as future directions to expand the implementation of CSD to other potential clinical applications. As CSD methods have proved to be more advantageous than using scalp potential data to understand topographic and source activations, its clinical applications offer promising potential, not only for a better understanding of a range of psychiatric conditions, but also for a variety of focal neurological disorders, including epilepsy and other conditions involving brain lesions and surgical interventions. PMID:25448264

Tonic pain and continuous EEG: prediction of subjective pain perception by alpha-1 power during stimulation and at rest.

PubMed

Nir, Rony-Reuven; Sinai, Alon; Moont, Ruth; Harari, Eyal; Yarnitsky, David

2012-03-01

Pain neurophysiology has been chiefly characterized via event-related potentials (ERPs), which are exerted using brief, phase-locked noxious stimuli. Striving for objectively characterizing clinical pain states using more natural, prolonged stimuli, tonic pain has been recently associated with the individual peak frequency of alpha oscillations. This finding encouraged us to explore whether alpha power, reflecting the magnitude of the synchronized activity within this frequency range, will demonstrate a corresponding relationship with subjective perception of tonic pain. Five-minute-long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with alpha-1 and alpha-2 power. NPSs and alpha power remained stable throughout the recording conditions (Ps⩾0.381). In the noxious condition, alpha-1 power obtained at the bilateral temporal scalp was negatively correlated with NPSs (Ps⩽0.04). Additionally, resting-state alpha-1 power recorded at the bilateral temporal scalp was negatively correlated with NPSs reported during the noxious condition (Ps⩽0.038). Current findings suggest alpha-1 power may serve as a direct, objective and experimentally stable measure of subjective perception of tonic pain. Furthermore, resting-state alpha-1 power might reflect individuals' inherent tonic pain responsiveness. The relevance of alpha-1 power to tonic pain perception may deepen the understanding of the mechanisms underlying the processing of prolonged noxious stimulation. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology.

PubMed

Kontoghiorghe, Christina N; Kolnagou, Annita; Kontoghiorghes, George J

2015-11-23

Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό)-plant, chele (χηλή)-claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries.

Emerging treatment options for refractory angina pectoris: ranolazine, shock wave treatment, and cell-based therapies.

PubMed

Gennari, Marco; Gambini, Elisa; Bassetti, Beatrice; Capogrossi, Maurizio; Pompilio, Giulio

2014-01-01

A challenge of modern cardiovascular medicine is to find new, effective treatments for patients with refractory angina pectoris, a clinical condition characterized by severe angina despite optimal medical therapy. These patients are not candidates for surgical or percutaneous revascularization. Herein we review the most up-to-date information regarding the modern approach to the patient with refractory angina pectoris, from conventional medical management to new medications and shock wave therapy, focusing on the use of endothelial precursor cells (EPCs) in the treatment of this condition. Clinical limitations of the efficiency of conventional approaches justify the search for new therapeutic options. Regenerative medicine is considered the next step in the evolution of organ replacement therapy. It is driven largely by the same health needs as transplantation and replacement therapies, but it aims further than traditional approaches, such as cell-based therapy. Increasing knowledge of the role of circulating cells derived from bone marrow (EPCs) on cardiovascular homeostasis in physiologic and pathologic conditions has prompted the clinical use of these cells to relieve ischemia. The current state of therapeutic angiogenesis still leaves many questions unanswered. It is of paramount importance that the treatment is delivered safely. Direct intramyocardial and intracoronary administration has demonstrated acceptable safety profiles in early trials, and may represent a major advance over surgical thoracotomy. The combined efforts of bench and clinical researchers will ultimately answer the question of whether cell therapy is a suitable strategy for treatment of patients with refractory angina.

Peri-implant diseases and conditions: Consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions.

PubMed

Berglundh, Tord; Armitage, Gary; Araujo, Mauricio G; Avila-Ortiz, Gustavo; Blanco, Juan; Camargo, Paulo M; Chen, Stephen; Cochran, David; Derks, Jan; Figuero, Elena; Hämmerle, Christoph H F; Heitz-Mayfield, Lisa J A; Huynh-Ba, Guy; Iacono, Vincent; Koo, Ki-Tae; Lambert, France; McCauley, Laurie; Quirynen, Marc; Renvert, Stefan; Salvi, Giovanni E; Schwarz, Frank; Tarnow, Dennis; Tomasi, Cristiano; Wang, Hom-Lay; Zitzmann, Nicola

2018-06-01

A classification for peri-implant diseases and conditions was presented. Focused questions on the characteristics of peri-implant health, peri-implant mucositis, peri-implantitis, and soft- and hard-tissue deficiencies were addressed. Peri-implant health is characterized by the absence of erythema, bleeding on probing, swelling, and suppuration. It is not possible to define a range of probing depths compatible with health; Peri-implant health can exist around implants with reduced bone support. The main clinical characteristic of peri-implant mucositis is bleeding on gentle probing. Erythema, swelling, and/or suppuration may also be present. An increase in probing depth is often observed in the presence of peri-implant mucositis due to swelling or decrease in probing resistance. There is strong evidence from animal and human experimental studies that plaque is the etiological factor for peri-implant mucositis. Peri-implantitis is a plaque-associated pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri-implant mucosa and subsequent progressive loss of supporting bone. Peri-implantitis sites exhibit clinical signs of inflammation, bleeding on probing, and/or suppuration, increased probing depths and/or recession of the mucosal margin in addition to radiographic bone loss. The evidence is equivocal regarding the effect of keratinized mucosa on the long-term health of the peri-implant tissue. It appears, however, that keratinized mucosa may have advantages regarding patient comfort and ease of plaque removal. Case definitions in day-to-day clinical practice and in epidemiological or disease-surveillance studies for peri-implant health, peri-implant mucositis, and peri-implantitis were introduced. The proposed case definitions should be viewed within the context that there is no generic implant and that there are numerous implant designs with different surface characteristics, surgical and loading protocols. It is recommended that the clinician obtain baseline radiographic and probing measurements following the completion of the implant-supported prosthesis. © 2018 American Academy of Periodontology and European Federation of Periodontology.

Quantification of ultrasonic texture intra-heterogeneity via volumetric stochastic modeling for tissue characterization.

PubMed

Al-Kadi, Omar S; Chung, Daniel Y F; Carlisle, Robert C; Coussios, Constantin C; Noble, J Alison

2015-04-01

Intensity variations in image texture can provide powerful quantitative information about physical properties of biological tissue. However, tissue patterns can vary according to the utilized imaging system and are intrinsically correlated to the scale of analysis. In the case of ultrasound, the Nakagami distribution is a general model of the ultrasonic backscattering envelope under various scattering conditions and densities where it can be employed for characterizing image texture, but the subtle intra-heterogeneities within a given mass are difficult to capture via this model as it works at a single spatial scale. This paper proposes a locally adaptive 3D multi-resolution Nakagami-based fractal feature descriptor that extends Nakagami-based texture analysis to accommodate subtle speckle spatial frequency tissue intensity variability in volumetric scans. Local textural fractal descriptors - which are invariant to affine intensity changes - are extracted from volumetric patches at different spatial resolutions from voxel lattice-based generated shape and scale Nakagami parameters. Using ultrasound radio-frequency datasets we found that after applying an adaptive fractal decomposition label transfer approach on top of the generated Nakagami voxels, tissue characterization results were superior to the state of art. Experimental results on real 3D ultrasonic pre-clinical and clinical datasets suggest that describing tumor intra-heterogeneity via this descriptor may facilitate improved prediction of therapy response and disease characterization. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions

PubMed Central

Valent, Peter; Orazi, Attilio; Steensma, David P.; Ebert, Benjamin L.; Haase, Detlef; Malcovati, Luca; van de Loosdrecht, Arjan A.; Haferlach, Torsten; Westers, Theresia M.; Wells, Denise A.; Giagounidis, Aristoteles; Loken, Michael; Orfao, Alberto; Lübbert, Michael; Ganser, Arnold; Hofmann, Wolf-Karsten; Ogata, Kiyoyuki; Schanz, Julie; Béné, Marie C.; Hoermann, Gregor; Sperr, Wolfgang R.; Sotlar, Karl; Bettelheim, Peter; Stauder, Reinhard; Pfeilstöcker, Michael; Horny, Hans-Peter; Germing, Ulrich; Greenberg, Peter; Bennett, John M.

2017-01-01

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of myeloid neoplasms characterized by peripheral cytopenia, dysplasia, and a variable clinical course with about 30% risk to transform to secondary acute myeloid leukemia (AML). In the past 15 years, diagnostic evaluations, prognostication, and treatment of MDS have improved substantially. However, with the discovery of molecular markers and advent of novel targeted therapies, new challenges have emerged in the complex field of MDS. For example, MDS-related molecular lesions may be detectable in healthy individuals and increase in prevalence with age. Other patients exhibit persistent cytopenia of unknown etiology without dysplasia. Although these conditions are potential pre-phases of MDS they may also transform into other bone marrow neoplasms. Recently identified molecular, cytogenetic, and flow-based parameters may add in the delineation and prognostication of these conditions. However, no generally accepted integrated classification and no related criteria are as yet available. In an attempt to address this challenge, an international consensus group discussed these issues in a working conference in July 2016. The outcomes of this conference are summarized in the present article which includes criteria and a proposal for the classification of pre-MDS conditions as well as updated minimal diagnostic criteria of MDS. Moreover, we propose diagnostic standards to delineate between ´normal´, pre-MDS, and MDS. These standards and criteria should facilitate diagnostic and prognostic evaluations in clinical studies as well as in clinical practice. PMID:29088721

Latest Insights on Food Protein-Induced Enterocolitis Syndrome: An Emerging Medical Condition.

PubMed

Vila Sexto, L

2018-01-01

Food protein-induced enterocolitis syndrome (FPIES) is a type of non-IgE-mediated gastrointestinal food hypersensitivity characterized by profuse vomiting that is frequently associated with pallor or/and lethargy and appears within 1 to 3 hours after ingestion of the offending food. A less frequent chronic form of FPIES is characterized by protracted vomiting, diarrhea, or both accompanied by poor growth. Although FPIES is considered a rare allergic disorder, increasing reports in recent years point to a real increase in incidence, or at least an increased awareness of this condition by pediatricians. The foods most frequently implicated are cow's milk, soy formula, grains, and fish, depending on the geographic area. Diagnosis is based on clinical manifestations and requires a high index of suspicion, since we still lack a diagnostic laboratory tool. Early recognition of FPIES and removal of the offending food are mandatory. International consensus guidelines on diagnosis and management have been published. Prognosis is usually good, with most children tolerating foods before 6 years of age.

Translational approaches to obsessive-compulsive disorder: from animal models to clinical treatment

PubMed Central

Fineberg, NA; Chamberlain, SR; Hollander, E; Boulougouris, V; Robbins, TW

2011-01-01

Obsessive-compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence links these conditions with underlying dysregulation of fronto-striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of ‘false alarms’ for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21486280

Persistent pain and comorbidity among Operation Enduring Freedom/Operation Iraqi Freedom/operation New Dawn veterans.

PubMed

Higgins, Diana M; Kerns, Robert D; Brandt, Cynthia A; Haskell, Sally G; Bathulapalli, Harini; Gilliam, Wesley; Goulet, Joseph L

2014-05-01

Chronic pain is a significant concern for the Veterans Health Administration (VHA), with chronic pain conditions among those most frequently reported by Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF)/Operation New Dawn (OND) veterans. The current study examined VHA electronic medical record data to examine variation in demographics and high prevalence and high impact medical and mental health conditions in order to characterize the differences between patients with persistent pain and no pain. A conservative operational definition of chronic or "persistent pain" based on multiple indicators of pain (i.e., pain intensity ratings, prescription opioids, pain clinic visits, International Classification of Diseases, Ninth Revision codes) was employed. Analyses included the entire roster of longitudinal clinical data on OEF/OIF/OND veterans who used VHA care to compare those with persistent pain with those with no clinical evidence of pain. Results of logistic regression models suggest that sex, race, education, military variables, body mass index (BMI), traumatic brain injury (TBI), and mental health conditions, but not age, reliably discriminate the two groups. Those with persistent pain were more likely to be Black, female, on active duty, enlisted, Army service members, have a high school education or less, and have diagnoses of mood disorders, post-traumatic stress disorder, substance use disorders, anxiety disorders, TBI, and have a BMI consistent with overweight and obesity. The operational definition of chronic pain used in this study may have research implications for examining predictors of incident and chronic pain. These data have important clinical implications in that addressing comorbid conditions of persistent pain may improve adaptive coping and functioning in these patients. Wiley Periodicals, Inc.

Advances in Basic and Clinical Immunology 2009

PubMed Central

Chinen, Javier; Shearer, William T.

2010-01-01

In 2009, reports on basic and clinical immunology had an increased focus on human disease mechanisms and management. The molecular pathogenesis of familial angioedema associated with estrogen was further explored to find possible factors affecting severity, including polymorphisms in enzymes and receptors related to bradykinin pathways. A placebo-controlled clinical trial of C1INH concentrate in hereditary angioedema patients demonstrated the safety of its use and the efficacy to reduce duration of angioedema attacks. The interaction of innate immunity and adaptive responses was further examined in several reports establishing the significant role of toll-like receptor stimulation for the development of optimal specific antibody responses. The 2009 update of the classification of primary immunodeficiencies introduced over 15 new genetic defects related to the immune response, including DOCK8 mutations responsible for the autosomal recessive form of the hyper IgE syndrome. Other reports expanded the clinical spectrum of disease and improved the characterization of conditions such as warts, hypogammaglobulinemia and myelokathexis (WHIM) syndrome, or the occurrence of mucormycosis and Serratia infections in chronic granulomatous disease. The frequent presentation of gastrointestinal disorders in humoral immunodeficiencies was recognized and recommendations for management were reviewed. Clinical research focused in severe combined immunodeficiency included the development and implementation of a state-wide newborn screening program for this condition, a desired goal considering the significant reduction of mortality rate when diagnosis is made early before opportunistic infections occur. PMID:20226292

Epidemiological and etiological aspects of burning mouth syndrome

PubMed Central

Coculescu, EC; Ţovaru, Ş; Coculescu, BI

2014-01-01

Abstract Burning mouth syndrome (BMS) is defined as a chronic pain condition characterized by a burning sensation in clinically healthy oral mucosa. Incidence BMS diagnosed in the Department of Oral Medicine - Oral Pathology Dental Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy Bucharest is 16,23%. The etiology of BMS remains far less known. This article makes an overview of the latest theories about possible etiopathogenic factors involved in the occurrence of BMS. PMID:25408745

Hyperostosis Frontalis Interna in a Child With Severe Traumatic Brain Injury

PubMed Central

Wang, Xin; Li, Yan

2017-01-01

Hyperostosis frontalis interna is an unexplained irregular thickening of the inner table of the frontal bone. Hyperostosis frontalis interna was first identified in 1719 by Morgagni as a symptom of a more generalized syndrome characterized by virilism and obesity. Most current studies have shown hyperostosis frontalis interna to be a sex- and age-dependent phenomenon, and females manifest a significantly higher prevalence of hyperostosis frontalis interna than males. In this article, the authors report the clinical case of hyperostosis frontalis interna in a 7-year-old child who had severe traumatic brain injury in the past; review the related literature; and discuss the clinical, radiological, and therapeutic features of this condition. PMID:28503629

Diuretics: a review.

PubMed

Wile, David

2012-09-01

Diuretics, in one form or another, have been around for centuries and this review sets out to chart their development and clinical use. Starting with the physiology of the kidney, it progresses to explain how diuretics actually work, via symports on the inside of the renal tubules. The different classes of diuretics are characterized, along with their mode of action. The clinical use of diuretics in conditions like congestive cardiac failure and hypertension, as well as some rarer, but clinically important, conditions is then examined. An account is given of the adverse effects of diuretics and how they come about. Common adverse effects like hypokalaemia and hyponatraemia are examined in some detail, and other electrolyte disturbances like hypomagnesaemia also gain a mention. Diuretic use in chronic kidney disease is examined and new guidelines that have been introduced are presented. A section on diuretic abuse is included as this is becoming an all too common clinical scenario, and the sometimes tragic consequences of this abuse are emphasized. Diuretics also find a role in the diagnosis of forms of renal tubular acidosis and this role is explored. Finally, a selection of some of the newer approaches to diuretic therapy are presented, often the consequence of the increasing development of molecular biology, and some of the novel compounds - which may be in drug formularies of the future - are revealed.

How disease advocacy organizations participate in clinical research: a survey of genetic organizations.

PubMed

Landy, David C; Brinich, Margaret A; Colten, Mary Ellen; Horn, Elizabeth J; Terry, Sharon F; Sharp, Richard R

2012-02-01

Disease advocacy organizations may assist in the conduct of research in a variety of ways. We sought to characterize how disease advocacy organizations participate in clinical research and perceive their contributions. Postal and electronic surveys administered to leaders of disease advocacy organizations for genetic conditions identified through the Genetic Alliance's Disease InfoSearch. Of the 201 disease advocacy organizations approached, 124 (62%) responded. In the past 2 years, 91% of these organizations had assisted in participant recruitment, 75% collected data, 60% provided a researcher with financial support, and 56% assisted with study design. Forty-five percent of these organizations also supported a research registry or biobank. Few disease advocacy organization leaders (12%) reported regrets about research studies they had supported. Most (68%) felt their involvement in clinical research had increased the amount of research on their condition and that researchers should consult organizations like theirs in deciding how to recruit participants (58%) and in selecting research topics (56%). In addition to providing financial support, disease advocacy organizations participate directly in multiple aspects of research, ranging from study design and patient recruitment to data collection and analysis. Leaders of these organizations feel strongly that scientists and research sponsors should engage them as partners in the conduct of clinical research.

Isolation, characterization and preclinical development of human glial-restricted progenitor cells for treatment of neurological disorders.

PubMed

Sandrock, Robert W; Wheatley, Will; Levinthal, Cynthia; Lawson, Jennifer; Hashimoto, Brooke; Rao, Mahendra; Campanelli, James T

2010-05-01

Glial-restricted progenitor cells (GRPs), a neural cell population that gives rise to astrocytes and oligodendrocytes both in vitro and in vivo, hold great promise as a cellular therapeutic for the treatment of demyelinating and neurodegenerative diseases of the CNS. The manufacturing and characterization protocols of human-derived GRPs (hGRPs; trade name Q-Cells) for use in a clinical setting that adhere to rigorous standards for their isolation, propagation, characterization and storage are presented. hGRPs, defined by their immunoreactivity with A2B5 antibodies, were isolated from fetal cadaver forebrain tissue of mice 17-24 weeks gestational age using Miltenyi paramagnetic bead cell separation technology. GRPs were grown in a defined xenobiotic-free medium for 6 days. At harvest, hGRPs were characterized using immunocytochemical techniques. Long-term cryopreservation and storage conditions, and viability upon freeze-thaw were determined. The phenotypic differentiation potential of hGRPs was determined by implantation experiments into the CNS of shiverer mice. hGRPs were isolated from over 50 neural tissues of either sex during gestational ages of 17-24 weeks. Cells expanded out to 6 days in vitro in a xenobiotic-free medium demonstrated very consistent immunocytochemical profiles. No residual antibody used in the purification process was detected after 6 days of growth in vitro. GRPs could be frozen at up to 24 million cells/ml and were over 70% viable upon freeze-thaw. Thawed hGRPs transplanted into the brain of the dysmyelinated shiverer mouse model were observed to differentiate into both glial fibrillary acidic protein-positive astrocytes and myelin basic protein-positive oligodendrocytes; no human-derived NeuN-positive neuronal cells were observed and no abnormal cell proliferation was observed. We demonstrate that hGRPs can be consistently obtained, propagated, cryopreserved and characterized using protocols that can be transferred to a good laboratory practice/good manufacturing practice setting for the manufacture of clinical-grade hGRP cellular therapeutics. Functional data demonstrate that cells manufactured under these conditions are able to differentiate into appropriate cellular phenotypes in an animal model of dysmyelination.

Perthes disease: A new finding in Floating-Harbor syndrome.

PubMed

Milani, Donatella; Scuvera, Giulietta; Gatti, Marta; Tolva, Gianluca; Bonarrigo, Francesca; Esposito, Susanna; Gervasini, Cristina

2018-03-01

Floating-Harbor Syndrome (FHS; OMIM #136140) is an ultra-rare autosomal dominant genetic condition characterized by expressive language delay, short stature with delayed bone mineralization, a triangular face with a prominent nose, and deep-set eyes, and hand anomalies. First reported in 1973, FHS is associated with mutations in the SRCAP gene, which encodes SNF2-related CREBBP activator protein. Mutations in the CREBBP gene cause Rubinstein-Taybi Syndrome (RSTS; OMIM #180849, #613684), another rare disease characterized by broad thumbs and halluces, facial dysmorphisms, short stature, and intellectual disability, which has a phenotypic overlap with FHS. We describe a case of FHS associated with a novel SRCAP mutation and characterized by Perthes disease, a skeletal anomaly described in approximately 3% of patients with RSTS. Thus Perthes disease can be added to the list of clinical features that overlap between FHS and RSTS. © 2018 Wiley Periodicals, Inc.

Diagnostic confounders of chronic widespread pain: not always fibromyalgia

PubMed Central

Häuser, Winfried; Perrot, Serge; Sommer, Claudia; Shir, Yoram; Fitzcharles, Mary-Ann

2017-01-01

Abstract Introduction: Chronic widespread pain (CWP) is the defining feature of fibromyalgia (FM), a worldwide prevalent condition. Chronic widespread pain is, however, not pathognomonic of FM, and other conditions may present similarly with CWP, requiring consideration of a differential diagnosis. Objectives: To conduct a literature search to identify medical conditions that may mimic FM and have highlighted features that may differentiate these various conditions from FM. Methods: A comprehensive literature search from 1990 through September 2016 was conducted to identify conditions characterized by CWP. Results: Conditions that may mimic FM may be categorized as musculoskeletal, neurological, endocrine/metabolic, psychiatric/psychological, and medication related. Characteristics pertaining to the most commonly identified confounding diagnoses within each category are discussed; clues to enable clinical differentiation from FM are presented; and steps towards a diagnostic algorithm for mimicking conditions are presented. Conclusion: Although the most likely reason for a complaint of CWP is FM, this pain complaint can be a harbinger of illness other than FM, prompting consideration of a differential diagnosis. This review should sensitize physicians to a broad spectrum of conditions that can mimic FM. PMID:29392213

Regression-based statistical mediation and moderation analysis in clinical research: Observations, recommendations, and implementation.

PubMed

Hayes, Andrew F; Rockwood, Nicholas J

2017-11-01

There have been numerous treatments in the clinical research literature about various design, analysis, and interpretation considerations when testing hypotheses about mechanisms and contingencies of effects, popularly known as mediation and moderation analysis. In this paper we address the practice of mediation and moderation analysis using linear regression in the pages of Behaviour Research and Therapy and offer some observations and recommendations, debunk some popular myths, describe some new advances, and provide an example of mediation, moderation, and their integration as conditional process analysis using the PROCESS macro for SPSS and SAS. Our goal is to nudge clinical researchers away from historically significant but increasingly old school approaches toward modifications, revisions, and extensions that characterize more modern thinking about the analysis of the mechanisms and contingencies of effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cushing's disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment.

PubMed

Buliman, A; Tataranu, L G; Paun, D L; Mirica, A; Dumitrache, C

2016-01-01

Cushing's disease is considered a rare condition characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. The clinical signs suggesting Cushing's disease, such as obesity, moon face, hirsutism, and facial plethora are already present on presentation. Endogenous hypercortisolism is associated with an increased risk of cardiovascular and metabolic manifestations, as well as respiratory disorders, psychiatric complications, osteoporosis and infections, leading to high rates of morbidity and mortality. It is vital to diagnose Cushing's disease as early as possible and to implement a treatment plan to lead to a successful prognosis and a low number of complications. The goal of this article was to review the clinical, diagnostic and treatment aspects of Cushing's disease using the most recent available guidelines.

Idiopathic noncirrhotic portal hypertension: current perspectives

PubMed Central

Riggio, Oliviero; Gioia, Stefania; Pentassuglio, Ilaria; Nicoletti, Valeria; Valente, Michele; d’Amati, Giulia

2016-01-01

The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis. PMID:27555800

Idiopathic noncirrhotic portal hypertension: current perspectives.

PubMed

Riggio, Oliviero; Gioia, Stefania; Pentassuglio, Ilaria; Nicoletti, Valeria; Valente, Michele; d'Amati, Giulia

2016-01-01

The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis.

Clinical germline diagnostic exome sequencing for hereditary cancer: Findings within novel candidate genes are prevalent.

PubMed

Powis, Zöe; Espenschied, Carin R; LaDuca, Holly; Hagman, Kelly D; Paudyal, Tripti; Li, Shuwei; Inaba, Hiroto; Mauer, Ann; Nathanson, Katherine L; Knost, James; Chao, Elizabeth C; Tang, Sha

2018-08-01

Clinical diagnostic exome sequencing (DES) has been effective in diagnosing individuals with suspected genetic conditions; nevertheless little has been described regarding its clinical utility in individuals with a personal and family history of cancer. This study aimed to assess diagnostic yield and clinical characteristics of pediatric and adult patients undergoing germline DES for hereditary cancer. We retrospectively reviewed 2171 patients referred for DES; cases with a personal and/or family history of cancer were further studied. Of 39 cancer patients, relevant alterations were found in eight individuals (21%), including one (3%) positive pathogenic alteration within a characterized gene, two (5%) uncertain findings in characterized genes, and five (13%) alterations in novel candidate genes. Two of the 5 pediatric patients, undergoing testing, (40%) had findings in novel candidate genes, with the remainder being negative. We include brief case studies to illustrate the variety of challenging issues related to these patients. Our observations demonstrate utility of family-based exome sequencing in patients for suspected hereditary cancer, including familial co-segregation analysis, and comprehensive medical review. DES may be particularly useful when traditional approaches do not result in a diagnosis or in families with unique phenotypes. This work also highlights the importance and complexity of analysis of uncharacterized genes in exome sequencing for hereditary cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Demodex Folliculitis of the Scalp: Clinicopathological Study of an Uncommon Entity.

PubMed

Helou, Wissam; Avitan-Hersh, Emily; Bergman, Reuven

2016-09-01

Demodex is a saprophytic mite in humans commonly present in the pilosebaceous units, which has been implicated as a pathogen in several skin conditions. The clinical presentation and histopathology of Demodex folliculitis of the scalp have been described in only a few case reports. This study was performed to further elucidate the clinicopathological features of this entity. We have studied 333 consecutively submitted scalp biopsies performed for hair loss and alopecia. All specimens were completely step-sectioned. Biopsies with Demodex mites were further studied histopathologically, and the patients' clinical files were reviewed. There were 17 biopsies (5.1%) with Demodex in at least 1 pilosebaceous unit. Based on the clinical presentation, histopathology, and response to therapy, Demodex was considered to be nonpathogenic in 13 cases. The remaining 4 cases were characterized by hair loss, scalp erythema, scales, and pustules. There were 2 or more pilosebaceous units with Demodex along mononuclear and/or neutrophilic infiltrates around and in the involved follicles and occasionally granulomas. All 4 cases responded completely to metronidazole therapy. In conclusion, Demodex is infrequently found in scalp biopsies for hair loss and alopecia, and, in most cases, it does not seem to be pathogenic. Occasionally, however, it is associated with folliculitis characterized by hair loss, erythema, scales, and pustules clinically; neutrophilic and/or mononuclear-cell folliculitis with occasional granulomas histopathologically; and a prompt response to anti-Demodex therapy.

Noise levels of dental equipment used in dental college of Damascus University.

PubMed

Qsaibati, Mhd Loutify; Ibrahim, Ousama

2014-11-01

In dental practical classes, the acoustic environment is characterized by high noise levels in relation to other teaching areas. The aims of this study were to measure noise levels produced during the different dental learning clinics, by equipments used in dental learning areas under different working conditions and by used and brand new handpieces under different working conditions. The noise levels were measured by using a noise level meter with a microphone, which was placed at a distance of 15 cm from a main noise source in pre-clinical and clinical areas. In laboratories, the microphone was placed at a distance of 15 cm and another reading was taken 2 m away. Noise levels of dental learning clinics were measured by placing noise level meter at clinic center. The data were collected, tabulated and statistically analyzed using t-tests. Significance level was set at 5%. In dental clinics, the highest noise was produced by micro motor handpiece while cutting on acrylic (92.2 dB) and lowest noise (51.7 dB) was created by ultrasonic scaler without suction pump. The highest noise in laboratories was caused by sandblaster (96 dB at a distance of 15 cm) and lowest noise by stone trimmer when only turned on (61.8 dB at a distance of 2 m). There was significant differences in noise levels of the equipment's used in dental laboratories and dental learning clinics (P = 0.007). The highest noise level recorded in clinics was at pedodontic clinic (67.37 dB). Noise levels detected in this study were considered to be close to the limit of risk of hearing loss 85 dB.

Noise levels of dental equipment used in dental college of Damascus University

PubMed Central

Qsaibati, Mhd. Loutify; Ibrahim, Ousama

2014-01-01

Background: In dental practical classes, the acoustic environment is characterized by high noise levels in relation to other teaching areas. The aims of this study were to measure noise levels produced during the different dental learning clinics, by equipments used in dental learning areas under different working conditions and by used and brand new handpieces under different working conditions. Materials and Methods: The noise levels were measured by using a noise level meter with a microphone, which was placed at a distance of 15 cm from a main noise source in pre-clinical and clinical areas. In laboratories, the microphone was placed at a distance of 15 cm and another reading was taken 2 m away. Noise levels of dental learning clinics were measured by placing noise level meter at clinic center. The data were collected, tabulated and statistically analyzed using t-tests. Significance level was set at 5%. Results: In dental clinics, the highest noise was produced by micro motor handpiece while cutting on acrylic (92.2 dB) and lowest noise (51.7 dB) was created by ultrasonic scaler without suction pump. The highest noise in laboratories was caused by sandblaster (96 dB at a distance of 15 cm) and lowest noise by stone trimmer when only turned on (61.8 dB at a distance of 2 m). There was significant differences in noise levels of the equipment's used in dental laboratories and dental learning clinics (P = 0.007). The highest noise level recorded in clinics was at pedodontic clinic (67.37 dB). Conclusions: Noise levels detected in this study were considered to be close to the limit of risk of hearing loss 85 dB. PMID:25540655

Characterizing breast conditions at an open-access breast clinic in South Africa: a model that is more than cancer care for a resource-limited setting.

PubMed

Rayne, Sarah; Lince-Deroche, Naomi; Hendrickson, Cheryl; Shearer, Kate; Moyo, Faith; Michelow, Pam; Rubin, Grace; Benn, Carol; Firnhaber, Cynthia

2017-01-21

While most breast-related research focuses on cancer, presentation of symptomatic persons in non-screened environments requires understanding the spectrum of breast diseases so as to plan services in resource-constrained settings. This study presents the variety of breast disease managed at a government, open-access breast clinic in South Africa. We performed a retrospective file review using a systematic random sample of patients 18 years and above presenting for breast care over a 14-month period. We collected demographics, clinical characteristics, management and final diagnoses from the first visit and twelve subsequent months. The final sample contained 365 individuals (97 · 5% women). Most were black, unmarried and South African citizens with a median age of 43 years (IQR 31-55) . Of those reporting their status (24 · 1%) 38 · 6% were HIV-positive. A mass (57 · 0%) and/or pain (28 · 5%) were the most common symptoms. Imaging and breast biopsies were required in 78 and 25% of individuals, respectively. Nearly half of biopsies identified breast cancer (44 · 1% of women ≤40 and 57 · 3% for women >40). Benign conditions (47 · 7%) and no abnormality (18 · 2%) were common final classifications among women. There was no difference between the final classifications of patients who self-referred versus those who were formally referred from another health care provider. Nearly half of the participants (46 · 6%) travelled 20 km or more to attend the clinic. Benign breast conditions far outweighed cancer diagnoses. As breast cancer awareness increases in resource-limited countries, facilities offering breast care require administrative and clinical preparation to manage a range of non-cancer related conditions.

Relation of Psychiatric Symptoms with Epilepsy, Asthma, and Allergy in Youth with ASD vs. Psychiatry Referrals.

PubMed

Weber, Rebecca J; Gadow, Kenneth D

2017-08-01

The present study aimed to characterize the association of psychopathology with the clinical correlates of epilepsy, asthma, and allergy within and between neurobehavioral syndromes. Participants were consecutively evaluated youth (6-18 years, 75 % male) with autism spectrum disorder (ASD; n = 589) and non-ASD outpatient psychiatry referrals (n = 653). Informants completed a background questionnaire (parents) and a psychiatric symptom severity rating scale (parents, teachers). Youth with ASD had higher rates of epilepsy and allergy but not asthma than psychiatry referrals, even when analyses were limited to youth with IQ ≥ 70. Somatic conditions evidenced variable associations with medical services utilization, educational interventions, family income, and maternal education. Youth with ASD with versus without epilepsy had more severe ASD social deficits (parents' ratings) and less severe ASD repetitive behaviors (teachers' ratings). Epilepsy was associated with more severe depression, mania, and schizophrenia symptoms in youth with ASD. Youth with allergy (psychiatry referrals only) had more severe anxiety and depression symptoms (parents' ratings) but less severe aggression (teachers' ratings) thus providing evidence of both context- and diagnostic-specificity. Youth with ASD versus non-ASD psychiatry referrals evidence a variable pattern of relations between somatic conditions and a range of clinical correlates, which suggests that the biologic substrates and psychosocial concomitants of neurodevelopmental disorders and their co-occurring somatic conditions may interact to produce unique clinical phenotypes.

Beyond Readability: Investigating Coherence of Clinical Text for Consumers

PubMed Central

Hetzel, Scott; Dalrymple, Prudence; Keselman, Alla

2011-01-01

Background A basic tenet of consumer health informatics is that understandable health resources empower the public. Text comprehension holds great promise for helping to characterize consumer problems in understanding health texts. The need for efficient ways to assess consumer-oriented health texts and the availability of computationally supported tools led us to explore the effect of various text characteristics on readers’ understanding of health texts, as well as to develop novel approaches to assessing these characteristics. Objective The goal of this study was to compare the impact of two different approaches to enhancing readability, and three interventions, on individuals’ comprehension of short, complex passages of health text. Methods Participants were 80 university staff, faculty, or students. Each participant was asked to “retell” the content of two health texts: one a clinical trial in the domain of diabetes mellitus, and the other typical Visit Notes. These texts were transformed for the intervention arms of the study. Two interventions provided terminology support via (1) standard dictionary or (2) contextualized vocabulary definitions. The third intervention provided coherence improvement. We assessed participants’ comprehension of the clinical texts through propositional analysis, an open-ended questionnaire, and analysis of the number of errors made. Results For the clinical trial text, the effect of text condition was not significant in any of the comparisons, suggesting no differences in recall, despite the varying levels of support (P = .84). For the Visit Note, however, the difference in the median total propositions recalled between the Coherent and the (Original + Dictionary) conditions was significant (P = .04). This suggests that participants in the Coherent condition recalled more of the original Visit Notes content than did participants in the Original and the Dictionary conditions combined. However, no difference was seen between (Original + Dictionary) and Vocabulary (P = .36) nor Coherent and Vocabulary (P = .62). No statistically significant effect of any document transformation was found either in the open-ended questionnaire (clinical trial: P = .86, Visit Note: P = .20) or in the error rate (clinical trial: P = .47, Visit Note: P = .25). However, post hoc power analysis suggested that increasing the sample size by approximately 6 participants per condition would result in a significant difference for the Visit Note, but not for the clinical trial text. Conclusions Statistically, the results of this study attest that improving coherence has a small effect on consumer comprehension of clinical text, but the task is extremely labor intensive and not scalable. Further research is needed using texts from more diverse clinical domains and more heterogeneous participants, including actual patients. Since comprehensibility of clinical text appears difficult to automate, informatics support tools may most productively support the health care professionals tasked with making clinical information understandable to patients. PMID:22138127

Familial atrophia maculosa varioliformis cutis.

PubMed

Kalayciyan, Aylin; Kotogyan, Agop; Demirkesen, Cuyan; Tüzün, Yalçin

2003-07-01

Atrophia maculosa varioliformis cutis (AVMC) was first described by Heidingsfeld in 1918, as a rarely reported form of idiopathic macular atrophy on the cheek (1). It is characterized, clinically, by shallow, sharply demarcated depressions in various shapes. Extrahepatic biliary atresia (2) and pachydermodactyly (3) have been the only conditions associated with AMVC reported in the past 80 years. Although keratosis pilaris is a common skin disorder, it is related to other idiopathic atrophic conditions considered in the differential diagnosis of AMVC, namely keratosis pilaris atrophicans (4). However, the two associations may be coincidental. We observed a patient with keratosis pilaris, and her brother and an unrelated young man, whose findings led to a diagnosis of AMVC.

Takotsubo cardiomyopathy with involvement of delayed-onset rhabdomyolysis and acute kidney injury after rosuvastatin treatment.

PubMed

Kamada, Tomohito; Hayashi, Mutsuharu; Yokoi, Hiroatsu; Fujiwara, Wakaya; Yoshikawa, Daiji; Mukaide, Daisuke; Sugishita, Yoshinori; Yoshinaga, Masataka; Ito, Takehiro; Ozaki, Yukio; Izawa, Hideo

2015-01-01

Takotsubo cardiomyopathy is a disorder characterized by left ventricular apical ballooning with preceding emotional and/or physical stressors. This condition is also an important differential diagnosis of acute coronary syndrome. We herein describe a case of Takotsubo cardiomyopathy, a significant clinical phenomenon, triggered by delayed-onset rhabdomyolysis following the administration of long-term statin treatment, without any preceding stressors or changes in the patient's medical condition, in association with complaints of non-specific muscle-related symptoms. Although an electrocardiogram showed remarkable ST-segment elevation, a careful reading of the electrocardiogram findings revealed the features of Takotsubo cardiomyopathy. Withdrawing the statin therapy improved the patient's cardiac function.

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.

[Neonatal diabetes mellitus].

PubMed

Gurgel, Lucimary C; Moisés, Regina S

2008-03-01

Neonatal diabetes is a rare condition characterized by hyperglycemia, requiring insulin treatment, diagnosed within the first months of life. The disorder may be either transient, resolving in infancy or early childhood with possible relapse later, or permanent in which case lifelong treatment is necessary. Both conditions are genetically heterogeneous; however, the majority of the cases of transient neonatal diabetes are due to abnormalities of an imprinted region of chromosome 6q24. For permanent neonatal diabetes, the most common causes are heterozygous activating mutations of KCNJ11, the gene encoding the Kir6.2 sub-unit of the ATP-sensitive potassium channel. In this article we discuss the clinical features of neonatal diabetes, the underlying genetic defects and the therapeutic implications.

Imaging normal pressure hydrocephalus: theories, techniques, and challenges.

PubMed

Keong, Nicole C H; Pena, Alonso; Price, Stephen J; Czosnyka, Marek; Czosnyka, Zofia; Pickard, John D

2016-09-01

The pathophysiology of NPH continues to provoke debate. Although guidelines and best-practice recommendations are well established, there remains a lack of consensus about the role of individual imaging modalities in characterizing specific features of the condition and predicting the success of CSF shunting. Variability of clinical presentation and imperfect responsiveness to shunting are obstacles to the application of novel imaging techniques. Few studies have sought to interpret imaging findings in the context of theories of NPH pathogenesis. In this paper, the authors discuss the major streams of thought for the evolution of NPH and the relevance of key imaging studies contributing to the understanding of the pathophysiology of this complex condition.

Electrical storm and calcium signaling: a review.

PubMed

Tsuji, Yukiomi

2011-01-01

Electrical storm (ES), characterized by recurrent ventricular tachycardia/fibrillation, is a serious condition, adversely affecting prognosis in patients with implantable cardioverter/defibrillators. Electrical storm patients often die of progressive heart failure, but the underlying molecular basis is poorly understood. We have recently created an animal model of ES that features repetitive implantable cardioverter/defibrillator firing for recurrent ventricular fibrillation and found that ES events cause striking activation of Ca(2+)/calmodulin-dependent protein kinase II and prominent alteration of Ca(2+)-handling protein phosphorylation, possibly explaining mechanical dysfunction and arrhythmia promotion that characterize ES. Here, the pathophysiology and potential therapeutic strategies for ES, based on experimental and clinical studies by us and others, are described. Copyright © 2011 Elsevier Inc. All rights reserved.

A Novel Loss-of-Sclerostin Function Mutation in a First Egyptian Family with Sclerosteosis

PubMed Central

Fayez, Alaaeldin; Aglan, Mona; Esmaiel, Nora; El Zanaty, Taher; Abdel Kader, Mohamed; El Ruby, Mona

2015-01-01

Sclerosteosis is a rare autosomal recessive condition characterized by increased bone density. Mutations in SOST gene coding for sclerostin are linked to sclerosteosis. Two Egyptian brothers with sclerosteosis and their apparently normal consanguineous parents were included in this study. Clinical evaluation and genomic sequencing of the SOST gene were performed followed by in silico analysis of the resulting variation. A novel homozygous frameshift mutation in the SOST gene, characterized as one nucleotide cytosine insertion that led to premature stop codon and loss of functional sclerostin, was identified in the two affected brothers. Their parents were heterozygous for the same mutation. To our knowledge this is the first Egyptian study of sclerosteosis and SOST gene causing mutation. PMID:25984533

Clinical relevance of cannabis tolerance and dependence.

PubMed

Jones, R T; Benowitz, N L; Herning, R I

1981-01-01

Psychoactive drugs are often widely used before tolerance and dependence is fully appreciated. Tolerance to cannabis-induced cardiovascular and autonomic changes, decreased intraocular pressure, sleep and sleep EEG, mood and behavioral changes is acquired and, to a great degree, lost rapidly with optimal conditions. Mechanisms appear more functional than metabolic. Acquisition rate depends on dose and dose schedule. Dependence, manifested by withdrawal symptoms after as little as 7 days of THC administration, is characterized by irritability, restlessness, insomnia, anorexia, nausea, sweating, salivation, increased body temperature, altered sleep and waking EEG, tremor, and weight loss. Mild and transient in the 120 subjects studied, the syndrome was similar to sedative drug withdrawal. Tolerance to drug side effects can be useful. Tolerance to therapeutic effects or target symptoms poses problems. Clinical significance of dependence is difficult to assess since drug-seeking behavior has many determinants. Cannabis-induced super sensitivity should be considered wherever chronic drug administration is anticipated in conditions like epilepsy, glaucoma or chronic pain. Cannabis pharmacology suggests ways of minimizing tolerance and dependence problems.

Subclinical hypothyroidism in children.

PubMed

Shriraam, M; Sridhar, M

2014-11-01

Subclinical hypothyroidism is a biochemical diagnosis characterized by raised thyroid stimulating hormone and normal free T4, without clinical features of hypothyroidism. This review analyzes the current evidence to arrive at a consensus and algorithm to manage this condition. We searched Pubmed, Cochrane and Embase for articles published between 1990 to 2014, and identified 13 relevant articles dealing with pediatric subclinical hypothyroidism which were suitable to include in our review. Subclinical hypothyroidism is often a benign problem which requires expectant management with periodic monitoring of thyroid function tests and natural progression to overt hypothyroidism occur lot less frequently than expected. There is a paucity of robust randomized intervention studies, especially studies focusing on clinical outcomes. Thyroid replacement therapy is not justified in children with subclinical hypothyroidism when Thyroid stimulating hormone is <10 mIU/L. The main risk factors for progression to overt hypothyroidism are female sex, goiter, family history of thyroid disorder, strongly positive thyroid peroxidase antibodies and symptoms suggesting hypothyroidism. An algorithm for managing this condition is suggested.

Inflammatory Responses, Spirometry, and Quality of Life in Subjects With Bronchiectasis Exacerbations.

PubMed

Guan, Wei-Jie; Gao, Yong-Hua; Xu, Gang; Lin, Zhi-Ya; Tang, Yan; Li, Hui-Min; Lin, Zhi-Min; Jiang, Mei; Zheng, Jin-Ping; Chen, Rong-Chang; Zhong, Nan-Shan

2015-08-01

Bronchiectasis exacerbations are critical events characterized by worsened symptoms and signs (ie, cough frequency, sputum volume, malaise). Our goal was to examine variations in airway and systemic inflammation, spirometry, and quality of life during steady state, bronchiectasis exacerbations, and convalescence (1 week following a 2-week antibiotic treatment) to determine whether potentially pathogenic microorganisms, including Pseudomonas aeruginosa, were associated with poorer conditions during bronchiectasis exacerbations. Peripheral blood and sputum were sampled to detect inflammatory mediators and bacterial densities. Spirometry and quality of life (St George Respiratory Questionnaire [SGRQ]) were assessed during the 3 stages. Forty-eight subjects with bronchiectasis (43.2 ± 14.2 y of age) were analyzed. No notable differences in species and density of potentially pathogenic microorganisms were found during bronchiectasis exacerbations. Except for CXCL8 and tumor necrosis factor alpha (TNF-α), serum inflammation was heightened during bronchiectasis exacerbations and recovered during convalescence. Even though sputum TNF-α was markedly higher during bronchiectasis exacerbations and remained heightened during convalescence, the variations in miscellaneous sputum markers were unremarkable. Bronchiectasis exacerbations were associated with notably higher SGRQ symptom and total scores, which recovered during convalescence. FVC, FEV1, and maximum mid-expiratory flow worsened during bronchiectasis exacerbations (median change from baseline of -2.2%, -0.8%, and -1.3%) and recovered during convalescence (median change from baseline of 0.6%, 0.7%, and -0.7%). Compared with no bacterial isolation, potentially pathogenic microorganism or P. aeruginosa isolation at baseline did not result in poorer clinical condition during bronchiectasis exacerbations. Bronchiectasis exacerbations are characterized by heightened inflammatory responses and poorer quality of life and spirometry, but not by increased bacterial density, which applies for subjects with and without potentially pathogenic microorganism isolation when clinically stable. (ClinicalTrials.gov registration NCT01761214.). Copyright © 2015 by Daedalus Enterprises.

Development of 3D culture models of plexiform neurofibroma and initial application for phenotypic characterization and drug screening.

PubMed

Kraniak, Janice M; Chalasani, Anita; Wallace, Margaret R; Mattingly, Raymond R

2018-01-01

Plexiform neurofibromas (PNs), which may be present at birth in up to half of children with type 1 neurofibromatosis (NF1), can cause serious loss of function, such as quadriparesis, and can undergo malignant transformation. Surgery is the first line treatment although the invasive nature of these tumors often prevents complete resection. Recent clinical trials have shown promising success for some drugs, notably selumetinib, an inhibitor of MAP kinase kinase (MEK). We have developed three-dimensional (3D) cell culture models of immortalized cells from NF1 PNs and of control Schwann cells (SCs) that we believe mimic more closely the in vivo condition than conventional two-dimensional (2D) cell culture. Our goal is to facilitate pre-clinical identification of potential targeted therapeutics for these tumors. Three drugs, selumetinib (a MEK inhibitor), picropodophyllin (an IGF-1R inhibitor) and LDN-193189 (a BMP2 inhibitor) were tested with dose-response design in both 2D and 3D cultures for their abilities to block net cell growth. Cell lines grown in 3D conditions showed varying degrees of resistance to the inhibitory actions of all three drugs. For example, control SCs became resistant to growth inhibition by selumetinib in 3D culture. LDN-193189 was the most effective drug in 3D cultures, with only slightly reduced potency compared to the 2D cultures. Characterization of these models also demonstrated increased proteolysis of collagen IV in the matrix by the PN driver cells as compared to wild-type SCs. The proteolytic capacity of the PN cells in the model may be a clinically significant property that can be used for testing the ability of drugs to inhibit their invasive phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

Mindfulness Meditation for Fibromyalgia: Mechanistic and Clinical Considerations.

