Idiopathic Juxtafoveolar Retinal Telangiectasis: A Current Review

PubMed Central

Nowilaty, Sawsan R.; Al-Shamsi, Hanan N.; Al-Khars, Wajeeha

2010-01-01

Idiopathic juxtafoveolar retinal telangiectasis (IJFT), also known as parafoveal telangiectasis or idiopathic macular telangiectasia, refers to a heterogeneous group of well-recognized clinical entities characterized by telangiectatic alterations of the juxtafoveolar capillary network of one or both eyes, but which differ in appearance, presumed pathogenesis, and management strategies. Classically, three groups of IJFT are identified. Group I is unilateral easily visible telangiectasis occurring predominantly in males, and causing visual loss as a result of macular edema. Group II, the most common, is bilateral occurring in both middle-aged men and women, and presenting with telangiectasis that is more difficult to detect on biomicroscopy, but with characteristic and diagnostic angiographic and optical coherence tomography features. Vision loss is due to retinal atrophy, not exudation, and subretinal neovascularization is common. Group III is very rare characterized predominantly by progressive obliteration of the perifoveal capillary network, occurring usually in association with a medical or neurologic disease. This paper presents a current review of juxtafoveolar retinal telangiectasis, reviewing the classification of these entities and focusing primarily on the two most common types encountered in clinical practice, i.e., groups I and II, describing their clinical features, histopathology, natural history, complications, latest results from imaging modalities and functional studies, differential diagnosis, and treatment modalities. PMID:20844678

Clinical manifestations of trisomy 4p syndrome.

PubMed

Patel, S V; Dagnew, H; Parekh, A J; Koenig, E; Conte, R A; Macera, M J; Verma, R S

1995-06-01

Trisomy 4p syndrome is a distinct clinical entity which was noted almost a quarter century ago by Wilson et al. [71] and later was delineated by Gonzalez and colleagues [29]. The variation in the length of duplicated segment usually associated with monosomy of other genetic material which has resulted in confusion and as a result a so-called 4p syndrome could not be recognized without cytogenetic analysis. We wish to draw the attention of clinicians to this subject by presenting the description of over 75 cases including one from our clinic and stress the point that molecular approaches are imperative to characterize this anomaly. After extensive review, it appears that patients retaining at least the distal two-thirds to the entire short arm share an overlapping phenotypic expression that constitutes pure trisomy 4p syndrome which includes prominent glabella, bulbous nose with flat or depressed nasal bridge, retrognathia, pointed chin, short neck with low hairline, enlarged ears with abnormal helix and antihelix, rocker-bottom feet with prominent heel. Arachnodactyly and camptodactyly. Molecular characterization of 4p is imperative. We have also included an extensive bibliography for clinicians who may find it useful as a single reference source for evaluating their future cases. The 4p-syndrome is a distinct entity but without cytogenetic evaluation, the syndrome can not be recognized.

Pleuroparenchymal fibroelastosis: is it also an idiopathic entity?

PubMed

Portillo, Karina; Guasch Arriaga, Ignasi; Ruiz-Manzano, Juan

2015-10-01

Pleuroparenchymal fibroelastosis (PPFE) is a rare disease that has been recently included in the updated consensus on idiopathic interstitial pneumonias. It shares some clinical features with other chronic interstitial pneumonias (dyspnea, dry cough), and is radiologically characterized by pleural and subpleural parenchymal fibrosis and elastosis, mainly in the upper lobes. The main histological findings include pleural fibrosis and prominent subpleural and parenchymal fibroelastosis. Its characterization is based on the increasing number of cases reported in the literature, so several aspects of the etiology, pathogenesis and natural history are still unknown. Although some cases have been described as idiopathic, PPFE has been reported as a complication after bone marrow transplantation, lung transplantation and chemotherapy, especially with alkylating agents.Spontaneous or iatrogenic pneumothorax is a frequently reported complication of invasive diagnostic tests for identifying PPFE. The disease course is variable, ranging from slow progression to rapid clinical deterioration. No treatment has shown evidence of efficacy, and lung transplantation remains the only option for patients who fulfill the diagnostic criteria for this option. Recognizing and disseminating the specific features of PPFE is essential to raise the level of clinical suspicion for this entity, and to implement appropriate multidisciplinary diagnostic management. Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.

Ontology-based reusable clinical document template production system.

PubMed

Nam, Sejin; Lee, Sungin; Kim, James G Boram; Kim, Hong-Gee

2012-01-01

Clinical documents embody professional clinical knowledge. This paper shows an effective clinical document template (CDT) production system that uses a clinical description entity (CDE) model, a CDE ontology, and a knowledge management system called STEP that manages ontology-based clinical description entities. The ontology represents CDEs and their inter-relations, and the STEP system stores and manages CDE ontology-based information regarding CDTs. The system also provides Web Services interfaces for search and reasoning over clinical entities. The system was populated with entities and relations extracted from 35 CDTs that were used in admission, discharge, and progress reports, as well as those used in nursing and operation functions. A clinical document template editor is shown that uses STEP.

[Moxiflaxin and iris transillumination].

PubMed

Broens, A; Collignon, N

2016-07-01

Bilateral Acute Iris Transillumination (BAIT) is a new clinical entity characterized by acute onset of pigment dispersion in the anterior chamber and angle, depigmentation of the iris stroma and permanent iris transillumination, masquerading as uveitis. An association with oral moxifloxacin is reported in some articles. We describe one case of bilateral acute iris transillumination, following the use of systemic moxifloxacin.

Normocalcemic primary hyperparathyroidism

PubMed Central

Bilezikian, John P.; Silverberg, Shonni J.

2011-01-01

SUMMARY Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. The historical view of this disease describes two distinct entities marked by two eras. When primary hyperparathyroidism was first discovered about 80 years ago, it was always symptomatic with kidney stones, bone disease and marked hypercalcemia. With the advent of the multichannel autoanalyzer about 40 years ago, the clinical phenotype changed to a disorder characterized by mild hypercalcemia and the absence of classical other features of the disease. We may now be entering a 3rd era in the history of this disease in which patients are being discovered with normal total and ionized serum calcium concentrations but with parathyroid hormone levels that are consistently elevated. In this article, we describe this new entity, normocalcemic primary hyperparathyroidism, a forme fruste of the disease. PMID:20485897

Assessing the Representation of Occupation Information in Free-Text Clinical Documents Across Multiple Sources

PubMed Central

Lindemann, Elizabeth A.; Chen, Elizabeth S.; Rajamani, Sripriya; Manohar, Nivedha; Wang, Yan; Melton, Genevieve B.

2017-01-01

There has been increasing recognition of the key role of social determinants like occupation on health. Given the relatively poor understanding of occupation information in electronic health records (EHRs), we sought to characterize occupation information within free-text clinical document sources. From six distinct clinical sources, 868 total occupation-related sentences were identified for the study corpus. Building off approaches from previous studies, refined annotation guidelines were created using the National Institute for Occupational Safety and Health Occupational Data for Health data model with elements added to increase granularity. Our corpus generated 2,005 total annotations representing 39 of 41 entity types from the enhanced data model. Highest frequency entities were: Occupation Description (17.7%); Employment Status – Not Specified (12.5%); Employer Name (11.0%); Subject (9.8%); Industry Description (6.2%). Our findings support the value for standardizing entry of EHR occupation information to improve data quality for improved patient care and secondary uses of this information. PMID:29295142

[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.

3M syndrome: a report of four cases in two families.

PubMed

Güven, Ayla; Cebeci, Ayşe Nurcan

2011-01-01

3M syndrome is a rare entity characterized by severe growth retardation, dysmorphic features and skeletal changes as its major components. It is differentiated from other types of dwarfism by its clinical features and by the typical slender long bones and foreshortened vertebral bodies that can be visualized radiographically. 3M syndrome has an autosomal recessive mode of inheritance. An early diagnosis is important for genetic counseling. In this report, we present four children (3 males, 1 female) from two families who were aged between 4(11/12) and 10(11/12) years and had clinical findings of 3M syndrome. One of these patients had received growth hormone (GH) treatment which was discontinued due to an inadequate height gain. Physicians should be aware of this entity in the differential diagnosis of children with severe short stature and mild skeletal changes.

3M Syndrome: A Report of Four Cases in Two Families

PubMed Central

Cebeci, Ayşe Nurcan

2011-01-01

3M syndrome is a rare entity characterized by severe growth retardation, dysmorphic features and skeletal changes as its major components. It is differentiated from other types of dwarfism by its clinical features and by the typical slender long bones and foreshortened vertebral bodies that can be visualized radiographically. 3M syndrome has an autosomal recessive mode of inheritance. An early diagnosis is important for genetic counseling. In this report, we present four children (3 males, 1 female) from two families who were aged between 411/12 and 1011/12 years and had clinical findings of 3M syndrome. One of these patients had received growth hormone (GH) treatment which was discontinued due to an inadequate height gain. Physicians should be aware of this entity in the differential diagnosis of children with severe short stature and mild skeletal changes. Conflict of interest:None declared. PMID:21911330

Naming unique entities in the semantic variant of primary progressive aphasia and Alzheimer's disease: Towards a better understanding of the semantic impairment.

PubMed

Montembeault, M; Brambati, S M; Joubert, S; Boukadi, M; Chapleau, M; Laforce, R Jr; Wilson, M A; Macoir, J; Rouleau, I

2017-01-27

While the semantic variant of primary progressive aphasia (svPPA) is characterized by a predominant semantic memory impairment, episodic memory impairments are the clinical hallmark of Alzheimer's disease (AD). However, AD patients also present with semantic deficits, which are more severe for semantically unique entities (e.g. a famous person) than for common concepts (e.g. a beaver). Previous studies in these patient populations have largely focused on famous-person naming. Therefore, we aimed to evaluate if these impairments also extend to other semantically unique entities such as famous places and famous logos. In this study, 13 AD patients, 9 svPPA patients, and 12 cognitively unimpaired elderly subjects (CTRL) were tested with a picture-naming test of non-unique entities (Boston Naming Test) and three experimental tests of semantically unique entities assessing naming of famous persons, places, and logos. Both clinical groups were overall more impaired at naming semantically unique entities than non-unique entities. Naming impairments in AD and svPPA extended to the other types of semantically unique entities, since a CTRL>AD>svPPA pattern was found on the performance of all naming tests. Naming famous places and famous persons appeared to be most impaired in svPPA, and both specific and general semantic knowledge for these entities were affected in these patients. Although AD patients were most significantly impaired on famous-person naming, only their specific semantic knowledge was impaired, while general knowledge was preserved. Post-hoc neuroimaging analyses also showed that famous-person naming impairments in AD correlated with atrophy in the temporo-parietal junction, a region functionally associated with lexical access. In line with previous studies, svPPA patients' impairment in both naming and semantic knowledge suggest a more profound semantic impairment, while naming impairments in AD may arise to a greater extent from impaired lexical access, even though semantic impairment for specific knowledge is also present. These results highlight the critical importance of developing and using a variety of semantically-unique-entity naming tests in neuropsychological assessments of patients with neurodegenerative diseases, which may unveil different patterns of lexical-semantic deficits. Copyright © 2016 Elsevier Ltd. All rights reserved.

The molecular biology of soft-tissue sarcomas and current trends in therapy.

PubMed

Quesada, Jorge; Amato, Robert

2012-01-01

Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors.

Disseminated Oligodendroglial-like Leptomeningeal Tumor in the Adult: Case Report and Review of the Literature.