PubMed

Adler-Neal, Adrienne L; Zeidan, Fadel

2017-09-01

Fibromyalgia is a disorder characterized by widespread pain and a spectrum of psychological comorbidities, rendering treatment difficult and often a financial burden. Fibromyalgia is a complicated chronic pain condition that requires a multimodal therapeutic approach to optimize treatment efficacy. Thus, it has been postulated that mind-body techniques may prove fruitful in treating fibromyalgia. Mindfulness meditation, a behavioral technique premised on non-reactive sensory awareness, attenuates pain and improves mental health outcomes. However, the impact of mindfulness meditation on fibromyalgia-related outcomes has not been comprehensively characterized. The present review delineates the existing evidence supporting the effectiveness and hypothesized mechanisms of mindfulness meditation in treating fibromyalgia-related outcomes. Mindfulness-based interventions premised on cultivating acceptance, non-attachment, and social engagement may be most effective in decreasing fibromyalgia-related pain and psychological symptoms. Mindfulness-based therapies may alleviate fibromyalgia-related outcomes through multiple neural, psychological, and physiological processes. Mindfulness meditation may provide an effective complementary treatment approach for fibromyalgia patients, especially when combined with other reliable techniques (exercise; cognitive behavioral therapy). However, characterizing the specific analgesic mechanisms supporting mindfulness meditation is a critical step to fostering the clinical validity of this technique. Identification of the specific analgesic mechanisms supporting mindfulness-based pain relief could be utilized to better design behavioral interventions to specifically target fibromyalgia-related outcomes.

Three-dimensional evaluation of postural stability in Parkinson's disease with mobile technology.

PubMed

Ozinga, Sarah J; Koop, Mandy Miller; Linder, Susan M; Machado, Andre G; Dey, Tanujit; Alberts, Jay L

2017-01-01

Postural instability is a hallmark of Parkinson's disease. Objective metrics to characterize postural stability are necessary for the development of treatment algorithms to aid in the clinical setting. The aim of this project was to validate a mobile device platform and resultant three-dimensional balance metric that characterizes postural stability. A mobile Application was developed, in which biomechanical data from inertial sensors within a mobile device were processed to characterize movement of center of mass in the medial-lateral, anterior-posterior and trunk rotation directions. Twenty-seven individuals with Parkinson's disease and 27 age-matched controls completed various balance tasks. A postural stability metric quantifying the amplitude (peak-to-peak) of sway acceleration in each movement direction was compared between groups. The peak-to-peak value in each direction for each individual with Parkinson's disease across all trials was expressed as a normalized value of the control data to identify individuals with severe postural instability, termed Cleveland Clinic-Postural Stability Index. In all conditions, the balance metric for peak-to-peak was significantly greater in Parkinson's disease compared to controls (p < 0.01 for all tests). The balance metric, in conjunction with mobile device sensors, provides a rapid and systematic metric for quantifying postural stability in Parkinson's disease.

Postural strategies assessed with inertial sensors in healthy and parkinsonian subjects

PubMed Central

Baston, Chiara; Mancini, Martina; Schoneburg, Bernadette; Horak, Fay; Rocchi, Laura

2015-01-01

The present study introduces a novel instrumented method to characterize postural movement strategies to maintain balance during stance (ankle and hip strategy), by means of inertial sensors, positioned on the legs and on the trunk. We evaluated postural strategies in subjects with2 types of parkinsonism: idiopathic Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP),and inage-matched control subjects standing under perturbed conditions implementedby the Sensory Organization Test (SOT).Coordination between the upper and lower segments of the body during postural sway was measured using a covariance index over time, by a sliding-window algorithm. Afterwards, a postural strategy index was computed. We also measuredthe amount of postural sway, as adjunctive information to characterize balance, by the root mean square of the horizontal trunk acceleration signal (RMS). Results showed that control subjects were able to change their postural strategy, whilst PSP and PD subjects persisted in use of an ankle strategy in all conditions.PD subjects had RMS values similar to control subjects even without changing postural strategy appropriately, whereas PSP subjects showed much larger RMS values than controls, resulting in several falls during the most challenging SOT conditions (5 and 6). Results are in accordance with the corresponding clinical literature describing postural behavior in the same kind of subjects. The proposed strategy index, based on the use ofinertial sensors on the upper and lower body segments, isa promising and unobtrusive toolto characterize postural strategies performed to attain balance. PMID:24656713

Clinical, Epidemiologic, Histopathologic and Molecular Features of an Unexplained Dermopathy

PubMed Central

Pearson, Michele L.; Selby, Joseph V.; Katz, Kenneth A.; Cantrell, Virginia; Braden, Christopher R.; Parise, Monica E.; Paddock, Christopher D.; Lewin-Smith, Michael R.; Kalasinsky, Victor F.; Goldstein, Felicia C.; Hightower, Allen W.; Papier, Arthur; Lewis, Brian; Motipara, Sarita; Eberhard, Mark L.

2012-01-01

Background Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. Methods A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006–2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin. Results We identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17–93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin. Conclusions This unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health-related quality of life. No common underlying medical condition or infectious source was identified, similar to more commonly recognized conditions such as delusional infestation. PMID:22295070

Clinical, epidemiologic, histopathologic and molecular features of an unexplained dermopathy.

PubMed

Pearson, Michele L; Selby, Joseph V; Katz, Kenneth A; Cantrell, Virginia; Braden, Christopher R; Parise, Monica E; Paddock, Christopher D; Lewin-Smith, Michael R; Kalasinsky, Victor F; Goldstein, Felicia C; Hightower, Allen W; Papier, Arthur; Lewis, Brian; Motipara, Sarita; Eberhard, Mark L

2012-01-01

Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006-2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin. We identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17-93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin. This unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health-related quality of life. No common underlying medical condition or infectious source was identified, similar to more commonly recognized conditions such as delusional infestation.

Convergence accommodation to convergence (CA/C) ratio in patients with intermittent exotropia and decompensated exophoria.

PubMed

Nonaka, Fumitaka; Hasebe, Satoshi; Ohtsuki, Hiroshi

2004-01-01

To evaluate the convergence accommodation to convergence (CA/C) ratio in strabismic patients and to clarify its clinical implications. Seventy-eight consecutive patients (mean age: 12.9 +/- 6.0 years) with intermittent exotropia and decompensated exophoria who showed binocular fusion at least at near viewing were recruited. The CA/C ratio was estimated by measuring accommodative responses induced by horizontal prisms with different magnitudes under accommodation feedback open-loop conditions. The CA/C ratios were compared with accommodative convergence to accommodation (AC/A) ratios and other clinical parameters. A linear regression analysis indicated that the mean (+/-SD) CA/C ratio was 0.080 +/- 0.043 D/prism diopter or 0.48 +/- 0.26 D/meter angle. There was no inverse or reciprocal relationship between CA/C and AC/A ratios. The patients with lower CA/C ratios tended to have smaller tonic accommodation under binocular viewing conditions and larger exodeviation at near viewing. The CA/C ratio, like the AC/A ratio, is an independent parameter that characterizes clinical features. A lower CA/C may be beneficial for the vergence control system to compensate for ocular misalignment with minimum degradation of accommodation accuracy.

Composition, Stability, and Bioavailability of Garlic Products Being Used in a Clinical Trial

PubMed Central

Lawson, Larry D.; Gardner, Christopher D.

2008-01-01

In support of a new clinical trial designed to compare the effects of crushed fresh garlic and two types of garlic supplement tablets (enteric-coated dried fresh garlic and dried aged garlic extract) on serum lipids, the three garlic products have been characterized for (a) composition (14 sulfur and 2 non-sulfur compounds), (b) stability of suspected active compounds, and (c) availability of allyl thiosulfinates (mainly allicin) under both simulated gastrointestinal (tablet dissolution) conditions and in vivo. The allyl thiosulfinates of blended fresh garlic were stable for at least two years when stored at −80 °C. The dissolution release of thiosulfinates from the enteric-coated garlic tablets was found to be >95%. The bioavailability of allyl thiosulfinates from these tablets, measured as breath allyl methyl sulfide, was found to be complete and equivalent to that of crushed fresh garlic. S-allylcysteine was stable for 12 months at ambient temperature. The stability of the suspected active compounds under the conditions of the study and the bioavailability of allyl thiosulfinates from the dried garlic supplement have validated the use of these preparations for comparison in a clinical trial. PMID:16076102

Characterization of a novel zinc transporter ZnuA acquired by Vibrio parahaemolyticus through horizontal gene transfer

PubMed Central

Liu, Ming; Yan, Meiying; Liu, Lizhang; Chen, Sheng

2013-01-01

Vibrio parahaemolyticus is a clinically important foodborne pathogen that causes acute gastroenteritis worldwide. It has been shown that horizontal gene transfer (HGT) contributes significantly to virulence development of V. parahaemolyticus. In this study, we identified a novel znuA homolog (vpa1307) that belongs to a novel subfamily of ZnuA, a bacterial zinc transporter. The vpa1307 gene is located upstream of the V. parahaemolyticus pathogenicity island (Vp-PAIs) in both tdh-positive and trh-positive V. parahaemolyticus strains. Phylogenetic analysis revealed the exogenous origin of vpa1307 with 40% of V. parahaemolyticus clinical isolates possessing this gene. The expression of vpa1307 gene in V. parahaemolyticus clinical strain VP3218 is induced under zinc limitation condition. Gene deletion and complementation assays confirmed that vpa1307 contributes to the growth of VP3218 under zinc depletion condition and that conserved histidine residues of Vpa1307 contribute to its activity. Importantly, vpa1307 contributes to the cytotoxicity of VP3218 in HeLa cells and a certain degree of virulence in murine model. These results suggest that the horizontally acquired znuA subfamily gene, vpa1307, contributes to the fitness and virulence of Vibrio species. PMID:24133656

Characterization of a novel zinc transporter ZnuA acquired by Vibrio parahaemolyticus through horizontal gene transfer.

PubMed

Liu, Ming; Yan, Meiying; Liu, Lizhang; Chen, Sheng

2013-01-01

Vibrio parahaemolyticus is a clinically important foodborne pathogen that causes acute gastroenteritis worldwide. It has been shown that horizontal gene transfer (HGT) contributes significantly to virulence development of V. parahaemolyticus. In this study, we identified a novel znuA homolog (vpa1307) that belongs to a novel subfamily of ZnuA, a bacterial zinc transporter. The vpa1307 gene is located upstream of the V. parahaemolyticus pathogenicity island (Vp-PAIs) in both tdh-positive and trh-positive V. parahaemolyticus strains. Phylogenetic analysis revealed the exogenous origin of vpa1307 with 40% of V. parahaemolyticus clinical isolates possessing this gene. The expression of vpa1307 gene in V. parahaemolyticus clinical strain VP3218 is induced under zinc limitation condition. Gene deletion and complementation assays confirmed that vpa1307 contributes to the growth of VP3218 under zinc depletion condition and that conserved histidine residues of Vpa1307 contribute to its activity. Importantly, vpa1307 contributes to the cytotoxicity of VP3218 in HeLa cells and a certain degree of virulence in murine model. These results suggest that the horizontally acquired znuA subfamily gene, vpa1307, contributes to the fitness and virulence of Vibrio species.

Genetic epileptic encephalopathies: is all written into the DNA?

PubMed

Striano, Pasquale; de Jonghe, Peter; Zara, Federico

2013-11-01

Epileptic encephalopathy is a condition in which epileptic activity, clinical or subclinical, is thought to be responsible for any disturbance of cognition, behavior, or motor control. However, experimental evidence supporting this clinical observation are still poor and the causal relationship between pharmacoresistant seizures and cognitive outcome is controversial. In the past two decades, genetic studies shed new light onto complex mechanisms underlying different severe epileptic conditions associated with intellectual disability and behavioral abnormalities, thereby providing important clues on the relationship between seizures and cognitive outcome. Dravet syndrome is a childhood disorder associated with loss-of-function mutations in SCN1A and is characterized by frequent seizures and severe cognitive impairment, thus well illustrating the concept of epileptic encephalopathy. However, it is difficult to determine the causative role of the underlying sodium channel dysfunction and that of the consequent seizures in influencing cognitive outcome in these children. It is also difficult to demonstrate whether a recognizable profile of cognitive impairment or a definite behavioral phenotype exists. Data from the laboratory and the clinics may provide greater insight into the degree to which epileptic activity may contribute to cognitive impairment in individual syndromes. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Thyro-stress.

PubMed

Kalra, Sanjay; Verma, Komal; Balhara, Yatan Pal Singh

2017-01-01

Our understanding of the biopsychosocial model of health, and its influence on chronic endocrine conditions, has improved over the past few decades. We can distinguish, for example, between diabetes distress and major depressive disorders in diabetes. Similar to diabetes distress, we suggest the existence of "thyrostress" in chronic thyroid disorders. Thyro-stress is defined as an emotional state, characterized by extreme apprehension, discomfort or dejection, caused by the challenges and demand of living with thyroid disorders such as hypothyroidism. This communication describes the etiology, clinical features, differential diagnosis, and management of thyro-stress.

[Croupous pneumonia: the history of studies (from S.P. Botkin to our days)].

PubMed

Fesenko, O V; Sinopal'nikov, A I

2012-01-01

Etiology of croupous pneumonia remaining a challenging problem has a long history of investigations. The term croupous pneumonia is traditionally used in this country to describe the form of the disease characterized by hyperergic inflammation and specific clinical/laboratory parameters. A valuable contribution to the study of this condition was made by S.P. Botkin. This paper deals with evolution of the views of epidemiology, etiology, pathomorphology, and methods of therapy of croupous pneumonia since Botkin's time to these days.

Identification, Purification and Characterization of Major Antigenic Proteins of Campylobacter jejuni

DTIC Science & Technology

1991-01-01

with i ht 1ris- KIl hiit ’,/r. standards I Hutk- adi and their weight ii dlaltoiits were: phoi spthor ’ rxse then eit her 51) ju oh sanmplce cor aiti... effect of extraction conditions on polymerization of PEB1, we ically related, and can be recognized by antiserum to PEB1 included water extract...and Clinical and epidemtiologic studies suggest it may be possible Wang. W. L. ( 1983)ý Infect. Immun. 42, 276-284 to develop an effective vaccine for

Chronic parotitis: a challenging disease entity.

PubMed

Harbison, John M; Liess, Benjamin D; Templer, Jerry W; Zitsch, Robert P; Wieberg, Jessica A

2011-03-01

Chronic parotitis is a troubling clinical condition characterized by repeated infection and inflammation of the parotid gland caused by decreased salivary flow or obstruction. Unilateral swelling, pain, and other associated symptoms occur during acute exacerbations of the disease. A variety of laboratory and radiographic tools are available to aid in the diagnosis. Multiple treatment options have been proposed, ranging from conservative medical management to surgical interventions. We present 2 patients with bilateral chronic parotitis who attempted prolonged medical management and ultimately required surgical parotidectomy for control of their disease.

Burning mouth syndrome.

PubMed

Thoppay, Jaisri R; De Rossi, Scott S; Ciarrocca, Katharine N

2013-07-01

Burning mouth syndrome (BMS) is a chronic condition that is characterized by burning symptoms of the oral mucosa without obvious clinical examination findings. This syndrome has complex characteristics, but its cause remains largely enigmatic, making treatment and management of patients with BMS difficult. Despite not being accompanied by evident organic changes, BMS can significantly reduce the quality of life for such patients. Therefore, it is incumbent on dental professionals to diagnose and manage patients with BMS as a part of comprehensive care. Copyright © 2013. Published by Elsevier Inc.

Acral peeling skin syndrome associated with a novel CSTA gene mutation.

PubMed

Muttardi, K; Nitoiu, D; Kelsell, D P; O'Toole, E A; Batta, K

2016-06-01

Acral peeling skin syndrome (APSS) is a rare autosomal recessive condition, characterized by asymptomatic peeling of the skin of the hands and feet, often linked to mutations in the gene TGM5. However, more recently recessive loss of function mutations in CSTA, encoding cystatin A, have been linked with APSS and exfoliative ichthyosis. We describe the clinical features in two sisters with APSS, associated with a novel large homozygous deletion encompassing exon 1 of CSTA. © 2015 British Association of Dermatologists.

The Database for Aggregate Analysis of ClinicalTrials.gov (AACT) and Subsequent Regrouping by Clinical Specialty

PubMed Central

Tasneem, Asba; Aberle, Laura; Ananth, Hari; Chakraborty, Swati; Chiswell, Karen; McCourt, Brian J.; Pietrobon, Ricardo

2012-01-01

Background The ClinicalTrials.gov registry provides information regarding characteristics of past, current, and planned clinical studies to patients, clinicians, and researchers; in addition, registry data are available for bulk download. However, issues related to data structure, nomenclature, and changes in data collection over time present challenges to the aggregate analysis and interpretation of these data in general and to the analysis of trials according to clinical specialty in particular. Improving usability of these data could enhance the utility of ClinicalTrials.gov as a research resource. Methods/Principal Results The purpose of our project was twofold. First, we sought to extend the usability of ClinicalTrials.gov for research purposes by developing a database for aggregate analysis of ClinicalTrials.gov (AACT) that contains data from the 96,346 clinical trials registered as of September 27, 2010. Second, we developed and validated a methodology for annotating studies by clinical specialty, using a custom taxonomy employing Medical Subject Heading (MeSH) terms applied by an NLM algorithm, as well as MeSH terms and other disease condition terms provided by study sponsors. Clinical specialists reviewed and annotated MeSH and non-MeSH disease condition terms, and an algorithm was created to classify studies into clinical specialties based on both MeSH and non-MeSH annotations. False positives and false negatives were evaluated by comparing algorithmic classification with manual classification for three specialties. Conclusions/Significance The resulting AACT database features study design attributes parsed into discrete fields, integrated metadata, and an integrated MeSH thesaurus, and is available for download as Oracle extracts (.dmp file and text format). This publicly-accessible dataset will facilitate analysis of studies and permit detailed characterization and analysis of the U.S. clinical trials enterprise as a whole. In addition, the methodology we present for creating specialty datasets may facilitate other efforts to analyze studies by specialty groups. PMID:22438982

The database for aggregate analysis of ClinicalTrials.gov (AACT) and subsequent regrouping by clinical specialty.

PubMed

Tasneem, Asba; Aberle, Laura; Ananth, Hari; Chakraborty, Swati; Chiswell, Karen; McCourt, Brian J; Pietrobon, Ricardo

2012-01-01

The ClinicalTrials.gov registry provides information regarding characteristics of past, current, and planned clinical studies to patients, clinicians, and researchers; in addition, registry data are available for bulk download. However, issues related to data structure, nomenclature, and changes in data collection over time present challenges to the aggregate analysis and interpretation of these data in general and to the analysis of trials according to clinical specialty in particular. Improving usability of these data could enhance the utility of ClinicalTrials.gov as a research resource. The purpose of our project was twofold. First, we sought to extend the usability of ClinicalTrials.gov for research purposes by developing a database for aggregate analysis of ClinicalTrials.gov (AACT) that contains data from the 96,346 clinical trials registered as of September 27, 2010. Second, we developed and validated a methodology for annotating studies by clinical specialty, using a custom taxonomy employing Medical Subject Heading (MeSH) terms applied by an NLM algorithm, as well as MeSH terms and other disease condition terms provided by study sponsors. Clinical specialists reviewed and annotated MeSH and non-MeSH disease condition terms, and an algorithm was created to classify studies into clinical specialties based on both MeSH and non-MeSH annotations. False positives and false negatives were evaluated by comparing algorithmic classification with manual classification for three specialties. The resulting AACT database features study design attributes parsed into discrete fields, integrated metadata, and an integrated MeSH thesaurus, and is available for download as Oracle extracts (.dmp file and text format). This publicly-accessible dataset will facilitate analysis of studies and permit detailed characterization and analysis of the U.S. clinical trials enterprise as a whole. In addition, the methodology we present for creating specialty datasets may facilitate other efforts to analyze studies by specialty groups.

Secondary conditions among males with Duchenne or Becker muscular dystrophy

PubMed Central

Latimer, Rebecca; Street, Natalie; Conway, Kristin Caspers; James, Kathy; Cunniff, Christopher; Oleszek, Joyce; Fox, Deborah; Ciafaloni, Emma; Westfield, Christina; Paramsothy, Pangaja

2017-01-01

Duchenne and Becker muscular dystrophy are X-linked neuromuscular disorders characterized by progressive muscle degeneration. Despite the involvement of multiple systems, secondary conditions among affected males have not been comprehensively described. Two hundred and nine caregivers of affected males (aged 3–31 years) identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network completed a mailed survey that included questions about secondary conditions impacting multiple body functions. The five most commonly reported conditions in males with Duchenne were cognitive deficits (38.4%), constipation (31.7%), anxiety (29.3%), depression (27.4%), and obesity (19.5%). Higher frequencies of anxiety, depression, and kidney stones, were found among non-ambulatory males compared to ambulatory males. Attention deficit hyperactivity disorder was more common in ambulatory than non-ambulatory males. These data support clinical care recommendations for monitoring of patients with Duchenne or Becker muscular dystrophy by a multidisciplinary team to prevent and treat conditions that may be secondary to the diagnosis. PMID:28393671

Clinical and molecular characterization of females affected by X-linked retinoschisis.

PubMed

Staffieri, Sandra E; Rose, Loreto; Chang, Andrew; De Roach, John N; McLaren, Terri L; Mackey, David A; Hewitt, Alex W; Lamey, Tina M

2015-01-01

X-linked retinoschisis (XLRS) is a leading cause of juvenile macular degeneration associated with mutations in the RS1 gene. XLRS has a variable expressivity in males and shows no clinical phenotype in carrier females. Clinical and molecular characterization of male and female individuals affected with XLRS in a consanguineous family. Consanguineous Eastern European-Australian family Four clinically affected and nine unaffected family members were genetically and clinically characterized. Deoxyribonucleic acid (DNA) analysis was conducted by the Australian Inherited Retinal Disease Register and DNA Bank. Clinical and molecular characterization of the causative mutation in a consanguineous family with XLRS. By direct sequencing of the RS1 gene, one pathogenic variant, NM_000330.3: c.304C > T, p. R102W, was identified in all clinically diagnosed individuals analysed. The two females were homozygous for the variant, and the males were hemizygous. Clinical and genetic characterization of affected homozygous females in XLRS affords the rare opportunity to explore the molecular mechanisms of XLRS and the manifestation of these mutations as disease in humans. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

Characterization of Paroxysmal Gluten‐Sensitive Dyskinesia in Border Terriers Using Serological Markers

PubMed Central

Garden, O.A.; Hadjivassiliou, M.; Sanders, D.S.; Powell, R.; Garosi, L.

2018-01-01

Background Paroxysmal gluten‐sensitive dyskinesia (PGSD) in border terriers (BTs) results from an immunologic response directed against transglutaminase (TG)2 and gliadin. Recent evidence suggests that PGSD is only one aspect of a range of possible manifestations of gluten sensitivity in the breed. Hypothesis/Objectives Gluten sensitivity in BTs is a heterogeneous disease process with a diverse clinical spectrum; to characterize the phenotype of PGSD using TG2 and gliadin autoantibodies as diagnostic markers. Animals One hundred twenty‐eight client‐owned BTs with various disorders. Methods Prospective study. BTs with paroxysmal episodes and a normal interictal examination were phenotyped using footage of a representative episode and assigned to 3 groups: idiopathic epilepsy (IE), paroxysmal dyskinesia (PD), or other. Owners of each dog completed a questionnaire to obtain information regarding clinical signs. Healthy BTs formed a control group. Serum antibodies against TG2 and AGA were measured in all dogs. Results One hundred twenty‐eight BTs were enrolled; 45 with PD, 28 with IE, 35 with other conditions, and 20 controls. Three overlapping phenotypes were identified; PD, signs suggestive of gastrointestinal disease, and dermatopathy. AGA‐IgG concentrations were increased in PD, compared with IE (P = 0.012), controls (P < 0.0001) and other (P = 0.018) conditions. Anti‐canine TG2‐IgA concentrations were increased in PD, compared with IE (P < 0.0001), controls (P < 0.0001) and other (P = 0.012) conditions. Serological markers are highly specific for PGSD but lack sensitivity. Conclusions PGSD appears part of a syndrome of gluten intolerance consisting of episodes of transient dyskinesia, signs suggestive of gastrointestinal disease, and dermatological hypersensitivity. PMID:29424456

Nonceliac Gluten Sensitivity.

PubMed

Krigel, Anna; Lebwohl, Benjamin

2016-11-01

Nonceliac gluten sensitivity (NCGS) refers to a clinical phenotype in which patients experience intestinal and extraintestinal symptoms related to ingesting a gluten-containing diet after a diagnosis of celiac disease (CD) or wheat allergy has been excluded. CD, an autoimmune disease characterized by villous atrophy triggered by the ingestion of gluten, has increased in prevalence in recent decades, although the majority of patients remain undiagnosed. There is now an increasing public awareness of NCGS and growing interest in the health effects of gluten among health professionals and the lay public. Several randomized controlled trials have explored NCGS but have left many questions unanswered surrounding the pathophysiology, biomarkers, and established diagnostic approach to patients with this condition. Future studies are necessary to establish biomarkers and to elucidate the pathophysiology of this condition because at present, NCGS likely comprises a heterogeneous patient population. In this review, we outline the clinical trials of NCGS as well as the approach to patients with possible NCGS as recommended by an international expert panel. Because maintaining a gluten-free diet has important health, social, and economic consequences, it is necessary for medical professionals to provide practical and evidence-based advice to patients with this condition. © 2016 American Society for Nutrition.

Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Acute Lung Injury and Other Inflammatory Lung Diseases

PubMed Central

Monsel, Antoine; Zhu, Ying-gang; Gudapati, Varun; Lim, Hyungsun; Lee, Jae W.

2017-01-01

Introduction Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives. Areas covered The current review summarizes the preclinical studies testing MSC conditioned medium and/or MSC extracellular vesicles as treatment for acute lung injury and other inflammatory lung diseases. Expert opinion While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification. PMID:27011289

Personomics: The Missing Link in the Evolution from Precision Medicine to Personalized Medicine.

PubMed

Ziegelstein, Roy C

2017-10-16

Clinical practice guidelines have been developed for many common conditions based on data from randomized controlled trials. When medicine is informed solely by clinical practice guidelines, however, the patient is not treated as an individual, but rather a member of a group. Precision medicine, as defined herein, characterizes unique biological characteristics of the individual or of specimens obtained from an individual to tailor diagnostics and therapeutics to a specific patient. These unique biological characteristics are defined by the tools of precision medicine: genomics, proteomics, metabolomics, epigenomics, pharmacogenomics, and other "-omics." Personalized medicine, as defined herein, uses additional information about the individual derived from knowing the patient as a person. These unique personal characteristics are defined by tools known as personomics which takes into account an individual's personality, preferences, values, goals, health beliefs, social support network, financial resources, and unique life circumstances that affect how and when a given health condition will manifest in that person and how that condition will respond to treatment. In this paradigm, precision medicine may be considered a necessary step in the evolution of medical care to personalized medicine, with personomics as the missing link.

[Juvenile idiopathic arthritis and oral health].

PubMed

Kobus, Agnieszka; Kierklo, Anna; Sielicka, Danuta; Szajda, Sławomir Dariusz

2016-05-04

Juvenile idiopathic arthritis (JIA) is the most common autoimmune inflammatory disease of connective tissue in children. It is characterized by progressive joint destruction which causes preserved changes in the musculoskeletal system. The literature describes fully clinical symptoms and radiological images in different subtypes of JIA. However, there is still a limited number of studies reporting on the medical condition of the oral cavity of ill children. JIA can affect hard and soft tissues of the oral cavity by: the general condition of the child's health, arthritis of the upper limbs, as the result of the pharmacotherapy, changes in secretion and composition of saliva, inflammation of the temporomandibular joint and facial deformity. The study summarizes the available literature on the condition of the teeth and periodontal and oral hygiene in the course of JIA. The presence of diverse factors that modify the oral cavity, such as facial growth, functioning of salivary glands, or the supervision and care provided by adults, prevents clear identification if JIA leads to severe dental caries and periodontal disease. Despite conflicting results in studies concerning the clinical oral status, individuals with JIA require special attention regarding disease prevention and maintenance of oral health.

Nonceliac Gluten Sensitivity12

PubMed Central

Krigel, Anna; Lebwohl, Benjamin

2016-01-01

Nonceliac gluten sensitivity (NCGS) refers to a clinical phenotype in which patients experience intestinal and extraintestinal symptoms related to ingesting a gluten-containing diet after a diagnosis of celiac disease (CD) or wheat allergy has been excluded. CD, an autoimmune disease characterized by villous atrophy triggered by the ingestion of gluten, has increased in prevalence in recent decades, although the majority of patients remain undiagnosed. There is now an increasing public awareness of NCGS and growing interest in the health effects of gluten among health professionals and the lay public. Several randomized controlled trials have explored NCGS but have left many questions unanswered surrounding the pathophysiology, biomarkers, and established diagnostic approach to patients with this condition. Future studies are necessary to establish biomarkers and to elucidate the pathophysiology of this condition because at present, NCGS likely comprises a heterogeneous patient population. In this review, we outline the clinical trials of NCGS as well as the approach to patients with possible NCGS as recommended by an international expert panel. Because maintaining a gluten-free diet has important health, social, and economic consequences, it is necessary for medical professionals to provide practical and evidence-based advice to patients with this condition. PMID:28140327

Advances in Urine Microscopy.

PubMed

Becker, Gavin J; Garigali, Giuseppe; Fogazzi, Giovanni B

2016-06-01

Urine microscopy is an important tool for the diagnosis and management of several conditions affecting the kidneys and urinary tract. In this review, we describe the automated instruments, based either on flow cytometry or digitized microscopy, that are currently in use in large clinical laboratories. These tools allow the examination of large numbers of samples in short periods. We also discuss manual urinary microscopy commonly performed by nephrologists, which we encourage. After discussing the advantages of phase contrast microscopy over bright field microscopy, we describe the advancements of urine microscopy in various clinical conditions. These include persistent isolated microscopic hematuria (which can be classified as glomerular or nonglomerular on the basis of urinary erythrocyte morphology), drug- and toxin-related cystalluria (which can be a clue for the diagnosis of acute kidney injury associated with intrarenal crystal precipitation), and some inherited conditions (eg, adenine phosphoribosyltransferase deficiency, which is associated with 2,8-dihydroxyadenine crystalluria, and Fabry disease, which is characterized by unique urinary lamellated fatty particles). Finally, we describe the utility of identifying "decoy cells" and atypical malignant cells, which can be easily done with phase contrast microscopy in unfixed samples. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Strategic characterization of anti-drug antibody responses for the assessment of clinical relevance and impact.

PubMed

Tatarewicz, Suzanna M; Mytych, Daniel T; Manning, Marta Starcevic; Swanson, Steven J; Moxness, Michael S; Chirmule, Narendra

2014-06-01

All therapeutic proteins have the potential to induce anti-drug antibodies (ADA). Clinically relevant ADA can impact efficacy and/or safety of a biological therapeutic. Immunogenicity assessment strategy evaluates binding and neutralizing ADA, and the need for additional characterization (e.g., epitope, titer and so on) is determined using a risk-based approach. The choice of characterization assays depends on the type, application and immunogenicity of the therapeutic. ADA characterization can impact the interpretation of the risk profile of a given therapeutic, and offers insight into opportunities for risk mitigation and management. This article describes common ADA characterization methods. Strategic assessment and characterization of clinically relevant ADA are discussed, in order to support clinical options for safe and effective patient care and disease management.

Burning mouth syndrome: A review on its diagnostic and therapeutic approach

PubMed Central

Aravindhan, R.; Vidyalakshmi, Santhanam; Kumar, Muniapillai Siva; Satheesh, C.; Balasubramanium, A. Murali; Prasad, V. Srinivas

2014-01-01

Burning mouth syndrome (BMS), a chronic and intractable orofacial pain syndrome is characterized by the presence of burning sensation of the oral mucosa in the absence of specific oral lesion. This condition affects chiefly of middle aged and elderly woman with hormonal changes or psychological disorders. In addition to burning sensation, patient with BMS also complains of oral mucosal pain, altered taste sensation, and dry mouth. This condition is probably of multifactorial origin, often idiopathic and its exact etiopathogenesis remains unclear. So far, there is no definitive cure for this condition and most of the treatment approaches, medications remains unsatisfactory. An interdisciplinary and systematic approach is required for better patient management. The purpose of this article is to present a review of epidemiology, clinical presentation, classification, etiopathogenesis, diagnosis and management of BMS. PMID:25210377

Clinical profile of dermatological emergencies and intensive care unit admissions in a tertiary care center - an Indian perspective.

PubMed

Samudrala, Suvarna; Dandakeri, Sukumar; Bhat, Ramesh M

2018-05-01

Although dermatology is largely considered as an outpatient specialty, dermatological conditions comprise 5-8% of cases presenting to the emergency department. The need for a dermatological intensive care unit is widely acknowledged due to the increasing incidence of acute skin failure. Very few studies have been done to characterize the common conditions seen in the emergency department and intensive care units. We undertook this study to analyze the spectrum of dermatological conditions presenting to the emergency department and the clinical profile of patients admitted to the intensive care unit. A prospective study was conducted for 9 months. Patients requiring primary dermatological consultation in the emergency department and patients admitted in the dermatology intensive care unit were examined, and their clinical variables were statistically analyzed. A total of 248 cases were seen in the emergency department, out of which 72 (29.1%) cases were admitted and 176 (70.9%) were treated in the emergency department on an outpatient basis. The most common condition seen in non-admitted patients was acute urticaria (28.9%). The most common cause for admission in patients presenting to the emergency department was erythroderma (23.6%). Sixty-two patients were admitted to the intensive care unit, the most common diagnosis being erythroderma (40.3%). This prospective study aimed to provide an insight into the types of cases evaluated in the emergency department by dermatologists in a large tertiary care hospital in coastal Karnataka in South India. © 2018 The International Society of Dermatology.

Preparation, characterization, and banking of clinical-grade cells for neural transplantation: Scale up, fingerprinting, and genomic stability of stem cell lines.

PubMed

Natalwala, Ammar; Kunath, Tilo

2017-01-01

Parkinson's disease is a complex and progressive neurodegenerative condition that is characterized by the severe loss of midbrain dopaminergic (mDA) neurons, which innervate the striatum. Cell transplantation therapies to rebuild this dopaminergic network have been attempted for over 30 years. The most promising outcomes were observed when human fetal mesencephalic tissue was used as the source of cells for transplantation. However, reliance on terminations for a Parkinson's therapy presents significant logistical and ethical hurdles. An alternative source of transplantable mDA neurons is urgently needed, and the solution may come from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). Protocols to differentiate hESCs/iPSCs toward mDA neurons are now robust and efficient, and upon grafting the cells rescue preclinical animal models of Parkinson's disease. The challenge now is to apply Good Manufacturing Practice (GMP) to the academic discoveries and protocols to produce clinical-grade transplantable mDA cells. Major technical and logistical considerations include (i) source of hESC or iPSC line, (ii) GMP compliance of the differentiation protocol and all reagents, (iii) characterization of the cell product in terms of identity, safety, and efficacy, (iv) characterization of genomic state and stability, and (v) banking of a transplantation-ready cell product. Approaches and solutions to these challenges are reviewed here. © 2017 Elsevier B.V. All rights reserved.

Characterization of lentiviral vector production using microwell suspension cultures of HEK293T-derived producer cells.

PubMed

Guy, Heather M; McCloskey, Laura; Lye, Gary J; Mitrophanous, Kyriacos A; Mukhopadhyay, Tarit K

2013-04-01

ProSavin(®) is a lentiviral vector (LV)-based gene therapy for Parkinson's disease. ProSavin(®) is currently in a Phase I/II clinical trial using material that was generated by transient transfection of adherent human embryonic kidney (HEK)293T cells. For future large-scale productions of ProSavin(®), we have previously reported the development and characterization of two inducible producer cell lines, termed PS5.8 and PS46.2. PS46.2 has been successfully adapted to grow in suspension cultures. The present study describes the creation of a small-scale (<2 ml) microwell-based experimental platform for the parallel investigation of ProSavin(®) production using suspension-adapted PS46.2. This is combined with statistical design of experiments (DoE) techniques to enable rapid characterization of the process conditions that impact cell growth and LV production. The effects of postinduction period, microwell liquid fill volume, and concentration of inducer (doxycycline) on ProSavin(®) titer and the particle:infectivity (P:I) ratio was investigated using three rounds of DoE, in order to identify appropriate factor ranges and optimize production conditions. We identified an optimal "harvest window" between approximately 26-46 hr within which maximal titers of around 6×10(4) transducing units (TU)/ml were obtained (an approximately 30-fold improvement compared to starting microwell conditions), providing that the fill volume was maintained at or below 1 ml and the doxycycline concentration was at least 1.0 μg/ml. Insights from the microwell studies were subsequently used to rapidly establish operating conditions for ProSavin(®) production in a 0.5-L wave bioreactor culture. The information presented herein thus aids the design and evaluation of scalable production processes for LVs.

Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis.

PubMed

Pangrazio, Alessandra; Puddu, Alessandro; Oppo, Manuela; Valentini, Maria; Zammataro, Luca; Vellodi, Ashok; Gener, Blanca; Llano-Rivas, Isabel; Raza, Jamal; Atta, Irum; Vezzoni, Paolo; Superti-Furga, Andrea; Villa, Anna; Sobacchi, Cristina

2014-02-01

Autosomal Recessive Osteopetrosis is a genetic disorder characterized by increased bone density due to lack of resorption by the osteoclasts. Genetic studies have widely unraveled the molecular basis of the most severe forms, while cases of intermediate severity are more difficult to characterize, probably because of a large heterogeneity. Here, we describe the use of exome sequencing in the molecular diagnosis of 2 siblings initially thought to be affected by "intermediate osteopetrosis", which identified a homozygous mutation in the CTSK gene. Prompted by this finding, we tested by Sanger sequencing 25 additional patients addressed to us for recessive osteopetrosis and found CTSK mutations in 4 of them. In retrospect, their clinical and radiographic features were found to be compatible with, but not typical for, Pycnodysostosis. We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative. In conclusion, we underline the difficulties of differential diagnosis in some patients whose clinical appearance does not fit the classical malignant or benign picture and recommend that CTSK gene be included in the molecular diagnosis of high bone density conditions. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Oral health conditions affect functional and social activities of terminally-ill cancer patients

PubMed Central

Fischer, D.J.; Epstein, J.B.; Yao, Y.; Wilkie, D.J.

2013-01-01

Purpose Oral conditions are established complications in terminally-ill cancer patients. Yet despite significant morbidity, the characteristics and impact of oral conditions in these patients are poorly documented. The study objective was to characterize oral conditions in terminally-ill cancer patients to determine the presence, severity, and the functional and social impact of these oral conditions. Methods This was an observational clinical study including terminally-ill cancer patients (2.5–3 week life expectancy). Data were obtained via the Oral Problems Scale (OPS) that measures the presence of subjective xerostomia, orofacial pain, taste change, and the functional/social impact of oral conditions and a demographic questionnaire. A standardized oral examination was used to assess objective salivary hypofunction, fungal infection, mucosal erythema, and ulceration. Regression analysis and t test investigated the associations between measures. Results Of 104 participants, most were ≥50 years of age, female, and high-school educated; 45% were African American, 43% Caucasian, and 37% married. Oral conditions frequencies were: salivary hypofunction (98%), mucosal erythema (50%), ulceration (20%), fungal infection (36%), and other oral problems (46%). Xerostomia, taste change, and orofacial pain all had significant functional impact; p<.001, p=.042 and p<.001, respectively. Orofacial pain also had a significant social impact (p<.001). Patients with oral ulcerations had significantly more orofacial pain with a social impact than patients without ulcers (p=.003). Erythema was significantly associated with fungal infection and with mucosal ulceration (p<.001). Conclusions Oral conditions significantly affect functional and social activities in terminally-ill cancer patients. Identification and management of oral conditions in these patients should therefore be an important clinical consideration. PMID:24232310

Purification, Characterization, and Optimum Conditions of Fermencin SD11, a Bacteriocin Produced by Human Orally Lactobacillus fermentum SD11.

PubMed

Wannun, Phirawat; Piwat, Supatcharin; Teanpaisan, Rawee

2016-06-01

Fermencin SD11, a bacteriocin produced by human orally Lactobacillus fermentum SD11, was purified, characterized, and optimized in conditions for bacterial growth and bacteriocin production. Fermencin SD11 was purified using three steps of ammonium sulfate precipitation, gel filtration chromatography, and reverse-phase high-performance liquid chromatography. The molecular weight was found to be 33,000 Da using SDS-PAGE and confirmed as 33,593.4 Da by liquid chromatography-mass spectrometry. Fermencin SD11 exhibited activity against a wide range of oral pathogens including cariogenic and periodontogenic pathogens and Candida. The active activity was stable between 60 - 80 °C in a pH range of 3.0 to 7.0. It was sensitive to proteolytic enzymes (proteinase K and trypsin), but it was not affected by α-amylase, catalase, lysozyme, and saliva. The optimum conditions for growth and bacteriocin production of L. fermentum SD11 were cultured at acidic with pH of 5.0-6.0 at 37 or 40 °C under aerobic or anaerobic conditions for 12 h. It is promising that L. fermentum SD11 and its bacteriocin may be an alternative approach for promoting oral health or prevention of oral diseases, e.g., dental caries and periodontitis, which would require further clinical trials.

Neurotuberculosis in cattle in southern Brazil.

PubMed

Konradt, Guilherme; Bassuino, Daniele Mariath; Bianchi, Matheus Viezzer; Bandinelli, Marcele Bettim; Driemeier, David; Pavarini, Saulo Petinatti

2016-06-01

Tuberculosis in cattle is a chronic infectious-contagious disease characterized by the development of nodular lesions (granulomas) in mainly the lungs and regional lymph nodes. It is caused by Mycobacterium tuberculosis complex, an acid-fast bacillus (AFB). Tuberculosis in the central nervous system is a rare condition in cattle. Herein, we describe the clinical and pathological findings of six neurotuberculosis cases in cattle diagnosed in Southern Brazil. The average age of the cattle affected was 12 months, and they varied in breed and sex. The clinical history ranged from 5 to 30 days and was characterized by motor incoordination, opisthotonus, blindness, and progression to recumbency. The cattle were euthanized, and grossly, the leptomeninges at the basilar brain showed marked and diffuse expansion, with nodular yellowish lesions ranging in size. On microscopic examination, there were multifocal granulomas located mainly in the meninges, though sometimes extending to adjacent neuropil or existing as isolated granulomas in neuropil. AFBs were observed in the cytoplasm of epithelioid macrophages and multinucleated giant cells through Ziehl-Neelsen histochemical staining and identified as Mycobacterium sp. through immunohistochemistry.

Differentiating hypochondriasis from panic disorder.

PubMed

Hiller, Wolfgang; Leibbrand, Rolf; Rief, Winfried; Fichter, Manfred M

2005-01-01

Hypochondriasis and panic disorder are both characterized by prevalent health anxieties and illness beliefs. Therefore, the question as to whether they represent distinct nosological entities has been raised. This study examines how clinical characteristics can be used to differentiate both disorders, taking the possibility of mixed symptomatologies (comorbidity) into account. We compared 46 patients with hypochondriasis, 45 with panic disorder, and 21 with comorbid hypochondriasis plus panic disorder. While panic patients had more comorbidity with agoraphobia, hypochondriasis was more closely associated with somatization. Patients with panic disorder were less pathological than hypochondriacal patients on all subscales of the Whiteley Index (WI) and the Illness Attitude Scales (IAS) except for illness behavior. These differences were independent of somatization. Patients with hypochondriasis plus panic had higher levels of anxiety, more somatization, more general psychopathology and a trend towards increased health care utilization. Clinicians were able to distinguish between patient groups based upon the tendency of hypochondriacal patients to demand unnecessary medical treatments. These results confirm that hypochondriasis and panic disorder are distinguishable clinical conditions, characterized by generally more psychopathology and distress in hypochondriasis.

Modeling Alzheimer’s disease in transgenic rats

PubMed Central

2013-01-01

Alzheimer’s disease (AD) is the most common form of dementia. At the diagnostic stage, the AD brain is characterized by the accumulation of extracellular amyloid plaques, intracellular neurofibrillary tangles and neuronal loss. Despite the large variety of therapeutic approaches, this condition remains incurable, since at the time of clinical diagnosis, the brain has already suffered irreversible and extensive damage. In recent years, it has become evident that AD starts decades prior to its clinical presentation. In this regard, transgenic animal models can shed much light on the mechanisms underlying this “pre-clinical” stage, enabling the identification and validation of new therapeutic targets. This paper summarizes the formidable efforts to create models mimicking the various aspects of AD pathology in the rat. Transgenic rat models offer distinctive advantages over mice. Rats are physiologically, genetically and morphologically closer to humans. More importantly, the rat has a well-characterized, rich behavioral display. Consequently, rat models of AD should allow a more sophisticated and accurate assessment of the impact of pathology and novel therapeutics on cognitive outcomes. PMID:24161192

[The response of the upper respiratory tract to the impact of atmospheric pollution].

PubMed

Mukhamadiev, R A; Ismagilov, Sh M

2015-01-01

The present literature review characterizes the environmental conditions in the Russian Federation in general and the Republic of Tatarstan in particular with special reference to the influence of atmospheric pollution on the development and the clinical picture of the diseases of the respiratory organs including pathology of the upper respiratory tract in the populations of the industrial centres and other environmentally unfriendly areas. The views of the domestic and foreign authors concerning the role of the environmental factors in the clinical picture of the upper respiratory tract disorders are described in detail. The authors emphasize the necessity of the further investigationsinto this problem and the development of the methods for the prevention of diseases of the upper respiratory react.

Anti-PIT-1 antibody syndrome; a novel clinical entity leading to hypopituitarism.

PubMed

Bando, Hironori; Iguchi, Genzo; Yamamoto, Masaaki; Hidaka-Takeno, Ryoko; Takahashi, Yutaka

2015-03-01

Various hypothalamic-pituitary diseases cause hypopituitarism. Inflammation related to autoimmunity also causes hypopituitarism. Hypophysitis is a representative disease caused by autoimmunity. Generally, anterior pituitary hormones are non-specifically impaired in this condition, but specific hormone defects have been reported in some cases. Anti-PIT-1 (pituitary-specific transcription factor 1) antibody syndrome is a novel clinical entity that presents an acquired combined pituitary hormone deficiency characterized by a specific defect in growth hormone, prolactin, and thyroid-stimulating hormone. Circulating anti-PIT-1 antibody along with various autoantibodies are detected with multiple endocrine organopathy, meeting the definition of autoimmune polyglandular syndrome. Mechanistically, cytotoxic T lymphocytes that specifically react with PIT-1 protein play an important role in the development of this syndrome.

Infantile bilateral glaucoma in a child with ectodermal dysplasia.