PubMed

Fiaschi, Pietro; Badaloni, Filippo; Cagetti, Bernarda; Bruzzone, Luca; Marucci, Gianluca; Dellachà, Anna; Pavanello, Marco; Ganci, Giuseppe; Padolecchia, Riccardo; Valsania, Valtero

2018-06-01

Diffuse leptomeningeal glioneuronal tumor (DLGNT) was recently added to the World Health Organization classification of central nervous system tumors. DLGNT is a rare entity that occurs more commonly in pediatric patients, but occasional cases have been reported in adults. This tumor has been recognized as a distinct pathologic entity; however, its biologic behavior remains unclear. It is considered an indolent neoplasm, although considerable morbidity has been reported. For this reason, further characterization and collection of evidence are crucial. In this article, we reported a case of a 36-year-old woman with a DLGNT characterized by rapid, aggressive behavior. We also performed a review of the literature for reported cases of low-grade and high-grade forms involving adults and children. DLGNTs should no longer be considered only as low-grade tumors affecting pediatric patients. The spectrum of presentations also includes aggressive tumors affecting adults. Further clinical and pathologic data supported by cytogenetic and molecular investigations are mandatory to better characterize DLGNTs. Copyright © 2018 Elsevier Inc. All rights reserved.

[Differential diagnosis of febrile exanthema].

PubMed

Aramă, St S; Anca, Ioana Alina; Munteanu, Daniela-Ioana; Aramă, Victoria; Hristea, Adriana; Moroti, Ruxandra; Ion, Daniela Adriana

2007-01-01

Febrile exanthema (FE) is an extremely polymorphous clinical entity, frequently seen in daily clinical practice. FE is characterized by diffuse rash and fever. FE is classified in 4 types, depending on the primary skin lesion: macular, maculopapular, vesicular, and bullous exanthema. It is of infectious and non-infectious cause. Among the infectious causes the most frequent is the viral one. FE may affect all ages, but especially children and young people. Usually, FE raises important issues of differential diagnosis, because its clinical and etiological complexity. To decide the most appropriate therapeutic and prophylactic measures for FE, it is important to know the clinical criteria and the specific diagnostic methods.

Mondor's disease of the breast. A retrospective review.

PubMed

Salemis, Nikolaos S; Merkouris, Stamatios; Kimpouri, Konstantina

2011-01-01

Mondor's disease is a rare benign clinical entity characterized by thrombophlebitis of the superficial veins of the anterolateral thoraco-abdominal wall. Although several predisposing factors have been reported, the exact pathogenesis remains unclear. We retrospectively reviewed the medical records of all patients older than 14 years who were diagnosed with Mondor's disease of the breast at the Breast Cancer Surgery Unit of Army General Hospital over a 3-year period. Five cases of Mondor's disease were identified among 5717 breast examinations performed during the study period. In 4 patients the disease was considered to be idiopathic. Ultrasonography established the diagnosis in all patients but mammography was inconclusive in two cases due to the presence of dense breast tissue. Four patients received symptomatic treatment. All patients had complete clinical resolution within 2-8 weeks of presentation, and they are well without any evidence of recurrence for 3 to 32 months later. No cases were associated with breast cancer. Mondor's disease of the breast is a rare benign self-limiting clinical entity. Ultrasonography is the diagnostic modality of choice but mammography may be inconclusive in the presence of dense breast tissue. Awareness of this rare entity is mandatory to prevent an unnecessary biopsy whereas the patients should be reassured of the benign nature of this disorder. Thorough evaluation is however necessary to rule out an underlying breast cancer or another systemic disease.

Pneumonitis in Adult Onset Still's Disease: Uncommon or Under Diagnosed?

PubMed

Fernandes, Silvia; Almeida, Margarida; Pereira da Silva, José Alberto; Romeu, José Carlos

2017-08-31

The adult onset Still's Disease is an uncommon entity characterized by multiple clinical manifestations. Pneumonitis, less often considered, deserves particular emphasis given the need for differential diagnosis and because it can progress to severe respiratory failure. With the aim to highlight the pulmonary parenchyma involvement in patients with adult onset Still's Disease, we present a case report which progresses with pneumonitis.

Shah-Waardenburg Syndrome

PubMed Central

Mahmoudi, Abdelhalim; Rami, Mohamed; Khattala, Khalid; Elmadi, Aziz; Afifi, My Abderrahmane; Youssef, Bouabdallah

2013-01-01

Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. Is a very rare congenital disorder with variable clinical expression. This report describes a 4-day-old male newborn with Waardenburg's syndrome associated with aganglionosis of the colon and terminal ileum, and review the relevant literature for draws attention to the causal relationship between these two entities. PMID:23565307

Shah-Waardenburg syndrome.

PubMed

Mahmoudi, Abdelhalim; Rami, Mohamed; Khattala, Khalid; Elmadi, Aziz; Afifi, My Abderrahmane; Youssef, Bouabdallah

2013-01-01

Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. Is a very rare congenital disorder with variable clinical expression. This report describes a 4-day-old male newborn with Waardenburg's syndrome associated with aganglionosis of the colon and terminal ileum, and review the relevant literature for draws attention to the causal relationship between these two entities.

42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis--an entity different from adults.

PubMed

DeLario, Melissa R; Sheehan, Andrea M; Ataya, Ramona; Bertuch, Alison A; Vega, Carlos; Webb, C Renee; Lopez-Terrada, Dolores; Venkateswaran, Lakshmi

2012-05-01

Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients. Copyright © 2012 Wiley Periodicals, Inc.

Aneurysmal Bone Cysts of the Spine: Two Case Reports

PubMed Central

Ozdemir, Seymen; Ozden, Ferhat; Kacira, Ozlem Kitiki; Kacira, Tibet

2014-01-01

Aneurysmal bone cysts are rare entities which causes expansile and destructive bone lesions characterized by reactive proliferation of connective tissue. They usually grow rapidly with hypervascularity. In clinical practice they can be easily misdiagnosed due to the rare occurance and having no such typical findings as radiologically. Most cases have uncommon pain symptoms, but rarely, if fractures occur, neurological findings can be seen and the surgical treatment, if needed, could be difficult. We will discuss our evaluations to two cases that we experienced in our clinic in this report. PMID:25620988

Aneurysmal bone cysts of the spine: two case reports.

PubMed

Ozdemir, Seymen; Yaldiz, Can; Ozden, Ferhat; Kacira, Ozlem Kitiki; Kacira, Tibet

2014-12-01

Aneurysmal bone cysts are rare entities which causes expansile and destructive bone lesions characterized by reactive proliferation of connective tissue. They usually grow rapidly with hypervascularity. In clinical practice they can be easily misdiagnosed due to the rare occurance and having no such typical findings as radiologically. Most cases have uncommon pain symptoms, but rarely, if fractures occur, neurological findings can be seen and the surgical treatment, if needed, could be difficult. We will discuss our evaluations to two cases that we experienced in our clinic in this report.

[Pearson syndrome. Case report].

PubMed

Cammarata-Scalisi, Francisco; López-Gallardo, Ester; Emperador, Sonia; Ruiz-Pesini, Eduardo; Da Silva, Gloria; Camacho, Nolis; Montoya, Julio

2011-09-01

Among the etiologies of anemia in the infancy, the mitochondrial cytopathies are infrequent. Pearson syndrome is diagnosed principally during the initial stages of life and it is characterized by refractory sideroblastic anemia with vacuolization of marrow progenitor cells, exocrine pancreatic dysfunction and variable neurologic, hepatic, renal and endocrine failures. We report the case of a 14 month-old girl evaluated by a multicentric study, with clinic and molecular diagnosis of Pearson syndrome, with the 4,977-base pair common deletion of mitochondrial DNA. This entity has been associated to diverse phenotypes within the broad clinical spectrum of mitochondrial disease.

[Mitochondrial disease due to the deficit of Q-cytochrome C oxidoreductase coenzyme in the respiratory chain. Report of a new case].

PubMed

Roldán, S; Lluch, M D; Navarro Quesada, F J; Hevia, A

1995-01-01

Reference has been made in the literature of the variability in the clinical presentation of deficiency of complex III of the respiratory chain, identifying up to the moment, four groups, the first of which is characterized by hipotonia and wearness starting at variable ages. We report a new case of mitochondrial myopathy due to deficiency of this complex and included within this first group, and consider the importance of defining the clinical and histochemical characteristics of this polymorphous entity.

[Primary perivascular epitheloid cell tumour (PEComa) of the liver - is a new entity of the liver tumors?].

PubMed

Panahova, S; Rempp, H; Sipos, B; Malek, N P; Boozari, B

2015-05-01

Perivascular epitheloid cell tumor (PEComa) is a rare tumor, characterized by dual Expression of smooth muscle and melanocytic markers. Due to the development of diagnostic procedures, we now diagnose PEComa more often. We report about a case of PEComa of the liver as an accidental finding. We analyze the clinical and morphological characteristics of this tumor and compare it with the data of the literature. Management of patients with PEComa is not yet standardized; therefore biopsy with immunhistochemical staining is necessary for the diagnosis. In case of liver tumors which cannot be classified by their morphology on imaging modalities, it is important to think about this rare entity. © Georg Thieme Verlag KG Stuttgart · New York.

Characterization of Change and Significance for Clinical Findings in Radiology Reports Through Natural Language Processing.

PubMed

Hassanpour, Saeed; Bay, Graham; Langlotz, Curtis P

2017-06-01

We built a natural language processing (NLP) method to automatically extract clinical findings in radiology reports and characterize their level of change and significance according to a radiology-specific information model. We utilized a combination of machine learning and rule-based approaches for this purpose. Our method is unique in capturing different features and levels of abstractions at surface, entity, and discourse levels in text analysis. This combination has enabled us to recognize the underlying semantics of radiology report narratives for this task. We evaluated our method on radiology reports from four major healthcare organizations. Our evaluation showed the efficacy of our method in highlighting important changes (accuracy 99.2%, precision 96.3%, recall 93.5%, and F1 score 94.7%) and identifying significant observations (accuracy 75.8%, precision 75.2%, recall 75.7%, and F1 score 75.3%) to characterize radiology reports. This method can help clinicians quickly understand the key observations in radiology reports and facilitate clinical decision support, review prioritization, and disease surveillance.

Massive ovarian oedema: a misleading clinical entity.

PubMed

Machairiotis, Nikolaos; Stylianaki, Aikaterini; Kouroutou, Paraskevi; Sarli, Polixeni; Alexiou, Nikolaos Konstantinos; Efthymiou, Elias; Maras, Athanasios; Alexiou, Nikolaos Georgios; Nikolaou, Spyridon Evaggelos; Courcoutsakis, Nikolaos; Papakonstantinou, Eleni; Zarogoulidis, Paul; Barbetakis, Nikolaos; Paliouras, Dimitrios; Gogakos, Apostolos; Machairiotis, Christodoulos

2016-02-03

Massive ovarian oedema is a rare non-neoplastic clinicopathologic entity has a higher incidence in women during their second and third life decade. The oedema can be presented in one or both ovaries as a result of partial intermittent torsion of the ovarian pedicle that interferes to the venal and lymphatic drainage of the ovary. We present a clinical case of a 16 year old with massive ovarian oedema and we performed a review of the literature. The pathophysiology of this entity is very complex. We tried to perform a complete review of the literature and focus on the complexity of this entity as far as its pathophysiological backround is concerned and as far as its clinical presentation is concerned. In conclusion, massive ovarian oedema is a rare, multi disease mimicking clinical entity, with an acute or progressive clinical presentation. It has also to be a part of our differential diagnosis in cases of acute abdominal pain and we have to try to treat her conservatively, in order to preserve fertility.

NELasso: Group-Sparse Modeling for Characterizing Relations Among Named Entities in News Articles.

PubMed

Tariq, Amara; Karim, Asim; Foroosh, Hassan

2017-10-01

Named entities such as people, locations, and organizations play a vital role in characterizing online content. They often reflect information of interest and are frequently used in search queries. Although named entities can be detected reliably from textual content, extracting relations among them is more challenging, yet useful in various applications (e.g., news recommending systems). In this paper, we present a novel model and system for learning semantic relations among named entities from collections of news articles. We model each named entity occurrence with sparse structured logistic regression, and consider the words (predictors) to be grouped based on background semantics. This sparse group LASSO approach forces the weights of word groups that do not influence the prediction towards zero. The resulting sparse structure is utilized for defining the type and strength of relations. Our unsupervised system yields a named entities' network where each relation is typed, quantified, and characterized in context. These relations are the key to understanding news material over time and customizing newsfeeds for readers. Extensive evaluation of our system on articles from TIME magazine and BBC News shows that the learned relations correlate with static semantic relatedness measures like WLM, and capture the evolving relationships among named entities over time.

[Clinical and molecular study in a child with X-linked hypohidrotic ectodermal dysplasia].

PubMed

Callea, Michele; Yavuz, Izzet; Clarich, Gabriella; Cammarata-Scalisi, Francisco

2015-12-01

Ectodermal dysplasia encompasses more than 200 clinically distinct entities, which affect at least two structures derived from the ectoderm, including the skin, hair, nails, teeth, sweat glands, and sebaceous glands. X-linked hypohidrotic ectodermal dysplasia is the most common type and is caused by mutation of the EDA gene that encodes Ectodysplasin-A. It occurs in less than 1 in 100 000 individuals and is clinically characterized by hypodontia, hypohidrosis, hypotrichosis, and eye dis orders. We present a child evaluated in a multidisciplinary manner with clinical and molecular diagnosis of X-linked hypohidrotic ectodermal dysplasia with type missense mutation c.1133C> T; p.T378M in EDA gene.

Progress in the development of animal models of acute kidney injury and its impact on drug discovery.

PubMed

Sanz, Ana B; Sanchez-Niño, María Dolores; Martín-Cleary, Catalina; Ortiz, Alberto; Ramos, Adrián M

2013-07-01

Acute kidney injury (AKI) is a clinical syndrome characterized by the acute loss of kidney function. AKI is increasingly frequent and is associated with impaired survival and chronic kidney disease progression. Experimental AKI models have contributed to a better understanding of pathophysiological mechanisms but they have not yet resulted in routine clinical application of novel therapeutic approaches. The authors present the advances in experimental AKI models over the last decade. Furthermore, the authors review their current and expected impact on novel drug discovery. New AKI models have been developed in rodents and non-rodents. Non-rodents allow the evaluation of specific aspects of AKI in both bigger animals and simpler organisms such as drosophila and zebrafish. New rodent models have recently reproduced described clinical entities, such as aristolochic and warfarin nephropathies, and have also provided better models for old entities such as thrombotic microangiopathy-induced AKI. Several therapies identified in animal models are now undergoing clinical trials in human AKI, including p53 RNAi and bone-marrow derived mesenchymal stem cells. It is conceivable that further refinement of animal models in combination with ongoing trials and novel trials based on already identified potential targets will eventually yield effective therapies for clinical AKI.

Anatomical Entity Recognition with a Hierarchical Framework Augmented by External Resources

PubMed Central

Xu, Yan; Hua, Ji; Ni, Zhaoheng; Chen, Qinlang; Fan, Yubo; Ananiadou, Sophia; Chang, Eric I-Chao; Tsujii, Junichi

2014-01-01

References to anatomical entities in medical records consist not only of explicit references to anatomical locations, but also other diverse types of expressions, such as specific diseases, clinical tests, clinical treatments, which constitute implicit references to anatomical entities. In order to identify these implicit anatomical entities, we propose a hierarchical framework, in which two layers of named entity recognizers (NERs) work in a cooperative manner. Each of the NERs is implemented using the Conditional Random Fields (CRF) model, which use a range of external resources to generate features. We constructed a dictionary of anatomical entity expressions by exploiting four existing resources, i.e., UMLS, MeSH, RadLex and BodyPart3D, and supplemented information from two external knowledge bases, i.e., Wikipedia and WordNet, to improve inference of anatomical entities from implicit expressions. Experiments conducted on 300 discharge summaries showed a micro-averaged performance of 0.8509 Precision, 0.7796 Recall and 0.8137 F1 for explicit anatomical entity recognition, and 0.8695 Precision, 0.6893 Recall and 0.7690 F1 for implicit anatomical entity recognition. The use of the hierarchical framework, which combines the recognition of named entities of various types (diseases, clinical tests, treatments) with information embedded in external knowledge bases, resulted in a 5.08% increment in F1. The resources constructed for this research will be made publicly available. PMID:25343498

Psoriasiform keratosis - case report.

PubMed

Pires, Carla Andréa Avelar; Sousa, Brena Andrade de; Nascimento, Carla do Socorro Silva do; Moutinho, Ana Thais Machado; Miranda, Mario Fernando Ribeiro de; Carneiro, Francisca Regina Oliveira

2014-01-01

Psoriasiform Keratosis is a rare clinic entity. The etiopathogenesis remains unknown and the disease is characterized by a solitary, scaly or keratotic papule, or plaque mainly located on the extremities. Histopathological features closely resemble those of psoriasis. We report the case of a 70-year-old woman presenting a solitary and asymptomatic keratotic plaque, located on the back of the left leg, unresponsive to topical corticosteroids. We performed an excisional biopsy and histopathology was consistent with psoriasiform keratosis.

[Airway-centered interstitial fibrosis related to exposure to fumes from cleaning products].

PubMed

Serrano, Mario; Molina-Molina, María; Ramírez, José; Sánchez, Marcelo; Xaubet, Antoni

2006-10-01

Airway-centered interstitial fibrosis is a little known clinical entity that has only recently been described in the literature. Its pathology is characterized by bronchial fibrosis and localized interstitial pulmonary fibrosis around the airways. The disease has been associated with inhalation of a variety of substances, environmental or occupational, organic or inorganic. Clinical signs, radiographic manifestations, and lung function in patients with airway-centered interstitial fibrosis are similar to those of patients with idiopathic interstitial pneumonia. We describe a case of airway-centered interstitial fibrosis related to exposure to fumes from cleaning products.

Heterotaxy syndrome with severe pulmonary hypertension in an adult.

PubMed

Brandenburg, Vincent M; Krueger, Stefan; Haage, Patrick; Mertens, Peter; Riehl, Jochen

2002-05-01

Heterotaxy syndrome is a rare clinical entity in adults, characterized by situs ambiguus, congenital heart defects, and splenic malformations. We report the case of an adult with heterotaxy syndrome (including situs ambiguus, bilateral superior vena cava, hypoplastic right-sided spleen and portosystemic shunts) presenting with dyspnea due to severe pulmonary hypertension. Vasodilatory therapy was initiated, leading to marked reduction of clinical symptoms. This case exhibits 2 particular and partially novel features: primary diagnosis of heterotaxy syndrome may be delayed until adulthood, and heterotaxy syndrome may be associated with pulmonary hypertension, possibly on the basis of longstanding portosystemic shunts.

Follicular vitiligo: A report of 8 cases.

PubMed

Gan, Emily Yiping; Cario-André, Muriel; Pain, Catherine; Goussot, Jean-Francois; Taïeb, Alain; Seneschal, Julien; Ezzedine, Khaled

2016-06-01

Follicular vitiligo, a recently proposed new subtype of vitiligo, has primary involvement of the hair follicle melanocytic reservoir. We sought to characterize follicular vitiligo through a case series of 8 patients. Patients with features of follicular vitiligo who were seen at the vitiligo clinic in the National Center for Rare Skin Disorders in Bordeaux, France, were recruited. A retrospective review of case records and clinical photographs was carried out. There were 8 male patients with a mean age of 48 years. All patients reported significant whitening of their body and, in some, scalp hairs before cutaneous depigmentation. Examination revealed classic generalized depigmented lesions of vitiligo and an impressive presence of leukotrichia, not only in the vitiliginous areas, but also in areas with clinically normal-appearing skin. Punch biopsy specimen of the leukotrichia and vitiligo lesions demonstrated loss of melanocytes and precursors in the basal epidermis and hair follicle. This was a cross-sectional study based on a single-center experience. Follicular vitiligo is a distinct entity within the spectrum of vitiligo. This entity may serve as the missing link between alopecia areata and vitiligo, with probable physiopathological similarities between these conditions. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Segmental stiff skin syndrome (SSS): A distinct clinical entity.

PubMed

Myers, Kathryn L; Mir, Adnan; Schaffer, Julie V; Meehan, Shane A; Orlow, Seth J; Brinster, Nooshin K

2016-07-01

Stiff skin syndrome (SSS) is a noninflammatory, fibrosing condition of the skin, often affecting the limb girdles. We present 4 new patients with SSS with largely unilateral, segmental distribution. To date, reported cases of SSS have been grouped based on generally accepted clinical and histopathologic findings. The purpose of this study was to analyze differences in clinical and histopathologic findings between previously reported SSS cases. This is a retrospective review of 4 new cases and 48 previously published cases of SSS obtained from PubMed search. Of 52 total cases, 18 (35%) were segmentally distributed and 34 (65%) were widespread. The average age of onset was 4.1 years versus 1.6 years for segmental versus widespread SSS, respectively. Limitation in joint mobility affected 44% of patients with segmental SSS and 97% of patients with widespread SSS. Histopathologic findings were common between the 2 groups. This was a retrospective study of previously published cases limited by the completeness and accuracy of the reviewed cases. We propose a distinct clinical entity, segmental SSS, characterized by a segmental distribution, later age of onset, and less severe functional limitation. Both segmental SSS and widespread SSS share common diagnostic histopathologic features. Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.

Automatic recognition of disorders, findings, pharmaceuticals and body structures from clinical text: an annotation and machine learning study.

PubMed

Skeppstedt, Maria; Kvist, Maria; Nilsson, Gunnar H; Dalianis, Hercules

2014-06-01

Automatic recognition of clinical entities in the narrative text of health records is useful for constructing applications for documentation of patient care, as well as for secondary usage in the form of medical knowledge extraction. There are a number of named entity recognition studies on English clinical text, but less work has been carried out on clinical text in other languages. This study was performed on Swedish health records, and focused on four entities that are highly relevant for constructing a patient overview and for medical hypothesis generation, namely the entities: Disorder, Finding, Pharmaceutical Drug and Body Structure. The study had two aims: to explore how well named entity recognition methods previously applied to English clinical text perform on similar texts written in Swedish; and to evaluate whether it is meaningful to divide the more general category Medical Problem, which has been used in a number of previous studies, into the two more granular entities, Disorder and Finding. Clinical notes from a Swedish internal medicine emergency unit were annotated for the four selected entity categories, and the inter-annotator agreement between two pairs of annotators was measured, resulting in an average F-score of 0.79 for Disorder, 0.66 for Finding, 0.90 for Pharmaceutical Drug and 0.80 for Body Structure. A subset of the developed corpus was thereafter used for finding suitable features for training a conditional random fields model. Finally, a new model was trained on this subset, using the best features and settings, and its ability to generalise to held-out data was evaluated. This final model obtained an F-score of 0.81 for Disorder, 0.69 for Finding, 0.88 for Pharmaceutical Drug, 0.85 for Body Structure and 0.78 for the combined category Disorder+Finding. The obtained results, which are in line with or slightly lower than those for similar studies on English clinical text, many of them conducted using a larger training data set, show that the approaches used for English are also suitable for Swedish clinical text. However, a small proportion of the errors made by the model are less likely to occur in English text, showing that results might be improved by further tailoring the system to clinical Swedish. The entity recognition results for the individual entities Disorder and Finding show that it is meaningful to separate the general category Medical Problem into these two more granular entity types, e.g. for knowledge mining of co-morbidity relations and disorder-finding relations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Cardiac involvement in antiphospholipid syndrome associated with Sneddon syndrome: a challenging diagnosis.