PubMed

Callea, Michele; Vinciguerra, Agatino; Willoughby, Colin E; Deroma, Laura; Clarich, Gabriella

2013-01-01

Ectodermal dysplasia is a rare disease which affects at least two ectodermal-derived structures such as hair, nails, skin, sweat glands and teeth. Approximately 200 different conditions have been classified as an ectodermal dysplasia and X-linked hypohidrotic ectodermal dysplasia (XHED) represents the commonest form. Clinically, XHED is characterized by hypotrichosis, hypohidrosis and hypodontia. A variety of ocular manifestations have been reported in XHED, the most common being dryness of eyes due to tear deficiency and instability of the film secondary to the absence of meibomian gland function. Here we report a child with the distinctive clinical features of XHED confirmed with molecular diagnosis who presented with infantile bilateral glaucoma, in addition to the classical ocular involvement in XHED.

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

Osteogenesis imperfecta: diagnosis and treatment.

PubMed

Burnei, Gheorghe; Vlad, Costel; Georgescu, Ileana; Gavriliu, Traian Stefan; Dan, Daniela

2008-06-01

Osteogenesis imperfecta is a heritable disorder characterized by extremely fragile bones, blue sclerae, dentinogenesis imperfecta, hearing loss, and scoliosis. In 1979, Sillence classified the condition into four types based on genetic and clinical criteria. Three more classifications have subsequently been added. Diagnosis of osteogenesis imperfecta may be done prenatally (in severe cases), clinically, radiographically, or via biochemical or genetic examination. Medical treatment consists of bisphosphonate use, even in patients younger than age 2 years. Surgical treatment consists of internal splinting of long bones. Research is currently being done on the use of smart intramedullary rods (ie, composed of nitinol shape-memory alloy) for correction of bone deformity and on the use of bone marrow transplantation to increase osteoblast density, thereby reducing fracture frequency.

Sleep-related movement disorders.

PubMed

Merlino, Giovanni; Gigli, Gian Luigi

2012-06-01

Several movement disorders may occur during nocturnal rest disrupting sleep. A part of these complaints is characterized by relatively simple, non-purposeful and usually stereotyped movements. The last version of the International Classification of Sleep Disorders includes these clinical conditions (i.e. restless legs syndrome, periodic limb movement disorder, sleep-related leg cramps, sleep-related bruxism and sleep-related rhythmic movement disorder) under the category entitled sleep-related movement disorders. Moreover, apparently physiological movements (e.g. alternating leg muscle activation and excessive hypnic fragmentary myoclonus) can show a high frequency and severity impairing sleep quality. Clinical and, in specific cases, neurophysiological assessments are required to detect the presence of nocturnal movement complaints. Patients reporting poor sleep due to these abnormal movements should undergo non-pharmacological or pharmacological treatments.

Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

PubMed

Mukhopadhyay, Sanjay; Parambil, Joseph G

2012-10-01

Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1

PubMed Central

Goldbach-Mansky, R

2012-01-01

The disease-based discovery of the molecular basis for autoinflammatory diseases has led not only to a rapidly growing number of clinically and genetically identifiable disorders, but has unmantled key inflammatory pathways such as the potent role of the alarm cytokine interleukin (IL)-1 in human disease. Following its initial failures in the treatment of sepsis and the moderate success in the treatment of rheumatoid arthritis, IL-1 blocking therapies had a renaissance in the treatment of a number of autoinflammatory conditions, and IL-1 blocking therapies have been Food and Drug Administration (FDA)-approved for the treatment of the autoinflammatory conditions: cryopyrin-associated periodic syndromes (CAPS). CAPS and deficiency of the IL-1 receptor antagonist (DIRA), both genetic conditions with molecular defects in the IL-1 pathway, have provided a pathogenic rationale to IL-1 blocking therapies, and the impressive clinical results confirmed the pivotal role of IL-1 in human disease. Furthermore, IL-1 blocking strategies have shown clinical benefit in a number of other genetically defined autoinflammatory conditions, and diseases with clinical similarities to the monogenic disorders and not yet identified genetic causes. The discovery that IL-1 is not only triggered by infectious danger signals but also by danger signals released from metabolically ‘stressed’ or even dying cells has extended the concept of autoinflammation to disorders such as gout, and those that were previously not considered inflammatory, such as type 2 diabetes, coronary artery disease, obesity and some degenerative diseases, and provided the conceptual framework to target IL-1 in these diseases. Despite the tremendous success of IL-1 blocking therapy, the use of these agents in a wider spectrum of autoinflammatory conditions has uncovered disease subsets that are not responsive to IL-1 blockade, including the recently discovered proteasome-associated autoinflammatory syndromes such as chronic atypical neutrophilic dermatitis with lipodystrophy and elevated temperatures (CANDLE), Japanese autoinflammatory syndrome with lipodystrophy (JASL), Nakajo–Nishimura syndrome (NNS) and joint contractures, muscle atrophy, panniculitis induced lipodystrophy (JMP), and urge the continued quest to characterize additional dysregulated innate immune pathways that cause autoinflammatory conditions. PMID:22288582

Taking stock of the CSHCN screener: a review of common questions and current reflections.

PubMed

Bethell, Christina D; Blumberg, Stephen J; Stein, Ruth E K; Strickland, Bonnie; Robertson, Julie; Newacheck, Paul W

2015-01-01

Since 2000, the Children with Special Health Care Needs (CSHCN) Screener (CS) has been widely used nationally, by states, and locally as a standardized and brief survey-based method to identify populations of children who experience chronic physical, mental, behavioral, or other conditions and who also require types and amounts of health and related services beyond those routinely used by children. Common questions about the CS include those related to its development and uses; its conceptual framework and potential for under- or overidentification; its ability to stratify CSHCN by complexity of service needs and daily life impacts; and its potential application in clinical settings and comparisons with other identification approaches. This review recaps the development, design, and findings from the use of the CS and synthesizes findings from studies conducted over the past 13 years as well as updated findings on the CS to briefly address the 12 most common questions asked about this tool through technical assistance provided regarding the CS since 2001. Across a range of analyses, the CS consistently identifies a subset of children with chronic conditions who need or use more than a routine type or amount of medical- and health-related services and who share common needs for health care, including care coordination, access to specialized and community-based services, and enhanced family engagement. Scoring algorithms exist to stratify CSHCN by complexity of needs and higher costs of care. Combining CS data with clinical diagnostic code algorithms may enhance capacity to further identify meaningful subgroups. Clinical application is most suited for identifying and characterizing populations of patients and assessing quality and system improvement impacts for children with a broad range of chronic conditions. Other clinical applications require further implementation research. Use of the CS in clinical settings is limited because integration of standardized patient-reported health information is not yet common practice in most settings or in electronic health records. The CS continues to demonstrate validity as a non-condition-specific, population-based tool that addresses many of the limits of condition or diagnosis checklists, including the relatively low prevalence of many individual conditions and substantial within-diagnosis variations and across-diagnoses similarities in health service needs, functioning, and quality of care. Copyright © 2015 Academic Pediatric Association. All rights reserved.

New thrombopoietin receptor agonists for platelet disorders.

PubMed

Homeida, S; Ebdon, C; Batty, P; Jackson, B; Kolade, S; Bateman, C; Peng, Y Y; Stasi, R

2012-04-01

Since thrombopoietin (TPO) was cloned in 1994, TPO receptor (TPO-R) agonists have been developed which have shown significant clinical activity in various conditions characterized by thrombocytopenia. First-generation TPO-R agonists were recombinant forms of human TPO. The clinical development of these molecules was discontinued after one of them, pegylated recombinant human megakaryocyte growth and development factor, was associated with the development of neutralizing autoantibodies cross-reacting with endogenous TPO. Second-generation TPO-R agonists are now available, which present no sequence homology to endogenous TPO. Two of these new agents, romiplostim and eltrombopag, have been granted marketing authorization for use in patients with primary immune thrombocytopenia unresponsive to conventional treatments. Clinical trials with TPO-R agonists are also ongoing in other thrombocytopenias, such as hepatitis C virus-related thrombocytopenia and the myelodysplastic syndromes. Copyright 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

Food protein-induced enterocolitis syndrome: a review of the new guidelines.

PubMed

Leonard, Stephanie A; Pecora, Valentina; Fiocchi, Alessandro Giovanni; Nowak-Wegrzyn, Anna

2018-01-01

Food protein-induced enterocolitis syndrome (FPIES) is a non IgE-mediated gastrointestinal food allergy that presents with delayed vomiting after ingestion primarily in infants. While the pathophysiology of FPIES is poorly understood, the clinical presentation of acute FPEIS reactions has been well characterized. The first International Consensus Guidelines for the Diagnosis and Management of Food Protein-induced Enterocolitis Syndrome were published in 2017 and reviewed epidemiology, clinical presentation, and prognosis of acute and chronic FPIES. The workgroup outlined clinical phenotypes, proposed diagnostic criteria, and made recommendations on management. This article summarizes the guidelines and adds recent updates. FPIES is gaining recognition, however there continues to be delays in diagnosis and misdiagnosis due to overlap of symptoms with over conditions, lack of a diagnostic test, and because some of the common trigger foods are not thought of as allergenic. More research into disease mechanisms and factors influencing differences between populations is needed.

Muscle wasting in cancer cachexia: clinical implications, diagnosis, and emerging treatment strategies.

PubMed

Dodson, Shontelle; Baracos, Vickie E; Jatoi, Aminah; Evans, William J; Cella, David; Dalton, James T; Steiner, Mitchell S

2011-01-01

Cancer cachexia is a complex metabolic condition characterized by loss of skeletal muscle. Common clinical manifestations include muscle wasting, anemia, reduced caloric intake, and altered immune function, which contribute to increased disability, fatigue, diminished quality of life, and reduced survival. The prevalence of cachexia and the impact of this disorder on the patient and family underscore the need for effective management strategies. Dietary supplementation and appetite stimulation alone are inadequate to reverse the underlying metabolic abnormalities of cancer cachexia and have limited long-term impact on patient quality of life and survival. Therapies that can increase muscle mass and physical performance may be a promising option; however, there are currently no drugs approved for the prevention or treatment of cancer cachexia. Several agents are in clinical development, including anabolic agents, such as selective androgen receptor modulators and drugs targeting inflammatory cytokines that promote skeletal muscle catabolism.

Perspectives on Creating Clinically Relevant Blast Models for Mild Traumatic Brain Injury and Post Traumatic Stress Disorder Symptoms

PubMed Central

Brenner, Lisa A.; Bahraini, Nazanin; Hernández, Theresa D.

2012-01-01

Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic), behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI) and/or post traumatic stress disorder (PTSD). Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full characterization of this type of injury, as well as in the testing and identification of potential treatment strategies. In this publication, existing diagnostic challenges and current treatment practices for mTBI and/or PTSD will be summarized, along with suggestions regarding how what has been learned from existing models of PTSD and traditional mechanism (e.g., non-blast) traumatic brain injury can be used to facilitate the development of clinically relevant blast models. PMID:22408635

[The Ehlers-Danlos syndrome: hystory of a clinical hendiadys].

PubMed

Brazzaventre, Cristina; Celletti, Claudia; Gobattoni, Paolo; Santilli, Valter; Camerota, Filippo

2013-01-01

Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility and tissue fragility, which results in easy bruising and abnormal scarring. The condition shows a phenotypic variance from milder to serious presentations. Complaints related to activity (hypermobility, dislocations, impaired balance), to pain (general pain, headache, jaw and tooth pain) and to skin (bruises, fragility, impaired wound healing) are frequent. It was first noted by Hippocrates in 400 BC in his writing 'Airs Water and Places' that the nomads Scythians had lax joints and multiple scars. Whereas the additional flexibility can give benefits in term of mobility and agility, adverse effects of tissue laxity and fragility can give rise to clinical consequences. We recognize that it is important that, in those hypermobility patients, who develop potentially debilitating symptoms of chronicfatigue or widespread pain, there should be prompt an appropriate intervention.

Clinical Guidelines for the Diagnosis and Treatment of Cushing's Disease in Korea

PubMed Central

Hur, Kyu Yeon; Kim, Jung Hee; Kim, Byung Joon; Kim, Min-Seon; Lee, Eun Jig

2015-01-01

Cushing's disease (CD) is a rare disorder characterized by the overproduction of adrenocorticotropic hormone due to a pituitary adenoma that ultimately stimulates excessive cortisol secretion from the adrenal glands. Prior to the detection of pituitary adenomas, various clinical signs of CD such as central obesity, moon face, hirsutism, and facial plethora are usually already present. Uncontrolled hypercortisolism is associated with metabolic, cardiovascular, and psychological disorders that result in increased mortality. Hence, the early detection and treatment of CD are not only important but mandatory. Because its clinical manifestations vary from patient to patient and are common in other obesity-related conditions, the precise diagnosis of CD can be problematic. Thus, the present set of guidelines was compiled by Korean experts in this field to assist clinicians with the screening, diagnoses, and treatment of patients with CD using currently available tests and treatment modalities. PMID:25827452

Cushing’s disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment

PubMed Central

Buliman, A; Tataranu, LG; Paun, DL; Mirica, A; Dumitrache, C

2016-01-01

Cushing’s disease is considered a rare condition characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. The clinical signs suggesting Cushing’s disease, such as obesity, moon face, hirsutism, and facial plethora are already present on presentation. Endogenous hypercortisolism is associated with an increased risk of cardiovascular and metabolic manifestations, as well as respiratory disorders, psychiatric complications, osteoporosis and infections, leading to high rates of morbidity and mortality. It is vital to diagnose Cushing’s disease as early as possible and to implement a treatment plan to lead to a successful prognosis and a low number of complications. The goal of this article was to review the clinical, diagnostic and treatment aspects of Cushing’s disease using the most recent available guidelines. PMID:27974908

Sensory over-responsivity in adults with autism spectrum conditions.

PubMed

Tavassoli, Teresa; Miller, Lucy J; Schoen, Sarah A; Nielsen, Darci M; Baron-Cohen, Simon

2014-05-01

Anecdotal reports and empirical evidence suggest that sensory processing issues are a key feature of autism spectrum conditions. This study set out to investigate whether adults with autism spectrum conditions report more sensory over-responsivity than adults without autism spectrum conditions. Another goal of the study was to identify whether autistic traits in adults with and without autism spectrum conditions were associated with sensory over-responsivity. Adults with (n = 221) and without (n = 181) autism spectrum conditions participated in an online survey. The Autism Spectrum Quotient, the Raven Matrices and the Sensory Processing Scale were used to characterize the sample. Adults with autism spectrum conditions reported more sensory over-responsivity than control participants across various sensory domains (visual, auditory, tactile, olfactory, gustatory and proprioceptive). Sensory over-responsivity correlated positively with autistic traits (Autism Spectrum Quotient) at a significant level across groups and within groups. Adults with autism spectrum conditions experience sensory over-responsivity to daily sensory stimuli to a high degree. A positive relationship exists between sensory over-responsivity and autistic traits. Understanding sensory over-responsivity and ways of measuring it in adults with autism spectrum conditions has implications for research and clinical settings.

Quantifying Data Quality for Clinical Trials Using Electronic Data Capture

PubMed Central

Nahm, Meredith L.; Pieper, Carl F.; Cunningham, Maureen M.

2008-01-01

Background Historically, only partial assessments of data quality have been performed in clinical trials, for which the most common method of measuring database error rates has been to compare the case report form (CRF) to database entries and count discrepancies. Importantly, errors arising from medical record abstraction and transcription are rarely evaluated as part of such quality assessments. Electronic Data Capture (EDC) technology has had a further impact, as paper CRFs typically leveraged for quality measurement are not used in EDC processes. Methods and Principal Findings The National Institute on Drug Abuse Treatment Clinical Trials Network has developed, implemented, and evaluated methodology for holistically assessing data quality on EDC trials. We characterize the average source-to-database error rate (14.3 errors per 10,000 fields) for the first year of use of the new evaluation method. This error rate was significantly lower than the average of published error rates for source-to-database audits, and was similar to CRF-to-database error rates reported in the published literature. We attribute this largely to an absence of medical record abstraction on the trials we examined, and to an outpatient setting characterized by less acute patient conditions. Conclusions Historically, medical record abstraction is the most significant source of error by an order of magnitude, and should be measured and managed during the course of clinical trials. Source-to-database error rates are highly dependent on the amount of structured data collection in the clinical setting and on the complexity of the medical record, dependencies that should be considered when developing data quality benchmarks. PMID:18725958

Non-traumatic rhabdomyolysis: Background, laboratory features, and acute clinical management.

PubMed

Cervellin, Gianfranco; Comelli, Ivan; Benatti, Mario; Sanchis-Gomar, Fabian; Bassi, Antonella; Lippi, Giuseppe

2017-08-01

Rhabdomyolysis is a relatively rare condition, but its clinical consequences are frequently dramatic in terms of both morbidity and mortality. Although no consensus has been reached so far about the precise definition of this condition, the term rhabdomyolysis describes a rapid breakdown of striated, or skeletal, muscle. It is hence characterized by the rupture and necrosis of muscle fibers, resulting in release of cell degradation products and intracellular elements within the bloodstream and extracellular space. Notably, the percentage of patients with rhabdomyolysis who develop acute kidney injury, the most dramatic consequence, varies from 13% to over 50% according to both the cause and the clinical and organizational setting where they are diagnosed. Despite direct muscle injury (i.e., traumatic rhabdomyolysis) remains the most common cause, additional causes, frequently overlapping, include hypoxic, physical, chemical or biological factors. The conventional triad of symptoms includes muscle pain, weakness and dark urine. The laboratory diagnosis is essentially based on the measurement of biomarkers of muscle injury, being creatine kinase (CK) the biochemical "gold standard" for diagnosis, and myoglobin the "gold standard" for prognostication, especially in patients with non-traumatic rhabdomyolysis. The essential clinical management in the emergency department is based on a targeted intervention to manage the underlying cause, combined with infusion of fluids and eventually sodium bicarbonate. We will present and discuss in this article the pathophysiological and clinical features of non-traumatic rhabdomyolysis, focusing specifically on Emergency Department (ED) management. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Exploring the role of negative cognitions in the relationship between ethnicity, sleep and pain in women with temporomandibular joint disorder.

PubMed

Lerman, Sheera F; Campbell, Claudia M; Buenaver, Luis F; Medak, Mary; Phillips, Jane; Polley, Michelle; Smith, Michael T; Haythornthwaite, Jennifer A

2018-06-08

Negative cognitions are central to the perpetuation of chronic pain and sleep disturbances. Patients with temporomandibular joint disorder (TMJD), a chronic pain condition characterized by pain and limitation in the jaw area, have a high comorbidity of sleep disturbances that possibly exacerbate their condition. Ethnic group differences are documented in pain, sleep and coping, yet the mechanisms driving these differences are still unclear, especially in clinical pain populations. 156 women (79% white, 21% African American (AA)) diagnosed with TMJD were recruited as part of a randomized controlled trial evaluating the effectiveness of interventions targeting sleep and pain catastrophizing on pain in TMJD. Analysis of baseline data demonstrated that relative to white participants, AA exhibited higher levels of clinical pain, insomnia severity and pain catastrophizing, yet there was no ethnic group difference in negative sleep-related cognitions. Mediation models revealed pain catastrophizing, but not sleep-related cognitions or insomnia severity, to be a significant single mediator of the relationship between ethnicity and clinical pain. Only the helplessness component of catastrophizing together with insomnia severity sequentially mediated the ethnicity-pain relationship. These findings identify pain catastrophizing as a potentially important link between ethnicity and clinical pain and suggest that interventions targeting pain-related helplessness could improve both sleep and pain especially for AA patients. Pain related helplessness and insomnia severity contribute to ethnic differences found in clinical pain among woman with temporomandibular joint disorder. Findings can potentially inform interventions that target insomnia and catastrophizing to assist in reducing ethnic disparities in clinical pain. Copyright © 2018. Published by Elsevier Inc.

American tertiary clinic-referred bipolar II disorder versus bipolar I disorder associated with hastened depressive recurrence.

PubMed

Dell'Osso, Bernardo; Shah, Saloni; Do, Dennis; Yuen, Laura D; Hooshmand, Farnaz; Wang, Po W; Miller, Shefali; Ketter, Terence A

2017-12-01

Bipolar disorder (BD) is a chronic, frequently comorbid condition characterized by high rates of mood episode recurrence and suicidality. Little is known about prospective longitudinal characterization of BD type II (BD II) versus type I (BD I) in relation to time to depressive recurrence and recovery from major depressive episode. We therefore assessed times to depressive recurrence/recovery in tertiary clinic-referred BD II versus I patients. Outpatients referred to Stanford BD Clinic during 2000-2011 were assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and with Clinical Monitoring Form during up to 2 years of naturalistic treatment. Prevalence and clinical correlates of bipolar subtype in recovered (euthymic ≥8 weeks) and depressed patients were assessed. Kaplan-Meier analyses assessed the relationships between bipolar subtype and longitudinal depressive severity, and Cox proportional hazard analyses assessed the potential mediators. BD II versus BD I was less common among 105 recovered (39.0 vs. 61.0%, p = 0.03) and more common among 153 depressed (61.4 vs. 38.6%, p = 0.006) patients. Among recovered patients, BD II was associated with 6/25 (24.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics and hastened depressive recurrence (p = 0.015). Among depressed patients, BD II was associated with 8/25 (33.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics, but only non-significantly associated with delayed depressive recovery. BD II versus BD I was significantly associated with current depression and hastened depressive recurrence, but only non-significantly associated with delayed depressive recovery. Research on bipolar subtype relationships with depressive recurrence/recovery is warranted to enhance clinical management of BD patients.

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets.

PubMed

Rb-Silva, Rita; Nobrega, Claudia; Reiriz, Eugénia; Almeida, Soraia; Sarmento-Castro, Rui; Correia-Neves, Margarida; Horta, Ana

2017-01-13

HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed. A 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4 + T cells and higher percentage of activated CD4 + T cells at HAART initiation. The percentage of memory CD4 + T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8 + T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset. Although both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.

Neurodevelopmental behavioral and cognitive disorders.

PubMed

Jeste, Shafali Spurling

2015-06-01

Neurodevelopmental disorders are a group of heterogeneous conditions characterized by a delay or disturbance in the acquisition of skills in a variety of developmental domains, including motor, social, language, and cognition. This article reviews the most commonly diagnosed neurodevelopmental disorders, which include attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, global developmental delay, and intellectual disability and also provides updates on diagnosis, neurobiology, treatment, and issues surrounding the transition to adulthood. Although symptoms emerge at discrete points in childhood, these disorders result from abnormal brain maturation that likely precedes clinical impairment. As a result, research has focused on the identification of predictive biological and behavioral markers, with the ultimate goal of initiating treatments that may either alter developmental trajectories or lessen clinical severity. Advances in the methods used to identify genetic variants, from chromosomal microarray analysis to whole exome sequencing, have facilitated the characterization of many genetic mutations and syndromes that share common pathways to abnormal circuit formation and brain development. Not only do genetic discoveries enrich our understanding of mechanisms underlying atypical development, but they also allow us to identify more homogeneous subgroups within this spectrum of conditions. Impairments do continue into adulthood, with challenges in the transition to adulthood including the management of comorbidities and the provision of educational and vocational supports. Advances in our understanding of the neurobiology and developmental trajectories of these disorders will pave the way for tremendous advances in treatment. Mechanism-based therapies for genetic syndromes are being studied with the goal of expanding targeted treatments to nonsyndromic forms of neurodevelopmental disorders.

Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting1234

PubMed Central

Gullett, Norleena P; Hebbar, Gautam

2010-01-01

This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, megestrol acetate) in malnutrition and other catabolic states has been the subject of considerable research during the past several decades. Research on the effects of these agents in cachexia or wasting conditions, characterized by progressive loss of skeletal muscle and adipose tissue, focused on patients with AIDS in the early 1990s, when the devastating effects of the loss of body weight, lean body mass, and adipose tissue were recognized as contributors to these patients' mortality. These same agents have also been studied as methods to attenuate the catabolic responses observed in cancer-induced cachexia and in wasting induced by chronic obstructive pulmonary disease, congestive heart failure, renal failure, and other conditions. This article provides an updated review of recent clinical trials that specifically examined the potential therapeutic roles of growth hormone, testosterone, oxandrolone, and megestrol acetate and emerging data on the orexigenic peptide ghrelin, in human cachexia and wasting. PMID:20164318

Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting.

PubMed

Gullett, Norleena P; Hebbar, Gautam; Ziegler, Thomas R

2010-04-01

This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, megestrol acetate) in malnutrition and other catabolic states has been the subject of considerable research during the past several decades. Research on the effects of these agents in cachexia or wasting conditions, characterized by progressive loss of skeletal muscle and adipose tissue, focused on patients with AIDS in the early 1990s, when the devastating effects of the loss of body weight, lean body mass, and adipose tissue were recognized as contributors to these patients' mortality. These same agents have also been studied as methods to attenuate the catabolic responses observed in cancer-induced cachexia and in wasting induced by chronic obstructive pulmonary disease, congestive heart failure, renal failure, and other conditions. This article provides an updated review of recent clinical trials that specifically examined the potential therapeutic roles of growth hormone, testosterone, oxandrolone, and megestrol acetate and emerging data on the orexigenic peptide ghrelin, in human cachexia and wasting.

Improvement of skin condition in striae distensae: development, characterization and clinical efficacy of a cosmetic product containing Punica granatum seed oil and Croton lechleri resin extract

PubMed Central

Bogdan, Cătălina; Iurian, Sonia; Tomuta, Ioan; Moldovan, Mirela

2017-01-01

Striae distensae are a frequent skin condition associated with pregnancy, weight change or lack of skin elasticity. The aim of this research was to obtain a topical product containing herbal active ingredients with documented antioxidant and anti-inflammatory activity (Punica granatum seed oil and Croton lechleri resin extract) and demonstrate its positive effect on prevention and treatment of striae distensae. First, the cream base formulation was optimized through experimental design. Secondly, the cream containing the two active ingredients was investigated in an interventional nonrandomized clinical trial. The clinical outcome was assessed through biophysical parameters and ultrasonographic evaluation. The state of the skin was evaluated by biophysical measurements and ultrasonography at the beginning of the study and after 3 and 6 weeks. The experimental design was successfully used to set the best ranges for the technological and formulation factors to obtain a cosmetic formulation with optimal characteristics. The study of clinical efficacy on the optimal formulation revealed an increase in the dermis thickness, hydration and elasticity values in both groups after 6 weeks of cream application. The new oil-in-water cream containing P. granatum seed oil and C. lechleri resin extract can be helpful in the prevention or improving of skin changes associated with striae. PMID:28280300

Bilirubin glucuronidation revisited: proper assay conditions to estimate enzyme kinetics with recombinant UGT1A1.

PubMed

Zhou, Jin; Tracy, Timothy S; Remmel, Rory P

2010-11-01

Bilirubin, an end product of heme catabolism, is primarily eliminated via glucuronic acid conjugation by UGT1A1. Impaired bilirubin conjugation, caused by inhibition of UGT1A1, can result in clinical consequences, including jaundice and kernicterus. Thus, evaluation of the ability of new drug candidates to inhibit UGT1A1-catalyzed bilirubin glucuronidation in vitro has become common practice. However, the instability of bilirubin and its glucuronides presents substantial technical challenges to conduct in vitro bilirubin glucuronidation assays. Furthermore, because bilirubin can be diglucuronidated through a sequential reaction, establishment of initial rate conditions can be problematic. To address these issues, a robust high-performance liquid chromatography assay to measure both bilirubin mono- and diglucuronide conjugates was developed, and the incubation conditions for bilirubin glucuronidation by human embryonic kidney 293-expressed UGT1A1 were carefully characterized. Our results indicated that bilirubin glucuronidation should be assessed at very low protein concentrations (0.05 mg/ml protein) and over a short incubation time (5 min) to assure initial rate conditions. Under these conditions, bilirubin total glucuronide formation exhibited a hyperbolic (Michaelis-Menten) kinetic profile with a K(m) of ∼0.2 μM. In addition, under these initial rate conditions, the relative proportions between the total monoglucuronide and the diglucuronide product were constant across the range of bilirubin concentration evaluated (0.05-2 μM), with the monoglucuronide being the predominant species (∼70%). In conclusion, establishment of appropriate incubation conditions (i.e., very low protein concentrations and short incubation times) is necessary to properly characterize the kinetics of bilirubin glucuronidation in a recombinant UGT1A1 system.

Investigating Misophonia: A Review of the Empirical Literature, Clinical Implications, and a Research Agenda

PubMed Central

Brout, Jennifer J.; Edelstein, Miren; Erfanian, Mercede; Mannino, Michael; Miller, Lucy J.; Rouw, Romke; Kumar, Sukhbinder; Rosenthal, M. Zachary

2018-01-01

Misophonia is a neurobehavioral syndrome phenotypically characterized by heightened autonomic nervous system arousal and negative emotional reactivity (e. g., irritation, anger, anxiety) in response to a decreased tolerance for specific sounds. The aims of this review are to (a) characterize the current state of the field of research on misophonia, (b) highlight what can be inferred from the small research literature to inform treatment of individuals with misophonia, and (c) outline an agenda for research on this topic. We extend previous reviews on this topic by critically reviewing the research investigating mechanisms of misophonia and differences between misophonia and other conditions. In addition, we integrate this small but growing literature with basic and applied research from other literatures in a cross-disciplinary manner. PMID:29467604

Investigating Misophonia: A Review of the Empirical Literature, Clinical Implications, and a Research Agenda.

PubMed

Brout, Jennifer J; Edelstein, Miren; Erfanian, Mercede; Mannino, Michael; Miller, Lucy J; Rouw, Romke; Kumar, Sukhbinder; Rosenthal, M Zachary

2018-01-01

Misophonia is a neurobehavioral syndrome phenotypically characterized by heightened autonomic nervous system arousal and negative emotional reactivity (e. g., irritation, anger, anxiety) in response to a decreased tolerance for specific sounds. The aims of this review are to (a) characterize the current state of the field of research on misophonia, (b) highlight what can be inferred from the small research literature to inform treatment of individuals with misophonia, and (c) outline an agenda for research on this topic. We extend previous reviews on this topic by critically reviewing the research investigating mechanisms of misophonia and differences between misophonia and other conditions. In addition, we integrate this small but growing literature with basic and applied research from other literatures in a cross-disciplinary manner.

Neural circuitry and immunity

PubMed Central

Pavlov, Valentin A.; Tracey, Kevin J.

2015-01-01

Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine. PMID:26512000

Oral findings in Rett syndrome: a systematic review of the dental literature.

PubMed

Fuertes-González, María-Cristina; Silvestre, Francisco-Javier; Almerich-Silla, José-Manuel

2011-01-01

Rett syndrome (RS) is a chromosome X-linked genetic neurological disorder characterized by developmental regression, particularly in relation to expressive language and use of the hands, together with profound mental retardation, that almost exclusively affects females. The present review describes the 35 cases of RS published in the indexed literature (Medline)--the first corresponding to 1985 and the last to the year 2007. Certain oral manifestations of the disease are derived from the drug treatment prescribed to control the disease, while others are common to other clinical conditions characterized by convulsion activity, difficulties for correct oral hygiene, walking problems and/or an excess of oral/digital-manual habits. In any case, bruxism is the oral habit most frequently associated with RS--the treatment of which remains the subject of controversy.

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

The Role of Brain MRI in Mitochondrial Neurogastrointestinal Encephalomyopathy

PubMed Central

Scarpelli, Mauro; Ricciardi, Giuseppe Kenneth; Beltramello, Alberto; Zocca, Isabella; Calabria, Francesca; Russignan, Anna; Zappini, Francesca; Cotelli, Maria Sofia; Padovani, Alessandro; Tomelleri, Giuliano; Filosto, Massimiliano; Tonin, Paola

2013-01-01

Summary Leukoencephalopathy is a hallmark of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) a devastating disorder characterized by ptosis, ophthalmoparesis, gastrointestinal dysfunction and polyneuropathy. To characterize MNGIE-associated leukoencephalopathy and to correlate it with clinical, biochemical and molecular data, four MNGIE patients with heterogeneous clinical phenotypes (enteropathic arthritis, exercise intolerance, CIDP-like phenotype and typical presentation) were studied by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC) maps were also obtained. In two patients we also investigated the role of brain MRI in monitoring the evolution of leukoencephalopathy by performing follow-up imaging studies at an interval of one and two years. The extension and distribution of leukoencephalopathy were not clearly linked with age, phenotype or disease severity, and did not seem to be related to TYMP mutations, enzyme activity or pyrimidine levels. In the studied patients MRS revealed reduced N-acetyl-aspartate and increased choline signals. Although DWI appeared normal in all patients but one, ADC maps always showed moderate increased diffusivity. Leukoencephalopathy worsened over a two-year period in two patients, regardless of the clinical course, indicating a lack of correlation between clinical phenotype, size and progression of white matter abnormalities during this period. Brain MRI should be considered a very useful tool to diagnose both classical and atypical MNGIE. Serial MRIs in untreated and treated MNGIE patients will help to establish whether the leukoencephalopathy is a reversible condition or not. PMID:24199812

Characterization of a Fiber Optic Coupled Dosimeter for Clinical Electron Beam Dosimetry

DTIC Science & Technology

2010-04-29

2010 2. REPORT TYPE 3. DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Characterization of a Fiber Optic Coupled Dosimeter for...Fiber Optic Coupled Dosimeter for Clinical Electron Beam Dosimetry. Abstract approved: Camille J. Lodwick Fiber-optic-coupled dosimeters ...Rights Reserved CHARACTERIZATION OF A FIBER OPTIC COUPLED DOSIMETER FOR CLINICAL ELECTRON

Orofacial functions and oral health associated with Treacher Collins syndrome.

PubMed

Asten, Pamela; Skogedal, Nina; Nordgarden, Hilde; Axelsson, Stefan; Akre, Harriet; Sjögreen, Lotta

2013-01-01

The aim of this study was to describe orofacial features and functions and oral health associated with Treacher Collins syndrome (TCS) in relation to the variable phenotypic expression of the condition. The Nordic Orofacial Test-Screening (NOT-S), MHC Questionnaire, MHC Observation chart and clinical examinations of nasal and pharyngeal conditions and chewing and swallowing function were used to assess 19 individuals aged 5-74 years (median 34 years). TCS severity scores were calculated by a clinical geneticist. Orofacial features characterizing the study group were altered profile, increased mandibular angle, narrow hypopharynx and facial asymmetry. Basic orofacial functions such as breathing, eating, facial expression and speech were affected in all subjects demonstrating orofacial dysfunction in at least two NOT-S domains (median NOT-S total score 4/12, range 2-7). Significant correlation was found between the TCS severity scores reflecting phenotypic expression and the NOT-S total scores reflecting orofacial function. Self-reported experience of dry oral mucosa was common. Overall, dental health was good with few carious lesions diagnosed, but considerable need for orthodontic treatment was documented. Altered orofacial features and functions in TCS are common and often persist into late adolescence and adulthood. The functional level was correlated with the phenotypic variability of the condition. The standard of oral health was satisfactory. The findings indicated that individuals with TCS are likely to require lifelong health services related to their oral condition.

Postural strategies assessed with inertial sensors in healthy and parkinsonian subjects.

PubMed

Baston, Chiara; Mancini, Martina; Schoneburg, Bernadette; Horak, Fay; Rocchi, Laura

2014-01-01

The present study introduces a novel instrumented method to characterize postural movement strategies to maintain balance during stance (ankle and hip strategy), by means of inertial sensors, positioned on the legs and on the trunk. We evaluated postural strategies in subjects with 2 types of Parkinsonism: idiopathic Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP), and in age-matched control subjects standing under perturbed conditions implemented by the Sensory Organization Test (SOT). Coordination between the upper and lower segments of the body during postural sway was measured using a covariance index over time, by a sliding-window algorithm. Afterwards, a postural strategy index was computed. We also measured the amount of postural sway, as adjunctive information to characterize balance, by the root mean square of the horizontal trunk acceleration signal (RMS). showed that control subjects were able to change their postural strategy, whilst PSP and PD subjects persisted in use of an ankle strategy in all conditions. PD subjects had RMS values similar to control subjects even without changing postural strategy appropriately, whereas PSP subjects showed much larger RMS values than controls, resulting in several falls during the most challenging SOT conditions (5 and 6). Results are in accordance with the corresponding clinical literature describing postural behavior in the same kind of subjects. The proposed strategy index, based on the use of inertial sensors on the upper and lower body segments, is a promising and unobtrusive tool to characterize postural strategies performed to attain balance. Copyright © 2014 Elsevier B.V. All rights reserved.

Reproducibility of Alzheimer’s Disease Cerebrospinal Fluid-Biomarker Measurements under Clinical Routine Conditions

PubMed Central

Vogelgsang, Jonathan; Wedekind, Dirk; Bouter, Caroline; Klafki, Hans-W.; Wiltfang, Jens

2018-01-01

Analysis of cerebrospinal fluid (CSF) is one of the key tools for the state-of-the-art differential diagnosis of dementias. Dementia due to Alzheimer’s disease (AD) is characterized by elevated CSF levels of total Tau (tTau) and phospho-181-Tau (pTau) and low CSF amyloid-β42 (Aβ42). Discrepancies in the laboratory analysis of human materials are well known and much effort has been put into harmonization procedures. In this study, we measured CSF biomarkers of more than 100 patients obtained under clinical routine conditions in two different clinical laboratories. The CSF biomarker levels obtained from the two different sites were significantly correlated: R2 = 0.7129 (tTau, p < 0.001), 0.7914 (pTau, p < 0.001), 0.5078 (Aβ42, p < 0.001), 0.5739 (Aβ40, p < 0.001), and 0.4308 (Aβ42/40, p < 0.001). However, the diagnostic classifications of the Aβ42, tTau, and pTau levels of identical subjects into normal versus pathological range made by the two different sites showed substantial discrepancies (31.5%, 29.6%, and 25.0% discordant cases, respectively). Applying Aβ42/40, instead of CSF Aβ42 alone, lead to a reduction of the discordant cases to 16.8%. Our findings suggest that CSF Aβ42/40 can outperform Aβ42 as a biomarker for AD neuropathology, not only under well-controlled study conditions but also in real life clinical routine. Thus, we recommend the inclusion of Aβ42/40 as a CSF biomarker in the diagnostic procedure. PMID:29439341

Implementing and Sustaining Team-Based Telecare for Bipolar Disorder: Lessons Learned from a Model-Guided, Mixed Methods Analysis.

PubMed

Bauer, Mark S; Krawczyk, Lois; Tuozzo, Kathy; Frigand, Cara; Holmes, Sally; Miller, Christopher J; Abel, Erica; Osser, David N; Franz, Aleda; Brandt, Cynthia; Rooney, Meghan; Fleming, Jerry; Smith, Eric; Godleski, Linda

2018-01-01

Telemental health interventions have empirical support from clinical trials and structured demonstration projects. However, their implementation and sustainability under less structured clinical conditions are not well demonstrated. We conducted a follow-up analysis of the implementation and sustainability of a clinical video teleconference-based collaborative care model for individuals with bipolar disorder treated in the Department of Veterans Affairs to (a) characterize the extent of implementation and sustainability of the program after its establishment and (b) identify barriers and facilitators to implementation and sustainability. We conducted a mixed methods program evaluation, assessing quantitative aspects of implementation according to the Reach, Efficacy, Adoption, Implementation, and Maintenance implementation framework. We conducted qualitative analysis of semistructured interviews with 16 of the providers who submitted consults, utilizing the Integrated Promoting Action on Research Implementation in the Health Services implementation framework. The program demonstrated linear growth in sites (n = 35) and consults (n = 915) from late 2011 through mid-2016. Site-based analysis indicated statistically significant sustainability beyond the first year of operation. Qualitative analysis identified key facilitators, including consult content, ease of use via electronic health record, and national infrastructure. Barriers included availability of telehealth space, equipment, and staff at the sites, as well as the labor-intensive nature of scheduling. The program achieved continuous growth over almost 5 years due to (1) successfully filling a need perceived by providers, (2) developing in a supportive context, and (3) receiving effective facilitation by national and local infrastructure. Clinical video teleconference-based interventions, even multicomponent collaborative care interventions for individuals with complex mental health conditions, can grow vigorously under appropriate conditions.

Clinical applications of bioactive milk components

PubMed Central

Newburg, David S.

2015-01-01

Milk represents a unique resource for translational medicine: It contains a rich pool of biologically active molecules with demonstrated clinical benefits. The ongoing characterization of the mechanistic process through which milk components promote development and immunity has revealed numerous milk-derived compounds with potential applications as clinical therapies in infectious and inflammatory disease, cancer, and other conditions. Lactoferrin is an effective antimicrobial and antiviral agent in high-risk patient populations and a potentially potent adjuvant to chemotherapy in lung cancer. Enteric nutrition formulas supplemented with transforming growth factor β, a milk cytokine, have been shown to promote remission in pediatric Crohn's disease. A number of milk glycans, including human milk oligosaccharides, show promise in preclinical studies as antimicrobial and anti-inflammatory agents. While active preclinical investigations of human milk may soon result in large-scale production of human milk molecules, bovine milk components in many instances represent a practical source of bioactive milk compounds for use in clinical trials. This review summarizes current efforts to translate the compounds derived from human and bovine milk into effective clinical therapies. These efforts suggest a common pathway for the translation of milk-derived compounds into clinical applications. PMID:26011900

Clinical applications of bioactive milk components.

PubMed

Hill, David R; Newburg, David S

2015-07-01

Milk represents a unique resource for translational medicine: It contains a rich pool of biologically active molecules with demonstrated clinical benefits. The ongoing characterization of the mechanistic process through which milk components promote development and immunity has revealed numerous milk-derived compounds with potential applications as clinical therapies in infectious and inflammatory disease, cancer, and other conditions. Lactoferrin is an effective antimicrobial and antiviral agent in high-risk patient populations and a potentially potent adjuvant to chemotherapy in lung cancer. Enteric nutrition formulas supplemented with transforming growth factor β, a milk cytokine, have been shown to promote remission in pediatric Crohn's disease. A number of milk glycans, including human milk oligosaccharides, show promise in preclinical studies as antimicrobial and anti-inflammatory agents. While active preclinical investigations of human milk may soon result in large-scale production of human milk molecules, bovine milk components in many instances represent a practical source of bioactive milk compounds for use in clinical trials. This review summarizes current efforts to translate the compounds derived from human and bovine milk into effective clinical therapies. These efforts suggest a common pathway for the translation of milk-derived compounds into clinical applications.

Impulsive behavior in a consumer culture.

PubMed

Hartston, Heidi J; Koran, Lorrin M

2002-01-01

Compulsive shopping behaviour has recently received long overdue attention as a clinical issue. Curiosity about this condition has led to questions about its identification, characterization as a disorder, and treatment. This article presents two case vignettes illustrating diagnostic criteria and points that distinguish this disorder from OCD hoarding or mania. These issues are discussed. The authors present some suggested treatment approaches Greater awareness of the prevalence and social consequences of compulsive shopping behaviour highlights the need for treatment and for educational resources for clinicians and the general public. (Int J Psych Clin Pract 2002; 6: 65-68).

Social communication impairments: pragmatics.

PubMed

Russell, Robert L

2007-06-01

Social communication or pragmatic impairments are characterized and illustrated as involving inappropriate or ineffective use of language and gesture in social contexts. Three clinical vignettes illustrate different pragmatic impairments and the wealth of diagnostic information that can be garnered from observation of a child's social communication behavior. Definitions of, and developmental milestones in, domains of pragmatic competence are provided. Several screening instruments are suggested for use in assessing pragmatic competence within the time-frame of a pediatric examination. Frequent comorbid psychiatric conditions are described and a sample of current neurobiologic research is briefly summarized.

Limbus Vertebra Presenting with Inflammatory Low Back Pain: A Case Report

PubMed Central

Özdemir, Tayfun; Öz, Hande Ece

2016-01-01

Limbus vertebra is a condition characterized by marginal interosseous herniation of the nucleus pulposus, and causes non specific symptoms like low back pain, back pain, muscle spasms and radiculopathy. It is frequently confused with vertebral fracture, infection, schmorl nodule or tumour because it has not a spesific symptom. It usually causes mechanical low back pain rather than inflammatory low back pain. We reported a patient presented with inflammatory low back pain and diagnosed with anterior limbus vertebra because it is rare and the patient has atypical clinical presentation. PMID:27134989

Smartphone chloridometer for point-of-care applications

NASA Astrophysics Data System (ADS)

Zhang, Chenji; Kim, Jimin P.; Creer, Michael; Yang, Jian; Liu, Zhiwen

2017-08-01

Chloride level in sweat is a major diagnostic criterion for cystic fibrosis (CF) and many other health conditions. In an effort to develop a low cost, point-of-care sweat diagnostics system for chloride concentration measurement, we demonstrated a smartphone-based chloridometer to measure sweat chloride by using our recently developed fluorescence chloride sensor. We characterized the performance of our device to validate its clinical potential. The study indicates that our smartphone-based chloridometer may potentially advance the point-of-care diagnostic system by reducing cost and improving diagnostic accuracy.

[Essential thrombocythemia and pregnancy].

PubMed

Baleiras, Carla; Silva, Ana; Serrano, Fátima

2003-01-01

Essencial Thrombocytemia is a rare chronic myeloproliferative disease of unknown etiology, characterized by markedly elevated platelet production (> 600,000/ml). It is more frequent among women above 50 years of age and may be associated with hemorrhagic or thrombotic tendencies. The authors report a case of Essencial Thrombocytemia diagnosed after several consecutive spontaneous abortions. Some clinical aspects, complications, differential diagnosis and management of this condition in pregnancy are also reviewed. An individualized, multidisciplinar approach and the treatment with acetylsalicylic acid, associated with interferon-alfa if necessary, will be the best therapeutic options for these patients.

Chiari type I malformation, syncope, headache, hypoglycemia and hepatic steatosis in an 8-year old girl: a causal association?

PubMed Central

Tarani, Luigi; Del Balzo, Francesca; Costantino, Francesco; Properzi, Enrico; D’Eufemia, Patrizia; Liberati, Natascia; Spalice, Alberto

2010-01-01

Chiari type I malformation (CMI) is a congenital hindbrain anomaly characterized by downward displacement of the cerebellar tonsils through the foramen magnum. Chiari type I malformation often presents with a complex clinical picture and can be sporadic or linked to a variety of genetic conditions. We report on a girl in whom Chiari type I malformation was associated with hypoglycemia, headache, vertigo, syncope and hepatic steatosis. We hypothesize that these symptoms are primarily a consequence of Chiari type I malformation. PMID:21589844

Priapism and glucose-6-phosphate dehydrogenase deficiency: An underestimated correlation?

PubMed

De Rose, Aldo Franco; Mantica, Guglielmo; Tosi, Mattia; Bovio, Giulio; Terrone, Carlo

2016-10-05

Priapism is a rare clinical condition characterized by a persistent erection unrelated to sexual excitement. Often the etiology is idiopathic. Three cases of priapism in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients have been described in literature. We present the case of a 39-year-old man with glucose- 6-phosphate dehydrogenase deficiency, who reached out to our department for the arising of a non-ischemic priapism without arteriolacunar fistula. We suggest that the glucose-6-phosphate dehydrogenase deficiency could be an underestimated risk factor for priapism.

Selective attention and avoidance on a pictorial cueing task during stress in clinically anxious and depressed participants.