PubMed

Faustino, Ana; Paiva, Luís; Morgadinho, Ana; Trigo, Emília; Botelho, Ana; Costa, Marco; Leitão-Marques, António

2014-02-01

Sneddon syndrome is a rare clinical entity characterized by the association of ischemic cerebrovascular disease and livedo reticularis. The authors report a case of stroke and myocardial infarction in a 39-year-old man with Sneddon syndrome and antiphospholipid syndrome who subsequently met some criteria for systemic lupus erythematosus, highlighting the complexity of cardiovascular involvement in systemic diseases. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Psoriasiform Keratosis - Case report*

PubMed Central

Pires, Carla Andréa Avelar; de Sousa, Brena Andrade; do Nascimento, Carla do Socorro Silva; Moutinho, Ana Thais Machado; de Miranda, Mario Fernando Ribeiro; Carneiro, Francisca Regina Oliveira

2014-01-01

Psoriasiform Keratosis is a rare clinic entity. The etiopathogenesis remains unknown and the disease is characterized by a solitary, scaly or keratotic papule, or plaque mainly located on the extremities. Histopathological features closely resemble those of psoriasis. We report the case of a 70-year-old woman presenting a solitary and asymptomatic keratotic plaque, located on the back of the left leg, unresponsive to topical corticosteroids. We performed an excisional biopsy and histopathology was consistent with psoriasiform keratosis. PMID:24770510

Primary immunodeficiencies appearing as combined lymphopenia, neutropenia, and monocytopenia.

PubMed

Dotta, Laura; Badolato, Raffaele

2014-10-01

Recurrent or prolonged severe infections associated to panleukopenia strongly suggest primary immune disorders. In recent years, new immunodeficiency syndromes turned up: besides the importance of continuous clinical characterization throughout added reports, the phenotype can easily lead to diagnosis of known rare entities. Our purpose is to review main emerging genetic syndromes featuring lymphopenia combined to neutropenia and/or monocytopenia in order to facilitate diagnosis of rare primary immune deficiencies. Copyright © 2013 Elsevier B.V. All rights reserved.

Primary cutaneous adenosquamous carcinoma of the penis: the first characterization of HPV status in this rare and diagnostically challenging entity with review of glandular carcinomas of the penis.

PubMed

Rush, P S; Shiau, J M; Hibler, B P; Longley, B J; Downs, T M; Bennett, D D

2016-12-01

Glandular and pseudoglandular tumors of the penile skin are extremely uncommon and can present diagnostic challenges. Primary adenosquamous carcinoma of the penis is an extremely rare tumor, composed of distinct areas of malignant squamous and glandular cells, making it a diagnostically challenging entity. The World Health Organization (WHO) recognizes several subtypes of squamous cell carcinoma (SCC), each with its own distinctive pathologic appearance, clinical associations and prognosis. Among these variants is the exceedingly uncommon adenosquamous carcinoma (ASC), representing 1%-2% of all SCC of the penis. Recent large studies have interrogated the presence of human papillomavirus (HPV) in malignant penile tumors and have shown specific morphologic patterns and clinical presentations to associate with HPV status. However, given the rarity of the adenosquamous variant of SCC, it has largely been excluded from these studies. The glandular components of these lesions can present a confusing appearance, particularly when a large tumor is represented on a small biopsy. Here we describe a difficult histologic presentation of this rare tumor, with the first published characterization of the HPV status of this subtype. This case represents a distinctly unusual case of metastatic HPV-positive primary cutaneous adenosquamous carcinoma of the penis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Semantic characteristics of NLP-extracted concepts in clinical notes vs. biomedical literature.

PubMed

Wu, Stephen; Liu, Hongfang

2011-01-01

Natural language processing (NLP) has become crucial in unlocking information stored in free text, from both clinical notes and biomedical literature. Clinical notes convey clinical information related to individual patient health care, while biomedical literature communicates scientific findings. This work focuses on semantic characterization of texts at an enterprise scale, comparing and contrasting the two domains and their NLP approaches. We analyzed the empirical distributional characteristics of NLP-discovered named entities in Mayo Clinic clinical notes from 2001-2010, and in the 2011 MetaMapped Medline Baseline. We give qualitative and quantitative measures of domain similarity and point to the feasibility of transferring resources and techniques. An important by-product for this study is the development of a weighted ontology for each domain, which gives distributional semantic information that may be used to improve NLP applications.

Context and Domain Knowledge Enhanced Entity Spotting in Informal Text

NASA Astrophysics Data System (ADS)

Gruhl, Daniel; Nagarajan, Meena; Pieper, Jan; Robson, Christine; Sheth, Amit

This paper explores the application of restricted relationship graphs (RDF) and statistical NLP techniques to improve named entity annotation in challenging Informal English domains. We validate our approach using on-line forums discussing popular music. Named entity annotation is particularly difficult in this domain because it is characterized by a large number of ambiguous entities, such as the Madonna album "Music" or Lilly Allen's pop hit "Smile".

A rare case of atypical pleomorphic adenoma arising from periocular ectopic lacrimal gland.

PubMed

Wajda, Brynn N; Mancini, Ronald; Evers, Bret; Nick Hogan, R

2018-06-23

To describe features of atypical pleomorphic adenoma, a rare clinical entity, particularly when found in ectopic periocular lacrimal gland tissue. Case report of biopsy-confirmed periocular atypical pleomorphic adenoma. A 35-year-old female presented with a unique orbital lesion found to be ectopic lacrimal gland demonstrating atypical pleomorphic adenoma on formal histopathologic review. Pleomorphic adenoma is pathologically characterized as an epithelial lesion intermixed with mesenchymal elements. It is further classified as atypical with the presence of features such as hypercellularity, regions of necrosis or hyalinization, cellular dysplasia, capsular violation, and malignant characteristics without frank local extension or distant metastases. Due to its rarity, the natural history and prognosis of atypical pleomorphic adenoma is unclear. Physicians need to recognize this entity, and complete surgical excision with strict follow-up regimens are likely warranted.

5 CFR 890.1003 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... a physician, hospital, clinic, or other individual or entity that, directly or indirectly, furnishes... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL... and equipment; and hospitals, clinics, or other institutional entities that furnish supplies and...

5 CFR 890.1003 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... a physician, hospital, clinic, or other individual or entity that, directly or indirectly, furnishes... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL... and equipment; and hospitals, clinics, or other institutional entities that furnish supplies and...

5 CFR 890.1003 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... a physician, hospital, clinic, or other individual or entity that, directly or indirectly, furnishes... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL... and equipment; and hospitals, clinics, or other institutional entities that furnish supplies and...

5 CFR 890.1003 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... a physician, hospital, clinic, or other individual or entity that, directly or indirectly, furnishes... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL... and equipment; and hospitals, clinics, or other institutional entities that furnish supplies and...

Unsupervised Biomedical Named Entity Recognition: Experiments with Clinical and Biological Texts

PubMed Central

Zhang, Shaodian; Elhadad, Nóemie

2013-01-01

Named entity recognition is a crucial component of biomedical natural language processing, enabling information extraction and ultimately reasoning over and knowledge discovery from text. Much progress has been made in the design of rule-based and supervised tools, but they are often genre and task dependent. As such, adapting them to different genres of text or identifying new types of entities requires major effort in re-annotation or rule development. In this paper, we propose an unsupervised approach to extracting named entities from biomedical text. We describe a stepwise solution to tackle the challenges of entity boundary detection and entity type classification without relying on any handcrafted rules, heuristics, or annotated data. A noun phrase chunker followed by a filter based on inverse document frequency extracts candidate entities from free text. Classification of candidate entities into categories of interest is carried out by leveraging principles from distributional semantics. Experiments show that our system, especially the entity classification step, yields competitive results on two popular biomedical datasets of clinical notes and biological literature, and outperforms a baseline dictionary match approach. Detailed error analysis provides a road map for future work. PMID:23954592

Clinical implications of a rare renal entity: Pleomorphic Hyalinizing Angiectatic Tumor (PHAT).

PubMed

Scalici Gesolfo, Cristina; Serretta, Vincenzo; Di Maida, Fabrizio; Giannone, Giulio; Barresi, Elisabetta; Franco, Vito; Montironi, Rodolfo

2017-02-01

Pleomorphic Hyalinizing Angiectatic Tumor (PHAT) is a rare benign lesion characterized by slow growth, infiltrative behavior and high rate of local recurrences. Only one case has been described in retroperitoneum, at renal hilum, but not involving pelvis or parenchyma. Here we present the first case of PHAT arising in the renal parenchyma. A nodular lesion in right kidney lower pole was diagnosed to a 61 year old woman. The patient underwent right nephrectomy. Microscopically, the lesion showed solid and pseudo-cystic components with hemorrhagic areas characterized by aggregates of ectatic blood vessels. Pleomorphic cells were characterized by large eosinophilic cytoplasm with irregular and hyperchromatic nuclei. Immunohistochemistry was performed and the lesion was classified as a Pleomorphic Hyalinizing Angiectatic Tumor (PHAT). Due to the clinical behavior of this tumor, in spite of its benign nature, review of the surgical margins and close follow up after partial nephrectomy are mandatory. Copyright © 2016. Published by Elsevier GmbH.

A study of machine-learning-based approaches to extract clinical entities and their assertions from discharge summaries.

PubMed

Jiang, Min; Chen, Yukun; Liu, Mei; Rosenbloom, S Trent; Mani, Subramani; Denny, Joshua C; Xu, Hua

2011-01-01

The authors' goal was to develop and evaluate machine-learning-based approaches to extracting clinical entities-including medical problems, tests, and treatments, as well as their asserted status-from hospital discharge summaries written using natural language. This project was part of the 2010 Center of Informatics for Integrating Biology and the Bedside/Veterans Affairs (VA) natural-language-processing challenge. The authors implemented a machine-learning-based named entity recognition system for clinical text and systematically evaluated the contributions of different types of features and ML algorithms, using a training corpus of 349 annotated notes. Based on the results from training data, the authors developed a novel hybrid clinical entity extraction system, which integrated heuristic rule-based modules with the ML-base named entity recognition module. The authors applied the hybrid system to the concept extraction and assertion classification tasks in the challenge and evaluated its performance using a test data set with 477 annotated notes. Standard measures including precision, recall, and F-measure were calculated using the evaluation script provided by the Center of Informatics for Integrating Biology and the Bedside/VA challenge organizers. The overall performance for all three types of clinical entities and all six types of assertions across 477 annotated notes were considered as the primary metric in the challenge. Systematic evaluation on the training set showed that Conditional Random Fields outperformed Support Vector Machines, and semantic information from existing natural-language-processing systems largely improved performance, although contributions from different types of features varied. The authors' hybrid entity extraction system achieved a maximum overall F-score of 0.8391 for concept extraction (ranked second) and 0.9313 for assertion classification (ranked fourth, but not statistically different than the first three systems) on the test data set in the challenge.

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.

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

Multidisciplinary Approach for Restoring Function and Esthetics in a Patient with Amelogenesis Imperfecta: A Clinical Report

PubMed Central

Kamble, Vaibhav D; Parkhedkar, Rambhau D

2013-01-01

Amelogenesis Imperfecta (AI) is a genetically determined and enamel mineralization defect reported, depicted as “Hereditary brown teeth.” AI is characterized as a clinical entity and its clinical manifestations, histological appearance, and genetic pattern are characterized by their heterogeneity. The need for prosthodontic management of this group of patients varies. Some patients need oral hygiene instructions only, whereas others need extensive dental treatment that includes composite restorations, metal ceramic crowns, all ceramic crowns, porcelain veneers. A 20-year-old male patient presented with sensitive, discoloured, and mutilated teeth, with a decreased vertical dimension of occlusion. The 4-year recall examination revealed no pathology associated with the full mouth rehabilitation, and the patient’s aesthetic and functional expectations were satisfied. The rehabilitation included all-ceramic crowns on anterior teeth and metal-ceramic crowns on posterior teeth following endodontic treatment and a crown-lengthening procedure for eliminating tooth sensitivity, improving the aesthetics and occlusion, and for restoring function. PMID:24551735

Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

PubMed

Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W

2015-06-01

CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir.

42 CFR 420.201 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... provider of services, an independent clinical laboratory, a renal disease facility, a rural health clinic..., common supporting staff, or common equipment). Indirect ownership interest means any ownership interest in an entity that has an ownership interest in the disclosing entity. The term includes an ownership...

42 CFR 420.201 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... provider of services, an independent clinical laboratory, a renal disease facility, a rural health clinic..., common supporting staff, or common equipment). Indirect ownership interest means any ownership interest in an entity that has an ownership interest in the disclosing entity. The term includes an ownership...

42 CFR 420.201 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... provider of services, an independent clinical laboratory, a renal disease facility, a rural health clinic..., common supporting staff, or common equipment). Indirect ownership interest means any ownership interest in an entity that has an ownership interest in the disclosing entity. The term includes an ownership...

[MCTD--mixed connective tissue disease].

PubMed

Haustein, Uwe-Frithjof

2005-02-01

Mixed connective tissue disease is a disease entity characterized by overlapping symptoms of lupus erythematosus (LE), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA). Diagnostic criteria include high titers of antibodies against U1RNP as well as the presence of at least 3 of 5 of the following clinical features: edema of hands, synovitis, myositis, Raynaud phenomenon and acroscierosis. In terms of the pathogenesis, genetic as well as infectious (viral) factors appear to play a role. The acceptance of MCTD as a distinct disease entity is controversial. Terms such as "undifferentiated connective tissue disease" or "overlapping syndromes" are not helpful. One-quarter of MCTD patients transform into LE, while one-third progress to SSc. Therapeutic recommendations are glucocorticoids in combination with immunosuppressive agents and endothelin receptor antagonists. Double blind studies are not available. The prognosis is relatively good. Causes of death include pulmonary hypertension, infections and both pulmonary and cardiac failure.

The specific scintigraphic pattern of "shin splints in the lower leg": concise communication.

PubMed

Holder, L E; Michael, R H

1984-08-01

The clinical entity, "shin splints," is now being recognized, and more specifically characterized by the findings of exercise-induced pain and tenderness to palpation along the posterior medial border of the tibia. In this prospective study, ten patients with this syndrome were evaluated using three-phase bone scintigrams, and a specific scintigraphic pattern was determined. Radionuclide angiograms and blood-pool images were all normal. On delayed images, tibial lesions involved the posterior cortex, were longitudinally oriented, were long, involving one third of the length of the bone, and often showed varying tracer uptake along that length. Obtaining both lateral and medial views was crucial. The location of activity suggested that this entity is related to the soleus muscle. These scintigraphic findings can be used to differentiate shin splints from stress fractures or other conditions causing pain in the lower leg in athletes.

Visual impairment caused by periorbital edema in an infant with acute hemorrhagic edema of infancy.

PubMed

Freitas, Priscila; Bygum, Anette

2013-01-01

Acute hemorrhagic edema of infancy (AHEI) is a cutaneous vasculitis seen in children. Many consider it to be a clinical variant of Schönlein-Henoch purpura, but others regard it as a separate entity because of its benign nature, age of onset, lack of visceral involvement, and frequent absence of vascular immunoglobulin A deposition. It is clinically characterized by large "cockade" or rosette-shaped, annular, purpuric lesions involving the face and extremities; erythematous edema; and mild fever. It seems to appear secondary to a history of viral or bacterial infection, course of antibiotics, or vaccination. Because of the unknown etiology and benign character, which leads to spontaneous complete recovery, there is no specific treatment necessary for AHEI, and according to the literature, systemic corticosteroids do not seem to alter the course of the disease. We report the case of an 11-month-old boy who manifested massive periorbital edema along with all of the clinical characteristics of this entity and showed clear improvement of the symptoms after a 24-hour administration of systemic corticosteroid therapy. Given the positive effect of this therapy, we propose that systemic corticosteroids should be used to ameliorate the acute manifestations and avoid the rapid progression of the disease. © 2012 Wiley Periodicals, Inc.

Non-Radiation-Related Osteonecrosis of the Jaws in Dogs: 14 Cases (1996–2014)

PubMed Central

Peralta, Santiago; Arzi, Boaz; Nemec, Ana; Lommer, Milinda J.; Verstraete, Frank J. M.

2015-01-01

Osteonecrosis of the jaws (ONJ) is an entity of major clinical impact characterized by chronically exposed necrotic mandibular or maxillary bone. Its clinicopathological characteristics and possible inciting or risk factors are well described in humans but only anecdotally reported in dogs. Treatment modalities and outcome vary depending on the inciting factors involved and the extent and severity of the lesions. The objectives of this study were to retrospectively describe the clinicopathological features of non-radiation-related ONJ in a series of 14 dogs, identify possible inciting or risk factors, and report on the surgical treatment and outcome. For all patients, the medical records were used to collect information regarding signalment, clinical signs, characteristics of the oral, jaw and dental lesions, diagnostic imaging findings, histopathological and microbiological analysis, treatment performed, and outcome. The data collected showed that non-radiation-related ONJ appears to be an infrequent clinical entity but of significant impact in dogs; that a history of systemic antibiotics and dental disease is common among affected dogs; that previous dental extractions are commonly associated with ONJ sites; that using a systematic diagnostic approach is essential for diagnosis; and that thorough surgical debridement combined with a course of oral antibiotics was effective in the described dogs affected by advanced non-radiation-related ONJ. PMID:26664936

Named Entity Recognition in Chinese Clinical Text Using Deep Neural Network.

PubMed

Wu, Yonghui; Jiang, Min; Lei, Jianbo; Xu, Hua

2015-01-01

Rapid growth in electronic health records (EHRs) use has led to an unprecedented expansion of available clinical data in electronic formats. However, much of the important healthcare information is locked in the narrative documents. Therefore Natural Language Processing (NLP) technologies, e.g., Named Entity Recognition that identifies boundaries and types of entities, has been extensively studied to unlock important clinical information in free text. In this study, we investigated a novel deep learning method to recognize clinical entities in Chinese clinical documents using the minimal feature engineering approach. We developed a deep neural network (DNN) to generate word embeddings from a large unlabeled corpus through unsupervised learning and another DNN for the NER task. The experiment results showed that the DNN with word embeddings trained from the large unlabeled corpus outperformed the state-of-the-art CRF's model in the minimal feature engineering setting, achieving the highest F1-score of 0.9280. Further analysis showed that word embeddings derived through unsupervised learning from large unlabeled corpus remarkably improved the DNN with randomized embedding, denoting the usefulness of unsupervised feature learning.

Identification and characterization of near-fatal asthma phenotypes by cluster analysis.

PubMed

Serrano-Pariente, J; Rodrigo, G; Fiz, J A; Crespo, A; Plaza, V

2015-09-01

Near-fatal asthma (NFA) is a heterogeneous clinical entity and several profiles of patients have been described according to different clinical, pathophysiological and histological features. However, there are no previous studies that identify in a unbiased way--using statistical methods such as clusters analysis--different phenotypes of NFA. Therefore, the aim of the present study was to identify and to characterize phenotypes of near fatal asthma using a cluster analysis. Over a period of 2 years, 33 Spanish hospitals enrolled 179 asthmatics admitted for an episode of NFA. A cluster analysis using two-steps algorithm was performed from data of 84 of these cases. The analysis defined three clusters of patients with NFA: cluster 1, the largest, including older patients with clinical and therapeutic criteria of severe asthma; cluster 2, with an high proportion of respiratory arrest (68%), impaired consciousness level (82%) and mechanical ventilation (93%); and cluster 3, which included younger patients, characterized by an insufficient anti-inflammatory treatment and frequent sensitization to Alternaria alternata and soybean. These results identify specific asthma phenotypes involved in NFA, confirming in part previous findings observed in studies with a clinical approach. The identification of patients with a specific NFA phenotype could suggest interventions to prevent future severe asthma exacerbations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Two rare entities in the same palate lesion: hyalinizing-type clear cell carcinoma and necrotizing sialometaplasia.

PubMed

Arpaci, Rabia Bozdoğan; Kara, Tuba; Porgali, Canan; Serinsoz, Ebru; Polat, Ayse; Vayisoglu, Yusuf; Ozcan, Cengiz

2014-05-01

Hyalinizing clear cell carcinoma is a low-grade malignant epithelial neoplasm of the salivary glands. The tumor has epithelial cells and lacks myoepithelial cells. Necrotizing sialometaplasia is a benign, self-limiting lesion of the salivary glands. The clinical and histologic features mimic those of mucoepidermoid carcinoma or squamous cell carcinoma. The importance of these entities are the rarity of both of them and their potential to be misdiagnosed as other lesions. Pathologists and clinicians should be aware of these entities to prevent misdiagnosis. This is the first clinical report of 2 rare and consecutive different entities of the same location on the hard palate to our knowledge.

Toxicosis in Helicobacter Pylori infection - a hypothesis

PubMed Central

BELASCU, MIHAI

2013-01-01

Background and aim We present a new clinical entity in relation to the Helicobacter pylori infection characterized by complex and varied clinical extra-digestive manifestations. Clinical findings such as asthenia, adynamia, sleep disorders, hair and nails modifications, digestive symptoms and heart rhythm disorders describe the clinical aspect of toxicosis associated with Helicobacter pylori infection. Methods The clinical presentation and therapy of patients with Helicobacter pylori infection were analyzed. Results Combined drug therapy: antibiotics + proton pump inhibitors + colloidal bismuth compound determinate remission of the symptoms in the first 3 to 5 days. The characteristic of the relation between Helicobacter pylori and the mucus-epithelial cell complex, the properties of the bacterial cell components, and the inflammatory and immunological response targeting other organs describe the immuno-pathological outbreak of Helicobacter pylori. Conclusion We support the term of toxicosis associated with Helicobacter pylori infection in selected cases. PMID:26527950

Successful treatment of suspected organizing pneumonia in a patient without typical imaging and pathological characteristic: A case report.

PubMed

Ailing, Liu; Ning, Xu; Tao, Qu; Aijun, Li

2017-01-01

Organizing pneumonia (OP) is a clinicopathological entity characterized by granulation tissue plugs in the lumen of small airways, alveolar ducts, and alveoli. Diagnosis of OP needs the combination of clinical features, imaging and pathology. But it occurs often that there are no typical pathological features to support the diagnosis, which poses a challenge for clinicians' diagnosis and treatment. We diagnosed a case of OP without typical imaging and pathological characteristic and treated successfully. Finally we confirmed the pathological diagnosis. Not every OP case is supported by pathological evidence and typical imaging changes. It is important for us to judge and decide the diagnosis according to clinical experience.

Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma

PubMed Central

Devitt, Katherine; Cerny, Jan; Switzer, Bradley; Ramanathan, Muthalagu; Nath, Rajneesh; Yu, Hongbo; Woda, Bruce A.; Chen, Benjamin J.

2014-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management. PMID:24955327

Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma.

PubMed

Devitt, Katherine; Cerny, Jan; Switzer, Bradley; Ramanathan, Muthalagu; Nath, Rajneesh; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

2014-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management.

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

PubMed

Ngo, Nyethane; Chang, Fuju

2007-07-01

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

[Autoimmune/inflammatory syndrome induced by adjuvants. A new clinical entity?

PubMed

Ferrer-Cosme, Belkis; Téllez-Martínez, Damiana; Batista-Duharte, Alexander

2017-01-01

Recently Shoenfeld and Agmon-Levin proposed a new clinical entity called autoimmune/inflammatory syndrome induced by adjuvants (ASIA), which includes four clinical entities called: 1) siliconosis, 2) Gulf War syndrome, 3) macrophage myofasciitis) and 4) post-vaccination phenomenon associated with adjuvants. They all have a common denominator: a prior exposure to immunoadjuvants, and, in addition, they also share several clinical criteria associated to chronic inflammation and autoimmune reactions. This proposal still needs to be validated by the scientific community, but nowadays is a topic of hot discussion in the literature and in various international conferences. In this revision article, we analyze the characteristics of this syndrome, the current mechanisms possibly involved in the pathogenesis, and the more recent reports regarding ASIA associated to vaccine and some foreign substances.