PubMed

Ellenbogen, Mark A; Schwartzman, Alex E

2009-02-01

Although it is well established that attentional biases exist in anxious populations, the specific components of visual orienting towards and away from emotional stimuli are not well delineated. The present study was designed to examine these processes. We used a modified spatial cueing task to assess the speed of engagement and disengagement from supraliminal and masked pictorial cues depicting threat, dysphoria, or neutral content in 36 clinically anxious, 41 depressed and 41 control participants. Participants were randomly assigned to a stress or neutral condition. During stress, anxious participants were slow to disengage from masked left hemifield pictures depicting threat or dysphoria, but were quick to disengage from supraliminal threat pictures. Information processing in anxious participants during stress was characterized by early selective attention of emotional stimuli, occurring prior to full conscious awareness, followed by effortful avoidance of threat. Depressed participants were distinct from the anxious group, displaying selective attention for stimuli depicting dysphoria, but not threat, during the neutral condition. In sum, attentional biases in clinical populations are associated with difficulties in the disengagement component of visual orienting. Further, a vigilant-avoidant pattern of attentional bias may represent a strategic attempt to compensate for the early activation of a fear response.

Bupropion Augmentation in a Case of Compulsive Buying Disorder.

PubMed

Sepede, Gianna; Di Iorio, Giuseppe; Sarchione, Fabiola; Fiori, Federica; Di Giannantonio, Massimo

Compulsive buying disorder (CBD) is a condition characterized by excessive preoccupations, impulses, and behaviors regarding buying, resulting in serious psychological, social, and financial problems. Even though it has not been included in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, "behavioral addictions" section, CBD is a hot topic in current clinical psychiatry, because of its relevant prevalence (at least 5% in adult populations) and severe effect on quality of life.The CBD shares some clinical features with substance-related and behavioral addictions, impulse control disorders, and obsessive compulsive disorder, and it is often comorbid with other psychiatric illnesses (especially depressive and anxiety disorders). The treatment of CBD is therefore difficult, and clear therapeutic guidelines are not yet available. Treating the comorbid disorders as the first-line approach, or combining drugs with different pharmacodynamic profiles, has been suggested to address this challenging condition. A 60-year-old woman affected by a severe form of CBD with comorbid major depressive disorder, resistant/intolerant to previous selective serotonin reuptake inhibitor treatments and only partially responder to mirtazapine, achieved a good clinical improvement adding bupropion. Combining 2 agents with different pharmacological profiles and mechanisms of action, such as bupropion and mirtazapine, could be a useful strategy in the management of complex CBD cases.

Factitious cheilitis: a case report

PubMed Central

Aydin, Erdinc; Gokoglu, Ozgur; Ozcurumez, Gamze; Aydin, Hakan

2008-01-01

Introduction Factitious cheilitis is a chronic condition characterized by crusting and ulceration that is probably secondary to chewing and sucking of the lips. Atopy, actinic damage, exfoliative cheilitis, cheilitis granulomatosa or glandularis, contact dermatitis, photosensitivity reactions and neoplasia should be considered in the differential diagnosis of crusted and ulcerated lesions of the lip. Case presentation We present a 56 year-old female with an ulcerated and crusted lesion on her lower lip. The biopsy showed granulation tissue and associated inflammation but no malignancy. Based on the tissue examination and through clinical evaluation the diagnosis of factitious cheilitis was rendered. Conclusion Thorough clinical history, utilization of basic laboratory tests and histopathologic evaluation are required to exclude other diseases and a thoruough psychiatric evaluation and treatment is vital for successful management of these patients. PMID:18226274

Impulsivity in Alcohol-Dependent Patients with and without ADHD: The Role of Atomoxetine.

PubMed

Coppola, Maurizio; Mondola, Raffaella

2018-06-07

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of hyperactivity, inattention, and impulsivity. As shown in the literature, this disorder is frequently associated with alcohol and drug abuse. Patients affected by ADHD show high levels of impulsivity and sensation seeking. These characteristics can significantly increase the risk of alcohol abuse, which is itself a clinical condition associated with high levels of impulsivity. Clinical studies suggest that atomoxetine is effective and safe in patients affected by both ADHD and alcohol dependence; however, information focused specifically on impulsivity is very limited. In an open-label study, we evaluated the difference in impulsivity level between alcohol-dependent patients with and without a diagnosis of ADHD. Furthermore, we hypothesized that, in patients with ADHD, atomoxetine could reduce the impulsivity trait.

Queues and care: how medical residents organize their work in a busy clinic.

PubMed

Finlay, W; Mutran, E J; Zeitler, R R; Randall, C S

1990-09-01

How do medical residents organize their work in settings where queue demands are heavy and resources are limited? Under such conditions, a queue theory would predict the delivery of care that is indifferent to clients' needs or that gets rid of clients as quickly as possible. In an exploratory case study of medical residents in a Veterans Administration outpatient clinic, we found instead that the medical residents' work was characterized by a high level of professional commitment: they provided thorough medical examinations and attempted to expedite patient care in other ways. We attribute the residents' professional ethos to opportunities provided in the VA hospital to learn the craft of routine medicine and to be directly responsible for patient care; such opportunities were not available in other settings.

[Cardio-renal axis: pathophysiological evidences and clinical implications].

PubMed

Di Lullo, Luca; Ronco, Claudio

2017-03-01

According to the recent definition proposed by the Consensus conference on Acute Dialysis Quality Initiative Group, the term cardio-renal syndrome CRS has been used to define different clinical conditions in which heart and kidney dysfunction overlap. Type 1 CRS acute cardio - renal syndrome is characterized by acute worsening of cardiac function leading to AKI in the setting of active cardiac disease such as ADHF, while type - 2 CRS occurs in a setting of chronic heart disease. Type 3 CRS is closely link to acute kidney injury, while type 4 represent cardiovascular involvement in chronic kidney disese patients. Type 5 CRS represent cardiac and renal involvement in several diseases such as sepsis, hepato - renal syndrome and immune - mediated diseases. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Excimer laser: a module of the alopecia areata common protocol.

PubMed

McMichael, Amy J

2013-12-01

Alopecia areata (AA) is an autoimmune condition characterized by T cell-mediated attack of the hair follicle. The inciting antigenic stimulus is unknown. A dense perbulbar lymphocytic infiltrate and reproducible immunologic abnormalities are hallmark features of the condition. The cellular infiltrate primarily consists of activated T lymphocytes and antigen-presenting Langerhans cells. The xenon chloride excimer laser emits its total energy at the wavelength of 308 nm and therefore is regarded as a "super-narrowband" UVB light source. Excimer laser treatment is highly effective in psoriasis, another T cell-mediated disorder that shares many immunologic features with AA. The excimer laser is superior in inducing T cell apoptosis in vitro compared with narrowband UVB, with paralleled improved clinical efficacy. The excimer laser has been used successfully in patients with AA. In this context, evaluation of the potential benefit of 308-nm excimer laser therapy in the treatment of AA is clinically warranted. Herein, the use of a common treatment protocol with a specifically designed module to study the outcome of excimer laser treatment on moderate-to-severe scalp AA in adults is described.

Engineering long term clinical success of advanced ceramic prostheses.

PubMed

Rekow, Dianne; Thompson, Van P

2007-01-01

Biocompatability and, in some applications, esthetics make all-ceramic prostheses compelling choices but despite significant improvements in materials properties and toughening mechanisms, these still have significant failure rates. Factors that contribute to the degradation in strength and survival include material selection and prosthesis design which set the upper limit for performance. However, fabrication operations introduce damage that can be exacerbated by environmental conditions and clinical function. Using all-ceramic dental crowns as an example, experimentally derived models provide insight into the relationships between materials properties and initial critical loads to failure. Analysis of fabrication operations suggests strategies to minimize damage. Environmental conditions can create viscoplastic flow of supporting components which can contribute additional stress within the prosthesis. Fatigue is a particularly challenging problem, not only providing the energy to propagate existing damage but, when combined with the wet environment, can create new damage modes. While much is known, the influence of these new damage modes has not been completely elucidated. The role of complex prosthesis geometry and its interaction with other factors on damage initiation and propagation has yet to be well characterized.

Uncertainty Quantification in Multi-Scale Coronary Simulations Using Multi-resolution Expansion

NASA Astrophysics Data System (ADS)

Tran, Justin; Schiavazzi, Daniele; Ramachandra, Abhay; Kahn, Andrew; Marsden, Alison

2016-11-01

Computational simulations of coronary flow can provide non-invasive information on hemodynamics that can aid in surgical planning and research on disease propagation. In this study, patient-specific geometries of the aorta and coronary arteries are constructed from CT imaging data and finite element flow simulations are carried out using the open source software SimVascular. Lumped parameter networks (LPN), consisting of circuit representations of vascular hemodynamics and coronary physiology, are used as coupled boundary conditions for the solver. The outputs of these simulations depend on a set of clinically-derived input parameters that define the geometry and boundary conditions, however their values are subjected to uncertainty. We quantify the effects of uncertainty from two sources: uncertainty in the material properties of the vessel wall and uncertainty in the lumped parameter models whose values are estimated by assimilating patient-specific clinical and literature data. We use a generalized multi-resolution chaos approach to propagate the uncertainty. The advantages of this approach lies in its ability to support inputs sampled from arbitrary distributions and its built-in adaptivity that efficiently approximates stochastic responses characterized by steep gradients.

The Behavioral Actions of Lithium in Rodent Models

PubMed Central

O’Donnell, Kelley C.; Gould, Todd D.

2007-01-01

For nearly as long as lithium has been in clinical use for the treatment of bipolar disorder, depression, and other conditions, investigators have attempted to characterize its effects on behaviors in rodents. Lithium consistently decreases exploratory activity, rearing, aggression, and amphetamine-induced hyperlocomotion; and it increases the sensitivity to pilocarpine-induced seizures, decreases immobility time in the forced swim test, and attenuates reserpine-induced hypolocomotion. Lithium also predictably induces conditioned taste aversion and alterations in circadian rhythms. The modulation of stereotypy, sensitization, and reward behavior are less consistent actions of the drug. These behavioral models may be relevant to human symptoms and to clinical endophenotypes. It is likely that the actions of lithium in a subset of these animal models are related to the therapeutic efficacy, as well the side effects, of the drug. We conclude with a brief discussion of various molecular mechanisms by which these lithium-sensitive behaviors may be mediated, and comment on the ways in which rat and mouse models can be used more effectively in the future to address persistent questions about the therapeutically relevant molecular actions of lithium. PMID:17532044

A Brief Overview of Preeclampsia

PubMed Central

Al-Jameil, Noura; Aziz Khan, Farah; Fareed Khan, Mohammad; Tabassum, Hajera

2014-01-01

Preeclampsia (PE) is a leading cause of maternal mortality and morbidity worldwide. It occurs in women with first or multiple pregnancies and is characterized by new onset hypertension and proteinuria. Improper placentation is mainly responsible for the disease. If PE remains untreated, it moves towards more serious condition known as eclampsia. Hypertension, diabetes mellitus, proteinuria, obesity, family history, nulliparity, multiple pregnancies and thrombotic vascular disease contribute as the risk factors for PE. PE triggered metabolic stress causes vascular injury, thus contributing to the development of cardiovascular disease (CVD) and/or chronic kidney disease (CKD) in future. This risk appears to be increased especially in women with a history of recurrent PE and eclampsia. Clinically increased serum levels of sFlt-1 and decreased placental growth factor (PIGF) and vascular endothelial growth factor (VEGF) represent the severe condition of PE. The clinical findings of sever PE are assorted by the presence of systemic endothelial dysfunction, microangiopathy, the liver (hemolysis, elevated liver function tests and low platelet count, namely HELLP syndrome) and the kidney (proteinuria). The early detection of PE is one of the most important goals in obstetrics. PMID:24400024

CHRONIC URTICARIA

PubMed Central

Sachdeva, Sandeep; Gupta, Vibhanshu; Amin, Syed Suhail; Tahseen, Mohd

2011-01-01

Chronic urticaria (CU) is a disturbing allergic condition of the skin. Although frequently benign, it may sometimes be a red flag sign of a serious internal disease. A multitude of etiologies have been implicated in the causation of CU, including physical, infective, vasculitic, psychological and idiopathic. An autoimmune basis of most of the ‘idiopathic’ forms is now hypothesized. Histamine released from mast cells is the major effector in pathogenesis and it is clinically characterized by wheals that have a tendency to recur. Laboratory investigations aimed at a specific etiology are not always conclusive, though may be suggestive of an underlying condition. A clinical search for associated systemic disease is strongly advocated under appropriate circumstances. The mainstay of treatment remains H1 antihistaminics. These may be combined with complementary pharmacopeia in the form of H2 blockers, doxepin, nifedipine and leukotriene inhibitors. More radical therapy in the form of immunoglobulins, plasmapheresis and cyclophosphamide may be required for recalcitrant cases. Autologous transfusion and alternative remedies like acupuncture have prospects for future. A stepwise management results in favorable outcomes. An update on CU based on our experience with patients at a tertiary care centre is presented. PMID:22345759

Bayés syndrome and acute cardioembolic ischemic stroke.

PubMed

Arboix, Adrià; Martí, Lucía; Dorison, Sebastien; Sánchez, María José

2017-03-16

Bayés syndrome is an under-recognized clinical condition characterized by advanced interatrial block. Bayés syndrome is a subclinical disease that manifests electrocardiographically as a prolonged P wave duration > 120 ms with biphasic morphology ± in the inferior leads. The clinical relevance of Bayés syndrome lies in the fact that is a clear arrhythmological syndrome and has a strong association with supraventricular arrhythmias, particularly atypical atrial flutter and atrial fibrillation. Likewise, Bayés syndrome has been recently identified as a novel risk factor for non-lacunar cardioembolic ischemic stroke and vascular dementia. Advanced interatrial block can be a risk for embolic stroke due to its known sequelae of left atrial dilation, left atrial electromechanical dysfunction or atrial tachyarrhythmia (paroxysmal or persistent atrial fibrillation), conditions predisposing to thromboembolism. Bayés syndrome may be responsible for some of the unexplained ischemic strokes and shall be considered and investigated as a possible cause for cryptogenetic stroke. In summary, Bayés syndrome is a poorly recognized cardiac rhythm disorder with important cardiologic and neurologic implications.

A brief overview of preeclampsia.

PubMed

Al-Jameil, Noura; Aziz Khan, Farah; Fareed Khan, Mohammad; Tabassum, Hajera

2014-02-01

Preeclampsia (PE) is a leading cause of maternal mortality and morbidity worldwide. It occurs in women with first or multiple pregnancies and is characterized by new onset hypertension and proteinuria. Improper placentation is mainly responsible for the disease. If PE remains untreated, it moves towards more serious condition known as eclampsia. Hypertension, diabetes mellitus, proteinuria, obesity, family history, nulliparity, multiple pregnancies and thrombotic vascular disease contribute as the risk factors for PE. PE triggered metabolic stress causes vascular injury, thus contributing to the development of cardiovascular disease (CVD) and/or chronic kidney disease (CKD) in future. This risk appears to be increased especially in women with a history of recurrent PE and eclampsia. Clinically increased serum levels of sFlt-1 and decreased placental growth factor (PIGF) and vascular endothelial growth factor (VEGF) represent the severe condition of PE. The clinical findings of sever PE are assorted by the presence of systemic endothelial dysfunction, microangiopathy, the liver (hemolysis, elevated liver function tests and low platelet count, namely HELLP syndrome) and the kidney (proteinuria). The early detection of PE is one of the most important goals in obstetrics.

Spine Conditions: Mechanical and Inflammatory Low Back Pain.

PubMed

Ledford, Christopher

2017-10-01

Mechanical low back pain (LBP) is an injury or derangement of an anatomic structure in the low back. When evaluating patients with LBP, clinicians should maintain clinical suspicion for vertebral fracture, cancer, and cauda equina syndrome. Management includes patient education focused on exercise, massage, and behavioral approaches such as cognitive behavioral therapy. Acupuncture can be an effective alternative and specific herbal supplements may provide short-term pain relief. The prognosis for patients with mechanical LBP is good. Inflammatory LBP is pain resulting from a systemic inflammatory condition, often referred to as axial spondyloarthritis. Ankylosing spondylitis is chronic inflammatory LBP characterized by early onset (mean age 24 years), with a higher prevalence in men. Five clinical parameters can help identify inflammatory LBP: improvement with exercise, pain at night, insidious onset, onset at younger than 40 years, and no improvement with rest. Management of inflammatory LBP typically includes nonsteroidal anti-inflammatory drugs and structured exercise programs, with emphasis on the involvement of a rheumatology subspecialist. Spondyloarthritis is associated with other rheumatic or autoimmune conditions, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. These should be considered when evaluating patients with inflammatory LBP. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Lymphoedema of the lower limbs: management problems in a developing country.

PubMed

Adigun, A I; Ogundipe, O K

2008-01-01

Lymphoedema is a clinical condition involving the extremities that is characterized by accumulation of protein rich fluid within the intercellular space of the skin and the subcutaneous tissue. It most frequently occurs in the extremities. Developing countries are mostly faced with cases of secondary lymphoedema where patients present lately. In addition to swollen limbs, there are lot of skin changes on the affected limb, these create a lot of problems to the managing clinician. We hereby present five cases out of several patients managed to highlight the challenges. We review the case notes of three patients managed by our unit and present the summary of each patient. Majority of our patients present late to the hospital, mainly because of the socio-cultural and spiritual beliefs concerning the aetiology of the condition. Most of them have visited the spiritualist, herbalist and the clergymen for solution. Clinicians in the developing countries are seriously handicapped by lack of modern equipment for both diagnostic and therapeutic management of these clinical conditions. Chronic lymphoedema is a major cause of permanent disability. Excisional surgery such as Charles procedure even though old is still very much relevant in our environment. Patients need to be enlightened on the need for early presentation, adequate post-operative care and prolonged follow-up.

Diet-Induced Low-Grade Metabolic Acidosis and Clinical Outcomes: A Review

PubMed Central

Carnauba, Renata Alves; Baptistella, Ana Beatriz; Paschoal, Valéria; Hübscher, Gilberti Helena

2017-01-01

Low-grade metabolic acidosis is a condition characterized by a slight decrease in blood pH, within the range considered normal, and feeding is one of the main factors that may influence the occurrence of such a condition. The excessive consumption of acid precursor foods (sources of phosphorus and proteins), to the detriment of those precursors of bases (sources of potassium, calcium, and magnesium), leads to acid-base balance volubility. If this condition occurs in a prolonged, chronic way, low-grade metabolic acidosis can become significant and predispose to metabolic imbalances such as kidney stone formation, increased bone resorption, reduced bone mineral density, and the loss of muscle mass, as well as the increased risk of chronic diseases such as type 2 diabetes mellitus, hypertension, and non-alcoholic hepatic steatosis. Considering the increase in the number of studies investigating the influence of diet-induced metabolic acidosis on clinical outcomes, this review gathers the available evidence evaluating the association of this disturbance and metabolic imbalances, as well as related mechanisms. It is necessary to look at the western dietary pattern of most countries and the increasing incidence of non-comunicable diseases for the balance between fruit and vegetable intake and the appropriate supply of protein, mainly from animal sources, so that it does not exceed the daily recommendations. PMID:28587067

Agrypnia excitata in a patient with progeroid short stature and pigmented Nevi (Mulvihill-Smith syndrome).

PubMed

Ferri, Raffaele; Lanuzza, Bartolo; Cosentino, Filomena I I; Iero, Ivan; Russo, Noemi; Tripodi, Mariangela; Bosco, Paolo

2005-12-01

We report the video-polysomnographic sleep characteristics of a 25-year-old woman with the Mulvihill-Smith syndrome, a rare clinical condition characterized by progeria-like aspect, peculiar multiple pigmented nevi, low stature, and cognitive impairment. Among the various exams, two overnight video-polysomnographic recordings were carried out; moreover, cerebral MRI and molecular analysis of the prion protein gene (PRNP) were also performed. The video-polysomnographic recordings showed the absence of clear sleep episodes but the presence of periods during which the patient had poor contact with the environment, stereotyped afinalistic movements of the upper limbs and hands, irregular or periodic breathing (with central apnea episodes), heart rate arrhythmia, and rapid eye movements. Cerebral MRI showed only diffuse mild enlargement of the cortical sulci and the molecular genetics analysis of the PRNP was normal. Our clinical and neurophysiological study seems to indicate that a particular condition of severe sleep disruption, similar to some extent to that reported in the fatal familial insomnia and in the Morvan fibrillary chorea, which has been indicated as Agrypnia Excitata in recent literature, might be associated with the Mulvihill-Smith syndrome. The inclusion of a detailed study on the sleep characteristics of eventual additional patients will certainly help our understanding of this rare condition.

Molecular method for the characterization of Coxiella burnetii from clinical and environmental samples: variability of genotypes in Spain

PubMed Central

2012-01-01

Background Coxiella burnetii is a highly clonal microorganism which is difficult to culture, requiring BSL3 conditions for its propagation. This leads to a scarce availability of isolates worldwide. On the other hand, published methods of characterization have delineated up to 8 different genomic groups and 36 genotypes. However, all these methodologies, with the exception of one that exhibited limited discriminatory power (3 genotypes), rely on performing between 10 and 20 PCR amplifications or sequencing long fragments of DNA, which make their direct application to clinical samples impracticable and leads to a scarce accessibility of data on the circulation of C. burnetii genotypes. Results To assess the variability of this organism in Spain, we have developed a novel method that consists of a multiplex (8 targets) PCR and hybridization with specific probes that reproduce the previous classification of this organism into 8 genomic groups, and up to 16 genotypes. It allows for a direct characterization from clinical and environmental samples in a single run, which will help in the study of the different genotypes circulating in wild and domestic cycles as well as from sporadic human cases and outbreaks. The method has been validated with reference isolates. A high variability of C. burnetii has been found in Spain among 90 samples tested, detecting 10 different genotypes, being those adaA negative associated with acute Q fever cases presenting as fever of intermediate duration with liver involvement and with chronic cases. Genotypes infecting humans are also found in sheep, goats, rats, wild boar and ticks, and the only genotype found in cattle has never been found among our clinical samples. Conclusions This newly developed methodology has permitted to demonstrate that C. burnetii is highly variable in Spain. With the data presented here, cattle seem not to participate in the transmission of C. burnetii to humans in the samples studied, while sheep, goats, wild boar, rats and ticks share genotypes with the human population. PMID:22656068

A De Novo Germline APC Mutation (3927del5) in a Patient with Familial Adenomatous Polyposis: Case Report and Literature Review

PubMed Central

Zeichner, Simon B.; Raj, Naveen; Cusnir, Mike; Francavilla, Michael; Hirzel, Alicia

2012-01-01

Introduction Characterized by the development of hundreds to thousands of colonic adenomas, classic familial adenomatous polyposis (FAP) is one of the most common hereditary syndromes associated with an increased risk of colorectal cancer. Several studies have attempted to correlate specific APC mutations with clinical phenotype.6 However, there is considerable variability in the expression of specific phenotypes within families and among individuals with identical mutations.7 Case presentation A 30 year-old Hispanic female presented to the emergency department with a 2-week history of persistent, worsening, left lower quadrant abdominal pain. She had no family history of malignancy. Sigmoidoscopy revealed innumerable polyps in the rectum and sigmoid colon and a large mass in the sigmoid colon. Biopsy of the mass revealed a moderately differentiated adenocarcinoma invading the subserosa. Endoscopy revealed innumerable polyps. Genetic testing of the patient via southern blot revealed a germline APC mutation 3927del5, resulting in a premature truncation of the APC protein at amino acid position 1312. Conclusion Genetic information has only recently started being incorporated into clinical care. More research and randomized clinical trials need to be conducted to definitively characterize random mutations. Once these mutations are further understood, FAP patients may be able to be risk stratified and this may ultimately improve the screening, diagnosis, and treatment of this rare condition. PMID:23115482

Cystic Neutrophilic Granulomatous Mastitis: Further Characterization of a Distinctive Histopathologic Entity Not Always Demonstrably Attributable to Corynebacterium Infection.

PubMed

D'Alfonso, Timothy M; Moo, Tracy-Ann; Arleo, Elizabeth K; Cheng, Esther; Antonio, Lilian B; Hoda, Syed A

2015-10-01

Granulomatous lobular mastitis (GLM) is an uncommon condition that typically occurs in parous, reproductive-aged women and can simulate malignancy on the basis of clinical and imaging features. A distinctive histologic pattern termed cystic neutrophilic granulomatous mastitis (CNGM) is seen in some cases of GLM and has been associated with Corynebacterium infection. We sought to further characterize the clinical, imaging, and histopathologic features of CNGM by studying 12 cases and attempted to establish the relationship of this disease with Corynebacterium infection. Patients were women ranging in age from 25 to 49 years (median: 34 y), and all presented with a palpable mass that was painful in half of the cases. In 2 of 9 cases, imaging was highly suspicious for malignancy (BI-RADS 5). CNGM was characterized by lobulocentric granulomas with mixed inflammation and clear vacuoles lined by neutrophils within granulomas. Gram-positive bacilli were identified in 5/12 cases. In 4 patients, the disease process worsened after the diagnostic core biopsy, with the development of a draining sinus in 2 cases. No growth of bacteria was seen in any microbial cultures. No bacterial DNA was identified by 16S rDNA polymerase chain reaction for 1 case that showed gram-positive bacilli on histology. Patients were treated with variable combinations of surgery, antibiotics, and steroids. The time to significant resolution of symptoms ranged from 2 weeks to 6 months. Similar to other forms of GLM, CNGM can mimic malignancy clinically and on imaging. When encountered in a needle core biopsy sample, recognition of the characteristic histologic pattern and its possible association with Corynebacterium infection can help guide treatment.

Subgroup of ADNI Normal Controls Characterized by Atrophy and Cognitive Decline Associated With Vascular Damage

PubMed Central

Nettiksimmons, Jasmine; Beckett, Laurel; Schwarz, Christopher; Carmichael, Owen; Fletcher, Evan; DeCarli, Charles

2013-01-01

Previous work examining Alzheimer’s Disease Neuroimaging Initiative (ADNI) normal controls using cluster analysis identified a subgroup characterized by substantial brain atrophy and white matter hyperintensities (WMH). We hypothesized that these effects could be related to vascular damage. Fifty-three individuals in the suspected vascular cluster (Normal 2) were compared with 31 individuals from the cluster characterized as healthy/typical (Normal 1) on a variety of outcomes, including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers, vascular risk factors and outcomes, cognitive trajectory, and medications for vascular conditions. Normal 2 was significantly older but did not differ on ApoE4+ prevalence. Normal 2 differed significantly from Normal 1 on all MRI measures but not on Amyloid-Beta1-42 or total tau protein. Normal 2 had significantly higher body mass index (BMI), Hachinksi score, and creatinine levels, and took significantly more medications for vascular conditions. Normal 2 had marginally significantly higher triglycerides and blood glucose. Normal 2 had a worse cognitive trajectory on the Rey’s Auditory Verbal Learning Test (RAVLT) 30-min delay test and the Functional Activity Questionnaire (FAQ). Cerebral atrophy associated with multiple vascular risks is common among cognitively normal individuals, forming a distinct subgroup with significantly increased cognitive decline. Further studies are needed to determine the clinical impact of these findings. PMID:23527743

Repetitive transcranial magnetic stimulation for clinical applications in neurological and psychiatric disorders: an overview.

PubMed

Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Vieira, Renata Teles; Caixeta, Leonardo; Novaes, Felipe; Marinho, Tamires; Almada, Leonardo Ferreira; Silva, Adriana Cardoso; Nardi, Antonio Egidio

2013-10-01

Neurological and psychiatric disorders are characterized by several disabling symptoms for which effective, mechanism-based treatments remain elusive. Consequently, more advanced non-invasive therapeutic methods are required. A method that may modulate brain activity and be viable for use in clinical practice is repetitive transcranial magnetic stimulation (rTMS). It is a non-invasive procedure whereby a pulsed magnetic field stimulates electrical activity in the brain. Here, we focus on the basic foundation of rTMS, the main stimulation parametters, the factors that influence individual responses to rTMS and the experimental advances of rTMS that may become a viable clinical application to treat neurological and psychiatric disorders. The findings showed that rTMS can improve some symptoms associated with these conditions and might be useful for promoting cortical plasticity in patients with neurological and psychiatric disorders. However, these changes are transient and it is premature to propose these applications as realistic therapeutic options, even though the rTMS technique has been evidenced as a potential modulator of sensorimotor integration and neuroplasticity. Functional imaging of the region of interest could highlight the capacity of rTMS to bring about plastic changes of the cortical circuitry and hint at future novel clinical interventions. Thus, we recommend that further studies clearly determine the role of rTMS in the treatment of these conditions. Finally, we must remember that however exciting the neurobiological mechanisms might be, the clinical usefulness of rTMS will be determined by its ability to provide patients with neurological and psychiatric disorders with safe, long-lasting and substantial improvements in quality of life.

Effects of testosterone supplementation on clinical and rehabilitative outcomes in older men undergoing on-pump CABG.

PubMed

Maggio, Marcello; Nicolini, Francesco; Cattabiani, Chiara; Beghi, Cesare; Gherli, Tiziano; Schwartz, Robert S; Valenti, Giorgio; Ceda, Gian Paolo

2012-07-01

Testosterone levels decrease with age. This decline is steeper during "critical illnesses". Cardiac surgery is a particular representative model of major clinical condition producing stress responses similar to those observed during severe nonsurgical illness. Cardiac revascularization with extracorporeal circulation is characterized by marked postoperative complications such as insulin resistance, a pro-inflammatory state, acute anemia and renal dysfunction. These phenomena are more evident in older subjects, who are particularly vulnerable in the post-operative state, a condition that has been recently termed as "acute postoperative frailty". We recently showed that in older men with low ejection fraction undergoing cardiac revascularization with extracorporeal circulation, there is a profound decline in anabolic hormones, including testosterone. After surgery testosterone concentration frequently declines to less than 200 ng/dl, a situation suggestive of overt hypogonadism. Since men with low testosterone levels have a high probability of developing mobility limitations, we considered this a rationale for the perioperative use of testosterone treatment in older men undergoing cardiac revasularization surgery. We hypothesized that testosterone supplementation at this time might attenuate the impressive post-surgical catabolic hormonal milieu. The aim of this manuscript is to elucidate an ongoing randomized clinical trial in older men (70+ years old) undergoing elective cardiovascular revascularization with extracorporeal circulation. This randomized clinical trial will evaluate the effects of intramuscular testosterone administration on clinical and functional outcomes in this population. The study will also address potential mechanisms underlying the expected beneficial effects of testosterone supplementation including improvement of insulin sensitivity, markers of inflammatory status and improved hemoglobin levels. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical Prediction Models for Cardiovascular Disease: Tufts Predictive Analytics and Comparative Effectiveness Clinical Prediction Model Database.

PubMed

Wessler, Benjamin S; Lai Yh, Lana; Kramer, Whitney; Cangelosi, Michael; Raman, Gowri; Lutz, Jennifer S; Kent, David M

2015-07-01

Clinical prediction models (CPMs) estimate the probability of clinical outcomes and hold the potential to improve decision making and individualize care. For patients with cardiovascular disease, there are numerous CPMs available although the extent of this literature is not well described. We conducted a systematic review for articles containing CPMs for cardiovascular disease published between January 1990 and May 2012. Cardiovascular disease includes coronary heart disease, heart failure, arrhythmias, stroke, venous thromboembolism, and peripheral vascular disease. We created a novel database and characterized CPMs based on the stage of development, population under study, performance, covariates, and predicted outcomes. There are 796 models included in this database. The number of CPMs published each year is increasing steadily over time. Seven hundred seventeen (90%) are de novo CPMs, 21 (3%) are CPM recalibrations, and 58 (7%) are CPM adaptations. This database contains CPMs for 31 index conditions, including 215 CPMs for patients with coronary artery disease, 168 CPMs for population samples, and 79 models for patients with heart failure. There are 77 distinct index/outcome pairings. Of the de novo models in this database, 450 (63%) report a c-statistic and 259 (36%) report some information on calibration. There is an abundance of CPMs available for a wide assortment of cardiovascular disease conditions, with substantial redundancy in the literature. The comparative performance of these models, the consistency of effects and risk estimates across models and the actual and potential clinical impact of this body of literature is poorly understood. © 2015 American Heart Association, Inc.

Saccharomyces boulardii CNCM I-745 in different clinical conditions.

PubMed

Dinleyici, Ener Cagri; Kara, Ates; Ozen, Metehan; Vandenplas, Yvan

2014-11-01

Saccharomyces boulardii is a well-known probiotic worldwide, and there are numerous studies including experimental and clinical trials in children and adults by the use of S. boulardii. The objective of the present report is to provide an update on the evidence for the efficacy of S. boulardii CNCM I-745 in different clinical conditions. Saccharomyces boulardii is one of the best-studied probiotics in acute gastroenteritis (AGE) and is shown to be safe and to reduce the duration of diarrhea and hospitalization by about 1 day. Saccharomyces boulardii is one of the recommended probiotics for AGE in children by European Society of Paediatric Infectious Diseases and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Saccharomyces boulardii is also a recommended probiotic for the prevention of antibiotic-associated diarrhea (AAD), and a recent study showed promising results for the treatment of AAD in children. There is insufficient evidence to recommend the long-term use of S. boulardii in patients with irritable bowel syndrome. Although some clinical studies showed positive effects of S. boulardii on inflammation, there is no clinical evidence that S. boulardii is useful in inflammatory bowel disease. Saccharomyces boulardii could be used in patients needing Helicobacter pylori eradication because the S. boulardii improves compliance, decreases the side effects and moderately increases the eradication rate. There are new promising results (improving feeding tolerance, shorten the course of hyperbilirubinemia), but we do still not recommend the routine use of S. boulardii in newborns. Saccharomyces boulardii CNCM I-745 is a good example for the statement that each probiotic needs to be taxonomically characterized and its efficacy and safety should be documented individually in different clinical settings.

Evaluation of RSA set-up from a clinical biplane fluoroscopy system for 3D joint kinematic analysis.

PubMed

Bonanzinga, Tommaso; Signorelli, Cecilia; Bontempi, Marco; Russo, Alessandro; Zaffagnini, Stefano; Marcacci, Maurilio; Bragonzoni, Laura

2016-01-01

dinamic roentgen stereophotogrammetric analysis (RSA), a technique currently based only on customized radiographic equipment, has been shown to be a very accurate method for detecting three-dimensional (3D) joint motion. The aim of the present work was to evaluate the applicability of an innovative RSA set-up for in vivo knee kinematic analysis, using a biplane fluoroscopic image system. To this end, the Authors describe the set-up as well as a possible protocol for clinical knee joint evaluation. The accuracy of the kinematic measurements is assessed. the Authors evaluated the accuracy of 3D kinematic analysis of the knee in a new RSA set-up, based on a commercial biplane fluoroscopy system integrated into the clinical environment. The study was organized in three main phases: an in vitro test under static conditions, an in vitro test under dynamic conditions reproducing a flexion-extension range of motion (ROM), and an in vivo analysis of the flexion-extension ROM. For each test, the following were calculated, as an indication of the tracking accuracy: mean, minimum, maximum values and standard deviation of the error of rigid body fitting. in terms of rigid body fitting, in vivo test errors were found to be 0.10±0.05 mm. Phantom tests in static and kinematic conditions showed precision levels, for translations and rotations, of below 0.1 mm/0.2° and below 0.5 mm/0.3° respectively for all directions. the results of this study suggest that kinematic RSA can be successfully performed using a standard clinical biplane fluoroscopy system for the acquisition of slow movements of the lower limb. a kinematic RSA set-up using a clinical biplane fluoroscopy system is potentially applicable and provides a useful method for obtaining better characterization of joint biomechanics.

An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease.

PubMed

Maltais, François; Decramer, Marc; Casaburi, Richard; Barreiro, Esther; Burelle, Yan; Debigaré, Richard; Dekhuijzen, P N Richard; Franssen, Frits; Gayan-Ramirez, Ghislaine; Gea, Joaquim; Gosker, Harry R; Gosselink, Rik; Hayot, Maurice; Hussain, Sabah N A; Janssens, Wim; Polkey, Micheal I; Roca, Josep; Saey, Didier; Schols, Annemie M W J; Spruit, Martijn A; Steiner, Michael; Taivassalo, Tanja; Troosters, Thierry; Vogiatzis, Ioannis; Wagner, Peter D

2014-05-01

Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed.

An Official American Thoracic Society/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease

PubMed Central

Maltais, François; Decramer, Marc; Casaburi, Richard; Barreiro, Esther; Burelle, Yan; Debigaré, Richard; Dekhuijzen, P. N. Richard; Franssen, Frits; Gayan-Ramirez, Ghislaine; Gea, Joaquim; Gosker, Harry R.; Gosselink, Rik; Hayot, Maurice; Hussain, Sabah N. A.; Janssens, Wim; Polkey, Micheal I.; Roca, Josep; Saey, Didier; Schols, Annemie M. W. J.; Spruit, Martijn A.; Steiner, Michael; Taivassalo, Tanja; Troosters, Thierry; Vogiatzis, Ioannis; Wagner, Peter D.

2014-01-01

Background: Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. Purpose: The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. Methods: An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. Results: We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. Conclusions: Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed. PMID:24787074

Characterization of Covalent-Reversible EGFR Inhibitors

PubMed Central

2017-01-01

Within the spectrum of kinase inhibitors, covalent-reversible inhibitors (CRIs) provide a valuable alternative approach to classical covalent inhibitors. This special class of inhibitors can be optimized for an extended drug-target residence time. For CRIs, it was shown that the fast addition of thiols to electron-deficient olefins leads to a covalent bond that can break reversibly under proteolytic conditions. Research groups are just beginning to include CRIs in their arsenal of compound classes, and, with that, the understanding of this interesting set of chemical warheads is growing. However, systems to assess both characteristics of the covalent-reversible bond in a simple experimental setting are sparse. Here, we have developed an efficient methodology to characterize the covalent and reversible properties of CRIs and to investigate their potential in targeting clinically relevant variants of the receptor tyrosine kinase EGFR.

NETopathies? Unraveling the Dark Side of Old Diseases through Neutrophils.

PubMed

Mitsios, Alexandros; Arampatzioglou, Athanasios; Arelaki, Stella; Mitroulis, Ioannis; Ritis, Konstantinos

2016-01-01

Neutrophil extracellular traps (NETs) were initially described as an antimicrobial mechanism of neutrophils. Over the last decade, several lines of evidence support the involvement of NETs in a plethora of pathological conditions. Clinical and experimental data indicate that NET release constitutes a shared mechanism, which is involved in a different degree in various manifestations of non-infectious diseases. Even though the backbone of NETs is similar, there are differences in their protein load in different diseases, which represent alterations in neutrophil protein expression in distinct disorder-specific microenvironments. The characterization of NET protein load in different NET-driven disorders could be of significant diagnostic and/or therapeutic value. Additionally, it will provide further evidence for the role of NETs in disease pathogenesis, and it will enable the characterization of disorders in which neutrophils and NET-dependent inflammation are of critical importance.

Reliable change on the Boston naming test.

PubMed

Sachs, Bonnie C; Lucas, John A; Smith, Glenn E; Ivnik, Robert J; Petersen, Ronald C; Graff-Radford, Neill R; Pedraza, Otto

2012-03-01

Serial assessments are commonplace in neuropsychological practice and used to document cognitive trajectory for many clinical conditions. However, true change scores may be distorted by measurement error, repeated exposure to the assessment instrument, or person variables. The present study provides reliable change indices (RCI) for the Boston Naming Test, derived from a sample of 844 cognitively normal adults aged 56 years and older. All participants were retested between 9 and 24 months after their baseline exam. Results showed that a 4-point decline during a 9-15 month retest period or a 6-point decline during a 16-24 month retest period represents reliable change. These cutoff values were further characterized as a function of a person's age and family history of dementia. These findings may help clinicians and researchers to characterize with greater precision the temporal changes in confrontation naming ability.

Clinical Characterization and Imaging of Triggered Attacks in Chronic Migraine and Posttraumatic Headache

DTIC Science & Technology

2016-02-01

A D Award Number: W81XWH-14-1-0573 TITLE: Clinical Characterization and Imaging of Triggered Attacks in Chronic Migraine and Posttraumatic Headache...DATES COVERED 30 Sep 2015 - 20 Jun 2015 4. TITLE AND SUBTITLE Clinical Characterization and Imaging of Triggered Attacks in Chronic Migraine and...terminated. 8. SUBJECT TERMS Post-traumatic headache, chronic migraine , PET, fMRI 9. SECURITY CLASSIFICATION OF: 10. LIMITATION OF ABSTRACT UU 11

Clinical Characterization and Imaging of Triggered Attacks in Chronic Migraine and Posttraumatic Headache

DTIC Science & Technology

2016-02-01

A D Award Number: W81XWH-14-1-0574 TITLE: Clinical Characterization and Imaging of Triggered Attacks in Chronic Migraine and Posttraumatic Headache...2015 - 20 Jun 2015 4. TITLE AND SUBTITLE Clinical Characterization and Imaging of Triggered Attacks in Chronic Migraine and Posttraumatic Headache...traumatic headache, chronic migraine , PET, fMRI 9. SECURITY CLASSIFICATION OF: 10. LIMITATION OF ABSTRACT UU 11. NUMBER OF PAGES 19a NAME OF

Mechanical and biocompatible characterizations of a readily available multilayer vascular graft

PubMed Central

Madhavan, Krishna; Elliott, Winston H; Bonani, Walter; Monnet, Eric; Tan, Wei

2013-01-01

There is always a considerable clinical need for vascular grafts. Considering the availability, physical and mechanical properties, and regenerative potential, we have developed and characterized readily available, strong, and compliant multilayer grafts that support cell culture and ingrowth. The grafts were made from heterogeneous materials and structures, including a thin, dense, nanofibrous core composed of poly-ε-caprolactone (PCL), and a thick, porous, hydrogel sleeve composed of genipin-crosslinked collagen–chitosan (GCC). Because the difference in physicochemical properties between PCL and GCC caused layer separation, the layer adhesion was identified as a determinant to graft property and integrity under physiological conditions. Thus, strategies to modify the layer interface, including increasing porosity of the PCL surface, decreasing hydrophobicity, and increasing interlayer crosslinking, were developed. Results from microscopic images showed that increasing PCL porosity was characterized by improved layer adhesion. The resultant graft was characterized by high compliance (4.5%), and desired permeability (528 mL/cm2/min), burst strength (695 mmHg), and suture strength (2.38 N) for readily grafting. Results also showed that PCL mainly contributed to the graft mechanical properties, whereas GCC reduced the water permeability. In addition to their complementary contributions to physical and mechanical properties, the distinct graft layers also provided layer-specific structures for seeding and culture of vascular endothelial and smooth muscle cells in vitro. Acellular graft constructs were readily used to replace abdominal aorta of rabbits, resulting in rapid cell ingrowth and flow reperfusion. The multilayer constructs capable of sustaining physiological conditions and promoting cellular activities could serve as a platform for future development of regenerative vascular grafts. PMID:23165922

All-Arthroscopic Treatment of Intra- and Extra-Articular Localized Villonodular Synovitis of Knee.

PubMed

Simonetta, Roberto; Florio, Michela; Familiari, Filippo; Gasparini, Giorgio; Rosa, Michele Attilio

2017-09-01

Pigmented villonodular synovitis (PVNS) is a rare, benign, proliferative neoplastic condition affecting synovial-lined anatomic spaces. PVNS is characterized by hypertrophy of a synovial membrane by villous, nodular, and villonodular proliferation, with pigmentation secondary to hemosiderin deposition. The two forms of PVNS that have been described are diffuse (DPVNS) and localized (LPVNS). The knee is the most commonly involved anatomic location, followed by hip, ankle, shoulder, and elbow. Diagnosis of PVNS is not always obvious clinically. Various imaging modalities are often necessary to exclude other conditions and narrow the diagnosis. Magnetic resonance imaging has become the modality of choice for diagnosing PVNS. We present a case of intra-articular LPVNS with an extra-articular extension through the posterior capsule that has been successfully removed in an all-arthroscopic fashion.

Mediators of low-grade chronic inflammation in polycystic ovary syndrome (PCOS).

PubMed

Ojeda-Ojeda, Miriam; Murri, Mora; Insenser, María; Escobar-Morreale, Héctor F

2013-01-01

Chronic low-grade subclinical inflammation has been increasingly recognized as an interposer in the endocrine, metabolic and reproductive disturbances that characterize the polycystic ovary syndrome (PCOS). Abdominal adiposity and obesity are often present in PCOS. Mounting evidence indicates that adipose tissue is involved in innate and adaptive immune responses. Continuous release of inflammatory mediators such as cytokines, acute phase proteins, and adipokines perpetuates the inflammatory condition associated with obesity in women with PCOS, possibly contributing to insulin resistance and other long-term cardiometabolic risk factors. Genetic variants in the genes encoding inflammation-related mediators underlie the development of PCOS and their interaction with environmental factors may contribute to the heterogeneous clinical phenotype of this syndrome. In the future, strategies ameliorating inflammation may prove useful for the management of PCOS and associated conditions.

[Catatonia].

PubMed

Bruijn, Dirk Jan; Blom, Jan Dirk

2010-01-01

Catatonia is a neuropsychiatric syndrome characterized by dysregulation of the motor system. It is associated with affective disorders, psychosis, and a number of somatic conditions. The condition tends to be undertreated due to under-recognition. This is unfortunate, because various cheap and effective treatment methods are widely available. In this clinical lesson, we present case studies of three patients with schizophrenia and severe catatonic symptoms. They were all treated with lorazepam, in dosages ranging from 2 to 60 mg a day, following which they achieved full remission of their catatonic symptoms. We recommend being alert for catatonia in patients with or without a psychiatric disorder. Early recognition and treatment is vital for the quality of life of these patients, and may in some cases be life-saving. In addition, we recommend a thorough analysis of possible underlying somatic disorders.

Idiopathic Pulmonary Fibrosis and Myasthenia Gravis: An Unusual Association

PubMed Central

Chogtu, Bharti; Malik, Daliparty Vasudev

2016-01-01

Idiopathic Pulmonary Fibrosis (IPF) is a chronic fibrosing lung condition with high morbidity and mortality, accounting for about 25% of the cases of interstitial lung diseases. It usually has a progressive course resulting in death due to respiratory failure. Myasthenia Gravis (MG) is an autoimmune neuromuscular disease, caused by antibody mediated activity against acetylcholine receptor at the neuromuscular junction. It is characterized by fluctuating muscle weakness and fatigue. Extensive literature search did not reveal any case report of an association between these two conditions. Here we present a case of a patient with IPF who also developed MG. The diagnosis of IPF was based on High Resolution Computed Tomography (HRCT) of the lung and that of MG was based on clinical criteria and electrophysiological testing. The case was successfully managed. PMID:27190866

Epidemiology of Heart Failure

PubMed Central

Roger, Véronique L.

2013-01-01

Heart failure (HF) has been singled out as an epidemic and is a staggering clinical and public health problem, associated with significant mortality, morbidity, and healthcare expenditures, particularly among those aged 65 and older. The case mix of HF is changing over time with a growing proportion of cases presenting with preserved ejection fraction for which there is no specific treatment. Despite progress in reducing HF-related mortality, hospitalizations for HF remain very frequent and rates of readmissions continuing to rise. To prevent hospitalizations, a comprehensive characterization of predictors of readmission in patients with HF is imperative and must integrate the impact of multimorbidity related to coexisting conditions. New models of patient-centered care that draw upon community-based resources to support HF patients with complex coexisting conditions are needed to decrease hospitalizations. PMID:23989710

An Ontology for Telemedicine Systems Resiliency to Technological Context Variations in Pervasive Healthcare

PubMed Central

Bults, Richard G. A.; Van Sinderen, Marten J.; Widya, Ing; Hermens, Hermie J.