Advances in the understanding and clinical management of mastocytosis and clonal mast cell activation syndromes

PubMed Central

2016-01-01

Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities. PMID:27909577

Advances in the understanding and clinical management of mastocytosis and clonal mast cell activation syndromes.

PubMed

González-de-Olano, David; Matito, Almudena; Orfao, Alberto; Escribano, Luis

2016-01-01

Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities.

Spinal bone marrow necrosis with vertebral compression fracture: differentiation of BMN from AVN.

PubMed

Nix, J S; Fitzgerald, R T; Samant, R S; Harrison, M; Angtuaco, E J

2014-09-01

Bone marrow necrosis (BMN) is a rare malignancy-associated hematologic disorder characterized by necrosis of myeloid and stromal marrow elements with preservation of cortical bone. Overlap between the imaging appearances of BMN and avascular necrosis (AVN) raises the potential for diagnostic confusion. We report a case of BMN presenting with a traumatic multi-level vertebral body collapse, and finding that may potentially confound distinction between the two entities. We discuss important pathophysiologic, clinical, and radiologic differences between BMN and AVN with emphasis on features important in the differential diagnosis.

Adult Onset Asthma and Periocular Xanthogranuloma (AAPOX), a Rare Entity With a Strong Link to IgG4-Related Disease

PubMed Central

London, Jonathan; Martin, Antoine; Soussan, Michael; Badelon, Isabelle; Gille, Thomas; Uzunhan, Yurdagul; Giroux-Leprieur, Bénédicte; Warzocha, Ursula; Régent, Alexis; Galatoire, Olivier; Dhote, Robin; Abad, Sébastien

2015-01-01

Abstract Adult onset asthma and periocular xanthogranuloma (AAPOX) is a rare non-Langerhans histiocytosis characterized histopathologically by a periocular infiltration of foamy histiocytes and Touton giant cells. Benign hyperplasia with plasma cell infiltration is classically described in eyelids or lymph nodes of AAPOX patients. It is also a characteristic feature of IgG4-related disease (IgG4-RD), a new entity defined by an IgG4-bearing plasma cell infiltration of organs. To determine if AAPOX syndrome shares clinical, biological, and histopathological characteristics with IgG4-RD, we used the comprehensive clinical diagnostic criteria for IgG4-RD in a retrospective case series of three consecutive patients with histologically-proven AAPOX. Patients who were diagnosed with AAPOX at a French academic referral center for orbital inflammation between November 1996 and March 2013 were enrolled. Biopsies from ocular adnexa or other organs were systematically reexamined. For each patient, clinical and serological data, radiologic findings, and treatment were retrospectively analyzed. Two AAPOX patients fulfilled all of the diagnostic criteria for a definite IgG4-RD. One patient who lacked the serological criteria fulfilled the criteria of a probable IgG4-RD. These 3 cases of AAPOX patients fulfilled the IgG4-RD comprehensive clinical diagnostic criteria. To our knowledge, this is the first observational case report study to clearly show a strong relationship between IgG4-RD and AAPOX syndrome. PMID:26512617

Mesomelic skeletal dysplasias.

PubMed

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

1976-01-01

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

Pathogenesis, Diagnosis, and Treatment of Cervical Vertigo.

PubMed

Li, Yongchao; Peng, Baogan

2015-01-01

Cervical vertigo is characterized by vertigo from the cervical spine. However, whether cervical vertigo is an independent entity still remains controversial. In this narrative review, we outline the basic science and clinical evidence for cervical vertigo according to the current literature. So far, there are 4 different hypotheses explaining the vertigo of a cervical origin, including proprioceptive cervical vertigo, Barré-Lieou syndrome, rotational vertebral artery vertigo, and migraine-associated cervicogenic vertigo. Proprioceptive cervical vertigo and rotational vertebral artery vertigo have survived with time. Barré-Lieou syndrome once was discredited, but it has been resurrected recently by increased scientific evidence. Diagnosis depends mostly on patients' subjective feelings, lacking positive signs, specific laboratory examinations and clinical trials, and often relies on limited clinical experiences of clinicians. Neurological, vestibular, and psychosomatic disorders must first be excluded before the dizziness and unsteadiness in cervical pain syndromes can be attributed to a cervical origin. Treatment for cervical vertigo is challenging. Manual therapy is recommended for treatment of proprioceptive cervical vertigo. Anterior cervical surgery and percutaneous laser disc decompression are effective for the cervical spondylosis patients accompanied with Barré-Liéou syndrome. As to rotational vertebral artery vertigo, a rare entity, when the exact area of the arterial compression is identified through appropriate tests such as magnetic resonance angiography (MRA), computed tomography angiography (CTA) or digital subtraction angiography (DSA) decompressive surgery should be the chosen treatment.

Idiopathic Noncirrhotic Portal Hypertension: An Appraisal

PubMed Central

Lee, Hwajeong; Rehman, Aseeb Ur; Fiel, M. Isabel

2016-01-01

Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity. PMID:26563701

Noncirrhotic portal hypertension.

PubMed

Da, Ben L; Koh, Christopher; Heller, Theo

2018-05-01

Noncirrhotic portal hypertension represents a heterogeneous group of liver disorders that is characterized by portal hypertension in the absence of cirrhosis. The purpose of this review is to serve as a guide on how to approach a patient with noncirrhotic portal hypertension with a focus on recent developments. Recent studies pertaining to noncirrhotic portal hypertension have investigated aetiological causes, mechanisms of disease, noninvasive diagnostic modalities, clinical characteristics in the paediatric population and novel treatment targets. Noncirrhotic portal hypertension is an underappreciated clinical entity that can be difficult to diagnosis without a healthy suspicion. Diagnosis then relies on a comprehensive understanding of the causes and clinical manifestations of this disease, as well as a careful interpretation of the liver biopsy. Noninvasive approaches to diagnosis may play a significant role moving forward in this disease. Treatment in NCPH remains largely targeted at the individual sequalae of portal hypertension.

Wolf in Sheep's Clothing: Primary Lung Cancer Mimicking Benign Entities.

PubMed

Snoeckx, Annemie; Dendooven, Amélie; Carp, Laurens; Desbuquoit, Damien; Spinhoven, Maarten J; Lauwers, Patrick; Van Schil, Paul E; van Meerbeeck, Jan P; Parizel, Paul M

2017-10-01

Lung cancer is the most common cancer worldwide. On imaging, it typically presents as mass or nodule. Recognition of these typical cases is often straightforward, whereas diagnosis of uncommon manifestations of primary lung cancer is far more challenging. Lung cancer can mimic a variety of benign entities, including pneumonia, lung abscess, postinfectious scarring, atelectasis, a mediastinal mass, emphysema and granulomatous diseases. Correlation with previous history, clinical and biochemical parameters is necessary in the assessment of these cases, but often aspecific and inconclusive. Whereas 18 F-fluorodeoxyglucose ( 18 F-FDG) Positron Emission Tomography is the cornerstone in staging of lung cancer, its role in diagnosis of these uncommon manifestations is less straightforward since benign entities can present with increased 18 F-FDG-uptake and, on the other hand, a number of these uncommon lung cancer manifestations do not exhibit increased uptake. Chest Computed Tomography (CT) is the imaging modality of choice for both lesion detection and characterization. In this pictorial review we present the wide imaging spectrum of CT-findings as well as radiologic-pathologic correlation of these uncommon lung cancer manifestations. Knowledge of the many faces of lung cancer is crucial for early diagnosis and subsequent treatment. A multidisciplinary approach in these cases is mandatory. Copyright © 2017 Elsevier B.V. All rights reserved.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE); a rare association with phyllodes tumour of breast.

PubMed

Sarkar, R N; Phaujdar, Sibaji; Banerjee, Siwalik; Siddhanta, Sattik; De, Dibyendu; Bhattachary, Kuntal; Pal, Hare Krishna

2012-04-01

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare entity mainly found in elderly males. It is characterized by pitting edema mainly of dorsum of both hands giving a "boxing glove hand" appearance; rarely involving feet also, acute in onset, negative rheumatoid factor and a good response to low dose corticosteroid therapy. Clinically it almost resembles a case of polymyalgia rheumatica, late onset rheumatoid arthritis or other seronegative spondyloarthropathy.Though there are multiple underlying factors causing this rare entity but it has very close associations with many malignancies.So far its association with solid tumours and hematological malignancies has been reported. Phyllodes tumour of breast shows wide spectrum of activity from a benign condition to a locally aggressive and sometimes metastatic tumour.One fourth of the cases recur after definitive treatment.Our case represent an unusual association with recurrent phyllodes tumour of breast with RS3PE.

Question mark ears, temporo-mandibular joint malformation and hypotonia: auriculo-condylar syndrome or a distinct entity?

PubMed

Priolo, M; Lerone, M; Rosaia, L; Calcagno, E P; Sadeghi, A K; Ghezzi, F; Ravazzolo, R; Silengo, M

2000-10-01

We report a boy with prominent, peculiarly malformed ears, abnormality of the ramus of the mandible and hypotonia. An isolated peculiar bilateral ear deformity named 'question mark ear' has been delineated in plastic reconstruction surgery reviews [Cosman et al., 1970 Plast Reconstr Surg 46:454-457; Cosman (1984) Plast Reconstr Surg 73:572-576; Takato et al. (1989) Ann Plast Surg 22:69-73; Brodovsky (1997) Plast Reconstr Surg 100:1254-1257; Park (1998) Plast Reconstr Surg 101:1620-1623; Al-Quattan (1998) Plast Reconstr Surg 102:439-441] and a similar deformity of the ear and changes in the temporo-mandibular joint and condyle has been described by Jampol et al. [(1998) Am J Med Genet 75:449-452] and by Guion-Almeida et al. [(1999) Am J Med Genet 86:130-133]. The present case may be the third description of this malformation complex with additional clinical features characterized by hypotonia and mild developmental delay, or possibly a new distinct entity.

Acquired bilateral telangiectatic macules: a distinct clinical entity.

PubMed

Park, Ji-Hye; Lee, Dong Jun; Lee, Yoo-Jung; Jang, Yong Hyun; Kang, Hee Young; Kim, You Chan

2014-09-01

We evaluated 13 distinct patients with multiple telangiectatic pigmented macules confined mostly to the upper arms to determine if the clinical and histopathological features of these cases might represent a specific clinical entity. We retrospectively investigated the clinical, histopathologic, and immunohistochemical features of 13 patients with multiple telangiectatic pigmented macules on the upper arms who presented between January 2003 and December 2012. Epidermal pigmentation, melanogenic activity, melanocyte number, vascularity, epidermal thickness, and perivascular mast cell number of the specimens were evaluated. Clinically, the condition favored middle-aged men. On histopathologic examination, the lesional skin showed capillary proliferation and telangiectasia in the upper dermis. Histochemical and immunohistochemical analysis revealed basal hyperpigmentation and increased melanogenic activity in the lesional skin (P < .05). No significant difference in epidermal thickness or mast cell number was observed between the normal perilesional skin and the lesional skin. The clinical and histopathologic features of these lesions were relatively consistent in all patients. In addition, the features are quite distinct from other diseases. Based on clinical and histologic features, we suggest the name acquired bilateral telangiectatic macules for this new entity.

Lichen planus hypertrophicus of the vulva - a rare entity.

PubMed

Job, Anupa Mary; Kaimal, Sowmya

2017-09-01

Vulvovaginal lichen planus is a type of chronic inflammatory dermatosis of the vulva, usually seen as a part of widespread lichen planus. The common clinical types of vulval lichen planus include papulosquamous, erosive and pigmented types. Hypertrophic lichen planus of the vulva is a rare entity. We report a case of hypertrophic lichen planus of the vulva which clinically simulated genital warts.

IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

PubMed Central

Divatia, Mukul; Kim, Sun A

2012-01-01

Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies. PMID:22187229

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.

Network analysis of named entity co-occurrences in written texts

NASA Astrophysics Data System (ADS)

Amancio, Diego Raphael

2016-06-01

The use of methods borrowed from statistics and physics to analyze written texts has allowed the discovery of unprecedent patterns of human behavior and cognition by establishing links between models features and language structure. While current models have been useful to unveil patterns via analysis of syntactical and semantical networks, only a few works have probed the relevance of investigating the structure arising from the relationship between relevant entities such as characters, locations and organizations. In this study, we represent entities appearing in the same context as a co-occurrence network, where links are established according to a null model based on random, shuffled texts. Computational simulations performed in novels revealed that the proposed model displays interesting topological features, such as the small world feature, characterized by high values of clustering coefficient. The effectiveness of our model was verified in a practical pattern recognition task in real networks. When compared with traditional word adjacency networks, our model displayed optimized results in identifying unknown references in texts. Because the proposed representation plays a complementary role in characterizing unstructured documents via topological analysis of named entities, we believe that it could be useful to improve the characterization of written texts (and related systems), specially if combined with traditional approaches based on statistical and deeper paradigms.

[Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

PubMed

Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

2016-07-01

Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

Clinical Named Entity Recognition Using Deep Learning Models.

PubMed

Wu, Yonghui; Jiang, Min; Xu, Jun; Zhi, Degui; Xu, Hua

2017-01-01

Clinical Named Entity Recognition (NER) is a critical natural language processing (NLP) task to extract important concepts (named entities) from clinical narratives. Researchers have extensively investigated machine learning models for clinical NER. Recently, there have been increasing efforts to apply deep learning models to improve the performance of current clinical NER systems. This study examined two popular deep learning architectures, the Convolutional Neural Network (CNN) and the Recurrent Neural Network (RNN), to extract concepts from clinical texts. We compared the two deep neural network architectures with three baseline Conditional Random Fields (CRFs) models and two state-of-the-art clinical NER systems using the i2b2 2010 clinical concept extraction corpus. The evaluation results showed that the RNN model trained with the word embeddings achieved a new state-of-the- art performance (a strict F1 score of 85.94%) for the defined clinical NER task, outperforming the best-reported system that used both manually defined and unsupervised learning features. This study demonstrates the advantage of using deep neural network architectures for clinical concept extraction, including distributed feature representation, automatic feature learning, and long-term dependencies capture. This is one of the first studies to compare the two widely used deep learning models and demonstrate the superior performance of the RNN model for clinical NER.

Clinical Named Entity Recognition Using Deep Learning Models

PubMed Central

Wu, Yonghui; Jiang, Min; Xu, Jun; Zhi, Degui; Xu, Hua

2017-01-01

Clinical Named Entity Recognition (NER) is a critical natural language processing (NLP) task to extract important concepts (named entities) from clinical narratives. Researchers have extensively investigated machine learning models for clinical NER. Recently, there have been increasing efforts to apply deep learning models to improve the performance of current clinical NER systems. This study examined two popular deep learning architectures, the Convolutional Neural Network (CNN) and the Recurrent Neural Network (RNN), to extract concepts from clinical texts. We compared the two deep neural network architectures with three baseline Conditional Random Fields (CRFs) models and two state-of-the-art clinical NER systems using the i2b2 2010 clinical concept extraction corpus. The evaluation results showed that the RNN model trained with the word embeddings achieved a new state-of-the- art performance (a strict F1 score of 85.94%) for the defined clinical NER task, outperforming the best-reported system that used both manually defined and unsupervised learning features. This study demonstrates the advantage of using deep neural network architectures for clinical concept extraction, including distributed feature representation, automatic feature learning, and long-term dependencies capture. This is one of the first studies to compare the two widely used deep learning models and demonstrate the superior performance of the RNN model for clinical NER. PMID:29854252

[Atypical hemolytic uremic syndrome].

PubMed

Blasco Pelicano, Miquel; Rodríguez de Córdoba, Santiago; Campistol Plana, Josep M

2015-11-20

The hemolytic uremic syndrome (HUS) is a clinical entity characterized by thrombocytopenia, non-immune hemolytic anemia and renal impairment. Kidney pathology shows thrombotic microangiopathy (TMA) with endothelial cell injury leading to thrombotic occlusion of arterioles and capillaries. Traditionally, HUS was classified in 2 forms: Typical HUS, most frequently occurring in children and caused by Shiga-toxin-producing bacteria, and atypical HUS (aHUS). aHUS is associated with mutations in complement genes in 50-60% of patients and has worse prognosis, with the majority of patients developing end stage renal disease. After kidney transplantation HUS may develop as a recurrence of aHUS or as de novo disease. Over the last years, many studies have demonstrated that complement dysregulation underlies the endothelial damage that triggers the development of TMA in most of these patients. Advances in our understanding of the pathogenic mechanisms of aHUS, together with the availability of novel therapeutic options, will enable better strategies for the early diagnosis and etiological treatment, which are changing the natural history of aHUS. This review summarizes the aHUS clinical entity and describes the role of complement dysregulation in the pathogenesis of aHUS. Finally, we review the differential diagnosis and the therapeutic options available to patients with aHUS. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Characterization of prostate neuroendocrine cancers and therapeutic management: a literature review.

PubMed

Sargos, P; Ferretti, L; Gross-Goupil, M; Orre, M; Cornelis, F; Henriques de Figueiredo, B; Houédé, N; Merino, C; Roubaud, G; Dallaudiére, B; Richaud, P; Fléchon, A

2014-09-01

Neuroendocrine prostate cancers (NEPCs) are rare. The current lack of consensus for clinical, biological and pathological characterization as well as therapeutic approach makes the management of those tumors a clinical challenge. This literature review aims to summarize available data on the characterization and management of patients with prostate cancer with a neuroendocrine element. We try to identify major controversies and uncertainties in order to understand all aspects of this particular entity. We searched for all articles published and registered in the MEDLINE database before 31 November 2013 with the following search terms: (('prostatic neoplasms' (MeSH Terms)) AND ('carcinoma, neuroendocrine' (MeSH Terms)) OR ('carcinoma, small cell' (MeSH Terms))) AND (English (Language)). Case reports, letters or comments were excluded. We then selected relevant articles from titles and abstracts. Overall, 278 articles published between 1976 and November 2013 were identified. No definition of NEPC seems to be clearly established. Natural history of the disease reveals poor prognosis with median survival of up to 10 to 13 months. Histological characterization appears difficult. Serum markers could be helpful with some controversies in terms of prognostic significance. Concerning management, the majority of patients received local treatment combined with chemotherapy in case of early and localized disease. Few clinical trials described strategy for metastatic disease. The exploration of the different pathways implicated in the neuroendocrine differentiation of prostate cancers is essential for the comprehension of castration-resistance mechanisms. It will enable the identification of optimal therapeutic strategies for which no recommendation is currently established. Inclusion in prospective clinical trials appears necessary to identify the adequate strategy.

Florid cemento-osseous dysplasia: review of an uncommon fibro-osseous lesion of the jaw with important clinical implications.

PubMed

Fenerty, Sarah; Shaw, Wei; Verma, Rahul; Syed, Ali B; Kuklani, Riya; Yang, Jie; Ali, Sayed

2017-05-01

Florid cemento-osseous dysplasia (FCOD) is a rare, benign, multifocal fibro-osseous dysplastic process affecting tooth-bearing areas of the jaw, characterized by replacement of normal trabecular bone with osseous tissue and dense acellular cementum in a fibrous stroma. It is one clinicopathologic variant in a spectrum of related non-neoplastic fibro-osseous lesions known as cemento-osseous dysplasias (CODs), thought to arise from elements of the periodontal ligament. Diagnosis primarily relies upon radiographic and clinical findings; unnecessary biopsy should be avoided, as inoculation with oral pathogens may precipitate chronic infection in these hypovascular lesions. Appropriate management of uncomplicated FCOD consists of periodic radiographic follow-up. Accordingly, it is important that both radiologists and clinicians performing endodontic interventions possess familiarity with this entity in order to prevent misdiagnosis and inappropriate intervention, which may result in a protracted clinical course. Lesions are usually asymptomatic in the absence of infection, typically discovered on routine dental radiographs or imaging performed for unrelated indications. Radiographically, the condition typically manifests as widespread non-expansile intraosseous masses of varying internal lucency and sclerosis that surround the root apices of vital teeth or edentulous areas in the posterior jaw. While all CODs share similar microscopic features, FCOD is distinguished by its multifocal distribution, involving two or more quadrants of the maxilla and mandible, often in a bilateral symmetric fashion. The vast majority of cases are sporadic, though few exhibit an autosomal dominant familial inheritance pattern. In this pictorial review, we discuss the radiologic characteristics of this entity, pertinent clinical and histologic features, differential diagnoses, and management options.

Gene panel sequencing in heritable thoracic aortic disorders and related entities - results of comprehensive testing in a cohort of 264 patients.

PubMed

Campens, Laurence; Callewaert, Bert; Muiño Mosquera, Laura; Renard, Marjolijn; Symoens, Sofie; De Paepe, Anne; Coucke, Paul; De Backer, Julie

2015-02-03

Heritable Thoracic Aortic Disorders (H-TAD) may present clinically as part of a syndromic entity or as an isolated (nonsyndromic) manifestation. About one dozen genes are now available for clinical molecular testing. Targeted single gene testing is hampered by significant clinical overlap between syndromic H-TAD entities and the absence of discriminating features in isolated cases. Therefore panel testing of multiple genes has now emerged as the preferred approach. So far, no data on mutation detection rate with this technique have been reported. We performed Next Generation Sequencing (NGS) based screening of the seven currently most prevalent H-TAD-associated genes (FBN1, TGFBR1/2, TGFB2, SMAD3, ACTA2 and COL3A1) on 264 samples from unrelated probands referred for H-TAD and related entities. Patients fulfilling the criteria for Marfan syndrome (MFS) were only included if targeted FBN1 sequencing and MLPA analysis were negative. A mutation was identified in 34 patients (13%): 12 FBN1, one TGFBR1, two TGFBR2, three TGFB2, nine SMAD3, four ACTA2 and three COL3A1 mutations. We found mutations in FBN1 (N = 3), TGFBR2 (N = 1) and COL3A1 (N = 2) in patients without characteristic clinical features of syndromal H-TAD. Six TAD patients harboring a mutation in SMAD3 and one TAD patient with a TGFB2 mutation fulfilled the diagnostic criteria for MFS. NGS based H-TAD panel testing efficiently reveals a mutation in 13% of patients. Our observations emphasize the clinical overlap between patients harboring mutations in syndromic and nonsyndromic H-TAD related genes as well as within syndromic H-TAD entities, justifying a widespread application of this technique.

Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location.

PubMed

Karremann, Michael; Gielen, Gerrit H; Hoffmann, Marion; Wiese, Maria; Colditz, Niclas; Warmuth-Metz, Monika; Bison, Brigitte; Claviez, Alexander; van Vuurden, Dannis G; von Bueren, André O; Gessi, Marco; Kühnle, Ingrid; Hans, Volkmar H; Benesch, Martin; Sturm, Dominik; Kortmann, Rolf-Dieter; Waha, Andreas; Pietsch, Torsten; Kramm, Christof M

2018-01-10

The novel entity of "diffuse midline glioma, H3 K27M-mutant" has been defined in the 2016 revision of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS). Tumors of this entity arise in CNS midline structures of predominantly pediatric patients and are associated with an overall dismal prognosis. They are defined by K27M mutations in H3F3A or HIST1H3B/C, encoding for histone 3 variants H3.3 and H3.1, respectively, which are considered hallmark events driving gliomagenesis. Here, we characterized 85 centrally reviewed diffuse gliomas on midline locations enrolled in the nationwide pediatric German HIT-HGG registry regarding tumor site, histone 3 mutational status, WHO grade, age, sex, and extent of tumor resection. We found 56 H3.3 K27M-mutant tumors (66%), 6 H3.1 K27M-mutant tumors (7%), and 23 H3-wildtype tumors (27%). H3 K27M-mutant gliomas shared an aggressive clinical course independent of their anatomic location. Multivariate regression analysis confirmed the significant impact of the H3 K27M mutation as the only independent parameter predictive of overall survival (P = 0.009). In H3 K27M-mutant tumors, neither anatomic midline location nor histopathological grading nor extent of tumor resection had an influence on survival. These results substantiate the clinical significance of considering diffuse midline glioma, H3 K27M-mutant, as a distinct entity corresponding to WHO grade IV, carrying a universally fatal prognosis. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

[Childhood scabies: a different entity].