2015-01-01

Clinical data are crucial for any medical case to study and understand a patient’s condition and to give the patient the best possible treatment. Pervasive healthcare systems apply information and communication technology to enable the usage of ubiquitous clinical data by authorized medical persons. However, quality of clinical data in these applications is, to a large extent, determined by the technological context of the patient. A technological context is characterized by potential technological disruptions that affect optimal functioning of technological resources. The clinical data based on input from these technological resources can therefore have quality degradations. If these degradations are not noticed, the use of this clinical data can lead to wrong treatment decisions, which potentially puts the patient’s safety at risk. This paper presents an ontology that specifies the relation among technological context, quality of clinical data, and patient treatment. The presented ontology provides a formal way to represent the knowledge to specify the effect of technological context variations in the clinical data quality and the impact of the clinical data quality on a patient’s treatment. Accordingly, this ontology is the foundation for a quality of data framework that enables the development of telemedicine systems that are capable of adapting the treatment when the quality of the clinical data degrades, and thus guaranteeing patients’ safety even when technological context varies. PMID:27170903

Weathering the storm: Improving therapeutic interventions for cytokine storm syndromes by targeting disease pathogenesis.

PubMed

Weaver, Lehn K; Behrens, Edward M

2017-03-01

Cytokine storm syndromes require rapid diagnosis and treatment to limit the morbidity and mortality caused by the hyperinflammatory state that characterizes these devastating conditions. Herein, we discuss the current knowledge that guides our therapeutic decision-making and personalization of treatment for patients with cytokine storm syndromes. Firstly, ICU-level supportive care is often required to stabilize patients with fulminant disease while additional diagnostic evaluations proceed to determine the underlying cause of cytokine storm. Pharmacologic interventions should be focused on removing the inciting trigger of inflammation and initiation of an individualized immunosuppressive regimen when immune activation is central to the underlying disease pathophysiology. Monitoring for a clinical response is required to ensure that changes in the therapeutic regimen can be made as clinically warranted. Escalation of immunosuppression may be required if patients respond poorly to the initial therapeutic interventions, while a slow wean of immunosuppression in patients who improve can limit medication-related toxicities. In certain scenarios, a decision must be made whether an individual patient requires hematopoietic cell transplantation to prevent recurrence of disease. Despite these interventions, significant morbidity and mortality remains for cytokine storm patients. Therefore, we use this review to propose a clinical schema to guide current and future attempts to design rational therapeutic interventions for patients suffering from these devastating conditions, which we believe speeds the diagnosis of disease, limits medication-related toxicities, and improves clinical outcomes by targeting the heterogeneous and dynamic mechanisms driving disease in each individual patient.

Development of Standardized Material Testing Protocols for Prosthetic Liners

PubMed Central

Cagle, John C.; Reinhall, Per G.; Hafner, Brian J.; Sanders, Joan E.

2017-01-01

A set of protocols was created to characterize prosthetic liners across six clinically relevant material properties. Properties included compressive elasticity, shear elasticity, tensile elasticity, volumetric elasticity, coefficient of friction (CoF), and thermal conductivity. Eighteen prosthetic liners representing the diverse range of commercial products were evaluated to create test procedures that maximized repeatability, minimized error, and provided clinically meaningful results. Shear and tensile elasticity test designs were augmented with finite element analysis (FEA) to optimize specimen geometries. Results showed that because of the wide range of available liner products, the compressive elasticity and tensile elasticity tests required two test maxima; samples were tested until they met either a strain-based or a stress-based maximum, whichever was reached first. The shear and tensile elasticity tests required that no cyclic conditioning be conducted because of limited endurance of the mounting adhesive with some liner materials. The coefficient of friction test was based on dynamic coefficient of friction, as it proved to be a more reliable measurement than static coefficient of friction. The volumetric elasticity test required that air be released beneath samples in the test chamber before testing. The thermal conductivity test best reflected the clinical environment when thermal grease was omitted and when liner samples were placed under pressure consistent with load bearing conditions. The developed procedures provide a standardized approach for evaluating liner products in the prosthetics industry. Test results can be used to improve clinical selection of liners for individual patients and guide development of new liner products. PMID:28233885

On ERPs detection in disorders of consciousness rehabilitation

PubMed Central

Risetti, Monica; Formisano, Rita; Toppi, Jlenia; Quitadamo, Lucia R.; Bianchi, Luigi; Astolfi, Laura; Cincotti, Febo; Mattia, Donatella

2013-01-01

Disorders of Consciousness (DOC) like Vegetative State (VS), and Minimally Conscious State (MCS) are clinical conditions characterized by the absence or intermittent behavioral responsiveness. A neurophysiological monitoring of parameters like Event-Related Potentials (ERPs) could be a first step to follow-up the clinical evolution of these patients during their rehabilitation phase. Eleven patients diagnosed as VS (n = 8) and MCS (n = 3) by means of the JFK Coma Recovery Scale Revised (CRS-R) underwent scalp EEG recordings during the delivery of a 3-stimuli auditory oddball paradigm, which included standard, deviant tones and the subject own name (SON) presented as a novel stimulus, administered under passive and active conditions. Four patients who showed a change in their clinical status as detected by means of the CRS-R (i.e., moved from VS to MCS), were subjected to a second EEG recording session. All patients, but one (anoxic etiology), showed ERP components such as mismatch negativity (MMN) and novelty P300 (nP3) under passive condition. When patients were asked to count the novel stimuli (active condition), the nP3 component displayed a significant increase in amplitude (p = 0.009) and a wider topographical distribution with respect to the passive listening, only in MCS. In 2 out of the 4 patients who underwent a second recording session consistently with their transition from VS to MCS, the nP3 component elicited by passive listening of SON stimuli revealed a significant amplitude increment (p < 0.05). Most relevant, the amplitude of the nP3 component in the active condition, acquired in each patient and in all recording sessions, displayed a significant positive correlation with the total scores (p = 0.004) and with the auditory sub-scores (p < 0.00001) of the CRS-R administered before each EEG recording. As such, the present findings corroborate the value of ERPs monitoring in DOC patients to investigate residual unconscious and conscious cognitive function. PMID:24312041

On ERPs detection in disorders of consciousness rehabilitation.

PubMed

Risetti, Monica; Formisano, Rita; Toppi, Jlenia; Quitadamo, Lucia R; Bianchi, Luigi; Astolfi, Laura; Cincotti, Febo; Mattia, Donatella

2013-01-01

Disorders of Consciousness (DOC) like Vegetative State (VS), and Minimally Conscious State (MCS) are clinical conditions characterized by the absence or intermittent behavioral responsiveness. A neurophysiological monitoring of parameters like Event-Related Potentials (ERPs) could be a first step to follow-up the clinical evolution of these patients during their rehabilitation phase. Eleven patients diagnosed as VS (n = 8) and MCS (n = 3) by means of the JFK Coma Recovery Scale Revised (CRS-R) underwent scalp EEG recordings during the delivery of a 3-stimuli auditory oddball paradigm, which included standard, deviant tones and the subject own name (SON) presented as a novel stimulus, administered under passive and active conditions. Four patients who showed a change in their clinical status as detected by means of the CRS-R (i.e., moved from VS to MCS), were subjected to a second EEG recording session. All patients, but one (anoxic etiology), showed ERP components such as mismatch negativity (MMN) and novelty P300 (nP3) under passive condition. When patients were asked to count the novel stimuli (active condition), the nP3 component displayed a significant increase in amplitude (p = 0.009) and a wider topographical distribution with respect to the passive listening, only in MCS. In 2 out of the 4 patients who underwent a second recording session consistently with their transition from VS to MCS, the nP3 component elicited by passive listening of SON stimuli revealed a significant amplitude increment (p < 0.05). Most relevant, the amplitude of the nP3 component in the active condition, acquired in each patient and in all recording sessions, displayed a significant positive correlation with the total scores (p = 0.004) and with the auditory sub-scores (p < 0.00001) of the CRS-R administered before each EEG recording. As such, the present findings corroborate the value of ERPs monitoring in DOC patients to investigate residual unconscious and conscious cognitive function.

Ehlers–Danlos syndrome type VIII is clinically heterogeneous disorder associated primarily with periodontal disease, and variable connective tissue features

PubMed Central

Reinstein, Eyal; DeLozier, Celia Dawn; Simon, Ziv; Bannykh, Serguei; Rimoin, David L; Curry, Cynthia J

2013-01-01

Ehlers–Danlos syndrome (EDS) type VIII (periodontitis type) is a distinct form of EDS characterized by periodontal disease leading to precocious dental loss and a spectrum of joint and skin manifestations. EDS type VIII is transmitted in an autosomal dominant pattern; however, the mutated gene has not been identified. There are insufficient data on the spectrum of clinical manifestations and natural history of the disorder, and only a limited number of patients and pedigrees with this condition have been reported. We present a four-generation EDS type VIII kindred and show that EDS VIII is clinically variable and although some cases lack the associated skin and joint manifestations, microscopic evidence of collagen disorganization is detectable. We further propose that the diagnosis of EDS type VIII should be considered in familial forms of periodontitis, even when the associated skin and joint manifestations are unconvincing for the diagnosis of a connective tissue disorder. This novel observation highlights the uncertainty of using connective tissue signs in clinical practice to diagnose EDS type VIII. PMID:22739343

Endometriosis and ovarian cancer: links, risks, and challenges faced.

PubMed

Pavone, Mary Ellen; Lyttle, Brianna M

2015-01-01

Endometriosis is a benign gynecological condition characterized by specific histological, molecular, and clinical findings. It affects 5%-10% of premenopausal women, is a cause of infertility, and has been implicated as a precursor for certain types of ovarian cancer. Advances in technology, primarily the ability for whole genome sequencing, have led to the discovery of new mutations and a better understanding of the function of previously identified genes and pathways associated with endometriosis associated ovarian cancers (EAOCs) that include PTEN, CTNNB1 (β-catenin), KRAS, microsatellite instability, ARID1A, and the unique role of inflammation in the development of EAOC. Clinically, EAOCs are associated with a younger age at diagnosis, lower stage and grade of tumor, and are more likely to occur in premenopausal women when compared with other ovarian cancers. A shift from screening strategies adopted to prevent EAOCs has resulted in new recommendations for clinical practice by national and international governing bodies. In this paper, we review the common histologic and molecular characteristics of endometriosis and ovarian cancer, risks associated with EAOCs, clinical challenges and give recommendations for providers.

Current Approaches to the Treatment of Systemic-Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH).

PubMed

Sobanski, Vincent; Launay, David; Hachulla, Eric; Humbert, Marc

2016-02-01

Pulmonary arterial hypertension (PAH) is a severe condition causing significant morbidity and mortality in patients with systemic sclerosis (SSc). Despite the use of specific treatments, SSc-PAH survival remains poorer than in idiopathic PAH (IPAH). Recent therapeutic advances in PAH show a lower magnitude of response in SSc-PAH and a higher risk of adverse events, as compared to IPAH. The multifaceted underlying mechanisms and the multisystem nature of SSc probably explain part of the worse outcomes in SSc-PAH compared to IPAH. This review describes the current management of SSc-PAH with an emphasis on the impact of the different organ involvements in the prognosis and treatment response. An earlier detection of PAH and a better characterization of the clinical phenotypes of SSc-PAH are warranted in clinical practice and future trials. Determinants of prognosis, surrogate markers of clinical improvement or worsening, and relevance of the common endpoints used in clinical trials should be evaluated in this specific population. A multidisciplinary approach in expert referral centers is mandatory for SSc-PAH management.

[Who benefits from the night clinic? - Value of a part-time treatment facility].

PubMed

Stutz, Constanze; Kawohl, Wolfram; Platz, Christoph; Warnke, Ingeborg; Jäger, Matthias

2017-12-01

The night clinic which is part of the psychiatric department of the University of Zurich is a part-time treatment option with psychiatric treatment and support in the evening. This study aimed to characterize the patients and detect different functions of the treatment setting. Data of 253 patients covering a six-year period from 2008 up to 2013 were retrospectively assessed using descriptive methods. Subgroups according to the situation before admission and after discharge were compared. Patients admitted from home differed considerably from those who were transferred from a psychiatric ward concerning sociodemographic and clinical factors. They were more frequently single, unemployed, received disability funds and suffered from a psychotic disorder. They were also more likely to be discharged in a supported housing condition. The night clinic serves as an alternative to full inpatient treatment for individuals who have work as well as a rehabilitative option for homeless patients with severe mental illness. It contributes to a reduction of avoidance of inpatients stays for those groups of patients.

Clinical Characterization and Treatment Patterns for the Frequent Exacerbator Phenotype in Chronic Obstructive Pulmonary Disease with Severe or Very Severe Airflow Limitation.

PubMed

Blasi, Francesco; Neri, Luca; Centanni, Stefano; Falcone, Franco; Di Maria, Giuseppe

2017-02-01

Chronic obstructive pulmonary disease (COPD) patients experiencing several episodes of acute clinical derangement suffer from increased morbidity, mortality, and accelerated decline in lung function. Nevertheless, the relationship between co-morbidity profile and exacerbation rates in the frequent exacerbator phenotype is poorly characterized, and evidence-based management guidelines are lacking. We sought to evaluate the co-morbidity profile and treatment patterns of "frequent exacerbators" with severe or very severe airflow limitation. We conducted a cross-sectional, multicenter study in 50 Italian hospitals. Pulmonologists abstracted clinical information from medical charts of 743 COPD frequent exacerbators. We evaluated the exacerbation risk and center-related variations in diagnostic testing. One-third of patients (n = 210) underwent a bronchodilator response test, and 163 (22%) received a computerized tomography (CT) scan; 35 had a partial response to bronchodilators, while 119 had a diagnosis of emphysema; 584 (79%) lacked sufficient diagnostic testing for classification. Only 17% of patients did not have any coexistent disease. Cardiovascular conditions were the most frequent co-morbidities. A history of heart failure [odds ratio (OR): 1.89; 95% confidence interval (CI) 1.48-2.3] and affective disorders (OR: 1.66; 95% CI 1.24-2.1) was associated with the frequency of exacerbations. Center membership was strongly associated with exacerbation risk, independent of casemix (variance partition coefficient = 29.6%). Examining the regional variation in health outcomes and health care behavior may help identify the best practices, especially when evidence-based recommendations are lacking and uncertainties surround clinical decision-making.

Unusual presentation of a severely ill patient having severe fever with thrombocytopenia syndrome: a case report.

PubMed

Kaneko, Masahiko; Maruta, Masaki; Shikata, Hisaharu; Asou, Kengo; Shinomiya, Hiroto; Suzuki, Tadaki; Hasegawa, Hideki; Shimojima, Masayuki; Saijo, Masayuki

2017-02-03

Severe fever with thrombocytopenia syndrome is an emerging infectious disease caused by a novel phlebovirus belonging to the family Bunyaviridate. Emergence of encephalitis/encephalopathy during severe fever with thrombocytopenia syndrome progression has been identified as a major risk factor associated with a poor prognosis. Here we report the case of a severely ill patient with severe fever with thrombocytopenia syndrome virus-associated encephalitis/encephalopathy characterized by a lesion of the splenium, which resolved later. A 56-year-old Japanese man presented with fever and diarrhea, followed by dysarthria. Diffusion-weighted magnetic resonance imaging demonstrated high signal intensity in the splenium of the corpus callosum. The severe fever with thrombocytopenia syndrome virus genome was detected in our patient's serum, and the clinical course was characterized by convulsion, stupor, and hemorrhagic manifestations, with disseminated intravascular coagulation and hemophagocytic lymphohistiocytosis. Supportive therapy not including administration of corticosteroids led to gradual improvement of the clinical and laboratory findings, and magnetic resonance imaging demonstrated resolution of the splenial lesion. The serum severe fever with thrombocytopenia syndrome viral copy number, which was determined with the quantitative reverse-transcription polymerase chain reaction, rapidly decreased despite the severe clinical course. Our patient's overall condition improved, allowing him to be eventually discharged. Patients with encephalitis/encephalopathy due to severe fever with thrombocytopenia syndrome virus infection may have a favorable outcome, even if they exhibit splenial lesions and a severe clinical course; monitoring the serum viral load may be of value for prediction of outcome and potentially enables the avoidance of corticosteroids to intentionally cause opportunistic infection.

Membrane lipidomics in schizophrenia patients: a correlational study with clinical and cognitive manifestations.

PubMed

Tessier, C; Sweers, K; Frajerman, A; Bergaoui, H; Ferreri, F; Delva, C; Lapidus, N; Lamaziere, A; Roiser, J P; De Hert, M; Nuss, P

2016-10-04

Schizophrenia is a severe mental condition in which several lipid abnormalities-either structural or metabolic-have been described. We tested the hypothesis that an abnormality in membrane lipid composition may contribute to aberrant dopamine signaling, and thereby symptoms and cognitive impairment, in schizophrenia (SCZ) patients. Antipsychotic-medicated and clinically stable SCZ outpatients (n=74) were compared with matched healthy subjects (HC, n=40). A lipidomic analysis was performed in red blood cell (RBC) membranes examining the major phospholipid (PL) classes and their associated fatty acids (FAs). Clinical manifestations were examined using the positive and negative syndrome scale (PANSS). Cognitive function was assessed using the Continuous Performance Test, Salience Attribution Test and Wisconsin Card Sorting Test. Sphingomyelin (SM) percentage was the lipid abnormality most robustly associated with a schizophrenia diagnosis. Two groups of patients were defined. The first group (SCZ c/SM-) is characterized by a low SM membrane content. In this group, all other PL classes, plasmalogen and key polyunsaturated FAs known to be involved in brain function, were significantly modified, identifying a very specific membrane lipid cluster. The second patient group (SCZ c/SM+) was similar to HCs in terms of RBC membrane SM composition. Compared with SCZ c/SM+, SCZ c/SM- patients were characterized by significantly more severe PANSS total, positive, disorganized/cognitive and excited psychopathology. Cognitive performance was also significantly poorer in this subgroup. These data show that a specific RBC membrane lipid cluster is associated with clinical and cognitive manifestations of dopamine dysfunction in schizophrenia patients. We speculate that this membrane lipid abnormality influences presynaptic dopamine signaling.

Role of Protein Carbonylation in Skeletal Muscle Mass Loss Associated with Chronic Conditions

PubMed Central

Barreiro, Esther

2016-01-01

Muscle dysfunction, characterized by a reductive remodeling of muscle fibers, is a common systemic manifestation in highly prevalent conditions such as chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD), cancer cachexia, and critically ill patients. Skeletal muscle dysfunction and impaired muscle mass may predict morbidity and mortality in patients with chronic diseases, regardless of the underlying condition. High levels of oxidants may alter function and structure of key cellular molecules such as proteins, DNA, and lipids, leading to cellular injury and death. Protein oxidation including protein carbonylation was demonstrated to modify enzyme activity and DNA binding of transcription factors, while also rendering proteins more prone to proteolytic degradation. Given the relevance of protein oxidation in the pathophysiology of many chronic conditions and their comorbidities, the current review focuses on the analysis of different studies in which the biological and clinical significance of the modifications induced by reactive carbonyls on proteins have been explored so far in skeletal muscles of patients and animal models of chronic conditions such as COPD, disuse muscle atrophy, cancer cachexia, sepsis, and physiological aging. Future research will elucidate the specific impact and sites of reactive carbonyls on muscle protein content and function in human conditions. PMID:28248228

Kappa-Opioid Antagonists for Psychiatric Disorders: From Bench to Clinical Trials.

PubMed

Carlezon, William A; Krystal, Andrew D

2016-10-01

Kappa-opioid receptor (KOR) antagonists are currently being considered for the treatment of a variety of neuropsychiatric conditions, including depressive, anxiety, and substance abuse disorders. A general ability to mitigate the effects of stress, which can trigger or exacerbate these conditions, may explain their putative efficacy across such a broad array of conditions. The discovery of their potentially therapeutic effects evolved from preclinical research designed to characterize the molecular mechanisms by which experience causes neuroadaptations in the nucleus accumbens (NAc), a key element of brain reward circuitry. This research established that exposure to drugs of abuse or stress increases the activity of the transcription factor CREB (cAMP response element binding protein) in the NAc, which leads to elevated expression of the opioid peptide dynorphin that in turn causes core signs of depressive- and anxiety-related disorders. Disruption of KORs-the endogenous receptors for dynorphin-produces antidepressant- and anxiolytic-like actions in screening procedures that identify standard drugs of these classes, and reduces stress effects in tests used to study addiction and stress-related disorders. Although interest in this target is high, prototypical KOR antagonists have extraordinarily persistent pharmacodynamic effects that complicate clinical trials. The development of shorter acting KOR antagonists together with more rapid designs for clinical trials may soon provide insight on whether these drugs are efficacious as would be predicted by preclinical work. If successful, KOR antagonists would represent a unique example in psychiatry where the therapeutic mechanism of a drug class is understood before it is shown to be efficacious in humans. © 2016 Wiley Periodicals, Inc.

Clinical Relevance and Cost-Savings of Levocarnitine Versus Ammonul in the Management Of Hyperammonemia in a Cancer Patient: The Impact of a Clinical Pharmacist.

PubMed

Anyanwu, Chukwuma; Ezeudu, Chinonso; Le, Hoa; Egwim, Oliver

2018-01-01

Hyperammonemia, a relatively uncommon condition characterized by elevated ammonia levels in the blood, presents with varied physiological etiologies that may send patients to the intensive care unit (ICU) with encephalopathy. An immediate decrease in ammonia levels is necessary to avert neurological damage. However, due to the multifaceted nature of hyperammonemia, a definite determination of etiology is not always possible. This case report examines the clinical and economic impact of a pharmacist in managing acute hyperammonemia of unknown etiology in a 62-year-old Hispanic man who had recently been diagnosed with metastatic medullary thyroid cancer and associated hypercalcemia. The patient was treated with levocarnitine after the failure of several other treatments. Levocarnitine therapy controlled the patient's ammonia levels, which had progressively reached extremely high levels. His mental status, which had deteriorated severely, returned to baseline. This case illustrates the importance of having a clinical pharmacist in the ICU. The pharmacist's expertise and knowledge helped avert adverse clinical consequences and promoted considerable cost-savings. This case also shows that levocarnitine may be an effective treatment for certain cases of hyperammonia-induced encephalopathy with unknown etiology.

Diagnosis and management of endometriosis: the role of the advanced practice nurse in primary care.

PubMed

Mao, Alexandra J; Anastasi, Joyce K

2010-02-01

To discuss the etiology, clinical presentation, diagnosis, and management of endometriosis for the advanced practice nurse (APN) in primary care. Selected research, clinical studies, clinical practice guidelines, and review articles. Commonly encountered by the APN in primary care, endometriosis is a chronic, progressive inflammatory disease characterized by endometrial lesions, cysts, fibrosis, or adhesions in the pelvic cavity, causing chronic pelvic pain and infertility in women of reproductive age. Because of its frequently normal physical examination findings, variable clinical presentations, and nonspecific, overlapping symptoms with other conditions, endometriosis can be difficult to diagnose. As there currently are no accurate noninvasive diagnostic tests specific for endometriosis, it is imperative for the APN to become knowledgeable about the etiology, clinical presentation, diagnosis, and current treatment options of this disease. The APN in primary care plays an essential role in health promotion through disease management and infertility prevention by providing support and much needed information to the patient with endometriosis. APNs can also facilitate quality of care and manage treatments effectively to improve quality of life, reduce pain, and prevent further progression of disease. Practice recommendations include timely diagnosis, pain management, infertility counseling, patient education, and support for quality of life issues.

Clinical characterization of 2D pressure field in human left ventricles

NASA Astrophysics Data System (ADS)

Borja, Maria; Rossini, Lorenzo; Martinez-Legazpi, Pablo; Benito, Yolanda; Alhama, Marta; Yotti, Raquel; Perez Del Villar, Candelas; Gonzalez-Mansilla, Ana; Barrio, Alicia; Fernandez-Aviles, Francisco; Bermejo, Javier; Khan, Andrew; Del Alamo, Juan Carlos

2014-11-01

The evaluation of left ventricle (LV) function in the clinical setting remains a challenge. Pressure gradient is a reliable and reproducible indicator of the LV function. We obtain 2D relative pressure field in the LV using in-vivo measurements obtained by processing Doppler-echocardiography images of healthy and dilated hearts. Exploiting mass conservation, we solve the Poisson pressure equation (PPE) dropping the time derivatives and viscous terms. The flow acceleration appears only in the boundary conditions, making our method weakly sensible to the time resolution of in-vivo acquisitions. To ensure continuity with respect to the discrete operator and grid used, a potential flow correction is applied beforehand, which gives another Poisson equation. The new incompressible velocity field ensures that the compatibility equation for the PPE is satisfied. Both Poisson equations are efficiently solved on a Cartesian grid using a multi-grid method and immersed boundary for the LV wall. The whole process is computationally inexpensive and could play a diagnostic role in the clinical assessment of LV function.

Comprehensive clinical approach to renal tubular acidosis.

PubMed

Sharma, Sonia; Gupta, Ankur; Saxena, Sanjiv

2015-08-01

Renal tubular acidosis (RTA) is essentially characterized by normal anion gap and hyperchloremic metabolic acidosis. It is important to understand that despite knowing the disease for 60-70 years, complexities in the laboratory tests and their interpretation still make clinicians cautious to diagnose and label types of tubular disorder. Hence, we are writing this mini-review to emphasize on the step wise approach to RTA with some understanding on its basic etiopathogenesis. This will definitely help to have an accurate interpretation of urine and blood reports in correlation with the clinical condition. RTA can be a primary or secondary defect and results either due to abnormality in bicarbonate ion absorption or hydrogen ion secretion. Primary defects are common in children due to gene mutation or idiopathic nature while secondary forms are more common in adults. We are focusing and explaining here in this review all the clinical and laboratory parameters which are essential for making the diagnosis of RTA and excluding the extrarenal causes of hyperchloremic, normal anion gap metabolic acidosis.

An Unusual Cause of Acute Upper Gastrointestinal Bleeding: Acute Esophageal Necrosis

PubMed Central

Tokala, Madhusudhan R.; Dhillon, Sonu; Pisoh, Watcoun-Nchinda; Walayat, Saqib; Vanar, Vishwas; Puli, Srinivas R.

2016-01-01

Acute esophageal necrosis (AEN), also called “black esophagus,” is a condition characterized by circumferential necrosis of the esophagus with universal distal involvement and variable proximal extension with clear demarcation at the gastroesophageal junction. It is an unusual cause of upper gastrointestinal bleeding and is recognized with distinct and striking mucosal findings on endoscopy. The patients are usually older and are critically ill with shared comorbidities, which include atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, chronic renal insufficiency, and malnutrition. Alcoholism and substance abuse could be seen in younger patients. Patients usually have systemic hypotension along with upper abdominal pain in the background of clinical presentation of hematemesis and melena. The endoscopic findings confirm the diagnosis and biopsy is not always necessary unless clinically indicated in atypical presentations. Herein we present two cases with distinct clinical presentation and discuss the endoscopic findings along with a review of the published literature on the management of AEN. PMID:27642529

Functional aerophagia in children: a frequent, atypical disorder.

PubMed

Morabito, Giuliana; Romeo, Claudia; Romano, Claudio

2014-01-01

Aerophagia is a functional gastrointestinal disorder characterized by repetitive air swallowing, abdominal distension, belching and flatulence. Pathologic aerophagia is a condition caused by the swallowing of excessive volumes of air with associated various gastrointestinal symptoms, such as burping, abdominal cramps, flatulence and a reduced appetite. It is a clinical entity that can simulate pediatric gastrointestinal motility disorders, such as gastroparesis, megacolon and intestinal pseudo-obstruction, and presents more frequently in children with mental retardation. Early recognition and diagnosis of functional aerophagia or pathologic aerophagia is required to avoid unnecessary, expensive diagnostic investigations or serious clinical complications. Functional aerophagia is frequent in the adult population, but rarely discussed in the pediatric literature. We present two pediatric clinical cases with a history of functional constipation in whom gaseous abdominal distension was the most important symptom. Mechanical intestinal obstruction, chronic intestinal pseudo-obstruction, malabsorption and congenital aganglionic megacolon were ruled out. Extensive gaseous abdominal distension was due to aerophagia, and treatment consisted of parents' reassurance and psychological counseling.

Functional Aerophagia in Children: A Frequent, Atypical Disorder

PubMed Central

Morabito, Giuliana; Romeo, Claudia; Romano, Claudio

2014-01-01

Aerophagia is a functional gastrointestinal disorder characterized by repetitive air swallowing, abdominal distension, belching and flatulence. Pathologic aerophagia is a condition caused by the swallowing of excessive volumes of air with associated various gastrointestinal symptoms, such as burping, abdominal cramps, flatulence and a reduced appetite. It is a clinical entity that can simulate pediatric gastrointestinal motility disorders, such as gastroparesis, megacolon and intestinal pseudo-obstruction, and presents more frequently in children with mental retardation. Early recognition and diagnosis of functional aerophagia or pathologic aerophagia is required to avoid unnecessary, expensive diagnostic investigations or serious clinical complications. Functional aerophagia is frequent in the adult population, but rarely discussed in the pediatric literature. We present two pediatric clinical cases with a history of functional constipation in whom gaseous abdominal distension was the most important symptom. Mechanical intestinal obstruction, chronic intestinal pseudo-obstruction, malabsorption and congenital aganglionic megacolon were ruled out. Extensive gaseous abdominal distension was due to aerophagia, and treatment consisted of parents’ reassurance and psychological counseling. PMID:24847194

The road to treating smoldering multiple myeloma.

PubMed

Korde, Neha; Mailankody, Sham; Landgren, Ola

2014-09-01

The management of smoldering multiple myeloma (SMM) has been a challenge to clinicians, ever since the condition was first characterized in 1980. While the risk of progression to symptomatic myeloma is greater for SMM (10% per year) compared to MGUS (1% per year), several SMM patients remain asymptomatic for years without evidence of disease progression. Early clinical trials focusing on early treatment of SMM have been equivocal with no clear benefit. However, the last decade has seen a greater understanding of the pathogenesis of plasma cell disorders, including SMM, and development of better therapeutics. A recent randomized trial has provided evidence of clinical benefit with early treatment of high-risk SMM. In this review, we summarize issues related to the early treatment of SMM including risk stratification and possible outcomes with therapy initiation. In the context of reviewing recent clinical trial data supporting early treatment, we define challenges faced by clinicians and provide future directions to the road to treating SMM. Published by Elsevier Inc.

Chemoenzymatic Synthesis, Characterization, and Scale-Up of Milk Thistle Flavonolignan Glucuronides.

PubMed

Gufford, Brandon T; Graf, Tyler N; Paguigan, Noemi D; Oberlies, Nicholas H; Paine, Mary F

2015-11-01

Plant-based therapeutics, including herbal products, continue to represent a growing facet of the contemporary health care market. Mechanistic descriptions of the pharmacokinetics and pharmacodynamics of constituents composing these products remain nascent, particularly for metabolites produced following herbal product ingestion. Generation and characterization of authentic metabolite standards are essential to improve the quantitative mechanistic understanding of herbal product disposition in both in vitro and in vivo systems. Using the model herbal product, milk thistle, the objective of this work was to biosynthesize multimilligram quantities of glucuronides of select constituents (flavonolignans) to fill multiple knowledge gaps in the understanding of herbal product disposition and action. A partnership between clinical pharmacology and natural products chemistry expertise was leveraged to optimize reaction conditions for efficient glucuronide formation and evaluate alternate enzyme and reagent sources to improve cost effectiveness. Optimized reaction conditions used at least one-fourth the amount of microsomal protein (from bovine liver) and cofactor (UDP glucuronic acid) compared with typical conditions using human-derived subcellular fractions, providing substantial cost savings. Glucuronidation was flavonolignan-dependent. Silybin A, silybin B, isosilybin A, and isosilybin B generated five, four, four, and three monoglucuronides, respectively. Large-scale synthesis (40 mg of starting material) generated three glucuronides of silybin A: silybin A-7-O-β-D-glucuronide (15.7 mg), silybin A-5-O-β-D-glucuronide (1.6 mg), and silybin A-4´´-O-β-D-glucuronide (11.1 mg). This optimized, cost-efficient method lays the foundation for a systematic approach to synthesize and characterize herbal product constituent glucuronides, enabling an improved understanding of mechanisms underlying herbal product disposition and action. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Chemoenzymatic Synthesis, Characterization, and Scale-Up of Milk Thistle Flavonolignan Glucuronides

PubMed Central

Gufford, Brandon T.; Graf, Tyler N.; Paguigan, Noemi D.; Oberlies, Nicholas H.

2015-01-01

Plant-based therapeutics, including herbal products, continue to represent a growing facet of the contemporary health care market. Mechanistic descriptions of the pharmacokinetics and pharmacodynamics of constituents composing these products remain nascent, particularly for metabolites produced following herbal product ingestion. Generation and characterization of authentic metabolite standards are essential to improve the quantitative mechanistic understanding of herbal product disposition in both in vitro and in vivo systems. Using the model herbal product, milk thistle, the objective of this work was to biosynthesize multimilligram quantities of glucuronides of select constituents (flavonolignans) to fill multiple knowledge gaps in the understanding of herbal product disposition and action. A partnership between clinical pharmacology and natural products chemistry expertise was leveraged to optimize reaction conditions for efficient glucuronide formation and evaluate alternate enzyme and reagent sources to improve cost effectiveness. Optimized reaction conditions used at least one-fourth the amount of microsomal protein (from bovine liver) and cofactor (UDP glucuronic acid) compared with typical conditions using human-derived subcellular fractions, providing substantial cost savings. Glucuronidation was flavonolignan-dependent. Silybin A, silybin B, isosilybin A, and isosilybin B generated five, four, four, and three monoglucuronides, respectively. Large-scale synthesis (40 mg of starting material) generated three glucuronides of silybin A: silybin A-7-O-β-d-glucuronide (15.7 mg), silybin A-5-O-β-d-glucuronide (1.6 mg), and silybin A-4´´-O-β-d-glucuronide (11.1 mg). This optimized, cost-efficient method lays the foundation for a systematic approach to synthesize and characterize herbal product constituent glucuronides, enabling an improved understanding of mechanisms underlying herbal product disposition and action. PMID:26316643

Oral health status and behaviours of children with Autism Spectrum Disorder: a case-control study.

PubMed

El Khatib, Amira A; El Tekeya, Magda M; El Tantawi, Maha A; Omar, Tarek

2014-07-01

Autism Spectrum Disorder (ASD) is a lifelong neuro-developmental disorder characterized by abnormalities in social interactions and communication and by stereotyped, repetitive activities. Assess the oral health status and behaviours of children with ASD. The study included 100 children with ASD and 100 healthy children from Alexandria, Egypt. Data were collected using a questionnaire and clinical examination. Questionnaire assessed socio-demographics, medical history, dental history, oral hygiene, dietary habits, and presence of self-injurious behaviours. Clinical examination assessed behaviour during examination, gingival condition, plaque accumulation, caries, and other oral conditions. Children with ASD had significantly poorer oral hygiene and gingival condition than healthy children (P < 0.001 for both). No significant differences were found in caries prevalence or experience in primary or permanent dentition. More children with ASD behaved 'negatively' or 'definitely negatively' (37% and 11%) than did healthy controls (11% and 2%) (P < 0.0001). Self-injurious behaviour and bruxism were more practised by children with ASD (32% of children with ASD and 2% of healthy children, P < 0.001). More children with ASD had difficulty in accessing dental care (P = 0.002). The oral condition of children with ASD might increase the risk of developing dental diseases. Their behaviour and life factors may complicate provision of services and limit access to dental care. Therefore, individualized oral health education programmes should be implemented for those children. © 2013 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

KBG syndrome involving a single-nucleotide duplication in ANKRD11

PubMed Central

Kleyner, Robert; Malcolmson, Janet; Tegay, David; Ward, Kenneth; Maughan, Annette; Maughan, Glenn; Nelson, Lesa; Wang, Kai; Robison, Reid; Lyon, Gholson J.

2016-01-01

KBG syndrome is a rare autosomal dominant genetic condition characterized by neurological involvement and distinct facial, hand, and skeletal features. More than 70 cases have been reported; however, it is likely that KBG syndrome is underdiagnosed because of lack of comprehensive characterization of the heterogeneous phenotypic features. We describe the clinical manifestations in a male currently 13 years of age, who exhibited symptoms including epilepsy, severe developmental delay, distinct facial features, and hand anomalies, without a positive genetic diagnosis. Subsequent exome sequencing identified a novel de novo heterozygous single base pair duplication (c.6015dupA) in ANKRD11, which was validated by Sanger sequencing. This single-nucleotide duplication is predicted to lead to a premature stop codon and loss of function in ANKRD11, thereby implicating it as contributing to the proband's symptoms and yielding a molecular diagnosis of KBG syndrome. Before molecular diagnosis, this syndrome was not recognized in the proband, as several key features of the disorder were mild and were not recognized by clinicians, further supporting the concept of variable expressivity in many disorders. Although a diagnosis of cerebral folate deficiency has also been given, its significance for the proband's condition remains uncertain. PMID:27900361

Is the desire for amputation related to disturbed emotion processing? A multiple case study analysis in BIID.

PubMed

Bottini, Gabriella; Brugger, Peter; Sedda, Anna

2015-01-01

Body integrity identity disorder (BIID) is characterized by the overwhelming desire to amputate one or more healthy limbs or to be paraplegic. Recently, a neurological explanation of this condition has been proposed, in part on the basis of findings that the insular cortex might present structural anomalies in these individuals. While these studies focused on body representation, much less is known about emotional processing. Importantly, emotional impairments have been found in psychiatric disorders, and a psychiatric etiology is still a valid alternative to purely neurological accounts of BIID. In this study, we explored, by means of a computerized experiment, facial emotion recognition and emotional responses to disgusting images in seven individuals with BIID, taking into account their clinical features and investigating in detail disgust processing, strongly linked to insular functioning. We demonstrate that BIID is not characterized by a general emotional impairment; rather, there is a selectively reduced disgust response to violations of the body envelope. Taken together, our results support the need to explore this condition under an interdisciplinary perspective, taking into account also emotional connotations and the social modulation of body representation.

Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear

PubMed Central

Rodriguez-Romaguera, Jose; Do Monte, Fabricio H. M.; Quirk, Gregory J.

2012-01-01

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces symptoms of intractable obsessive-compulsive disorder (OCD), but the mechanism of action is unknown. OCD is characterized by avoidance behaviors that fail to extinguish, and DBS could act, in part, by facilitating extinction of fear. We investigated this possibility by using auditory fear conditioning in rats, for which the circuits of fear extinction are well characterized. We found that DBS of the VS (the VC/VS homolog in rats) during extinction training reduced fear expression and strengthened extinction memory. Facilitation of extinction was observed for a specific zone of dorsomedial VS, just above the anterior commissure; stimulation of more ventrolateral sites in VS impaired extinction. DBS effects could not be obtained with pharmacological inactivation of either dorsomedial VS or ventrolateral VS, suggesting an extrastriatal mechanism. Accordingly, DBS of dorsomedial VS (but not ventrolateral VS) increased expression of a plasticity marker in the prelimbic and infralimbic prefrontal cortices, the orbitofrontal cortex, the amygdala central nucleus (lateral division), and intercalated cells, areas known to learn and express extinction. Facilitation of fear extinction suggests that, in accord with clinical observations, DBS could augment the effectiveness of cognitive behavioral therapies for OCD. PMID:22586125

Protecting the Health of Astronauts: Enhancing Occupational Health Monitoring and Surveillance for Former NASA Astronauts to Understand Long-Term Outcomes of Spaceflight-Related Exposures

NASA Technical Reports Server (NTRS)

Rossi, Meredith; Lee, Lesley; Wear, Mary; Van Baalen, Mary; Rhodes, Bradley

2017-01-01

The astronaut community is unique, and may be disproportionately exposed to occupational hazards not commonly seen in other communities. The extent to which the demands of the astronaut occupation and exposure to spaceflight-related hazards affect the health of the astronaut population over the life course is not completely known. A better understanding of the individual, population, and mission impacts of astronaut occupational exposures is critical to providing clinical care, targeting occupational surveillance efforts, and planning for future space exploration. The ability to characterize the risk of latent health conditions is a significant component of this understanding. Provision of health screening services to active and former astronauts ensures individual, mission, and community health and safety. Currently, the NASA-Johnson Space Center (JSC) Flight Medicine Clinic (FMC) provides extensive medical monitoring to active astronauts throughout their careers. Upon retirement, astronauts may voluntarily return to the JSC FMC for an annual preventive exam. However, current retiree monitoring includes only selected screening tests, representing an opportunity for augmentation. The potential long-term health effects of spaceflight demand an expanded framework of testing for former astronauts. The need is two-fold: screening tests widely recommended for other aging populations are necessary to rule out conditions resulting from the natural aging process (e.g., colonoscopy, mammography); and expanded monitoring will increase NASA's ability to better characterize conditions resulting from astronaut occupational exposures. To meet this need, NASA has begun an extensive exploration of the overall approach, cost, and policy implications of e an Astronaut Occupational Health program to include expanded medical monitoring of former NASA astronauts. Increasing the breadth of monitoring services will ultimately enrich the existing evidence base of occupational health risks to astronauts. Such an expansion would therefore improve the understanding of the health of the astronaut population as a whole, and the ability to identify, mitigate, and manage such risks in preparation for deep space exploration missions.

Reminder: NCI Requests Cancer Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

Cancer.gov

In an effort to improve rigor and reproducibility, the National Cancer Institute (NCI) Antibody Characterization Program requests cancer-related protein targets for monoclonal antibody production and distribution to the scientific community. The program from The Office of Cancer Clinical Proteomics Research provides well-characterized

Recommendations for Self-Report Outcome Measures in Vulvodynia Clinical Trials.

PubMed

Pukall, Caroline F; Bergeron, Sophie; Brown, Candace; Bachmann, Gloria; Wesselmann, Ursula

2017-08-01

Vulvodynia (idiopathic chronic vulvar pain) is a prevalent condition associated with significant and negative impacts in many areas of function. Despite the increased research interest in vulvodynia in recent years, recommendations for outcome measures for use in clinical trials are missing. The purpose of this paper, therefore, was to provide recommendations for outcome measures for vulvodynia clinical trials so that consistent measures are used across trials to facilitate between-study comparisons and the conduct of large multicenter trials, and to improve measurement of the multiple dimensions of vulvodynia. Given that provoked vestibulodynia (PVD)-characterized by provoked pain localized to the vaginal opening-is the most common subtype of vulvodynia and the current main focus of clinical trials, this paper focused on recommended outcome measures in PVD clinical trials. The framework used to guide the selection of outcome measures was based on the one proposed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). The IMMPACT framework provided a well-suited guideline for outcome measure recommendations in PVD clinical trials. However, given the provoked presentation of PVD and the significant impact it has on sexuality, modifications to some of the IMMPACT recommendations were made and specific additional measures were suggested. Measures that are specific to vulvovaginal pain are ideal for adoption in PVD clinical trials, and many such measures currently exist that allow the relevant IMMPACT domains to be captured.

Delayed hematologic toxicity following rattlesnake envenomation unresponsive to crotalidae polyvalent antivenom.

PubMed

Bailey, Abby M; Justice, Stephanie; Davis, George A; Weant, Kyle

2017-07-01

North American rattlesnake envenomations are known to produce coagulopathies and thrombocytopenia. However, the occurrence of delayed hematologic toxicity (less than seven days after envenomation) is poorly characterized in the medical literature. While the recurrence of hematologic derangements has been documented following envenomation, it is usually in the absence of clinically significant bleeding. Although commonly recommended to treat delayed coagulopathies, the effectiveness of crotalidae polyvalent immune Fab ovine (CroFab®) in managing this condition remains in question and warrants further investigation and exploration. We describe the case of a 19-year-old male who presented following rattlesnake envenomation at a church service who was treated with antivenin for 48 h and discharged home only to return four days later with profound thrombocytopenia, coagulopathy, and clinically significant bleeding. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuropsychiatric manifestations of alkali metal deficiency and excess

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

Yung, C.Y.

1984-01-01

The alkali metals from the Group IA of the periodic table (lithium, sodium, potassium, rubidium, cesium and francium) are reviewed. The neuropsychiatric aspects of alkali metal deficiencies and excesses (intoxications) are described. Emphasis was placed on lithium due to its clinical uses. The signs and symptoms of these conditions are characterized by features of an organic brain syndrome with delirium and encephalopathy prevailing. There are no clinically distinctive features that could be reliably used for diagnoses. Sodium and potassium are two essential alkali metals in man. Lithium is used as therapeutic agent in bipolar affective disorders. Rubidium has been investigatedmore » for its antidepressant effect in a group of psychiatric disorders. Cesium is under laboratory investigation for its role in carcinogenesis and in depressive illness. Very little is known of francium due to its great instability for experimental study.« less

Efficacy of long-term intralesional triamcinolone in Morbihan's disease and its possible association with mast cell infiltration.

PubMed

Tsiogka, Aikaterini; Koller, Josef

2018-04-23

Morbihan's disease is characterized by chronic persistent facial edema of the upper half of the face, absence of typical diagnostic findings, and refractoriness to treatment. A 44-year-old man was diagnosed with Morbihan's disease based on clinical signs and histopathology, which showed dermal edema in upper dermis, discrete lymphocytic infiltrate without granulomatous reaction, and mast cell infiltration. After long-term therapy with intralesional triamcinolone a remarkable objective and subjective clinical response was observed. Reported cases of Morbihan's disease are reviewed, with respect to their treatment and histopathological findings. Mast cell infiltration has been observed on histopathology in most patients who responded to intralesional triamcinolone, suggesting a possible marker of response. The long-lasting response seen in our case indicates the efficacy of intralesional triamcinolone in this rare condition. © 2018 Wiley Periodicals, Inc.

Automatic 3D segmentation of multiphoton images: a key step for the quantification of human skin.

PubMed

Decencière, Etienne; Tancrède-Bohin, Emmanuelle; Dokládal, Petr; Koudoro, Serge; Pena, Ana-Maria; Baldeweck, Thérèse

2013-05-01

Multiphoton microscopy has emerged in the past decade as a useful noninvasive imaging technique for in vivo human skin characterization. However, it has not been used until now in evaluation clinical trials, mainly because of the lack of specific image processing tools that would allow the investigator to extract pertinent quantitative three-dimensional (3D) information from the different skin components. We propose a 3D automatic segmentation method of multiphoton images which is a key step for epidermis and dermis quantification. This method, based on the morphological watershed and graph cuts algorithms, takes into account the real shape of the skin surface and of the dermal-epidermal junction, and allows separating in 3D the epidermis and the superficial dermis. The automatic segmentation method and the associated quantitative measurements have been developed and validated on a clinical database designed for aging characterization. The segmentation achieves its goals for epidermis-dermis separation and allows quantitative measurements inside the different skin compartments with sufficient relevance. This study shows that multiphoton microscopy associated with specific image processing tools provides access to new quantitative measurements on the various skin components. The proposed 3D automatic segmentation method will contribute to build a powerful tool for characterizing human skin condition. To our knowledge, this is the first 3D approach to the segmentation and quantification of these original images. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

A taxonomy of adolescent health: development of the adolescent health profile-types.

PubMed

Riley, A W; Green, B F; Forrest, C B; Starfield, B; Kang, M; Ensminger, M E

1998-08-01

The aim of this study was to develop a taxonomy of health profile-types that describe adolescents' patterns of health as self-reported on a health status questionnaire. The intent was to be able to assign individuals to mutually exclusive and exhaustive groups that characterize the important aspects of their health and need for health services. Cluster analytic empirical methods and clinically based conceptual methods were used to identify patterns of health in samples of adolescents from schools and from clinics that serve adolescents with chronic conditions and acute illnesses. Individuals with similar patterns of scores across multiple domains were assigned to the same profile-type. Results from the empirical and conceptually based methods were integrated to produce a practical system for assigning youths to profile-types. Four domains of health (Satisfaction, Discomfort, Risks and Resilience) were used to group individuals into 13 distinct profile-types. The profile-types were characterized primarily by the number of domains in which health is poor, identifying the unique combinations of problems that characterize different subgroups of adolescents. This method of reporting the information available on health status surveys is potentially a more informative way of identifying and classifying the health needs of subgroups in the population than is available from global scores or multiple scale scores. The reliability and validity of this taxonomy of health profile-types for the purposes of planning and evaluating health services must be demonstrated. That is the purpose of the accompanying study.

Cancer vaccine characterization: from bench to clinic.

PubMed

de la Luz-Hernández, K; Rabasa, Y; Montesinos, R; Fuentes, D; Santo-Tomás, J F; Morales, O; Aguilar, Y; Pacheco, B; Castillo, A

2014-05-19

The development of safe, effective, and affordable vaccines has become a global effort due to its vast impact on overall world health conditions. A brief overview of vaccine characterization techniques, especially in the area of high-resolution mass spectrometry, is presented. It is highly conceivable that the proper use of advanced technologies such as high-resolution mass spectrometry, along with the appropriate chemical and physical property evaluations, will yield tremendous in-depth scientific understanding for the characterization of vaccines in various stages of vaccine development. This work presents the physicochemical and biological characterization of cancer vaccine Racotumomab/alumina, a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH)3, in several clinical trials for melanoma, breast, and lung cancer. Racotumomab was obtained from ascites fluid, transferred to fermentation in stirred tank at 10 L and followed to a scale up to 41 L. The mass spectrometry was used for the determination of intact molecule, light and heavy chains masses; amino acids sequence analysis, N- and C-terminal, glycosylation and posttranslational modifications. Also we used the DLS for the size distribution and zeta potential analysis. The biological analyses were performed in mice and chickens. We observed differences in glycosylation pattern, charge heterogeneity and structural stability between in vivo-produced and bioreactor-obtained Racotumomab products. Interestingly, these modifications had no significant impact on the immune responses elicited in two different animal models. We are demonstrated that this approach could potentially be more efficient and effective for supporting vaccine research and development. Copyright © 2014. Published by Elsevier Ltd.

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

[Rocky mountain spotted fever: report of two cases].

PubMed

Martínez-Medina, Miguel Angel; Padilla-Zamudio, Guillermo; Solís-Gallardo, Lilia Patricia; Guevara-Tovar, Marcela

2005-01-01

Rocky Mountain spotted fever (RMSF) is an acute febrile illness caused by infection with Ricketsia Rickettsii, characterized by the presence of petechial rash. Even though the etiology, clinical characteristics and availability of effective antibiotics are known, RMSF related deaths have a prevalence of 4%. In its early stages RMFS can resemble many others infectious conditions and the diagnosis can be difficult. The present paper reports two patients with RMSF; these cases underscore the importance of prompt diagnosis and appropriate antimicrobial therapy, and consider RMSF as a differential diagnosis in any patient who develops fever and rash in an endemic area.

Symbolic use of size and color in freehand drawing of the tree: myth or reality?

PubMed

Picard, Delphine; Lebaz, Samuel

2010-03-01

In this study, we tested whether children and young adults varied the size and color of their tree drawings based on hypotheses related to the emotional characterization of the drawn topic. We asked a sample of 80 5- to 11-year-old children and adults to draw a tree (baseline drawing) and then a happy versus sad tree from their imagination. Results indicate that size, but not color, is used to express emotion under free drawing conditions. We discuss implications for clinical psychologists and practitioners interpreting drawings of the tree.

Burning mouth syndrome

PubMed Central

Jimson, Sudha; Rajesh, E.; Krupaa, R. Jayasri; Kasthuri, M.

2015-01-01

Burning mouth syndrome (BMS) is a complex disorder that is characterized by warm or burning sensation in the oral mucosa without changes on physical examination. It occurs more commonly in middle-aged and elderly women and often affects the tip of the tongue, lateral borders, lips, hard and soft palate. This condition is probably of multi-factorial origin, often idiopathic, and its etiopathogensis is unknown. BMS can be classified into two clinical forms namely primary and secondary BMS. As a result, a multidisciplinary approach is required for better control of the symptoms. In addition, psychotherapy and behavioral feedback may also help eliminate the BMS symptoms. PMID:26015707

Prevalence of Hb S (HHB: c.20A > T) in a Honduran population of African descent.

PubMed

Erazo, Brian M; Ramírez, Gilberto A; Cerrato, Linda E; Pinto, Luis J; Castro, Edder J; Yanez, Néstor J; Montoya, Brayan; Fontecha, Gustavo A

2015-01-01

Sickle cell disease is the most common hemoglobinopathy worldwide, particularly in Africa and among people of African descent. Serious clinical consequences characterize the homozygous condition. To determine the prevalence of Hb S (HBB: c.20A > T) and anemia in a community of people of African descent from Honduras, 202 individuals were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The high prevalence found indicates that it is necessary to implement a program to prevent the consequences of this disease in vulnerable populations of Honduras.

Adaptation: paradigm for the gut and an academic career.

PubMed

Warner, Brad W

2013-01-01

Adaptation is an important compensatory response to environmental cues resulting in enhanced survival. In the gut, the abrupt loss of intestinal length is characterized by increased rates of enterocyte proliferation and apoptosis and culminates in adaptive villus and crypt growth. In the development of an academic pediatric surgical career, adaptation is also an important compensatory response to survive the ever changing research, clinical, and economic environment. The ability to adapt in both situations is critical for patients and a legacy of pediatric surgical contributions to advance our knowledge of multiple conditions and diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

Eosinophilic pustular folliculitis in infancy: report of a new case.

PubMed

Alonso-Castro, L; Pérez-García, B; González-García, C; Jaén-Olasolo, P

2012-10-15

We report a new case of eosinophilic pustular folliculitis in a 23-month-old boy. He presented with a seven-month history of recurrent episodes of pustular lesions on the scalp after having been treated with oral antifungal and topic antibiotics without response. The diagnosis was based on the clinical course and typical histopathological findings. Eosinophilic pustular folliculitis in infancy is an idiopathic and rare inflammatory disease characterized by recurrent crops of sterile pustules involving mainly the scalp. Because it is a benign, self-limiting condition an accurate diagnosis is essential to avoid unnecessary therapies.

New Therapeutic Approaches for Familial Hypercholesterolemia.

PubMed

Ajufo, Ezim; Rader, Daniel J

2018-01-29

Familial hypercholesterolemia (FH) is a common genetic condition characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C), premature atherosclerotic cardiovascular disease, and considerable unmet medical need with conventional LDL-C-lowering therapies. Between 2012 and 2015, the US Food and Drug Administration approved four novel LDL-C-lowering agents for use in patients with FH based on the pronounced LDL-C-lowering efficacy of these medicines. We review the four novel approved agents, as well as promising LDL-C-lowering agents in clinical development, with a focus on their mechanism of action, efficacy in FH cohorts, and safety.

[Isolation and Characterization of Multipotent Precursor Cells from Murine Adipose Tissue using a Clinically Approved Cell Separation System].

PubMed

Krug, C; Beer, A; Saller, M M; Aszodi, A; Holzbach, T; Giunta, R E; Volkmer, E

2016-04-01

Recent studies underscored the clinical potential of adipose-derived multipotent stem-/precursor cells (ASPCs). One of the main hurdles en route to clinical application was to isolate cells without having to perform expansion cultures outside the OR. A new generation of clinically approved, commercially available cell separation systems claims to provide ASPCs ready for application without further expansion cultures. However, it is unclear if the new systems yield sufficient cells of adequate quality for the use in autologous murine models. The aim of this study was to isolate and characterize adipose-derived precursor cells taken from the inguinal fat pat of wistar rats using InGeneron's clinically approved ARC™-cell separation system. We isolated cells from the inguinal fat pad of 3 male Wistar rats according to the manufacturer's protocol. In order to reduce the influence of the atmospheric oxygen on the multipotent precursor cells, one half of the cell suspension was cultivated under hypoxia (2% O2) simulating physiological conditions for ASPCs. As a control, the other half of the cells were cultivated under normoxia (21% O2). Cell surface markers CD90, CD29, CD45 and CD11b/c were analyzed by FACS, and osteogenic and adipogenic differentiation of the ASPCs was performed. Finally, cellular growth characteristics were assessed by evaluation of the cumulative population doublings and CFU assay, and metabolic activity was evaluated by WST-1 assay. Processing time was 90 (± 12) min. 1 g of adipose tissue yielded approximately 60 000 plastic adhering cells. Both groups showed a high expression of the mesenchymal stem cell markers CD90 and CD29 while they were negative for the leucocyte markers CD45 and CD11b/c. A strong osteogenic differentiation and a sufficient adipogenic differentiation potential was proven for all ASPCs. Under hypoxia, ASPCs showed increased proliferation characteristics and CFU efficiency as well as a significantly increased metabolic activity. This study showed that sufficient multipotent ASPCs of appropriate quality can be isolated from the inguinal fat pad of Wistar rats using the ARC™-cell separation system. As shown in previous studies, cultivation of cells under hypoxic conditions increased their stemness. Our findings will enable future studies that focus on autologous transplantation of ASPCs in a rat model, which most closely resembles a possible clinical application. © Georg Thieme Verlag KG Stuttgart · New York.

Severe tricuspid regurgitation in the aged: atrial remodeling associated with long-standing atrial fibrillation.

PubMed

Yamasaki, Naohito; Kondo, Fumiaki; Kubo, Toru; Okawa, Makoto; Matsumura, Yoshihisa; Kitaoka, Hiroaki; Yabe, Toshikazu; Furuno, Takashi; Doi, Yoshinori

2006-12-01

Severe idiopathic tricuspid regurgitation (TR) occurs in the aged, but the mechanism of TR is unclear and there is little information on atrial abnormalities associated with this condition. This study retrospectively analyzed patients with severe functional TR presenting with common clinical features suggesting a distinct syndrome. Eleven patients with severe functional TR were identified by reviewing the records of 16,235 consecutive patients. All patients had undergone clinical evaluation including echocardiography, electrocardiography and laboratory data. The median age of patients with severe functional TR was 78 years. All had a long-standing history of atrial fibrillation (median duration, 23 years). Clinical features are characterized by severe functional TR due to annular dilation, markedly dilated right atrium, episodes of right-sided heart failure, absent or diminished fibrillation waves on electrocardiogram, bradycardia probably due to partial atrial standstill, and decreased atrial natriuretic peptide secretion. During long-term follow up, right atrial size progressively increased in association with worsening TR. Severe functional TR occurs with long-standing atrial fibrillation and causes right-sided heart failure. The TR is caused by tricuspid valve systolic coaptation loss due to tricuspid annular dilation associated with atrial dilation. This condition is associated with atrial abnormalities, such as atrial standstill and impaired atrial natriuretic peptide secretion. We propose that atrial remodeling associated with atrial fibrillation is central to the occurrence of the syndrome.

NETopathies? Unraveling the Dark Side of Old Diseases through Neutrophils

PubMed Central

Mitsios, Alexandros; Arampatzioglou, Athanasios; Arelaki, Stella; Mitroulis, Ioannis; Ritis, Konstantinos

2017-01-01

Neutrophil extracellular traps (NETs) were initially described as an antimicrobial mechanism of neutrophils. Over the last decade, several lines of evidence support the involvement of NETs in a plethora of pathological conditions. Clinical and experimental data indicate that NET release constitutes a shared mechanism, which is involved in a different degree in various manifestations of non-infectious diseases. Even though the backbone of NETs is similar, there are differences in their protein load in different diseases, which represent alterations in neutrophil protein expression in distinct disorder-specific microenvironments. The characterization of NET protein load in different NET-driven disorders could be of significant diagnostic and/or therapeutic value. Additionally, it will provide further evidence for the role of NETs in disease pathogenesis, and it will enable the characterization of disorders in which neutrophils and NET-dependent inflammation are of critical importance. PMID:28123386

Atypical angioimmunoblastic T-cell lymphomas masquerading as systemic polyclonal B-immunoblastic proliferation.

PubMed

Papadi, Bhavesh; Polski, Jacek M; Clarkson, David R; Liu-Dumlao, Theresa O

2012-09-01

Angioimmunoblastic T cell lymphoma (AITL) is a relatively rare peripheral T cell lymphoma derived from follicular T helper cells. AITL has a varied presentation, both clinically and morphologically. AITL can pose a diagnostic challenge as it may be difficult to identify and characterize the neoplastic cells among the polymorphous infiltrates composed of polyclonal B immunoblasts and plasma cells. In AITL, the reactive B cell and plasma cell proliferation is secondary to dysregulated secretion of cytokines such as interleukin-6 by the neoplastic follicular T helper cells. SPBIP is a condition of unknown etiopathogenesis characterized by systemic involvement by polyclonal B immunoblasts and plasma cells. We report two cases of AITL, which are presented with atypical findings making it difficult to diagnose. The cases had features similar to SPBIP. Our cases highlight the importance of screening cases of polyclonal plasmacytosis and SPBIP like cases for underlying AITL.

Electroglottogram waveform types.

PubMed

Painter, C

1988-01-01

Electroglottography is a useful, non-invasive technique that can assist in the assessment of vocal fold dysfunction. However, if it is to become a useful clinical tool, there is a need for normative studies of the electroglottogram waveform types that characterize trained professional voice users, untrained non-professional speakers and patients with voice disorders and for a way of quantifying and objectively comparing similarities and differences. This report describes our methodology and an investigation into the waveform types characterizing one trained professional voice user phonating in 15 experimental sessions under various fundamental frequency, intensity and voice quality conditions. A number of strong tendencies were noted. In normal voice the lower frequencies and intensities represent one pole of a scale of a mode of phonation, while the higher frequencies and intensities depict the other pole. In these studies breathy voice data overlapped the lower end of the scale and tense voice data overlapped the upper end.

Targeting PSMA by radioligands in non-prostate disease-current status and future perspectives.

PubMed

Backhaus, Philipp; Noto, Benjamin; Avramovic, Nemanja; Grubert, Lena Sophie; Huss, Sebastian; Bögemann, Martin; Stegger, Lars; Weckesser, Matthias; Schäfers, Michael; Rahbar, Kambiz

2018-05-01

Prostate-specific membrane antigen (PSMA) is the up-and-coming target for molecular imaging of prostate cancer. Despite its name, non-prostate-related PSMA expression in physiologic tissue as well as in benign and malignant disease has been reported in various publications. Unlike in prostate cancer, PSMA expression is only rarely observed in non-prostate tumor cells. Instead, expression occurs in endothelial cells of tumor-associated neovasculature, although no endothelial expression is observed under physiologic conditions. The resulting potential for tumor staging in non-prostate malignant tumors has been demonstrated in first patient studies. This review summarizes the first clinical studies and deduces future perspectives in staging, molecular characterization, and PSMA-targeted radionuclide therapy based on histopathologic examinations of PSMA expression. The non-exclusivity of PSMA in prostate cancer opens a window to utilize the spectrum of available radioactive PSMA ligands for imaging and molecular characterization and maybe even therapy of non-prostate disease.

Isolation and Characterization of Canine Amniotic Membrane-Derived Multipotent Stem Cells

PubMed Central

Kim, Hyung-Sik; Kang, Kyung-Sun

2012-01-01

Recent studies have shown that amniotic membrane tissue is a rich source of stem cells in humans. In clinical applications, the amniotic membrane tissue had therapeutic effects on wound healing and corneal surface reconstruction. Here, we successfully isolated and identified multipotent stem cells (MSCs) from canine amniotic membrane tissue. We cultured the canine amniotic membrane-derived multipotent stem cells (cAM-MSCs) in low glucose DMEM medium. cAM-MSCs have a fibroblast-like shape and adhere to tissue culture plastic. We characterized the immunophenotype of cAM-MSCs by flow cytometry and measured cell proliferation by the cumulative population doubling level (CPDL). We performed differentiation studies for the detection of trilineage multipotent ability, under the appropriate culture conditions. Taken together, our results show that cAM-MSCs could be a rich source of stem cells in dogs. Furthermore, cAM-MSCs may be useful as a cell therapy application for veterinary regenerative medicine. PMID:23024756

An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions

PubMed Central

Pattee, Gary L.; Wymer, James P.; Lomen-Hoerth, Catherine; Appel, Stanley H.; Formella, Andrea E.; Pope, Laura E.

2014-01-01

Abstract Background: Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient’s emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. Objective: To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Methods: Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Clinical trial registration: #NCT00056524. Results: A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose. Conclusions: DM/Q was generally well tolerated over this 52 week trial in patients with PBA associated with a wide range of neurological conditions. PMID:25062507

Effects of age condition on the distribution and integrity of inorganic fillers in dental resin composites.

PubMed

D'Alpino, Paulo Henrique Perlatti; Svizero, Nádia da Rocha; Bim Júnior, Odair; Valduga, Claudete Justina; Graeff, Carlos Frederico de Oliveira; Sauro, Salvatore

2016-06-01

The aim of this study is to evaluate the distribution of the filler size along with the zeta potential, and the integrity of silane-bonded filler surface in different types of restorative dental composites as a function of the material age condition. Filtek P60 (hybrid composite), Filtek Z250 (small-particle filled composite), Filtek Z350XT (nanofilled composite), and Filtek Silorane (silorane composite) (3M ESPE) were tested at different stage condition (i.e., fresh/new, aged, and expired). Composites were submitted to an accelerated aging protocol (Arrhenius model). Specimens were obtained by first diluting each composite specimen in ethanol and then dispersed in potassium chloride solution (0.001 mol%). Composite fillers were characterized for their zeta potential, mean particle size, size distribution, via poly-dispersion dynamic light scattering. The integrity of the silane-bonded surface of the fillers was characterized by FTIR. The material age influenced significantly the outcomes; Zeta potential, filler characteristics, and silane integrity varied both after aging and expiration. Silorane presented the broadest filler distribution and lowest zeta potential. Nanofilled and silorane composites exhibited decreased peak intensities in the FTIR analysis, indicating a deficiency of the silane integrity after aging or expiry time. Regardless to the material condition, the hybrid and the small-particle-filled composites were more stable overtime as no significant alteration in filler size distribution, diameter, and zeta potential occurred. A deficiency in the silane integrity in the nanofilled and silorane composites seems to be affected by the material stage condition. The materials conditions tested in this study influenced the filler size distribution, the zeta potential, and integrity of the silane adsorbed on fillers in the nanofilled and silorane composites. Thus, this may result in a decrease of the clinical performance of aforementioned composites, in particular, if these are used after inappropriate storage conditions.

Repetitive Transcranial Magnetic Stimulation for Clinical Applications in Neurological and Psychiatric Disorders: An Overview

PubMed Central

Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Vieira, Renata Teles; Caixeta, Leonardo; Novaes, Felipe; Marinho, Tamires; Almada, Leonardo Ferreira; Silva, Adriana Cardoso; Nardi, Antonio Egidio

2013-01-01

Neurological and psychiatric disorders are characterized by several disabling symptoms for which effective, mechanism-based treatments remain elusive. Consequently, more advanced non-invasive therapeutic methods are required. A method that may modulate brain activity and be viable for use in clinical practice is repetitive transcranial magnetic stimulation (rTMS). It is a non-invasive procedure whereby a pulsed magnetic field stimulates electrical activity in the brain. Here, we focus on the basic foundation of rTMS, the main stimulation parametters, the factors that influence individual responses to rTMS and the experimental advances of rTMS that may become a viable clinical application to treat neurological and psychiatric disorders. The findings showed that rTMS can improve some symptoms associated with these conditions and might be useful for promoting cortical plasticity in patients with neurological and psychiatric disorders. However, these changes are transient and it is premature to propose these applications as realistic therapeutic options, even though the rTMS technique has been evidenced as a potential modulator of sensorimotor integration and neuroplasticity. Functional imaging of the region of interest could highlight the capacity of rTMS to bring about plastic changes of the cortical circuitry and hint at future novel clinical interventions. Thus, we recommend that further studies clearly determine the role of rTMS in the treatment of these conditions. Finally, we must remember that however exciting the neurobiological mechanisms might be, the clinical usefulness of rTMS will be determined by its ability to provide patients with neurological and psychiatric disorders with safe, long-lasting and substantial improvements in quality of life. PMID:25610279

Localized scleroderma: a clinical study at a single center in Korea.

PubMed

Noh, Jung Won; Kim, Jinseok; Kim, Jae-Wang

2013-08-01

Localized scleroderma (morphea) is a rare autoimmune disease limited to the skin, characterized by cutaneous fibrosing and obstructive vasculopathy. Localized scleroderma may invade into the subcutaneous fat layer and cause permanent functional disability. Because of its rarity, there have been few clinical surveys of patients with localized scleroderma in Korea. The aim of this study was to elucidate the clinical presentation, serological data, and clinical outcomes of localized scleroderma. This was a retrospective survey conducted by reviewing available medical records during a 7 year-period from 2004 to 2010 in a single medical center in Jeju Island, South Korea. In total 43 patients with localized scleroderma were included. Localized scleroderma occurred primarily in females (female to male ratio 2.6 : 1.0). Most patients were between 10 and 29 years of age and the mean age at diagnosis was 26.2 years. Plaque (51.2%) and linear morphea (37.2%) were most common. No case was associated with systemic scleroderma (systemic sclerosis). The most common site of plaque morphea was the trunk (47.8%). In the linear type, the most common site was head-neck (52.9%). Fluorescent antinuclear antibody was positive in 23.3% of all cases. Treatment included systemic corticosteroids, colchicine, anti-malarial agents, D-penicillamine or intralesional triamcinolone injection. Clinical improvement, including significant and partial response, was seen in only 62.8% of treated patients. Localized scleroderma is a chronic inflammatory condition confined to the skin. In order to exclude other conditions, thorough history taking, physical examination, serologic studies and histopathologic examinations should be conducted. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Angelman syndrome assessed by neurological and molecular cytogenetic investigations.

PubMed

Hou, J W; Wang, P J; Wang, T R

1997-01-01

Angelman syndrome (AS) is characterized by severe psychomotor retardation, speech impairment, happy disposition with bursts of laughter, ataxia, convulsions, and some distinct physical anomalies. Correct diagnosis of AS is important because of its clinical implications, and once the disease is confirmed, familial genetic counseling becomes crucial. We evaluated 22 patients with a putative diagnosis of AS by both clinical and molecular cytogenetic analysis. A deletion of the region 15q11-13 could be identified cytogenetically in 11 cases by high-resolution technique (group I). Four additional cases were confirmed by fluorescence in situ hybridization (FISH) study with D15S11, SNRPN, D15S10, and GABRB 3 [Prader-Willi syndrome (PWS)/AS region probes] (group II). The common deletion of GABRB 3 was documented in those AS cases (n = 15) by FISH. The other 7 cases exhibited no deletion over 15q11-13 at either the cytogenetic or molecular level (group III). We compared the following associated neurological disorders: convulsions and abnormal EEG, microcephaly, sleep and behavior problems, brain anomalies proved by image studies, sexual precocity with pineal tumor among the three groups, as well as other clinical conditions including congenital heart disease, obesity, scoliosis, and hypopigmentation. In the present study, the differences in neurological and facial characteristics were not distinct among these groups. However, the associated conditions were more frequently observed in the patients with deletion than in those without deletion. The EEG features of AS appear to be less sufficient in helping identify patients at an early age before the clinical features become obvious. Therefore, a region involved in the major As phenotypes may contain only one or more tightly contiguous genes around the GABRB 3 locus, which may explain the clinical heterogeneity in AS.

Optical tweezers for measuring the interaction of the two single red blood cells in flow condition

NASA Astrophysics Data System (ADS)

Lee, Kisung; Muravyov, Alexei; Semenov, Alexei; Wagner, Christian; Priezzhev, Alexander

2017-03-01

Aggregation of red blood cells (RBCs) is an intrinsic property of blood, which has direct effect on the blood viscosity and therefore affects overall the blood circulation throughout the body. It is attracting interest for the research in both fundamental science and clinical application. Despite of the intensive research, the aggregation mechanism is remaining not fully clear. Recent advances in methods allowed measuring the interaction between single RBCs in a well-defined configuration leading the better understanding of the mechanism of the process. However the most of the studies were made on the static cells. Thus, the measurements in flow mimicking conditions are missing. In this work, we aim to study the interaction of two RBCs in the flow conditions. We demonstrate the characterization of the cells interaction strength (or flow tolerance) by measuring the flow velocity to be applied to separate two aggregated cells trapped by double channel optical tweezers in a desired configuration. The age-separated cells were used for this study. The obtained values for the minimum flow velocities needed to separate the two cells were found to be 78.9 +/- 6.1 μm/s and 110 +/- 13 μm/s for old and young cells respectively. The data obtained is in agreement with the observations reported by other authors. The significance of our results is in ability for obtaining a comprehensible and absolute physical value characterizing the cells interaction in flow conditions (not like the Aggregation Index measured in whole blood suspensions by other techniques, which is some abstract parameter)

Immunophenotypic and Molecular Analysis of Human Dental Pulp Stem Cells Potential for Neurogenic Differentiation

PubMed Central

Fatima, Nikhat; Khan, Aleem A.; Vishwakarma, Sandeep K.

2017-01-01

Background: Growing evidence shows that dental pulp (DP) tissues could be a potential source of adult stem cells for the treatment of devastating neurological diseases and several other conditions. Aims: Exploration of the expression profile of several key molecular markers to evaluate the molecular dynamics in undifferentiated and differentiated DP-derived stem cells (DPSCs) in vitro. Settings and Design: The characteristics and multilineage differentiation ability of DPSCs were determined by cellular and molecular kinetics. DPSCs were further induced to form adherent (ADH) and non-ADH (NADH) neurospheres under serum-free condition which was further induced into neurogenic lineage cells and characterized for their molecular and cellular diversity at each stage. Statistical Analysis Used: Statistical analysis used one-way analysis of variance, Student's t-test, Livak method for relative quantification, and R programming. Results: Immunophenotypic analysis of DPSCs revealed >80% cells positive for mesenchymal markers CD90 and CD105, >70% positive for transferring receptor (CD71), and >30% for chemotactic factor (CXCR3). These cells showed mesodermal differentiation also and confirmed by specific staining and molecular analysis. Activation of neuronal lineage markers and neurogenic growth factors was observed during lineage differentiation of cells derived from NADH and ADH spheroids. Greater than 80% of cells were found to express β-tubulin III in both differentiation conditions. Conclusions: The present study reported a cascade of immunophenotypic and molecular markers to characterize neurogenic differentiation of DPSCs under serum-free condition. These findings trigger the future analyses for clinical applicability of DP-derived cells in regenerative applications. PMID:28566856

All-Arthroscopic Treatment of Intra- and Extra-Articular Localized Villonodular Synovitis of Knee

PubMed Central

Simonetta, Roberto; Florio, Michela; Familiari, Filippo; Gasparini, Giorgio; Rosa, Michele Attilio

2017-01-01

Pigmented villonodular synovitis (PVNS) is a rare, benign, proliferative neoplastic condition affecting synovial-lined anatomic spaces. PVNS is characterized by hypertrophy of a synovial membrane by villous, nodular, and villonodular proliferation, with pigmentation secondary to hemosiderin deposition. The two forms of PVNS that have been described are diffuse (DPVNS) and localized (LPVNS). The knee is the most commonly involved anatomic location, followed by hip, ankle, shoulder, and elbow. Diagnosis of PVNS is not always obvious clinically. Various imaging modalities are often necessary to exclude other conditions and narrow the diagnosis. Magnetic resonance imaging has become the modality of choice for diagnosing PVNS. We present a case of intra-articular LPVNS with an extra-articular extension through the posterior capsule that has been successfully removed in an all-arthroscopic fashion. PMID:29270551

Prevention and treatment of the metabolic syndrome in the elderly.

PubMed

Firdaus, Muhammad

2005-02-01

The metabolic syndrome is a term used to indicate the presence of a cluster of conditions associated with increased risk for type 2 diabetes, hypertension, coronary artery disease, stroke, and early mortality. A fairly common condition in the elderly, it is caused primarily by physical inactivity and excessive calorie intake and characterized by abdominal obesity, insulin resistance, impaired fasting glucose, dyslipidemia, and prehypertension. Numerous clinical trials have demonstrated that a lifestyle of moderate-intensity, physical activity for 30 minutes a day, most days of the week, combined with weight loss of 5-7%, can reverse individual components of the metabolic syndrome. When lifestyle modifications are insufficient, a multidrug regimen may be necessary to treat different components of the metabolic syndrome. This paper reviews current literature on the metabolic syndrome, including its causes, incidence and approaches for successful treatment.

Climate change and malaria in Canada: a systems approach.

PubMed

Berrang-Ford, L; Maclean, J D; Gyorkos, Theresa W; Ford, J D; Ogden, N H

2009-01-01

This article examines the potential for changes in imported and autochthonous malaria incidence in Canada as a consequence of climate change. Drawing on a systems framework, we qualitatively characterize and assess the potential direct and indirect impact of climate change on malaria in Canada within the context of other concurrent ecological and social trends. Competent malaria vectors currently exist in southern Canada, including within this range several major urban centres, and conditions here have historically supported endemic malaria transmission. Climate change will increase the occurrence of temperature conditions suitable for malaria transmission in Canada, which, combined with trends in international travel, immigration, drug resistance, and inexperience in both clinical and laboratory diagnosis, may increase malaria incidence in Canada and permit sporadic autochthonous cases. This conclusion challenges the general assumption of negligible malaria risk in Canada with climate change.

Simple Schizophrenia Remains a Complicated Diagnosis: Case Report and Literature Review.

PubMed

Agarwal, Vishesh; Maheshwari, Subani; Agarwal, Vivek; Kalra, Inder Darshan

2016-01-01

The diagnosis of simple schizophrenia has been challenged and criticized since it was first described by Otto Diem in 1903. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), released by the American Psychiatric Association in May 2013, classified it as a condition for further study with the name "attenuated psychosis syndrome." This clinical condition has undergone several revisions with each edition of the DSM. It is characterized by oddities in conduct, inability to meet the demands of society, and decline in total performance in the absence of obvious psychotic symptoms. We discuss the case of a 35-year-old man who presented with symptoms fitting the criteria for simple schizophrenia and review the various definitions and case reports published over the years that defend the diagnosis of simple schizophrenia.

Climate Change and Malaria in Canada: A Systems Approach

PubMed Central

Berrang-Ford, L.; MacLean, J. D.; Gyorkos, Theresa W.; Ford, J. D.; Ogden, N. H.

2009-01-01

This article examines the potential for changes in imported and autochthonous malaria incidence in Canada as a consequence of climate change. Drawing on a systems framework, we qualitatively characterize and assess the potential direct and indirect impact of climate change on malaria in Canada within the context of other concurrent ecological and social trends. Competent malaria vectors currently exist in southern Canada, including within this range several major urban centres, and conditions here have historically supported endemic malaria transmission. Climate change will increase the occurrence of temperature conditions suitable for malaria transmission in Canada, which, combined with trends in international travel, immigration, drug resistance, and inexperience in both clinical and laboratory diagnosis, may increase malaria incidence in Canada and permit sporadic autochthonous cases. This conclusion challenges the general assumption of negligible malaria risk in Canada with climate change. PMID:19277107

Rodent models of insomnia: a review of experimental procedures that induce sleep disturbances.

PubMed

Revel, Florent G; Gottowik, Juergen; Gatti, Sylvia; Wettstein, Joseph G; Moreau, Jean-Luc

2009-06-01

Insomnia, the most common sleep disorder, is characterized by persistent difficulty in falling or staying asleep despite adequate opportunity to sleep, leading to daytime fatigue and mental dysfunction. As sleep is a sophisticated physiological process generated by a network of neuronal systems that cannot be reproduced in-vitro, pre-clinical development of hypnotic drugs requires in-vivo investigations. Accordingly, this review critically evaluates current and putative rodent models of insomnia which could be used to screen novel hypnotics. Only few valid insomnia models are currently available, although many experimental conditions lead to disturbance of physiological sleep. We categorized these conditions as a function of the procedure used to induce perturbation of sleep, and we discuss their respective advantages and pitfalls with respect to validity, feasibility and translational value to human research.

Body-focused repetitive behavior disorders in ICD-11.

PubMed

Grant, Jon E; Stein, Dan J

2014-01-01

This article addresses the question of how body-focused repetitive behavior disorders (e.g., trichotillomania and skin-picking disorder) should be characterized in ICD-11. The article reviews the historical nosology of the two disorders and the current approaches in DSM-5 and ICD-10. Although data are limited and mixed regarding the optimal relationship between body-focused repetitive behavior disorders and nosological categories, these conditions should be included within the obsessive-compulsive and related disorders category, as this is how most clinicians see these behaviors, and as this may optimize clinical utility. The descriptions of these disorders should largely mirror those in DSM-5, given the evidence from recent field surveys. The recommendations regarding ICD-11 and body-focused repetitive behavior disorders should promote the global identification and treatment of these conditions in primary care settings.

A comparison of light spot hydrophone and fiber optic probe hydrophone for lithotripter field characterization.

PubMed

Smith, N; Sankin, G N; Simmons, W N; Nanke, R; Fehre, J; Zhong, P

2012-01-01

The performance of a newly developed light spot hydrophone (LSHD) in lithotripter field characterization was compared to that of the fiber optic probe hydrophone (FOPH). Pressure waveforms produced by a stable electromagnetic shock wave source were measured by the LSHD and FOPH under identical experimental conditions. In the low energy regime, focus and field acoustic parameters matched well between the two hydrophones. At clinically relevant high energy settings for shock wave lithotripsy, the measured leading compressive pressure waveforms matched closely with each other. However, the LSHD recorded slightly larger |P_| (p < 0.05) and secondary peak compressive pressures (p < 0.01) than the FOPH, leading to about 20% increase in total acoustic pulse energy calculated in a 6 mm radius around the focus (p = 0.06). Tensile pulse durations deviated ~5% (p < 0.01) due to tensile wave shortening from cavitation activity using the LSHD. Intermittent compression spikes and laser light reflection artifacts have been correlated to bubble activity based on simultaneous high-speed imaging analysis. Altogether, both hydrophones are adequate for lithotripter field characterization as specified by the international standard IEC 61846.

Abnormal white matter tractography of visual pathways detected by high-angular-resolution diffusion imaging (HARDI) corresponds to visual dysfunction in cortical/cerebral visual impairment

PubMed Central

Bauer, Corinna M.; Heidary, Gena; Koo, Bang-Bon; Killiany, Ronald J.; Bex, Peter; Merabet, Lotfi B.

2014-01-01

Cortical (cerebral) visual impairment (CVI) is characterized by visual dysfunction associated with damage to the optic radiations and/or visual cortex. Typically it results from pre- or perinatal hypoxic damage to postchiasmal visual structures and pathways. The neuroanatomical basis of this condition remains poorly understood, particularly with regard to how the resulting maldevelopment of visual processing pathways relates to observations in the clinical setting. We report our investigation of 2 young adults diagnosed with CVI and visual dysfunction characterized by difficulties related to visually guided attention and visuospatial processing. Using high-angular-resolution diffusion imaging (HARDI), we characterized and compared their individual white matter projections of the extrageniculo-striate visual system with a normal-sighted control. Compared to a sighted control, both CVI cases revealed a striking reduction in association fibers, including the inferior frontal-occipital fasciculus as well as superior and inferior longitudinal fasciculi. This reduction in fibers associated with the major pathways implicated in visual processing may provide a neuroanatomical basis for the visual dysfunctions observed in these patients. PMID:25087644

Acute generalized, widespread bleeding. Diagnosis and management.

PubMed

Rocha, E; Páramo, J A; Montes, R; Panizo, C

1998-11-01

Acute generalized, widespread bleeding is often related to disseminated intravascular coagulation (DIC), a pathologic process which complicates the clinical course of many diseases and is characterized by huge amounts of thrombin and plasmin within the circulation. The final result is the consumption of platelets, coagulation factors and inhibitors, as well as secondary hyperfibrinolysis, all leading to diffuse hemorrhage and microthromboses. This review article examines the present attitudes to the diagnosis and treatment of overt DIC in clinical practice, emphasizing the importance of an accurate differential diagnosis from some other processes characterized by acute generalized, widespread bleeding. The authors have been working in this field, both at experimental and clinical levels, contributing original papers for many years. In addition, material examined in this review includes articles published in journals covered by MedLine, recent reviews in journals with high impact factor and in relevant books on hemostasis and thrombosis. DIC is an intermediary mechanism of disease which complicates the clinical course of many well-known disorders. Although the systemic hemorrhagic syndrome is the predominant clinical manifestation, massive intravascular thrombosis frequently occurs contributing to ischemia and associated organ damage, making the mortality rate of this condition high. Current concepts on the pathophysiology, laboratory diagnosis and management of DIC are presented. Complex pathophysiological interrelations make the diagnosis of the etiology of the DIC difficult in clinical practice, although simple tests are useful for identification of patients with the process. Laboratory diagnosis of DIC is mainly based on screening assays, which allow a rapid diagnosis, whereas some other highly sensitive but more complex assays are not always available to routine clinical laboratories. The management of DIC is based on the treatment of the underlying disease, supportive and replacement therapies and the control of the coagulation mechanisms. Although some advances have been achieved, management decisions are still controversial, so that therapy should be highly individualized depending on the nature of the DIC and severity of clinical symptoms. Many syndromes sharing common findings with DIC, such as primary hyperfibrinolysis or thrombotic thrombocytopenic purpura, should be excluded. Finally, new therapeutic approaches to the management of this potentially catastrophic syndrome are required.

Neuronal ceroid-lipofuscinosis in longhaired Chihuahuas: clinical, pathologic, and MRI findings.

PubMed

Nakamoto, Yuya; Yamato, Osamu; Uchida, Kazuyuki; Nibe, Kazumi; Tamura, Shinji; Ozawa, Tsuyoshi; Ueoka, Naotami; Nukaya, Aya; Yabuki, Akira; Nakaichi, Munekazu

2011-01-01

Neuronal ceroid-lipofuscinosis (NCL) is a rare group of inherited neurodegenerative lysosomal storage diseases characterized histopathologically by the abnormal accumulation of ceroid- or lipofuscin-like lipopigments in neurons and other cells throughout the body. The present article describes the clinical, pathologic, and magnetic resonance imaging (MRI) findings of the NCL in three longhaired Chihuahuas between 16 mo and 24 mo of age. Clinical signs, including visual defects and behavioral abnormalities, started between 16 mo and 18 mo of age. Cranial MRI findings in all the dogs were characterized by diffuse severe dilation of the cerebral sulci, dilated fissures of diencephalons, midbrain, and cerebellum, and lateral ventricular enlargement, suggesting atrophy of the forebrain. As the most unusual feature, diffuse meningeal thickening was observed over the entire cerebrum, which was strongly enhanced on contrast T1-weighted images. The dogs' conditions progressed until they each died subsequent to continued neurologic deterioration between 23 mo and 24 mo of age. Histopathologically, there was severe to moderate neuronal cell loss with diffuse astrogliosis throughout the brain. The remaining neuronal cells showed intracytoplasmic accumulation of pale to slightly yellow lipopigments mimicking ceroid or lipofuscin. The thickened meninges consisted of the proliferation of connective tissues with abundant collagen fibers and mild infiltration of inflammatory cells suggesting neuroimmune hyperactivity. Although the etiology of this neuroimmune hyperactivity is not currently known, MRI findings such as meningeal thickening may be a useful diagnostic marker of this variant form of canine NCL.

A molecular epidemiology study based on VP2 gene sequences reveals that a new genotype of infectious bursal disease virus is dominantly prevalent in Italy.

PubMed

Lupini, Caterina; Giovanardi, Davide; Pesente, Patrizia; Bonci, Michela; Felice, Viviana; Rossi, Giulia; Morandini, Emilio; Cecchinato, Mattia; Catelli, Elena

2016-08-01

A distinctive infectious bursal disease (IBD) virus genotype (ITA) was detected in IBD-live vaccinated broilers in Italy without clinical signs of IBD. It was isolated in specific-pathogen-free eggs and molecularly characterized in the hypervariable region of the virus protein (VP) 2. Phylogenetic analysis showed that ITA strains clustered separately from other homologous reference sequences of IBDVs, either classical or very virulent, retrieved from GenBank or previously reported in Italy, and from vaccine strains. The new genotype shows peculiar molecular characteristics in key positions of the VP2 hypervariable region, which affect charged or potentially glycosylated amino acids virtually associated with important changes in virus properties. Characterization of 41 IBDV strains detected in Italy between 2013 and 2014 showed that ITA is emergent in densely populated poultry areas of Italy, being 68% of the IBDV detections made during routine diagnostic activity over a two-year period, in spite of the immunity induced by large-scale vaccination. Four very virulent strains (DV86) and one classical strain (HPR2), together with eight vaccine strains, were also detected. The currently available epidemiological and clinical data do not allow the degree of pathogenicity of the ITA genotype to be defined. Only in vivo experimental pathogenicity studies conducted in secure isolation conditions, through the evaluation of clinical signs and macro/microscopic lesions, will clarify conclusively the virulence of the new Italian genotype.

Identification and molecular characterization of Corynebacterium xerosis isolated from a sheep cutaneous abscess: first case report in Mexico.

PubMed

Hernández-León, Fernando; Acosta-Dibarrat, Jorge; Vázquez-Chagoyán, Juan Carlos; Rosas, Pomposo Fernandez; de Oca-Jiménez, Roberto Montes

2016-07-22

Corynebacterium xerosis is a commensal organism found in skin and mucous membranes of humans. It is considered an unusual pathogen, and it is rarely found in human and animal clinical samples. Here we describe the isolation of C. xerosis from a 4-months-old Pelifolk lamb located in Tesistán, central western Mexico. This microorganism should be considered for differential diagnosis in cutaneous abscessed lesions in sheep, as it represents a zoonotic risk factor for human infection in sheep farms. The animal exhibited a hard-consistency, 5 cm diameter abscess, without drainage, in the neck. The presumptive clinical diagnosis was caseous lymphadenitis, caused by Corynebacterium pseudotuberculosis. Samples were obtained by puncture and cultured in 8 % sheep blood agar under microaerophilic conditions. Colonies were non-haemolytic, brown-yellowish and showed microscopic and biochemical features similar to C. pseudotuberculosis, except for the urea test. A multiplex-PCR for the amplification of partial sequences of the pld, rpoB and intergenic fragment from 16S to 23S genes suggested that isolate could be C. xerosis, which was later confirmed by sequencing analysis of the rpoB gene. This study shows for the first time isolation and molecular characterization of C. xerosis from a clinical sample of an ovine cutaneous abscess in Mexico. This finding highlights the need for differential diagnosis of this pathogen in ovine skin abscesses, as well as epidemiological and control studies of this pathogen in sheep farms.

Neural tube defects in Waardenburg syndrome: A case report and review of the literature.

PubMed

Hart, Joseph; Miriyala, Kalpana

2017-09-01

Waardenburg syndrome type 1 (WS1) is an autosomal dominant genetic condition characterized by sensorineural deafness and pigment abnormalities, and is caused by variants in the PAX3 homeodomain. PAX3 variants have been associated with severe neural tube defects in mice and humans, but the frequency and clinical manifestations of this symptom remain largely unexplored in humans. Consequently, the role of PAX3 in human neural tube formation remains a study of interest, for clinical as well as research purposes. Though the association between spina bifida and WS1 is now well-documented, no study has attempted to characterize the range of spina bifida phenotypes seen in WS. Spina bifida encompasses several diagnoses with a wide scope of clinical severity, ranging from spina bifida occulta to myelomeningocele. We present a patient with Waardenburg syndrome type 1 caused by a novel missense variant in PAX3, presenting with myelomeningocele, Arnold-Chiari malformation, and hydrocephalus at birth. Additionally, we review 32 total cases of neural tube defects associated with WS. Including this report, there have been 15 published cases of myelomeningocele, 10 cases of unspecified spina bifida, 3 cases of sacral dimples, 0 cases of meningocele, and 4 cases of miscellaneous other neural tube defects. Though the true frequency of each phenotype cannot be determined from this collection of cases, these results demonstrate that Waardenburg syndrome type 1 carries a notable risk of severe neural tube defects, which has implications in prenatal and genetic counseling. © 2017 Wiley Periodicals, Inc.

Implementation of early intensive behavioural intervention for children with autism in Switzerland.

PubMed

Studer, Nadja; Gundelfinger, Ronnie; Schenker, Tanja; Steinhausen, Hans-Christoph

2017-01-21

There is a major gap between the US and most European countries regarding the implementation of early intensive behavioural intervention (EIBI) for children with autism. The present paper reports on the current status of EIBI in Switzerland and on the effectiveness of EIBI under clinical conditions in a Swiss pilot project. The paper combines a narrative report of the care system for children with autism in Switzerland and an initial evaluation of EIBI as implemented in the Department of Child and Adolescent Psychiatry, University of Zurich. The current situation of the implementation of EIBI for children with autism in Switzerland is characterized by marked deficits in its acceptance. Major reasons include insufficient governmental approval and lacking legal and financial support. In addition, ignorance among health care providers and educational professionals has contributed to this situation precluding that children with autism receive the most beneficial assistance. The authors have initiated and been working in an intervention centre offering EIBI for a decade and report on their experience with the implementation of EIBI. Based on their clinical practice, they document that EIBI also works efficiently under ordinary mental health service conditions. EIBI needs to be implemented more intensively in Switzerland. Although the effects of EIBI as implemented in Zurich are promising, the results are not as pronounced as under controlled research conditions.

Multidisciplinary surgical management of cherubism complicated by neurofibromatosis type 1.

PubMed

Hachach-Haram, Nadine; Gerarchi, Paul; Benyon, Sarah L; Saggar, Anand; McLellan, Guy; Kirkpatrick, W Niall A

2011-11-01

Cherubism is a rare, autosomal dominant, mostly self-limiting disease of the jaw. It is characterized by bilateral fibrous tissue hyperplasia, giant cell proliferation, and bony degeneration in the lower facial skeleton, which can result in a massive and severely deforming prominence of the maxillomandibular structure. This case study examines the multidisciplinary management of a severe case of cherubism complicated by neurofibromatosis type 1, 2 codominant nonsegregating conditions that were clinically and genetically diagnosed, an extremely rare combination. Adequate mandibular reduction, reconstruction, and dental implantation afforded good restoration of oral function as well as a marked aesthetic improvement. A 14-year-old Fijian girl was referred to our unit for management of severe overgrowth of her mandible that compromised her speech and deglutition. In addition, she displayed clinical features consistent with neurofibromatosis type 1. Radiologic, histologic, and genetic analyses confirmed the diagnosis of both conditions. Our craniofacial multidisciplinary team undertook mandibular reconstruction followed by placement of osseointegrated dental implants. Mandibular reduction, reconstruction, and dental implantation resulted in a significantly improved functional and aesthetic outcome with no further regrowth at 3-year follow-up when she returned to the United Kingdom for osseointegrated dental implant insertion. The successful outcome of this surgically challenging, grossly disfiguring, and rare condition was largely a result of the combined input from our multidisciplinary team, adequate preoperative planning, and the use of a novel surgical technique in debulking and reconstructing her mandible.

Quantitative skin color measurements in acanthosis nigricans patients: colorimetry and diffuse reflectance spectroscopy.

PubMed

Pattamadilok, Bensachee; Devpura, Suneetha; Syed, Zain U; Agbai, Oma N; Vemulapalli, Pranita; Henderson, Marsha; Rehse, Steven J; Mahmoud, Bassel H; Lim, Henry W; Naik, Ratna; Hamzavi, Iltefat H

2012-08-01

Tristimulus colorimetry and diffuse reflectance spectroscopy (DRS) are white-light skin reflectance techniques used to measure the intensity of skin pigmentation. The tristimulus colorimeter is an instrument that measures a perceived color and the DRS instrument measures biological chromophores of the skin, including oxy- and deoxyhemoglobin, melanin and scattering. Data gathered from these tools can be used to understand morphological changes induced in skin chromophores due to conditions of the skin or their treatments. The purpose of this study was to evaluate the use of these two instruments in color measurements of acanthosis nigricans (AN) lesions. Eight patients with hyperinsulinemia and clinically diagnosable AN were seen monthly. Skin pigmentation was measured at three sites: the inner forearm, the medial aspect of the posterior neck, and anterior neck unaffected by AN. Of the three, measured tristimulus L*a*b* color parameters, the luminosity parameter L* was found to most reliably distinguish lesion from normally pigmented skin. The DRS instrument was able to characterize a lesion on the basis of the calculated melanin concentration, though melanin is a weak indicator of skin change and not a reliable measure to be used independently. Calculated oxyhemoglobin and deoxyhemoglobin concentrations were not found to be reliable indicators of AN. Tristimulus colorimetry may provide reliable methods for respectively quantifying and characterizing the objective color change in AN, while DRS may be useful in characterizing changes in skin melanin content associated with this skin condition. © 2012 John Wiley & Sons A/S.

Three cases of melorheostosis with foot and ankle involvement.

PubMed

Pino, Alejandro E; Temple, H Thomas

2012-08-01

Melorheostosis is a rare and poorly understood condition of bone and soft tissue with a wide range of clinical presentations. This condition is typically characterized by cortical hyperostosis and pain in the involved extremity, but can also be associated with soft-tissue masses and limb deformities that may be additional sources of disability for those affected by this disease. Characteristic radiographic findings can aid in establishing an accurate diagnosis and the condition should not be mistaken for more aggressive neoplasms. This chronic condition is typically managed nonoperatively, but more invasive measures may be necessary when nonoperative measures fail. In cases of surgical intervention, physicians and patients should be aware that this disease has a high recurrence rate. Although there are only a few reports of melorheostosis in the foot and ankle, it is important to be aware of the difficulties the condition may cause in this anatomical location. Melorheostosis can be a source of significant morbidity when the foot and ankle are involved, especially when complicated by symptomatic soft-tissue masses. In this article, we report 3 cases of melorheostosis in the foot and ankle with distinct presentations and variations in outcomes.

Early clinics of the cardiac forms of Chagas' disease: Discovery and study of original medical files (1909-1915).

PubMed

Gachelin, Gabriel; Bestetti, Reinaldo B

2017-10-01

We have uncovered 80 medical files corresponding to original cases of Chagas' disease used for the classical description of the acute and cardiac forms of the disease. Sixty of them were diagnosed cardiac forms of the disease. The detailed clinical description of these 60 files is in excellent agreement with the nosography of progressive heart disease given by Chagas in his original 1922 paper. The reports we had access to, characterize a novel form of cardiac disease, dominated by progressive AV block, enlargement and displacement of the heart and sudden death, in relatively young adults including juveniles. In contrast to that remarkable clinical description, the assertion made by Chagas that this set of clinical signs was the consequence of an earlier infection by Trypanosoma cruzi rests on weak evidence, due to the difficulty to identify the parasite in most patients. Moreover, the association of thyroid dysfunction with cardiac disease emphasized by Chagas cannot be deduced from the files we have examined. Finally, the main reason why the disease had not been recognized for long as a defined clinical entity, is likely the absence of markedly distinctive clinical signs compared to most other parasitic diseases, poor sanitary conditions and the probable lack of clinical skills of the rare doctors working in the area where the disease was described. Copyright © 2017 Elsevier B.V. All rights reserved.

Validation of the Italian version of the Apathy Evaluation Scale (AES-I) in institutionalized geriatric patients.

PubMed

Borgi, Marta; Caccamo, Floriana; Giuliani, Alessandro; Piergentili, Alessandro; Sessa, Sonia; Reda, Emilia; Alleva, Enrico; Cirulli, Francesca; Miraglia, Fabio

2016-01-01

Apathy is a very common symptom in the institutionalized elderly and represents a condition of both clinical and public health importance. The Apathy Evaluation Scale (AES) has been shown to be a valid and reliable tool for characterizing, quantifying and differentiating apathy in various health conditions. The aims of this study were to establish the validity and reliability of the Italian version of the AES, and to assess the severity of apathy in a sample of Italian institutionalized geriatric patients. Data were collected from clinical interviews using the AES informant version (AES-I). Associations between measures of apathy and depression, cognitive functioning and perceived quality of life were evaluated, as well as the effects of the living environment on apathetic symptoms. Multiple forms of reliability and validity (i.e. test-retest, internal consistency, discriminability of apathy rating from a standard measure of depression) were satisfied. Our results also show that the characteristics of the care setting may affect the severity of apathetic symptoms. The AES-I Italian version is a reliable and valid instrument for measuring apathy in Italian patients, also allowing a direct comparison with data gathered in other countries.

Mental retardation in Nance-Horan syndrome: clinical and neuropsychological assessment in four families.

PubMed

Toutain, A; Ayrault, A D; Moraine, C

1997-08-22

Nance-Horan syndrome (NHS) is a rare X-linked condition comprising congenital cataract with microcornea, distinctive dental, and evocative facial anomalies. Intellectual handicap was mentioned in seven published NHS patients. We performed a clinical study focused on psychomotor development, intellectual abilities, and behavior in 13 affected males in four NHS families, and present the results of a neuropsychological evaluation in 7 of them. Our study confirms that mental retardation (MR) can be a major component of the NHS. Combining our data with those from the literature leads to a frequency of MR in NHS of around 30%. In most cases, MR is mild or moderate (80%) and not associated with motor delay. Conversely, a profound mental handicap associated with autistic traits may be observed. MR has intra- and inter-familial variability but does not appear to be expressed in carriers. Awareness of MR in NHS may be of importance in the management of the patients, especially in terms of education. Cloning and characterization of the gene and analysis of mutations will be an important step towards understanding the molecular basis of mental deficiency in NHS, and in delineation from the other XLMR conditions at Xp22.

Soft tissue gas gangrene: a severe complication of emphysematous cholecystitis.

PubMed

Safioleas, Michael; Stamatakos, Michael; Kanakis, Meletios; Sargedi, Constantina; Safioleas, Constantinos; Smirnis, Anastasios; Vaiopoulos, George

2007-12-01

Soft tissue gas gangrene with myonecrosis is a severe complication of traumatic and non-traumatic conditions with a potentially lethal outcome. Emphysematous cholecystitis is a complication of acute cholecystitis, which is characterized by air accumulation in the gallbladder wall and is reported in the literature as a rare causative factor of soft tissue gas gangrene. Here we report 4 patients who developed soft tissue gas gangrene as a complication of emphysematous cholecystitis. Two patients were female octogenarians (one with a history of diabetes mellitus), and underwent percutaneous trans-gallbladder drainage and fascia incisions of the affected soft tissue with prompt administration of antibiotics. Finally, both of them died. The other two patients were male (32 years old diabetic and 47 years old with a history of chronic alcoholism). They underwent open cholecystectomy. Fascia incisions of the gangrenous areas and antibiotic therapy administration were also performed. Both of them were discharged from the hospital and are currently in excellent clinical status. We also present the ultrasonographic and/or radiologic images of these four patients. Soft tissue gas gangrene may complicate emphysematous cholecystitis, and clinicians should be aware of the coexistence of these two clinical conditions, since immediate management is needed in order to prevent fatal outcome.

Distinct responses to predictable and unpredictable threat in anxiety pathologies: effect of panic attack.

PubMed

Grillon, Christian; O'Connell, Katherine; Lieberman, Lynne; Alvarez, Gabriella; Geraci, Marilla; Pine, Daniel S; Ernst, Monique

2017-10-01

Delineating specific clinical phenotypes of anxiety disorders is a crucial step toward better classification and understanding of these conditions. The present study sought to identify differential aversive responses to predictable and unpredictable threat of shock in healthy comparisons and in non-medicated anxiety patients with and without a history of panic attacks (PAs). 143 adults (72 healthy controls; 71 patients with generalized anxiety disorder (GAD) or/and social anxiety disorder (SAD), 24 with and 47 without PAs) were exposed to three conditions: 1) predictable shocks signaled by a cue, 2) unpredictable shocks, and 3) no shock. Startle magnitude was used to assess aversive responses. Across disorders, a PA history was specifically associated with hypersensitivity to unpredictable threat. By disorder, SAD was associated with hypersensitivity to predictable threat, whereas GAD was associated with exaggerated baseline startle. These results identified three physiological patterns. The first is hypersensitivity to unpredictable threat in individuals with PAs. The second is hypersensitivity to predictable threat, which characterizes SAD. The third is enhanced baseline startle in GAD, which may reflect propensity for self-generated anxious thoughts in the absence of imminent danger. These results inform current thinking by linking specific clinical features to particular physiology profiles.

Acute and chronic pseudo-obstruction: a current update.

PubMed

Bernardi, Maria-Pia; Warrier, Satish; Lynch, A Craig; Heriot, Alexander G

2015-10-01

Acute colonic pseudo-obstruction (ACPO) and chronic intestinal pseudo-obstruction (CIPO) are distinct clinical entities in which patients present similarly with symptoms of a mechanical obstruction without an occlusive lesion. Unfortunately, they also share the issues related to a delay in diagnosis, including inappropriate management and poor outcomes. Advancements have been made in our understanding of the aetiologies of both conditions. Several predisposing factors linked to critical illness have been implicated in ACPO. CIPO is a functional motility disorder, historically misdiagnosed, with unnecessary surgery being performed in many patients with dire consequences. This review discusses the pathophysiology, clinical and diagnostic features, and treatment of each. For ACPO, a safer pharmacological approach to treatment is presented in a modified up-to-date algorithm. The importance of CIPO as a differential diagnosis when seeing patients with recurrent admissions for abdominal pain and distention is also discussed, as well as specific indications for surgery. While surgery is often a last resort, the role of the surgeon in the management of both ACPO and CIPO cannot be undervalued. By characterizing each condition in a common review, the knowledge gleaned aims to optimize outcomes for these frequently complex patients. © 2015 Royal Australasian College of Surgeons.

Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines.

PubMed

Mocellin, Simone; Nitti, Donato

2008-05-01

Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed at reverting the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation. Copyright (c) 2007 Wiley-Periodicals, Inc.

[EPIDEMIOLOGIC FEATURES OFNOROVIRUS INFECTION OUTBREAK IN THE REPUBLIC OF NORTH OSSETIA-ALANIA].

PubMed

Maletskaya, O V; Tibilov, A G; Prislegina, D A; Gazieva, G K; Otaraeva, N I; Volynkina, A S; Saveliev, V N; Lyamkin, G I; Zaitsev, A A; Kulichenko, A N

2016-01-01

Analysis of epidemiologic features of a norovirus outbreak in Alagir city of the Republic of North Ossetia-Alania and effectiveness of measures of its liquidation. Data from maps-schemes of water supply system of Alagir city and statistical documentation of Centre of Hygiene and Epidemiology in the Republic of North Ossetia-Alania were used in the study. Indication of norovirus in clinical material and water samples was carried out bypolymerase chain reaction method. Etiological agent of outbreak disease was established--genotype II norovirus. Realization of fecal-oral mechanisms of water transmission pathway of the causative agent of norovirus infection was detected. Conditions facilitating emergence and development of the indicated outbreak were determined--non-satisfactory sanitary-technical condition of water. supply system of the city. The studied water outbreak of norovirus infection was caused by GII.17 genotype virus, that currently gradually displaces GII.IV genotype, and was characterized by an intensive start, involvement of all population age groups into the epidemic process (with primary infection of adults), low family focality, predominance of average severity disease forms in the clinical presentation. The counter-epidemic measures carried out ensured rapid localization and liquidation of the norovirus infection outbreak.

Microbial immigration across the Mediterranean via airborne dust

PubMed Central

Rosselli, Riccardo; Fiamma, Maura; Deligios, Massimo; Pintus, Gabriella; Pellizzaro, Grazia; Canu, Annalisa; Duce, Pierpaolo; Squartini, Andrea; Muresu, Rosella; Cappuccinelli, Pietro

2015-01-01

Dust particles lifting and discharge from Africa to Europe is a recurring phenomenon linked to air circulation conditions. The possibility that microorganisms are conveyed across distances entails important consequences in terms of biosafety and pathogens spread. Using culture independent DNA-based analyses via next generation sequencing of the 16 S genes from the airborne metagenome, the atmospheric microbial community was characterized and the hypothesis was tested that shifts in species diversity could be recorded in relation to dust discharge. As sampling ground the island of Sardinia was chosen, being an ideal cornerstone within the Mediterranean and a crossroad of wind circulation amidst Europe and Africa. Samples were collected in two opposite coastal sites and in two different weather conditions comparing dust-conveying winds from Africa with a control situation with winds from Europe. A major conserved core microbiome was evidenced but increases in species richness and presence of specific taxa were nevertheless observed in relation to each wind regime. Taxa which can feature strains with clinical implications were also detected. The approach is reported as a recommended model monitoring procedure for early warning alerts in frameworks of biosafety against natural spread of clinical microbiota across countries as well as to prevent bacteriological warfare. PMID:26542754

Infant botulism: clinical spectrum and epidemiology.

PubMed

Thompson, J A; Glasgow, L A; Warpinski, J R; Olson, C

1980-12-01

Between 1977 and 1979, 12 cases of infant botulism were diagnosed in Utah, and 87 control patients (normal, nonbotulism neurologic disease, and nonbotulism systemic disease) were evaluated. Observations from these patients suggest an expanded clinical spectrum of infant botulism including asymptomatic carriers of organism; mild hypotonia and failure to thrive; typical cases with constipation, bulbar weakness, and hypotonia; and children with a picture compatible with sudden infant death syndrome. Clostridium botulinum was isolated from the stools of three normal control infants and nine control infants who had neurologic diseases that were clearly not infant botulism. These infants were termed "asymptomatic carriers" of the organism. The occurrence of the asymptomatic carrier state suggests that a diagnosis of infant botulism cannot be made on a basis of culture results alone, but must rest in historical documentation and physical confirmation of progressive bulbar and extremity weakness with ultimate complete resolution of symptoms and findings over a period of several months. A common set of environmental features characterizes the home environment of children with infant botulism and "asymptomatic carriers" and includes: nearby constructional or agricultural soil disruption, dusty and windy conditions, a high water table, and alkaline soil conditions.

Polydactylous Transverse Erythronychia: Report of a Patient with Multiple Horizontal Red Bands Affecting the Fingernails.

PubMed

Chang, Carina; Beutler, Bryce D; Cohen, Philip R

2017-06-01

Redness of the nail plate-erythronychia-is a common condition involving one or multiple digits. It may affect the entire nail or present as longitudinal red bands that extend from the proximal nail fold to the distal tip of the nail plate. Rarely, red bands may traverse the nail bed horizontally. Although erythronychia is often idiopathic, it has also been associated with amyloidosis, Darier's disease, lichen planus, and various other cutaneous conditions. We describe the clinical features of a 64-year-old Caucasian man who presented with transverse and longitudinal erythronychia affecting his fingernails. In addition, we review the classification of erythronychia and summarize the acute and chronic conditions that have been associated with this clinical finding. The features of a man with polydactylous transverse and longitudinal erythronychia are presented. In addition, PubMed was used to search the following terms: erythronychia, longitudinal erythronychia, red lunulae, and subungual. All papers were reviewed, and relevant articles, along with their references, were evaluated. Informed consent was obtained from the patient for being included in the study. A 64-year-old Caucasian man with a past medical history significant for testicular cancer and pulmonary embolism presented with multiple horizontal pink-red bands affecting his fingernails. The discoloration was most prominent in the region distal to the lunula. In addition, the nails of the fifth digit of his left hand and third digit of his right hand featured longitudinal red bands extending from the distal curvature of the lunula to the free edge of the nail plate. A diagnosis of polydactylous longitudinal and transverse erythronychia, based on the clinical presentation, was established. Our patient's red bands were asymptomatic and he was not concerned about the cosmetic appearance of his nails; therefore, no additional investigation or treatment was required. Polydactylous transverse erythronychia is a rare condition characterized by the development of horizontal red bands affecting the fingernails or toe nails. It has only been previously described in a man with multiple system atrophy. In our patient, both transverse and longitudinal red bands were present simultaneously. Therefore, it is possible that horizontal erythronychia is an early clinical manifestation of longitudinal erythronychia.

Requests Cancer Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

Cancer.gov

In an effort to provide well-characterized monoclonal antibodies to the scientific community, the National Cancer Institute (NCI) Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. The program from The Office of Cancer Clinical Proteomics Research provides reagents and other critical resources that support protein and/or peptide measurements and analysis.

Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes.

PubMed

Russo, Ethan B

2016-01-01

Medicine continues to struggle in its approaches to numerous common subjective pain syndromes that lack objective signs and remain treatment resistant. Foremost among these are migraine, fibromyalgia, and irritable bowel syndrome, disorders that may overlap in their affected populations and whose sufferers have all endured the stigma of a psychosomatic label, as well as the failure of endless pharmacotherapeutic interventions with substandard benefit. The commonality in symptomatology in these conditions displaying hyperalgesia and central sensitization with possible common underlying pathophysiology suggests that a clinical endocannabinoid deficiency might characterize their origin. Its base hypothesis is that all humans have an underlying endocannabinoid tone that is a reflection of levels of the endocannabinoids, anandamide (arachidonylethanolamide), and 2-arachidonoylglycerol, their production, metabolism, and the relative abundance and state of cannabinoid receptors. Its theory is that in certain conditions, whether congenital or acquired, endocannabinoid tone becomes deficient and productive of pathophysiological syndromes. When first proposed in 2001 and subsequently, this theory was based on genetic overlap and comorbidity, patterns of symptomatology that could be mediated by the endocannabinoid system (ECS), and the fact that exogenous cannabinoid treatment frequently provided symptomatic benefit. However, objective proof and formal clinical trial data were lacking. Currently, however, statistically significant differences in cerebrospinal fluid anandamide levels have been documented in migraineurs, and advanced imaging studies have demonstrated ECS hypofunction in post-traumatic stress disorder. Additional studies have provided a firmer foundation for the theory, while clinical data have also produced evidence for decreased pain, improved sleep, and other benefits to cannabinoid treatment and adjunctive lifestyle approaches affecting the ECS.

Autobiographical memory: a clinical perspective.

PubMed

Urbanowitsch, Nadja; Gorenc, Lina; Herold, Christina J; Schröder, Johannes

2013-12-10

Autobiographical memory (ABM) comprises memories of one's own past that are characterized by a sense of subjective time and autonoetic awareness. Although ABM deficits are among the primary symptoms of patients with major psychiatric conditions such as mild cognitive impairment (MCI) and Alzheimer Disease (AD) or chronic schizophrenia large clinical studies are scarce. We therefore summarize and discuss the results of our clinical studies on ABM deficits in the respective conditions. In these studies ABM was assessed by using the same instrument - i.e., the Erweitertes Autobiographisches Gedächtnis Inventar (E-AGI) - thus allowing a direct comparison between diagnostic groups. Episodic ABM, especially the richness of details was impaired already in MCI and in beginning AD. Semantic memories were spared until moderate stages, indicating a dissociation between both memory systems. A recency effect was detectable in cognitively unimpaired subjects and vanished in patients with AD. A similar pattern of deficits was found in patients with chronic schizophrenia but not in patients with major depression. These ABM deficits were not accounted for by gender, or education level and did not apply for the physiological ageing process in otherwise healthy elderly. In conclusion, ABM deficits are frequently found in AD and chronic schizophrenia and primarily involve episodic rather than semantic memories. This dissociation corresponds to the multiple trace theory which hypothesized that these memory functions refer to distinct neuronal systems. The semi-structured interview E-AGI used to discern ABM changes provided a sufficient reliability measures, moreover potential effects of a number of important confounders could be falsified so far. These findings underline the relevance of ABM-assessments in clinical practice.

42 CFR 484.48 - Condition of participation: Clinical records.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition of participation: Clinical records. 484....48 Condition of participation: Clinical records. A clinical record containing pertinent past and... information; name of physician; drug, dietary, treatment, and activity orders; signed and dated clinical and...

Pediatric lymphangiectasia: an imaging spectrum.

PubMed

Malone, Ladonna J; Fenton, Laura Z; Weinman, Jason P; Anagnost, Miran R; Browne, Lorna P

2015-04-01

Lymphangiectasia is a rarely encountered lymphatic dysplasia characterized by lymphatic dilation without proliferation. Although it can occur anywhere, the most common locations are the central conducting lymphatics and the pulmonary and intestinal lymphatic networks. Recent advances in lymphatic interventions have resulted in an increased reliance on imaging to characterize patterns of disease. To describe the patient populations, underlying conditions, and imaging features of lymphangiectasia encountered at a tertiary pediatric institution over a 10-year period and correlate these with pathology and patient outcomes. We retrospectively reviewed the pathology database from 2002 to 2012 to identify patients with pathologically or surgically proven lymphangiectasia who had undergone cross-sectional imaging. Medical records were reviewed for patient demographics, underlying conditions, treatment and outcome. Thirteen children were identified, ranging in age from 1 month to 16 years. Five had pulmonary lymphangiectasia, four intestinal and four diffuse involvement. Pulmonary imaging findings include diffuse or segmental interlobular septal thickening, pleural effusions and dilated mediastinal lymphatics. Intestinal imaging findings include focal or diffuse bowel wall thickening with central lymphatic dilation. Diffuse involvement included dilation of the central lymphatics and involvement of more than one organ system. Children with infantile presentation and diffuse pulmonary, intestinal or diffuse lymphatic abnormalities had a high mortality rate. Children with later presentations and segmental involvement demonstrated clinical improvement with occasional regression of disease. Three children with dilated central lymphatics on imaging underwent successful lymphatic duct ligation procedures with improved clinical course. Lymphangiectasia is a complex disorder with a spectrum of presentations, imaging appearances, treatments and outcomes. Cross-sectional imaging techniques distinguish segmental involvement of a single system (pulmonary or intestinal) from diffuse disease and may show dilated central conducting lymphatics, which may benefit from interventions such as ligation or occlusion.

Assessing Telemedicine Utilization by Using Medicaid Claims Data.

PubMed

Douglas, Megan Daugherty; Xu, Junjun; Heggs, Akilah; Wrenn, Glenda; Mack, Dominic H; Rust, George

2017-02-01

This study characterized telemedicine utilization among Medicaid enrollees by patients' demographic characteristics, geographic location, enrollment type, eligibility category, and clinical conditions. This study used 2008-2009 Medicaid claims data from 28 states and the District of Columbia to characterize telemedicine claims (indicated by GT for professional fee claims or Q3014 for facility fees) on the basis of patients' demographic characteristics, geographic location, enrollment type, eligibility category, and clinical condition as indicated by ICD-9 codes. States lacking Medicaid telemedicine reimbursement policies were excluded. Chi-square tests were used to compare telemedicine utilization rates and one-way analysis of variance was used to estimate mean differences in number of telemedicine encounters among subgroups. A total of 45,233,602 Medicaid enrollees from the 22 states with telemedicine reimbursement policies were included in the study, and .1% were telemedicine users. Individuals ages 45 to 64 (16.4%), whites (11.3%), males (8.5%), rural residents (26.0%), those with managed care plans (7.9%), and those categorized as aged, blind, and disabled (28.1%) were more likely to receive telemedicine (p<.001). Nearly 95% of telemedicine claims were associated with a behavioral health diagnosis, of which over 50% were for bipolar disorder and attention-deficit disorder or attention-deficit hyperactivity disorder (29.3% and 23.4%, respectively). State-level variation was high, ranging from .0 to 59.91 claims per 10,000 enrollees (Arkansas and Arizona, respectively). Despite the touted potential for telemedicine to improve health care access, actual utilization of telemedicine in Medicaid programs was low. It was predominantly used to treat behavioral health diagnoses. Reimbursement alone is insufficient to support broad utilization for Medicaid enrollees.

Patient Engagement and Study Design of PROP UP: A multi-site patient-centered prospective observational study of patients undergoing hepatitis C treatment

PubMed Central

Evon, Donna M.; Golin, Carol E.; Stewart, Paul; Fried, Michael W.; Alston, Shani; Reeve, Bryce; Lok, Anna S.; Sterling, Richard K.; Lim, Joseph K.; Reau, Nancy; Sarkar, Souvik; Nelson, David R.; Reddy, K. Rajender; Di Bisceglie, Adrian M.

2017-01-01

Background New highly efficacious direct-acting antiviral (DAA) therapies are available to treat chronic hepatitis C viral (HCV) infection. Real-world, patient-centered data on harms and benefits associated with these therapies are needed. Methods PROP UP is a multi-center prospective observational study that plans to enroll 1,600 patients starting treatment with recently-approved DAA regimens. Informed by extensive input from a HCV patient engagement group who prioritized outcomes most important to them, patient-reported outcomes will be characterized using surveys at five time points: Baseline (T1), treatment week 4 (T2), end of treatment (T3), 12 weeks post-treatment (T4), 12 months post-treatment (T5). Outcomes (1) Changes in side effects, functioning, pre-existing conditions, and out-of-pocket costs during therapy (T1 vs T2/T3); (2) Medication adherence in relation to a history of mental health/substance abuse, treatment regimens, pill burden, reasons for missed doses, and cure rates; (3) Short term impact of cure on functioning and amelioration of symptoms (T1 vs T4); (4) Long-term treatment harms or benefits of cure on symptoms, side effects, pre-existing conditions, and functioning (T1 vs T5). Similarities between regimens will be examined where comparisons are appropriate and meaningful. Conclusion PROP UP complements previous clinical trials by focusing on patient-reported outcomes in a representative sample of patients treated in clinical practice, by collaborating with a patient engagement group, by characterizing the experiences of vulnerable subgroups, and by investigating long-term harms and benefits of treatments. PROP UP is designed to provide novel and detailed information to support informed decision-making for patients and providers contemplating HCV treatment (PCORI CER-1408-20660; NCT02601820). PMID:28342989

Eosinophilic pustular folliculitis of infancy: a series of 15 cases and review of the literature.

PubMed

Hernández-Martín, Ángela; Nuño-González, Almudena; Colmenero, Isabel; Torrelo, Antonio

2013-01-01

Eosinophilic pustular folliculitis (EPF) of infancy is characterized by the presence of pustular lesions containing eosinophils. It is the least well-characterized of the EPF diseases. We sought to define the clinical and histopathologic features of the condition. We conducted a retrospective review of the clinical data and histologic findings of 15 patients given the diagnosis of EPF of infancy at the Hospital Niño Jesús, Madrid, Spain, from 1995 to 2011, and of patient data published in MEDLINE with such a diagnosis from the disease description (1984-2011). A total of 61 cases were collected. The disease was more common in males than females (ratio 4:1), and presented before 14 months of life in 95% of cases (mean 6.1 months; median 5 months). All patients had recurrent outbreaks and scalp involvement, and 65% had lesions on areas of the body other than the scalp. Tissue eosinophilia was present in all cases; however, true follicular involvement was observed only in 62% of cases in which histologic study was available. More than 80% of the patients were cured by 3 years of age (mean 25.3 months; median 18 months). Topical steroids were effective in 90% of cases. This was a retrospective study. EPF of infancy presents most often in the first 14 months of life and usually resolves by 3 years of age. All patients showed scalp involvement, tissue eosinophilia, and recurrent outbreaks. The condition does not require aggressive treatment, as it is benign and self-limiting. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Assessing Telemedicine Utilization by Using Medicaid Claims Data

PubMed Central

Douglas, Megan Daugherty; Xu, Junjun; Heggs, Akilah; Wrenn, Glenda; Mack, Dominic H.; Rust, George

2017-01-01

Objective This study characterized telemedicine utilization among Medicaid enrollees by patients’ demographic characteristics, geographic location, enrollment type, eligibility category, and clinical conditions. Methods This study used 2008–2009 Medicaid claims data from 28 states and the District of Columbia to characterize telemedicine claims (indicated by GT for professional fee claims or Q3014 for facility fees) on the basis of patients’ demographic characteristics, geographic location, enrollment type, eligibility category, and clinical condition as indicated by ICD-9 codes. States lacking Medicaid telemedicine reimbursement policies were excluded. Chi-square tests were used to compare telemedicine utilization rates and one-way analysis of variance was used to estimate mean differences in number of telemedicine encounters among subgroups. Results A total of 45,233,602 Medicaid enrollees from the 22 states with telemedicine reimbursement policies were included in the study, and .1% were telemedicine users. Individuals ages 45 to 64 (16.4%), whites (11.3%), males (8.5%), rural residents (26.0%), those with managed care plans (7.9%), and those categorized as aged, blind, and disabled (28.1%) were more likely to receive telemedicine (p<.001). Nearly 95% of telemedicine claims were associated with a behavioral health diagnosis, of which over 50% were for bipolar disorder and attention-deficit disorder or attention-deficit hyperactivity disorder (29.3% and 23.4%, respectively). State-level variation was high, ranging from .0 to 59.91 claims per 10,000 enrollees (Arkansas and Arizona, respectively). Conclusions Despite the touted potential for telemedicine to improve health care access, actual utilization of telemedicine in Medicaid programs was low. It was predominantly used to treat behavioral health diagnoses. Reimbursement alone is insufficient to support broad utilization for Medicaid enrollees. PMID:27691381

Investigation of the Virulence Factors and Molecular Characterization of the Clonal Relations of Multidrug-Resistant Acinetobacter baumannii Isolates.

PubMed

Ali, Hayssam M; Salem, Mohamed Z M; El-Shikh, Mohamed S; Megeed, Ahmed Abdel; Alogaibi, Yahya A; Talea, Ibrahim Ahmed

2017-01-01

Multidrug-resistant (MDR) Acinetobacter baumannii infections are a great public health concern and demand continuous surveillance and antibiotic stewardship. Virulence traits and the pathogenicity of Acinetobacter are less studied compared with the molecular epidemiological and antibiotic resistance profile of this organism. In our present study, we investigated the primary characteristics contributing to the virulence of MDR A. baumannii isolates and compared them with avirulent isolates. A total of 32 well-characterized MDR A. baumannii clinical isolates and 22 avirulent isolates from a healthy individual were subjected to multilocus sequence typing and polymerase chain reaction (PCR) for a variety of biofilm-associated genes. Additionally, a number of in vitro tests were performed to determine virulence properties. Isolates were found to relate to six sequence types (STs) in which the dominant sequence was ST557 in clinical isolates, followed by ST195 and ST208. However, ST557 and ST222 were absent in avirulent isolates. All STs belonged to clonal complex 2 and clonal lineage 2, which is considered to be a universal clone. PCR analysis showed that most clinical isolates were positive for biofilm-forming genes, such as csu and bap, and also carried pga and ompA genes, which were less common in avirulent isolates. Biofilm formation, phospholipase C production, hemolytic activity, and acinetobactin production occurred significantly more frequently in clinical isolates compared with avirulent isolates. Though A. baumannii clonal lineages showed common virulence traits, they differed in virulent phenotype expression. These findings further support previous studies indicating that A. baumannii is a versatile pathogen with an ability to acquire iron and survive in iron-limiting conditions, highlighting the acinetobactin-mediated iron acquisition mechanisms involved in the pathogenesis of A. baumannii infections.

[Genotype/phenotype correlation in autism: genetic models and phenotypic characterization].

PubMed

Bonnet-Brilhault, F

2011-02-01

Autism spectrum disorders are a class of conditions categorized by communication problems, ritualistic behaviors, and deficits in social behaviors. This class of disorders merges a heterogeneous group of neurodevelopmental disorders regarding some phenotypic and probably physiopathological aspects. Genetic basis is well admitted, however, considering phenotypic and genotypic heterogeneity, correspondences between genotype and phenotype have yet to be established. To better identify such correspondences, genetic models have to be identified and phenotypic markers have to be characterized. Recent insights show that a variety of genetic mechanisms may be involved in autism spectrum disorders, i.e. single gene disorders, copy number variations and polygenic mechanisms. These current genetic models are described. Regarding clinical aspects, several approaches can be used in genetic studies. Nosographical approach, especially with the concept of autism spectrum disorders, merges a large group of disorders with clinical heterogeneity and may fail to identify clear genotype/phenotype correlations. Dimensional approach referred in genetic studies to the notion of "Broad Autism Phenotype" related to a constellation of language, personality, and social-behavioral features present in relatives that mirror the symptom domains of autism, but are much milder in expression. Studies of this broad autism phenotype may provide a potentially important complementary approach for detecting the genes involved in these domains. However, control population used in those studies need to be well characterized too. Identification of endophenotypes seems to offer more promising results. Endophenotypes, which are supposed to be more proximal markers of gene action in the same biological pathway, linking genes and complex clinical symptoms, are thought to be less genetically complex than the broader disease phenotype, indexing a limited aspect of genetic risk for the disorder as a whole. However, strategies useful to characterize such phenotypic markers (for example, electrophysiological markers) have to take into account that autism is an early neurodevelopmental disorder occurring during childhood when brain development and maturation are in process. Recent genetic results have improved our knowledge in genetic basis in autism. Nevertheless, correspondences with phenotypic markers remain challenging according to phenotypic and genotypic heterogeneity. Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer.

PubMed

Rojas-Sepúlveda, Daniel; Tittarelli, Andrés; Gleisner, María Alejandra; Ávalos, Ignacio; Pereda, Cristián; Gallegos, Iván; González, Fermín Eduardo; López, Mercedes Natalia; Butte, Jean Michel; Roa, Juan Carlos; Fluxá, Paula; Salazar-Onfray, Flavio

2018-03-29

Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials. In these studies, 60% of stage IV melanoma DC-treated patients showed immunological responses correlating with improved survival. Further studies showed that an essential part of the clinical efficacy was associated with the use of conditioned lysates. Gallbladder cancer (GBC) is a high-incidence malignancy in South America. Here, we evaluated the feasibility of producing effective DCs using heat-conditioned cell lysates derived from gallbladder cancer cell lines (GBCCL). By characterizing nine different GBCCLs and several fresh tumor tissues, we found that they expressed some tumor-associated antigens such as CEA, MUC-1, CA19-9, Erb2, Survivin, and several carcinoembryonic antigens. Moreover, heat-shock treatment of GBCCLs induced calreticulin translocation and release of HMGB1 and ATP, both known to act as danger signals. Monocytes stimulated with combinations of conditioned lysates exhibited a potent increase of DC-maturation markers. Furthermore, conditioned lysate-matured DCs were capable of strongly inducing CD4 + and CD8 + T cell activation, in both allogeneic and autologous cell co-cultures. Finally, in vitro stimulated CD8 + T cells recognize HLA-matched GBCCLs. In summary, GBC cell lysate-loaded DCs may be considered for future immunotherapy approaches.

The Volume-Outcome Relationship in Critical Care

PubMed Central

Wallace, David J.; Yordanov, Youri; Trinquart, Ludovic; Blomkvist, Josefin; Angus, Derek C.; Kahn, Jeremy M.; Ravaud, Philippe; Guidet, Bertrand

2015-01-01

OBJECTIVE: The purpose of this study was to systematically review the research on volume and outcome relationships in critical care. METHODS: From January 1, 2001, to April 30, 2014, MEDLINE and EMBASE were searched for studies assessing the relationship between admission volume and clinical outcomes in critical illness. Bibliographies were reviewed to identify other articles of interest, and experts were contacted about missing or unpublished studies. Of 127 studies reviewed, 46 met inclusion criteria, covering seven clinical conditions. Two investigators independently reviewed each article using a standardized form to abstract information on key study characteristics and results. RESULTS: Overall, 29 of the studies (63%) reported a statistically significant association between higher admission volume and improved outcomes. The magnitude of the association (mortality OR between the lowest vs highest stratum of volume centers), as well as the thresholds used to characterize high volume, varied across clinical conditions. Critically ill patients with cardiovascular (n = 7, OR = 1.49 [1.11-2.00]), respiratory (n = 12, OR = 1.20 [1.04-1.38]), severe sepsis (n = 4, OR = 1.17 [1.03-1.33]), hepato-GI (n = 3, OR = 1.30 [1.08-1.78]), neurologic (n = 3, OR = 1.38 [1.22-1.57]), and postoperative admission diagnoses (n = 3, OR = 2.95 [1.05-8.30]) were more likely to benefit from admission to higher-volume centers compared with lower-volume centers. Studies that controlled for ICU or hospital organizational factors were less likely to find a significant volume-outcome relationship than studies that did not control for these factors. CONCLUSIONS: Critically ill patients generally benefit from care in high-volume centers, with more substantial benefits in selected high-risk conditions. This relationship may in part be mediated by specific ICU and hospital organizational factors. PMID:25927593

In vitro characterization of design and compressive properties of 3D-biofabricated/decellularized hybrid grafts for tracheal tissue engineering.

PubMed

Johnson, Christopher; Sheshadri, Priyanka; Ketchum, Jessica M; Narayanan, Lokesh K; Weinberger, Paul M; Shirwaiker, Rohan A

2016-06-01

Infection or damage to the trachea, a thin walled and cartilage reinforced conduit that connects the pharynx and larynx to the lungs, leads to serious respiratory medical conditions which can often prove fatal. Current clinical strategies for complex tracheal reconstruction are of limited availability and efficacy, but tissue engineering and regenerative medicine approaches may provide viable alternatives. In this study, we have developed a new "hybrid graft" approach that utilizes decellularized tracheal tissue along with a resorbable polymer scaffold, and holds promise for potential clinical applications. First, we evaluated the effect of our decellularization process on the compression properties of porcine tracheal segments, and noted approximately 63% decrease in resistance to compression following decellularization. Next we developed four C-shape scaffold designs by varying the base geometry and thickness, and fabricated polycaprolactone scaffolds using a combination of 3D-Bioplotting and thermally-assisted forming. All scaffolds designs were evaluated in vitro under three different environmental testing conditions to determine the design that offered the best resistance to compression. These were further studied to determine the effect of gamma radiation sterilization and cyclic compression loading. Finally, hybrid grafts were developed by securing these optimal design scaffolds to decellularized tracheal segments and evaluated in vitro under physiological testing conditions. Results show that the resistance to compression offered by the hybrid grafts created using gamma radiation sterilized scaffolds was comparable to that of fresh tracheal segments. Given that current clinical attempts at tracheal transplantation using decellularized tissue have been fraught with luminal collapse and complications, our data support the possibility that future embodiments using a hybrid graft approach may reduce the need for intraluminal stenting in tracheal transplant recipients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Concurrent medical conditions among pregnant women - ignore at their peril: report from an antenatal anesthesia clinic.

PubMed

Weiniger, Carolyn F; Einav, Sharon; Elchalal, Uriel; Ozerski, Vladislav; Shatalin, Daniel; Ioscovich, Alexander; Ginosar, Yehuda

2018-03-19

Care of pregnant women with concurrent medical conditions can be optimized by multidisciplinary antenatal management. In the current study we describe women with concurrent medical conditions who attended our antenatal anesthesia clinic over a 14-year period, 2002-2015 and, based on the findings, we suggest new policies, strategies and practices to improve antenatal care. In 2002, an antenatal anesthesia clinic was established in Hadassah Medical Center. Each consultation focused on the concurrent medical condition. A written anesthesia strategy according to the medical condition and its anesthesia considerations was discussed and given to the patient. Data regarding clinic visits were recorded. A total of 451 clinic women attended the antenatal anesthesia clinic. Maternal age was 31.7 ± 6.0 years (mean ± SD), with gestational age of pregnancy 33.0 ± 5.4 weeks at the clinic visit. Musculoskeletal conditions (23% of all the women seen) were the most frequent concurrent conditions, followed by anesthesia related concerns 20%, neurologic conditions 19%, and cardiac conditions 15%. Women were provided plans that were deliberated carefully rather than being concocted during labor. A wide range of concurrent medical conditions was seen in the antenatal anesthesia clinic, however fewer women attended the clinic than expected according to known population frequencies of concurrent medical conditions. Women with concurrent medical conditions should have labor and anesthesia plans considered during the nine months of pregnancy, prior to delivery, and hospitals should have a means of obtaining this information in a timely manner. Finally, there is a need to develop additional antenatal anesthesia clinics.

Sepsis reconsidered: Identifying novel metrics for behavioral landscape characterization with a high-performance computing implementation of an agent-based model.

PubMed

Cockrell, Chase; An, Gary

2017-10-07

Sepsis affects nearly 1 million people in the United States per year, has a mortality rate of 28-50% and requires more than $20 billion a year in hospital costs. Over a quarter century of research has not yielded a single reliable diagnostic test or a directed therapeutic agent for sepsis. Central to this insufficiency is the fact that sepsis remains a clinical/physiological diagnosis representing a multitude of molecularly heterogeneous pathological trajectories. Advances in computational capabilities offered by High Performance Computing (HPC) platforms call for an evolution in the investigation of sepsis to attempt to define the boundaries of traditional research (bench, clinical and computational) through the use of computational proxy models. We present a novel investigatory and analytical approach, derived from how HPC resources and simulation are used in the physical sciences, to identify the epistemic boundary conditions of the study of clinical sepsis via the use of a proxy agent-based model of systemic inflammation. Current predictive models for sepsis use correlative methods that are limited by patient heterogeneity and data sparseness. We address this issue by using an HPC version of a system-level validated agent-based model of sepsis, the Innate Immune Response ABM (IIRBM), as a proxy system in order to identify boundary conditions for the possible behavioral space for sepsis. We then apply advanced analysis derived from the study of Random Dynamical Systems (RDS) to identify novel means for characterizing system behavior and providing insight into the tractability of traditional investigatory methods. The behavior space of the IIRABM was examined by simulating over 70 million sepsis patients for up to 90 days in a sweep across the following parameters: cardio-respiratory-metabolic resilience; microbial invasiveness; microbial toxigenesis; and degree of nosocomial exposure. In addition to using established methods for describing parameter space, we developed two novel methods for characterizing the behavior of a RDS: Probabilistic Basins of Attraction (PBoA) and Stochastic Trajectory Analysis (STA). Computationally generated behavioral landscapes demonstrated attractor structures around stochastic regions of behavior that could be described in a complementary fashion through use of PBoA and STA. The stochasticity of the boundaries of the attractors highlights the challenge for correlative attempts to characterize and classify clinical sepsis. HPC simulations of models like the IIRABM can be used to generate approximations of the behavior space of sepsis to both establish "boundaries of futility" with respect to existing investigatory approaches and apply system engineering principles to investigate the general dynamic properties of sepsis to provide a pathway for developing control strategies. The issues that bedevil the study and treatment of sepsis, namely clinical data sparseness and inadequate experimental sampling of system behavior space, are fundamental to nearly all biomedical research, manifesting in the "Crisis of Reproducibility" at all levels. HPC-augmented simulation-based research offers an investigatory strategy more consistent with that seen in the physical sciences (which combine experiment, theory and simulation), and an opportunity to utilize the leading advances in HPC, namely deep machine learning and evolutionary computing, to form the basis of an iterative scientific process to meet the full promise of Precision Medicine (right drug, right patient, right time). Copyright © 2017. Published by Elsevier Ltd.

Endoscopic thymectomy: a neurologist’s perspective

PubMed Central

Melfi, Franca; Maestri, Michelangelo; De Rosa, Anna; Petsa, Afroditi; Lucchi, Marco; Mussi, Alfredo

2016-01-01

Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by the presence of antibodies interacting at the neuromuscular junction (NMJ), resulting in loss of strength and severe exhaustibility of striated muscles. The abnormal production of these antibodies is triggered mainly in the thymus, and hence thymectomy in MG is considered a universally recommended treatment in order to improve the symptomatologic condition of this pathology. Currently, minimally invasive thymectomy using the Da Vinci robot system is certainly one of the most innovative techniques, performed in Pisa since 2001. This approach provides a valuable alternative to the traditional thymectomy through median sternotomy. The contribution of a neurologist is fundamental for preoperative patient selection and for the peri-operative clinical assistance in both approaches. We believe that in the robotic approach, the multidisciplinary collaboration between the neurologist, thoracic surgeon and anesthetist is important in reducing perioperative complications and ensuring a higher rate of complete remission or stable clinical improvement of MG. PMID:26904430

Clinical application of diffusion tensor magnetic resonance imaging in skeletal muscle

PubMed Central

Longwei, Xu

2012-01-01

Summary Diffusion tensor magnetic resonance imaging (DTI) is increasingly applied in the detection and characterization of skeletal muscle. This promising technique has aroused much enthusiasm and generated high expectations, because it is able to provide some specific information of skeletal muscle that is not available from other imaging modalities. Compared with conventional MRI, DTI could reconstruct the trajectories of skeletal muscle fibers. It makes it possible to non-invasively detect several physiological values (diffusion values), like fractional anisotropy (FA) and apparent diffusion coefficient (ADC), which have a great association with the muscle physiology and pathology. Furthermore, other advantages of DTI are the capability of investigating the muscle biomechanics and also investigate the pathological condition of skeletal muscle. Finally, several challenges, which limit the wide application of DTI in skeletal muscle, were discussed. It is believed that this review may arouse in-depth studies on the clinical application of DTI in skeletal muscle in future. PMID:23738269

Disorders associated with systemic or local iron overload: from pathophysiology to clinical practice.

PubMed

Sebastiani, Giada; Pantopoulos, Kostas

2011-10-01

In healthy subjects, the rate of dietary iron absorption, as well as the amount and distribution of body iron are tightly controlled by hepcidin, the iron regulatory hormone. Disruption of systemic iron homeostasis leads to pathological conditions, ranging from anemias caused by iron deficiency or defective iron traffic, to iron overload (hemochromatosis). Other iron-related disorders are caused by misregulation of cellular iron metabolism, which results in local accumulation of the metal in mitochondria. Brain iron overload is observed in neurodegenerative disorders. Secondary hemochromatosis develops as a complication of another disease. For example, repeated blood transfusions, a standard treatment of various anemias characterized by ineffective erythropoiesis, promote transfusional siderosis, while chronic liver diseases are often associated with mild to moderate secondary iron overload. In this critical review, we discuss pathophysiological and clinical aspects of all types of iron metabolism disorders (265 references). This journal is © The Royal Society of Chemistry 2011

The choice of amniotic fluid in metabolomics for the monitoring of fetus health.

PubMed

Palmas, Francesco; Fattuoni, Claudia; Noto, Antonio; Barberini, Luigi; Dessì, Angelica; Fanos, Vassilios

2016-01-01

Amniotic fluid (AF) is a biological fluid in which metabolite transport is regulated by the placenta, the permeable skin, fetal lung egress and gastric fluid. During pregnancy, the composition of AF changes from similar to the interstitial fluid of the mother, to a more complex system, influenced by the fetus's urine. Since AF reflects the mother's and the fetus's health status at the same time, it may be an important diagnostic tool for a wider spectrum of clinical conditions. Indeed, the metabolic characterization of AF in relation to pathological occurrences may lead to the discovery of new biomarkers for a better clinical practice. For this reason, metabolomics may be the most suitable strategy for this task. In this review, research works on metabolomic AF analysis are discussed according to the morbidity of interest, being preterm birth/labor, gestational age and diabetes and fetal malformations, along with a number of other important studies.

A mechanistic review on plant-derived natural compounds as dietary supplements for prevention of inflammatory bowel disease.

PubMed

Farzaei, Mohammad Hosein; Bahramsoltani, Roodabeh; Abdolghaffari, Amir Hossein; Sodagari, Hamid Reza; Esfahani, Shadi A; Rezaei, Nima

2016-06-01

Inflammatory bowel disease (IBD) is a recurrent idiopathic inflammatory condition, characterized by disruption of the gut mucosal barrier. This mechanistic review aims to highlight the significance of plant-derived natural compounds as dietary supplements, which can be used in addition to restricted conventional options for the prevention of IBD and induction of remission. Various clinical trials confirmed the effectiveness and tolerability of natural supplements in patients with IBD. Mounting evidence suggests that these natural compounds perform their protective and therapeutic effect on IBD through numerous molecular mechanisms, including anti-inflammatory and immunoregulatory, anti-oxidative stress, modulation of intracellular signaling transduction pathways, as well as improving gut microbiota. In conclusion, natural products can be considered as dietary supplements with therapeutic potential for IBD, provided that their safety and efficacy is confirmed in future well-designed clinical trials with adequate sample size.

[Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus].

PubMed

Krysiak, Robert; Okopień, Bogusław

2015-01-01

Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract

DOORS syndrome: phenotype, genotype and comparison with Coffin-Siris syndrome.

PubMed

Campeau, Philippe M; Hennekam, Raoul C

2014-09-01

DOORS syndrome (Deafness, Onychodystrophy, Osteodystrophy, mental Retardation, Seizures) is characterized mainly by sensorineural deafness, shortened terminal phalanges with small nails of hands and feet, intellectual deficiency, and seizures. Half of the patients with all clinical features have mutations in TBC1D24. We review here the manifestations of patients clinically diagnosed with DOORS syndrome. In this cohort of 32 families (36 patients) we detected 13 individuals from 10 families with TBC1D24 mutations. Subsequent whole exome sequencing in the cohort showed the same de novoSMARCB1 mutation (c.1130G>A), known to cause Coffin-Siris syndrome, in two patients. Distinguishing features include retinal anomalies, Dandy-Walker malformation, scoliosis, rocker bottom feet, respiratory difficulties and absence of seizures, and 2-oxoglutaric aciduria in the patients with the SMARCB1 mutation. We briefly discuss the heterogeneity of the DOORS syndrome phenotype and the differential diagnosis of this condition. © 2014 Wiley Periodicals, Inc.

Verbal learning on depressive pseudodementia: accentuate impairment of free recall, moderate on learning processes, and spared short-term and recognition memory.

PubMed

Paula, Jonas Jardim de; Miranda, Débora Marques; Nicolato, Rodrigo; Moraes, Edgar Nunes de; Bicalho, Maria Aparecida Camargos; Malloy-Diniz, Leandro Fernandes

2013-09-01

Depressive pseudodementia (DPD) is a clinical condition characterized by depressive symptoms followed by cognitive and functional impairment characteristics of dementia. Memory complaints are one of the most related cognitive symptoms in DPD. The present study aims to assess the verbal learning profile of elderly patients with DPD. Ninety-six older adults (34 DPD and 62 controls) were assessed by neuropsychological tests including the Rey auditory-verbal learning test (RAVLT). A multivariate general linear model was used to assess group differences and controlled for demographic factors. Moderate or large effects were found on all RAVLT components, except for short-term and recognition memory. DPD impairs verbal memory, with large effect size on free recall and moderate effect size on the learning. Short-term storage and recognition memory are useful in clinical contexts when the differential diagnosis is required.

Mathematical model of susceptibility, resistance, and resilience in the within-host dynamics between a Plasmodium parasite and the immune system.

PubMed

Yan, Yi; Adam, Brian; Galinski, Mary; C Kissinger, Jessica; Moreno, Alberto; Gutierrez, Juan B

2015-12-01

We developed a coupled age-structured partial differential equation model to capture the disease dynamics during blood-stage malaria. The addition of age structure for the parasite population, with respect to previous models, allows us to better characterize the interaction between the malaria parasite and red blood cells during infection. Here we prove that the system we propose is well-posed and there exist at least two global states. We further demonstrate that the numerical simulation of the system coincides with clinically observed outcomes of primary and secondary malaria infection. The well-posedness of this system guarantees that the behavior of the model remains smooth, bounded, and continuously dependent on initial conditions; calibration with clinical data will constrain domains of parameters and variables to physiological ranges. Copyright © 2015 Elsevier Inc. All rights reserved.

Lafora's-like disease in a fennec fox (Vulpes zerda).

PubMed

Honnold, Shelley P; Schulman, F Yvonne; Bauman, Karen; Nelson, Kevin

2010-09-01

A 6-yr-old captive-born female fennec fox (Vulpes zerda) had a history of multiple seizures and was treated with diazepam and phenobarbital therapy. Despite medical treatment, the seizures continued. They were intermittent and progressive, resulting in neurologic deficits and death of the animal within 6 mo of onset of the clinical signs. At necropsy, the animal was in good nutritional condition, and no gross lesions were noted in the brain. Histologically, amphophilic to basophilic, periodic acid-Schiff (PAS) positive, diastase-resistant inclusions were present in the brain, heart, and liver. Ultrastructurally, the inclusions were variably electron dense, fibrillary to occasionally granular, and non-membrane bound. The clinical, histologic, and ultrastructural findings were consistent with Lafora's disease, which in humans is a rare, fatal, autosomal recessive hereditary neurometabolic disorder characterized by progressive myoclonic epilepsy. This is the first report of Lafora's-like disease in a fennec fox.

An electrochemical immunosensor for quantitative detection of ficolin-3

NASA Astrophysics Data System (ADS)

San, Lili; Zeng, Dongdong; Song, Shiping; Zuo, Xiaolei; Zhang, Huan; Wang, Chenguang; Wu, Jiarui; Mi, Xianqiang

2016-06-01

Diabetes mellitus (DM) is one of the most common metabolic disorders in the world, of which more than 90% is type-2 diabetes mellitus (T2DM). There is a rather urgent need for reliable, sensitive and quick detection techniques in clinical application of T2DM. Ficolin-3 is a potential biomarker of T2DM, because serum ficolin-3 levels are associated with insulin resistance and predict the incidence of T2DM. Herein, a sandwich-type electrochemical immunosensor was developed for the detection of ficolin-3 in human serum. Cyclic voltammetry and the amperometric current versus time were used to characterize the performance of the immunosensor. Under optimal conditions, the detection limitation of ficolin-3 was 100 ng ml-1 and the linear dynamic range was between 2 and 50 μg ml-1. The method has ideal accuracy, excellent stability and selectivity and has wide application prospects in clinical research.

[Pott's Disease in Upper Thoracic Vertebrae in a Two-Year-Old Boy: Case Report].

PubMed

Cortez-Bazán, Nathaly; Delgado, Jennifer R; Galdos, Omar; Huicho, Luis

2018-01-01

Pott's disease is a health problem in developing countries and its diagnosis in children is a challenge. Here we present the case of a two-year-old boy with Pott's disease involving T1 to T3 thoracic vertebrae. The clinical presentation was characterized by difficulty walking, fever, cough, and dyspnea. At physical examination, kyphosis and bony prominence were observed in the cervicodorsal area. A positive tuberculin test was obtained, and Mycobacterium tuberculosis was isolated via culture of the gastric aspiration sample. The spine MRI showed a chronic abscess, destruction of two vertebrae, and bone marrow compression. The patient experienced some improvement with anti-TB therapy. Here, we emphasize the importance of giving consideration to the clinical suspicion for the early detection of this condition, as well as a quick TB-treatment start so as to avoid the disability and mortality associated to this disease.

Tourette's syndrome in famous musicians.

PubMed

Camargo, Carlos Henrique F; Bronzini, Augusto

2015-12-01

Tourette's syndrome (TS) is defined as a disorder characterized by multiple motor tics and at least one vocal tic that have lasted for not less than one year. It is a relatively complex neurobehavioral disorder, in which patients may present with coexistent attention deficit hyperactivity disorder, obsessive-compulsive disorder or other behavioral comorbidities. The musical genius Wolfgang Amadeus Mozart (1756-1791) and the rock star Kurt Cobain (1967-1994) may both have suffered from TS, and some contemporary musicians have had their clinical condition confirmed as TS. Our hypothetical diagnosis of TS in Mozart and Cobain is based on the presence of tics and psychiatric comorbidities. In contemporary musicians, such as Michael Wolff, Nick Van Bloss and James Durbin, TS has often only been diagnosed after a considerable delay. This delay in diagnosis and the controversies surrounding the clinical case of Mozart show how difficult a confirmatory diagnosis of this complex disease is.

Management strategies for fibromyalgia

PubMed Central

Le Marshall, Kim Francis; Littlejohn, Geoffrey Owen

2011-01-01

Clinical question What are the effective, evidence-based strategies available for the management of fibromyalgia? Conclusion There are a number of management strategies available with robust evidence to support their use in clinical practice. Definition Fibromyalgia is a complex pain syndrome characterized by widespread, chronic muscular pain and tenderness, disordered sleep, emotional distress, cognitive disturbance, and fatigue. Its prevalence is estimated to be 3%–5% in the population and higher yet in patients with comorbid rheumatic diseases. Level of evidence Systematic reviews, meta-analyses, randomized controlled trials (RCTs). Search sources PubMed, Cochrane Library, manual search Consumer summary Key messages for patients and clinicians are: There are many effective pharmacological management strategies available for fibromyalgia.A nonpharmacological, multicomponent approach utilizing education, aerobic exercise, psychological therapy, and other strategies is also effective for fibromyalgia.Despite the significant and, at times, disabling physical and psychological symptoms, fibromyalgia can be a manageable condition with a potentially good outcome. PMID:27790003

Spinal schwannomatosis in the absence of neurofibromatosis: A very rare condition

PubMed Central

Landi, A.; Dugoni, D.E.; Marotta, N.; Mancarella, C.; Delfini, R.

2010-01-01

Schwannomatosis is defined as an extremely rare tumors syndrome characterized by the presence of multiple schwannomas in the absence of typical signs of NF1 and NF2 syndromes. The genetic and molecular analysis performed on these tumors makes it possible to name schwannomatosis as distinct clinical and genetic syndrome. The treatment in the case of symptomatic lesions is surgical removal; if the lesions are asymptomatic it is better to perform serial MRI studies. Given the high incidence of developing additional lesions in patients with schwannomatosis, it remains imperative to perform serial brain and spinal cord MRI studies during follow-up. The differential diagnosis is important including clinical and radiological criteria plus molecular genetic analysis of tumor cells and lymphocyte DNA. We report a rare case of spinal schwannomatosis in which genetic analysis performed on surgical samples showed two different mutations in the cells of the two lesions. PMID:22096683

Spinal schwannomatosis in the absence of neurofibromatosis: A very rare condition.

PubMed

Landi, A; Dugoni, D E; Marotta, N; Mancarella, C; Delfini, R

2011-01-01

Schwannomatosis is defined as an extremely rare tumors syndrome characterized by the presence of multiple schwannomas in the absence of typical signs of NF1 and NF2 syndromes. The genetic and molecular analysis performed on these tumors makes it possible to name schwannomatosis as distinct clinical and genetic syndrome. The treatment in the case of symptomatic lesions is surgical removal; if the lesions are asymptomatic it is better to perform serial MRI studies. Given the high incidence of developing additional lesions in patients with schwannomatosis, it remains imperative to perform serial brain and spinal cord MRI studies during follow-up. The differential diagnosis is important including clinical and radiological criteria plus molecular genetic analysis of tumor cells and lymphocyte DNA. We report a rare case of spinal schwannomatosis in which genetic analysis performed on surgical samples showed two different mutations in the cells of the two lesions.

Algodystrophy: complex regional pain syndrome and incomplete forms

PubMed Central

Giannotti, Stefano; Bottai, Vanna; Dell’Osso, Giacomo; Bugelli, Giulia; Celli, Fabio; Cazzella, Niki; Guido, Giulio

2016-01-01

Summary The algodystrophy, also known as complex regional pain syndrome (CRPS), is a painful disease characterized by erythema, edema, functional impairment, sensory and vasomotor disturbance. The diagnosis of CRPS is based solely on clinical signs and symptoms, and for exclusion compared to other forms of chronic pain. There is not a specific diagnostic procedure; careful clinical evaluation and additional test should lead to an accurate diagnosis. There are similar forms of chronic pain known as bone marrow edema syndrome, in which is absent the history of trauma or triggering events and the skin dystrophic changes and vasomotor alterations. These incomplete forms are self-limited, and surgical treatment is generally not needed. It is still controversial, if these forms represent a distinct self-limiting entity or an incomplete variant of CRPS. In painful unexplained conditions such as frozen shoulder, post-operative stiff shoulder or painful knee prosthesis, the algodystrophy, especially in its incomplete forms, could represent the cause. PMID:27252736

An introduction to Chuna manual medicine in Korea: History, insurance coverage, education, and clinical research in Korean literature.

PubMed

Park, Tae-Yong; Moon, Tae-Woong; Cho, Dong-Chan; Lee, Jung-Han; Ko, Youn-Seok; Hwang, Eui-Hyung; Heo, Kwang-Ho; Choi, Tae-Young; Shin, Byung-Cheul

2014-06-01

The objectives of this study were to summarize the curriculum, history, and clinical researches of Chuna in Korea and to ultimately introduce Chuna to Western medicine. Information about the history and insurance coverage of Chuna was collected from Chuna-related institutions and papers. Data on Chuna education in all 12 Korean medicine (KM) colleges in Korea were reconstructed based on previously published papers. All available randomized controlled trials (RCTs) of Chuna in clinical research were searched using seven Korean databases and six KM journals. As a result, during the modern Chuna era, one of the three periods of Chuna, which also include the traditional Chuna era and the suppressed Chuna era, Chuna developed considerably because of a solid Korean academic system, partial insurance coverage, and the establishment of a Chuna association in Korea. All of the KM colleges offered courses on Chuna-related subjects (CRSs); however, the total number of hours dedicated to lectures on CRSs was insufficient to master Chuna completely. Overall, 17 RCTs were reviewed. Of the 14 RCTs of Chuna in musculoskeletal diseases, six reported Chuna was more effective than a control condition, and another six RCTs proposed Chuna had the same effect as a control condition. One of these 14 RCTs made the comparison impossible because of unreported statistical difference; the last RCT reported Chuna was less effective than a control condition. In addition, three RCTs of Chuna in neurological diseases reported Chuna was superior to a control condition. In conclusion, Chuna was not included in the regular curriculum in KM colleges until the modern Chuna era; Chuna became more popular as the result of it being covered by Korean insurance carriers and after the establishment of a Chuna association. Meanwhile, the currently available evidence is insufficient to characterize the effectiveness of Chuna in musculoskeletal and neurological diseases.

Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue

PubMed Central

Korutla, Laxminarayana; Habertheuer, Andreas; Yu, Ming; Rostami, Susan; Yuan, Chao-Xing; Reddy, Sanjana; Korutla, Varun; Koeberlein, Brigitte; Trofe-Clark, Jennifer; Rickels, Michael R.; Naji, Ali

2017-01-01

In transplantation, there is a critical need for noninvasive biomarker platforms for monitoring immunologic rejection. We hypothesized that transplanted tissues release donor-specific exosomes into recipient circulation and that the quantitation and profiling of donor intra-exosomal cargoes may constitute a biomarker platform for monitoring rejection. Here, we have tested this hypothesis in a human-into-mouse xenogeneic islet transplant model and validated the concept in clinical settings of islet and renal transplantation. In the xenogeneic model, we quantified islet transplant exosomes in recipient blood over long-term follow-up using anti-HLA antibody, which was detectable only in xenoislet recipients of human islets. Transplant islet exosomes were purified using anti-HLA antibody–conjugated beads, and their cargoes contained the islet endocrine hormone markers insulin, glucagon, and somatostatin. Rejection led to a marked decrease in transplant islet exosome signal along with distinct changes in exosomal microRNA and proteomic profiles prior to appearance of hyperglycemia. In the clinical settings of islet and renal transplantation, donor exosomes with respective tissue specificity for islet β cells and renal epithelial cells were reliably characterized in recipient plasma over follow-up periods of up to 5 years. Collectively, these findings demonstrate the biomarker potential of transplant exosome characterization for providing a noninvasive window into the conditional state of transplant tissue. PMID:28319051

Performance comparison of two commercial BGO-based PET/CT scanners using NEMA NU 2-2001.

PubMed

Bolard, Grégory; Prior, John O; Modolo, Luca; Delaloye, Angelika Bischof; Kosinski, Marek; Wastiel, Claude; Malterre, Jérôme; Bulling, Shelley; Bochud, François; Verdun, Francis R

2007-07-01

Combined positron emission tomography and computed tomography (PET/CT) scanners play a major role in medicine for in vivo imaging in an increasing number of diseases in oncology, cardiology, neurology, and psychiatry. With the advent of short-lived radioisotopes other than 18F and newer scanners, there is a need to optimize radioisotope activity and acquisition protocols, as well as to compare scanner performances on an objective basis. The Discovery-LS (D-LS) was among the first clinical PET/CT scanners to be developed and has been extensively characterized with older National Electrical Manufacturer Association (NEMA) NU 2-1994 standards. At the time of publication of the latest version of the standards (NU 2-2001) that have been adapted for whole-body imaging under clinical conditions, more recent models from the same manufacturer, i.e., Discovery-ST (D-ST) and Discovery-STE (D-STE), were commercially available. We report on the full characterization both in the two- and three-dimensional acquisition mode of the D-LS according to latest NEMA NU 2-2001 standards (spatial resolution, sensitivity, count rate performance, accuracy of count losses, and random coincidence correction and image quality), as well as a detailed comparison with the newer D-ST widely used and whose characteristics are already published.

Same Phenotype in Children with Growth Hormone Deficiency and Resistance

PubMed Central

Ioimo, Irene; Guarracino, Carmen; Meazza, Cristina; Domené, Horacio M.

2018-01-01

By definition, about 2.5% of children show a short stature due to several causes. Two clinical conditions are characterized by serum IGF-I low levels, idiopathic GH deficiency (IGHD), and GH insensitivity (GHI), and the phenotypic appearance of these patients may be very similar. We studied two children with short stature and similar phenotypes. The first case showed frontal bossing, doll face, acromicria, and truncal obesity, with a GH peak <0.05 ng/ml after stimuli and undetectable serum IGF-I levels. After PCR amplification of the whole GH1 gene, type IA idiopathic GHD was diagnosed. The second case had cranium hypoplasia, a large head, protruding forehead, saddle nose, underdeveloped mandible, and a micropenis. Basal GH levels were high (28.4 ng/ml) while serum IGF-I levels were low and unchangeable during the IGF-I generation test. Laron syndrome was confirmed after the molecular analysis of the GH receptor (GHR) gene. IGHD type IA and Laron syndrome is characterized by opposite circulating levels of GH, while both have reduced levels of IGF-I, with an overlapping clinical phenotype, lacking the effects of IGF-I on cartilage. These classical cases show the importance of differential diagnosis in children with severe short stature. PMID:29850346

Performance comparison of two commercial BGO-based PET/CT scanners using NEMA NU 2-2001

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

Bolard, Gregory; Prior, John O.; Modolo, Luca

2007-07-15

Combined positron emission tomography and computed tomography (PET/CT) scanners play a major role in medicine for in vivo imaging in an increasing number of diseases in oncology, cardiology, neurology, and psychiatry. With the advent of short-lived radioisotopes other than {sup 18}F and newer scanners, there is a need to optimize radioisotope activity and acquisition protocols, as well as to compare scanner performances on an objective basis. The Discovery-LS (D-LS) was among the first clinical PET/CT scanners to be developed and has been extensively characterized with older National Electrical Manufacturer Association (NEMA) NU 2-1994 standards. At the time of publication ofmore » the latest version of the standards (NU 2-2001) that have been adapted for whole-body imaging under clinical conditions, more recent models from the same manufacturer, i.e., Discovery-ST (D-ST) and Discovery-STE (D-STE), were commercially available. We report on the full characterization both in the two- and three-dimensional acquisition mode of the D-LS according to latest NEMA NU 2-2001 standards (spatial resolution, sensitivity, count rate performance, accuracy of count losses, and random coincidence correction and image quality), as well as a detailed comparison with the newer D-ST widely used and whose characteristics are already published.« less

Reconsidering the Placebo Response from a Broad Anthropological Perspective

PubMed Central

Thompson, Jennifer Jo; Ritenbaugh, Cheryl; Nichter, Mark

2009-01-01

This paper considers how the full range of human experience may catalyze a placebo response. The placebo effect has been characterized as something to control in clinical research, something to cultivate in clinical practice, and something present in all healing encounters. We examine domains in which the term ‘placebo’ is used in discourse: clinical research, clinical practice, media representations of treatment efficacy, and lay interpretations of placebo—an under-researched topic. We briefly review major theoretical frameworks proposed to explain the placebo effect: classical conditioning, expectancy, the therapeutic relationship, and sociocultural ‘meaning.’ As a corrective to what we see as an over-emphasis on conscious cognitive approaches to understanding placebo, we reorient the discussion to argue that direct embodied experience may take precedence over meaning-making in the healing encounter. As an example, we examine the neurobiology of rehearsing or visualizing wellness as a mode of directly (performatively) producing an outcome often dismissed as a ‘placebo response.’ Given body/mind/emotional resonance, we suggest that the placebo response is an evolutionarily adaptive trait and part of healing mechanisms operating across many levels—from genetic and cellular to social and cultural. PMID:19107582

Florid Cemento-Osseous Dysplasia Simultaneous the Chronic Suppurative Osteomyelitis in Mandible.

PubMed

Cavalcante, Mateus Barros; de Oliveira Lima, Amanda Laísa; Júnior, Marcus Antônio Brêda; Santos, Milkle Bruno Pessoa

2016-11-01

The florid cemento-osseous dysplasia is an uncommon condition nonneoplastic, of unknown cause with higher prevalence in melanodermic women, limited the maxillary bones, is characterized by the presence of dispersed and diffuse radiopaque calcifications, constituted of bone and dense cemento; however, when the bone is infected it induces the suppuration and formation of osseous sequestra, thus resulting in an osteomyelitis frame. The patient was attended in a Dental Specialties Center in the state of Alagoas, Brazil, presenting on clinical examination edema and extra oral fistula with pus drainage in hemiface submandibular of the right side. Radiographically it was possible to observe area of sclerosis and osseous sequestra involving the right side region of the mandible body, and it increases zones of the bone density. In association with clinical data and complementary diagnosis examinations, the option of treatment adopted was the complete removal of the bone fragment, followed by adaptation and plate fixation and titanium screws to reduce the risk of mandibular fracture. The aim of the present paper was to relate a clinical patient of florid cemento-osseous dysplasia simultaneous the chronic suppurative osteomyelitis, highlighting their clinical, radiographic, and histological characteristics, as well as their diagnosis and treatment.

Recipient area folliculitis after follicular-unit transplantation: characterization of clinical features and analysis of associated factors.

PubMed

Bunagan, M J Kristine S; Pathomvanich, Damkerng; Laorwong, Kongkiat

2010-07-01

Postoperative recipient-area folliculitis may be a cause of less or delayed growth of transplanted hair and an obvious cause of distress to the patient. No study has been done to elaborate on its clinical features and assess possible factors that may correlate with its occurrence. To study the clinical features and possible factors that may be associated with the development of recipient-area folliculitis after follicular-unit transplantation (FUT). Retrospective analysis of 27 patients who developed folliculitis after FUT and 28 patients without such complication. Lesion onset ranged from 2 days to 6 months after FUT (mean 1.44 months). Lesions were mostly pustules that resolved without sequela. Statistical analysis showed that, in terms of patient characteristics (e.g., hair features, scalp condition) and the number of grafts transplanted, there was no statistically significant difference in assessed parameters between those with and without folliculitis (p<.05). Main clinical features of postoperative folliculitis consist mostly of few to moderate self-limited pustules. In this study, regardless of management, lesions healed without scarring and without affecting graft growth. Neither patient characteristics nor number of grafts transplanted was associated with this complication.

Nutraceuticals: A paradigm of proactive medicine.

PubMed

Santini, Antonello; Tenore, Gian Carlo; Novellino, Ettore

2017-01-01

Nutraceuticals define a new category which shades the frontier between drugs and food. As per its definition, a nutraceutical is "a food or part of a food that provides benefits health in addition to its nutritional content". Active substances either way extracted from plants (phytocomplexes) or of animal origin, when extracted, concentrated and administered in a suitable pharmaceutical form, can create a very promising toolbox useful to prevent and/or support the therapy of some pathologic conditions given their proven clinical efficacy. It is worldwide recognized that diet and lifestyle are essential to promote and maintain well-being and nice-being condition, other than help to prevent diseases possible onset. Both non-correct dietary habits and lifestyle can in fact determine pathological conditions. The metabolic syndrome, a worldwide epidemic threat, can be named an outstanding example. This syndrome is characterized by a cascade of cardio metabolic risk factors which include obesity, insulin resistance, hypertension, and dyslipidemia. Prevention is the key strategy for an effective proactive medicine, in which efforts are addressed to prevention and, consequently, to lower the risk connected to some lifestyle related diseases reducing, at the same time, any National Health Systems cost needed to guarantee the proper therapeutic approach based on pharmaceuticals. Nutraceuticals use in prevention is a proactive reverse approach tool to pre-clinical health conditions. They can be effectively used, by including in the daily diet, in an area which shades in the range "beyond the diet, before drugs", since they combine both nutritional and beneficial healthy properties of food extracts with the healing properties of natural active compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders

PubMed Central

Smith, Ann; McCulloh, Russell J.

2015-01-01

The goal here is to describe our current understanding of heme metabolism and the deleterious effects of “free” heme on immunological processes, endothelial function, systemic inflammation, and various end-organ tissues (e.g., kidney, lung, liver, etc.), with particular attention paid to the role of hemopexin (HPX). Because heme toxicity is the impetus for much of the pathology in sepsis, sickle cell disease (SCD), and other hemolytic conditions, the biological importance and clinical relevance of HPX, the predominant heme binding protein, is reinforced. A perspective on the function of HPX and haptoglobin (Hp) is presented, updating how these two proteins and their respective receptors act simultaneously to protect the body in clinical conditions that entail hemolysis and/or systemic intravascular (IVH) inflammation. Evidence from longitudinal studies in patients supports that HPX plays a Hp-independent role in genetic and non-genetic hemolytic diseases without the need for global Hp depletion. Evidence also supports that HPX has an important role in the prognosis of complex illnesses characterized predominantly by the presence of hemolysis, such as SCD, sepsis, hemolytic-uremic syndrome, and conditions involving IVH and extravascular hemolysis (EVH), such as that generated by extracorporeal circulation during cardiopulmonary bypass (CPB) and from blood transfusions. We propose that quantitating the amounts of plasma heme, HPX, Hb-Hp, heme-HPX, and heme-albumin levels in various disease states may aid in the diagnosis and treatment of the above-mentioned conditions, which is crucial to developing targeted plasma protein supplementation (i.e., “replenishment”) therapies for patients with heme toxicity due to HPX depletion. PMID:26175690

Vocal cord dysfunction in former World Trade Center (WTC) rescue and recovery workers and volunteers.

PubMed

de la Hoz, Rafael E; Shohet, Michael R; Bienenfeld, Laura A; Afilaka, Aboaba A; Levin, Stephen M; Herbert, Robin

2008-03-01

Vocal cord dysfunction (VCD) is a condition characterized by paradoxical partial adduction of the vocal cords on inspiration. It has been associated with exposures to irritants, as well as with psychological illnesses and conditions. Workers who participated in the recovery of the WTC disaster site were exposed to a large amount of irritants as well as considerable psychological stressors. We describe the clinical characteristics of 10 symptomatic former WTC workers diagnosed with this condition, as well as the frequency of spirometric findings suggestive of variable extrathoracic obstruction. Workers who became symptomatic after their WTC work experience have been evaluated clinically by a multidisciplinary team at an academic medical center. The evaluation included history, physical examination, chest radiograph, blood tests, and pre- and post-bronchodilator spirometry in all patients. Additional evaluations and diagnostic tests included otolaryngological evaluation with flexible rhinolaryngoscopy and stroboscopy, gastroenterological and psychiatric evaluations. A randomly selected sample of 172 spirometry results were reviewed for evidence of inspiratory flow limitation. Variable extrathoracic obstruction was found in 18.6% of the spirometries. Ten patients were diagnosed with VCD. In addition to symptoms suggestive of co-morbid conditions (particularly rhinitis and acid reflux disease), most of the 10 patients had (1) hoarseness, (2) dyspnea that was not associated with bronchial hyperreactivity, or (3) dyspnea associated with asthma, with either mild bronchial hyperreactivity and/or poor response to asthma treatment. VCD appears to be part of the spectrum of airway disorders caused by occupational exposures at the WTC disaster site. Further study of this association is warranted.

Combined Occurrence of Autosomal Dominant Aniridia and Autosomal Recessive Albinism in Several Members of a Family.

PubMed

Yahalom, Claudia; Sharon, Dror; Dalia, Eli; Simhon, Shiran Ben; Shemesh, Efrat; Blumenfeld, Anat

2015-06-01

To characterize clinical and genetic aspects of a family with a unique combination of two hereditary blinding eye diseases. Comprehensive eye examination of proband and family members. Molecular analyses of the TYR and PAX6 genes. A young couple, both legally blind, requested genetic counselling regarding their ocular condition. The female was previously diagnosed with oculocutaneous albinism (OCA1A) and her spouse was diagnosed with Peters anomaly. A comprehensive clinical examination revealed that the female had OCA1A combined with signs of another ocular disease, showing some similarity to aniridia. A complete ocular examination of her family members revealed that her brother also suffered from the same combined phenotype, her father had typical OCA1A signs, and her mother and sister had aniridia-like phenotype, without clinical diagnosis until the time of presentation. Molecular analysis identified two compound heterozygous TYR mutations known to cause OCAIA and cosegregate with oculocutaneous albinism. In addition, we identified a novel heterozygous PAX6 mutation confirming the atypical aniridia phenotype. We report here a unique and rare clinical phenotype that is explained by the segregation of two severe inherited eye diseases. The clinical and genetic analysis in this family allowed them to receive accurate genetic counseling.

Addressing narcissistic personality features in the context of medical care: integrating diverse perspectives to inform clinical practice.

PubMed

Magidson, J F; Collado-Rodriguez, A; Madan, A; Perez-Camoirano, N A; Galloway, S K; Borckardt, J J; Campbell, W K; Miller, J D

2012-04-01

Narcissistic personality disorder (NPD) is characterized by an unrealistic need for admiration, lack of empathy toward others, and feelings of superiority. NPD presents a unique and significant challenge in clinical practice, particularly in medical settings with limited provider contact time, as health professionals treat individuals who often require excessive admiration and have competing treatment needs. This practice review highlights real case examples across three distinct medically oriented clinical settings (inpatient and outpatient behavioral medicine and a Level I trauma center) to demonstrate the difficult and compromising situations that providers face when treating patients with general medical conditions and comorbid narcissistic personality features. The main goal of this article is to discuss the various challenges and obstacles associated with these cases in medical settings and discuss some strategies that may prove successful. A second goal is to bridge diverse conceptualizations of narcissism/NPD through the discussion of theoretical and empirical perspectives that can inform understanding of the clinical examples. Despite differing perspectives regarding the underlying motivation of narcissistic behavior, this practice review highlights that these paradigms can be integrated when sharing the same ultimate goal: to improve delivery of care across medically oriented clinical settings for patients with narcissistic features.

Development and Characterization of Reference Materials for Genetic Testing: Focus on Public Partnerships.

PubMed

Kalman, Lisa V; Datta, Vivekananda; Williams, Mickey; Zook, Justin M; Salit, Marc L; Han, Jin Yeong

2016-11-01

Characterized reference materials (RMs) are needed for clinical laboratory test development and validation, quality control procedures, and proficiency testing to assure their quality. In this article, we review the development and characterization of RMs for clinical molecular genetic tests. We describe various types of RMs and how to access and utilize them, especially focusing on the Genetic Testing Reference Materials Coordination Program (Get-RM) and the Genome in a Bottle (GIAB) Consortium. This review also reinforces the need for collaborative efforts in the clinical genetic testing community to develop additional RMs.

Characterization of Vibrio cholerae O1 El Tor Biotype Variant Clinical Isolates from Bangladesh and Haiti, Including a Molecular Genetic Analysis of Virulence Genes ▿

PubMed Central

Son, Mike S.; Megli, Christina J.; Kovacikova, Gabriela; Qadri, Firdausi; Taylor, Ronald K.

2011-01-01

Vibrio cholerae serogroup O1, the causative agent of the diarrheal disease cholera, is divided into two biotypes: classical and El Tor. Both biotypes produce the major virulence factors toxin-coregulated pilus (TCP) and cholera toxin (CT). Although possessing genotypic and phenotypic differences, El Tor biotype strains displaying classical biotype traits have been reported and subsequently were dubbed El Tor variants. Of particular interest are reports of El Tor variants that produce various levels of CT, including levels typical of classical biotype strains. Here, we report the characterization of 10 clinical isolates from the International Centre for Diarrhoeal Disease Research, Bangladesh, and a representative strain from the 2010 Haiti cholera outbreak. We observed that all 11 strains produced increased CT (2- to 10-fold) compared to that of wild-type El Tor strains under in vitro inducing conditions, but they possessed various TcpA and ToxT expression profiles. Particularly, El Tor variant MQ1795, which produced the highest level of CT and very high levels of TcpA and ToxT, demonstrated hypervirulence compared to the virulence of El Tor wild-type strains in the infant mouse cholera model. Additional genotypic and phenotypic tests were conducted to characterize the variants, including an assessment of biotype-distinguishing characteristics. Notably, the sequencing of ctxB in some El Tor variants revealed two copies of classical ctxB, one per chromosome, contrary to previous reports that located ctxAB only on the large chromosome of El Tor biotype strains. PMID:21880975

An Approach to Differential Diagnosis of Antiphospholipid Antibody Syndrome and Related Conditions

PubMed Central

Emmi, Giacomo; Silvestri, Elena; Squatrito, Danilo; D'Elios, Mario Milco; Pengo, Vittorio; Prisco, Domenico

2014-01-01

The antiphospholipid antibody syndrome is a systemic, acquired, immune-mediated disorder characterized by episodes of venous, arterial, or microcirculation thrombosis and/or pregnancy abnormalities, associated with the persistent presence of autoantibodies, confirmed at least in two occasions 12 weeks apart, directed to molecular complexes consisting of phospholipids and proteins. Antiphospholipid antibody syndrome should always be considered as a potential diagnosis especially for young patients presenting with a history of thrombotic events, in particular when they occur without any obvious external trigger or any inherited thrombophilic mutation (even if 2006 criteria do not exclude antiphospholipid antibody syndrome in patients with other inherited or acquired prothrombotic conditions), or for women with recurrent pregnancy losses or later fetal deaths. Many other disorders are able to mimic antiphospholipid antibody syndrome, so a broad range of alternative diagnoses should be investigated and ruled out during clinical workup. PMID:25374937

Cytarabine syndrome despite corticosteroid premedication in an adult undergoing induction treatment for acute myelogenous leukemia.

PubMed

Jirasek, Matthew A; Herrington, Jon D

2016-12-01

Cytarabine syndrome is a rare clinical condition characterized by fever, malaise, myalgia, arthralgia, and/or rash that occurs after receipt of cytarabine. Our patient developed fever, malaise, and diffuse body pain shortly following cytarabine initiation despite receiving prophylactic dexamethasone. The patient's discomfort was treated with intravenous morphine and her other symptoms were controlled with a higher dose of dexamethasone. Although the exact cause is not fully understood, cytarabine syndrome is hypothesized to be an immune-mediated response following cytarabine-induced apoptosis that results in a rapid increase in proinflammatory cytokines. While there is no standard therapy for cytarabine syndrome, corticosteroids appear to play a role in the treatment and prevention of the condition by suppressing the proinflammatory response. Since our case describes the development of cytarabine syndrome despite dexamethasone, clinicians should monitor for this adverse event if patients begin exhibiting characteristics of this syndrome. © The Author(s) 2015.

Evidence from animal models on the pathogenesis of PCOS.

PubMed

Walters, K A; Bertoldo, M J; Handelsman, D J

2018-06-01

Polycystic ovarian syndrome (PCOS) is the most common endocrine condition in women, and is characterized by reproductive, endocrine and metabolic features. However, there is no simple unequivocal diagnostic test for PCOS, its etiology remains unknown and there is no cure. Hence, the management of PCOS is suboptimal as it relies on the ad hoc empirical management of its symptoms only. Decisive studies are required to unravel the origins of PCOS, but due to ethical and logistical reasons these are not possible in humans. Experimental animal models for PCOS have been established which have enhanced our understanding of the mechanisms underlying PCOS and propose novel mechanism-based therapies to treat the condition. This review examines the findings from various animal models to reveal the current knowledge of the mechanisms underpinning the development of PCOS, and also provides insights into the implications from these studies for improved clinical management of this disorder. Copyright © 2018 Elsevier Ltd. All rights reserved.

The diagnosis and treatment of chronic migraine

PubMed Central

2015-01-01

Migraine is the most common disabling brain disorder. Chronic migraine, a condition characterized by the experience of migrainous headache on at least 15 days per month, is highly disabling. Patients with chronic migraine present to primary care, are often referred for management to secondary care, and make up a large proportion of patients in specialist headache clinics. Many patients with chronic migraine also have medication overuse, defined as using a compound analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All doctors will encounter patients with chronic headaches. A basic working knowledge of the common primary headaches, and a rational manner of approaching the patient with these conditions, allows a specific diagnosis of chronic migraine to be made quickly and safely, and by making this diagnosis one opens up a substantial number of acute and preventive treatment options. This article discusses the current state of management of chronic migraine. PMID:25954496

[Incontinentia pigmenti with defect in cellular immunity].

PubMed

Zamora-Chávez, Antonio; Escobar-Sánchez, Argelia; Sadowinski-Pine, Stanislaw; Saucedo-Ramírez, Omar Josué; Delgado-Barrera, Palmira; Enríquez-Quiñones, Claudia G

Incontinentia pigmenti is a rare, X-linked genetic disease and affects all ectoderm-derived tissues such as skin, appendages, eyes, teeth and central nervous system as well as disorders of varying degree of cellular immunity characterized by decreasing melanin in the epidermis and increase in the dermis. When the condition occurs in males, it is lethal. We present the case of a 2-month-old infant with severe incontinentia pigmenti confirmed by histological examination of skin biopsy. The condition evolved with severe neurological disorders and seizures along with severe cellular immune deficiency, which affected the development of severe infections and caused the death of the patient. The importance of early clinical diagnosis is highlighted along with the importance of multidisciplinary management of neurological disorders and infectious complications. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Postmenopausal frontal fibrosing alopecia.

PubMed

Naz, E; Vidaurrázaga, C; Hernández-Cano, N; Herranz, P; Mayor, M; Hervella, M; Casado, M

2003-01-01

Recently a new entity, postmenopausal frontal fibrosing alopecia, was added to the established subtypes of scarring alopecias affecting postmenopausal women. This condition is characterized by a progressive frontal hairline recession associated with scarring. We studied the clinical and histopathologic features in four women with this disorder. Of note, a history of bilateral oophorectomy in two of them appears to be a new association. All four cases had frontoparietal recession of the hairline and two of them also had loss of their eyebrows. None of our four patients had any mucous membrane or other skin lesions. Histological examination showed perifollicular fibrosis and lymphocytic inflammation around the isthmus and infundibular areas of the follicles. No effective treatments have emerged for this type of postmenopausal alopecia, but progression of the hair loss and scarring appears to be self-limiting. We believe that this condition is a distinct clinicopathological variant of lichen planopilaris.

[Rare consciousness disturbances in toxicological practice: akinetic mutism, somnambulism, locked-in syndrome, and psychogenic coma].

PubMed

Ciszowski, Krzysztof; Mietka-Ciszowska, Aneta

2013-01-01

The toxicity of xenobiotics can result inrare disorders of consciousness, such as akinetic mutism and somnambulism as well as syndromes mimicking consciousness disturbances, such as locked-in syndrome and psychogenic coma. Akinetic mutism is a condition characterized by a lack of spontaneous movements and little or no vocalization. Somnambulism include performing of complex motor activity in an automatic manner during deep sleep, without any awareness of its execution. The locked-in syndrome is a state with quadriplegia coexisting with cranial nerves palsies and mutism, but with fully preserved consciousness. Psychogenic coma is a condition in which the patient has preserved level of consciousness and awareness, but does not communicate with theenvironment and does not exhibit the external manifestations of consciousness. This paper presents the etiology, clinical characteristics, as well as diagnostic and therapeutic issues for the above syndromes.

PET Timing Performance Measurement Method Using NEMA NEC Phantom

NASA Astrophysics Data System (ADS)

Wang, Gin-Chung; Li, Xiaoli; Niu, Xiaofeng; Du, Huini; Balakrishnan, Karthik; Ye, Hongwei; Burr, Kent

2016-06-01

When comparing the performance of time-of-flight whole-body PET scanners, timing resolution is one important benchmark. Timing performance is heavily influenced by detector and electronics design. Even for the same scanner design, measured timing resolution is a function of many factors including the activity concentration, geometry and positioning of the radioactive source. Due to lack of measurement standards, the timing resolutions reported in the literature may not be directly comparable and may not describe the timing performance under clinically relevant conditions. In this work we introduce a method which makes use of the data acquired during the standard NEMA Noise-Equivalent-Count-Rate (NECR) measurements, and compare it to several other timing resolution measurement methods. The use of the NEMA NEC phantom, with well-defined dimensions and radioactivity distribution, is attractive because it has been widely accepted in the industry and allows for the characterization of timing resolution across a more relevant range of conditions.

Differential diagnosis in hypersomnia.

PubMed

Dauvilliers, Yves

2006-03-01

Hypersomnia includes a group of disorders in which the primary complaint is excessive daytime sleepiness. Chronic hypersomnia is characterized by at least 3 months of excessive sleepiness prior to diagnosis and may affect 4% to 6% of the population. The severity of daytime sleepiness needs to be quantified by subjective scales (at least the Epworth sleepiness scale) and objective tests such as the multiple sleep latency test. Chronic hypersomnia does not correspond to an individual clinical entity but includes numerous different etiologies of hypersomnia as recently reported in the revised International Classification of Sleep Disorders. This review details most of those disorders, including narcolepsy with and without cataplexy, idiopathic hypersomnia with and without long sleep time, recurrent hypersomnia, behaviorally induced insufficient sleep syndrome, hypersomnia due to medical condition, hypersomnia due to drug or substance, hypersomnia not due to a substance or known physiologic condition, and also sleep-related disordered breathing and periodic leg movement disorders.

Electromechanical Nerve Stimulator

NASA Technical Reports Server (NTRS)

Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

1993-01-01

Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

Bronchiectasis in Children: Current Concepts in Immunology and Microbiology.

PubMed

Pizzutto, Susan J; Hare, Kim M; Upham, John W

2017-01-01

Bronchiectasis is a complex chronic respiratory condition traditionally characterized by chronic infection, airway inflammation, and progressive decline in lung function. Early diagnosis and intensive treatment protocols can stabilize or even improve the clinical prognosis of children with bronchiectasis. However, understanding the host immunologic mechanisms that contribute to recurrent infection and prolonged inflammation has been identified as an important area of research that would contribute substantially to effective prevention strategies for children at risk of bronchiectasis. This review will focus on the current understanding of the role of the host immune response and important pathogens in the pathogenesis of bronchiectasis (not associated with cystic fibrosis) in children.

Phenotypic and genotypic characterization of biofilm formation in Staphylococcus haemolyticus.

PubMed

Barros, Elaine M; Lemos, Moara; Souto-Padrón, Thais; Giambiagi-deMarval, Marcia

2015-06-01

Staphylococcus haemolyticus is one of the most frequently isolated coagulase-negative staphylococci. The ability to produce biofilm has contributed to its emergence as a nosocomial pathogen. In this study, some growth conditions were tested to determine their influence on biofilm formation. Brain-heart infusion (BHI) broth containing glucose was used to screen 64 clinical strains. A strong biofilm producer strain showed cells surrounded by a thick layer of extracellular matrix. The presence of atlE, fbp, bap, and icaA genes was analyzed. We concluded that S. haemolyticus biofilm production can be increased with cells grown in BHI, and highlighted that it could be an ica-independent process.

Giant lymphedema of the penis and scrotum: a case report.

PubMed

Vives, Franklin; García-Perdomo, Herney Andrés; Ocampo-Flórez, Ginna Marcela

2016-01-01

Lymphedema of the penis and scrotum is a rare entity characterized by enlargement of the skin and subcutaneous tissue of the genital region due to lymphatic drainage impairment. This clinical condition is more frequent in tropical countries due to a higher incidence of filariasis, which, in turn, is the main etiology. We describe the case of a 33-year-old man with large lymphedema of the scrotum and penis due to an acute and chronic inflammatory process, foreign body granuloma, and marked hyalinization. Four consecutive surgical interventions were necessary to remove the great part of the affected tissue, which enabled satisfactory results and improved the patient's quality of life.

Obstructive Sleep Apnea in Children: Implications for the Developing Central Nervous System

PubMed Central

Gozal, David

2008-01-01

Recent increases in our awareness to the high prevalence of sleep disorders in general, and of sleep-disordered breathing among children, in particular, has led to concentrated efforts aiming to understand the pathophysiological mechanisms, clinical manifestations and potential consequences of such conditions. In this review, I will briefly elaborate on some of the pathogenetic elements leading to the occurrence of obstructive sleep apnea (OSA) in children, focus on the psycho-behavioral consequences of pediatric OSA, and review the evidence on the potential mechanisms underlying the close association between CNS morbidity and the episodic hypoxia and sleep fragmentation that characterize OSA. PMID:18555196

Paracentric inversion of Yq and review of the literature.

PubMed

Aiello, V; Astolfi, N; Gruppioni, R; Buldrini, B; Prontera, P; Bonfatti, A; Sensi, A; Calzolari, E

2007-01-01

We report on the second prenatal diagnosis of familial paracentric inversion of the long arm of Y chromosome [46, X, inv(Y)(q11.2q12)]. The anomaly was detected through an amniocentesis performed because of advanced maternal age. The inversion has been detected by standard GTG banding methods and better characterized by FISH with painting probe and specific satellite probes DYZ1 and DYZ3. The inversion derived from phenotypically normal father. Pregnancy was uneventful and an healthy child was born. We discuss the issue concerning genetic prenatal counselling of this rare condition and we report the clinical follow up of the child.