PubMed

Níguez Carbonell, J C; García-Marcos Alvarez, L; Sebastián Raz, J M; García Marcos, V; Guillén Pérez, J J

1988-01-01

Epidemiological, clinical, diagnostic and therapeutic aspects that make scabies a clinical entity with a special personality in the pediatric field, are reviewed. On the epidemiological aspects, a special mention of its unsuspected frequency in this age is made. Scabies is an endemic disease in our country among the more deprived people. On the clinical aspects, the great importance of clinical history and distribution of skin lesions for the early diagnosis is pointed out. Some "alert pointers" are described for this early diagnosis. On the therapeutic field, the importance of the primary care prevention is discussed, and the drug approach for its relieve is commented.

Gene expression profiling in multiple myeloma--reporting of entities, risk, and targets in clinical routine.

PubMed

Meissner, Tobias; Seckinger, Anja; Rème, Thierry; Hielscher, Thomas; Möhler, Thomas; Neben, Kai; Goldschmidt, Hartmut; Klein, Bernard; Hose, Dirk

2011-12-01

Multiple myeloma is an incurable malignant plasma cell disease characterized by survival ranging from several months to more than 15 years. Assessment of risk and underlying molecular heterogeneity can be excellently done by gene expression profiling (GEP), but its way into clinical routine is hampered by the lack of an appropriate reporting tool and the integration with other prognostic factors into a single "meta" risk stratification. The GEP-report (GEP-R) was built as an open-source software developed in R for gene expression reporting in clinical practice using Affymetrix microarrays. GEP-R processes new samples by applying a documentation-by-value strategy to the raw data to be able to assign thresholds and grouping algorithms defined on a reference cohort of 262 patients with multiple myeloma. Furthermore, we integrated expression-based and conventional prognostic factors within one risk stratification (HM-metascore). The GEP-R comprises (i) quality control, (ii) sample identity control, (iii) biologic classification, (iv) risk stratification, and (v) assessment of target genes. The resulting HM-metascore is defined as the sum over the weighted factors gene expression-based risk-assessment (UAMS-, IFM-score), proliferation, International Staging System (ISS) stage, t(4;14), and expression of prognostic target genes (AURKA, IGF1R) for which clinical grade inhibitors exist. The HM-score delineates three significantly different groups of 13.1%, 72.1%, and 14.7% of patients with a 6-year survival rate of 89.3%, 60.6%, and 18.6%, respectively. GEP reporting allows prospective assessment of risk and target gene expression and integration of current prognostic factors in clinical routine, being customizable about novel parameters or other cancer entities. ©2011 AACR.

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

PubMed

Herrera, Guillermo A

2014-10-01

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

Clinical course and outcome of essential thrombocythemia and prefibrotic myelofibrosis according to the revised WHO 2016 diagnostic criteria

PubMed Central

Rumi, Elisa; Boveri, Emanuela; Bellini, Marta; Pietra, Daniela; Ferretti, Virginia V.; Sant’Antonio, Emanuela; Cavalloni, Chiara; Casetti, Ilaria C.; Roncoroni, Elisa; Ciboddo, Michele; Benvenuti, Pietro; Landini, Benedetta; Fugazza, Elena; Troletti, Daniela; Astori, Cesare; Cazzola, Mario

2017-01-01

The recently revised World Health Organization (WHO) classification of myeloid neoplasms recognizes prefibrotic myelofibrosis (prePMF) as a distinct entity, characterized by well-defined histopathologic features together with minor clinical criteria (leukocytes, anemia, increased LDH, splenomegaly). The aim of the study was to examine the clinical relevance of distinguishing prePMF from essential thrombocythemia (ET). We identified in our database all patients affected with ET, prePMF and primary myelofibrosis (PMF) diagnosed according to 2008 WHO criteria with a bone marrow fibrosis grade 0-1 at diagnosis and one DNA sample to define the mutational status. The bone marrow morphology of all 404 identified patients was reviewed by an expert pathologist and patients were reclassified according to the 2016 WHO criteria. After reclassification, our cohort included 269 ET, 109 prePMF, and 26 myeloproliferative neoplasm unclassificable. In comparison with ET, patients with prePMF had higher leukocyte count, lower hemoglobin level, higher platelet count, higher LDH values, and higher number of circulating CD34-positive cells; they showed more frequently splenomegaly (all P values < ·001). CALR mutations were more frequent in prePMF than in ET (35·8% vs 17·8%, P < ·001). PrePMF patients had shorter overall survival (P < ·001) and a trend to a higher incidence of leukemic evolution (P ·067) compared to ET patients, while they did not differ in terms of thrombotic and bleeding complications. In conclusion, ET and prePMF diagnosed according to 2016 WHO criteria are two entities with a different clinical phenotype at diagnosis and a different clinical outcome. PMID:29254200

Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants.

PubMed

Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.

Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants

PubMed Central

Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12–17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations. PMID:28721389

Endodontic treatment and esthetic management of a primary double tooth with direct composite using silicone buildup guide.

PubMed

Kulkarni, Vinaya Kumar; Ragavendra, T Raju; Deshmukh, Jeevanand; Vanka, Amit; Duddu, Mahesh Kumar; Patil, Anand Kumar G

2012-04-01

Gemination and fusion are morphological dental anomalies, characterized by the formation of a clinically wide tooth. Gemination occurs when one tooth bud tries to divide, while fusion occurs if two buds unite. The terms double teeth, double formation, conjoined teeth, geminifusion, vicinifusion and dental twinning are often used to describe fusion and gemination. Double teeth are associated with clinical problems such as poor esthetics, spacing problems and caries susceptibility. Management of such cases requires a comprehensive knowledge of the clinical entity as well as the problems associated with it. This report presents a case of primary double tooth in a 6-year-old boy involving maxillary left central incisor. The anomalous tooth was carious and pulpally involved. This was treated conservatively by endodontic treatment and esthetic rehabilitation was done with direct composite restoration using a silicone buildup guide. The treated tooth was followed up until exfoliation.

Endodontic treatment and esthetic management of a primary double tooth with direct composite using silicone buildup guide

PubMed Central

Kulkarni, Vinaya Kumar; Ragavendra, T. Raju; Deshmukh, Jeevanand; Vanka, Amit; Duddu, Mahesh Kumar; Patil, Anand Kumar G.

2012-01-01

Gemination and fusion are morphological dental anomalies, characterized by the formation of a clinically wide tooth. Gemination occurs when one tooth bud tries to divide, while fusion occurs if two buds unite. The terms double teeth, double formation, conjoined teeth, geminifusion, vicinifusion and dental twinning are often used to describe fusion and gemination. Double teeth are associated with clinical problems such as poor esthetics, spacing problems and caries susceptibility. Management of such cases requires a comprehensive knowledge of the clinical entity as well as the problems associated with it. This report presents a case of primary double tooth in a 6-year-old boy involving maxillary left central incisor. The anomalous tooth was carious and pulpally involved. This was treated conservatively by endodontic treatment and esthetic rehabilitation was done with direct composite restoration using a silicone buildup guide. The treated tooth was followed up until exfoliation. PMID:22629077

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.

Rethinking cancer nanotheranostics

NASA Astrophysics Data System (ADS)

Chen, Hongmin; Zhang, Weizhong; Zhu, Guizhi; Xie, Jin; Chen, Xiaoyuan

2017-07-01

Advances in nanoparticle synthesis and engineering have produced nanoscale agents affording both therapeutic and diagnostic functions that are often referred to by the portmanteau 'nanotheranostics'. The field is associated with many applications in the clinic, especially in cancer management. These include patient stratification, drug-release monitoring, imaging-guided focal therapy and post-treatment response monitoring. Recent advances in nanotheranostics have expanded this notion and enabled the characterization of individual tumours, the prediction of nanoparticle-tumour interactions, and the creation of tailor-designed nanomedicines for individualized treatment. Some of these applications require breaking the dogma that a nanotheranostic must combine both therapeutic and diagnostic agents within a single, physical entity; instead, it can be a general approach in which diagnosis and therapy are interwoven to solve clinical issues and improve treatment outcomes. In this Review, we describe the evolution and state of the art of cancer nanotheranostics, with an emphasis on clinical impact and translation.

FTIR microspectroscopic characterization of Spitz nevi

NASA Astrophysics Data System (ADS)

Giorgini, Elisabetta; Tosi, Giorgio; Conti, Carla; Staibano, Stefania; Ilardi, Gennaro; Sabbatini, Simona

2015-04-01

In the last 10 years, few efforts have been carried out to apply vibrational spectroscopy in the study of dermal pathologies in order to characterize the most relevant spectral markers for distinguishing benign from cancerous lesions. Spitz nevi are a special group of benign melanocytic lesions, characterized by spindled and/or epithelioid nevomelanocytes, with peculiar clinical, dermoscopic and histopathological features. The "atypical forms" of Spitz nevi are among the commonest problems of differential diagnosis with the so-called "spitzoid melanomas". The clinical and histological criteria for discriminating these two entities are very subtle and often still quite subjective, and, in a significant percentage of cases, can lead to diagnostic pitfalls and inadequate therapies. Therefore, it is noteworthy to outline that the diagnosis of melanocytic lesions still represents a challenging problem and a continue matter of discussion. We exploited FTIR microspectroscopy to study the different kinds of spitzoid melanocytes, in order to define the most relevant spectral markers of each specimen and to achieve objective information on "borderline" histologically atypical lesions. In particular, the spectroscopic investigation was carried out on melanocytes deriving from normal skin (as a normal control), malignant melanoma and Spitz nevi. The presence of the characteristic bands of melanin was investigated, too.

Spasm of the near reflex: a spectrum of anomalies.

PubMed

Goldstein, J H; Schneekloth, B B

1996-01-01

Spasm of the near reflex has been characterized as the variable appearance of pseudomyopia, convergent strabismus and miosis. These characteristics may appear together or separately. In addition, abnormalities of accommodation may appear not only as pseudomyopia, but may also be manifest in cases with significant hypermetropia in which the patient is unable to relax accommodation even when plus lenses are used. The intent of this review is to identify the various clinical presentations of anomalies of the entire near reflex as well as the component parts. The relationship to functional and organic disorders are discussed as well as the related neuroanatomy. We suggest that one may more readily understand the clinical manifestations as a spectrum of anomalies of the near reflex rather than a multitude of disconnected entities.

Canine gastritis.

PubMed

Webb, Craig; Twedt, David C

2003-09-01

Gastritis--inflammation of the stomach--is a frequently cited differential yet rarely characterized diagnosis in cases of canine anorexia and vomiting. Although the list of rule-outs for acute or chronic gastritis is extensive, a review of the veterinary literature reveals fewer than 15 articles that have focused on clinical cases of canine gastritis over the last 25 years. The dog frequently appears in the human literature as an experimentally manipulated model for the study of endoscopic techniques or the effect of medications on gastric mucosa. In the veterinary patient, cases of acute gastritis are rarely pursued with the complete diagnostic armamentarium, and cases of chronic gastritis are rarely found to occur as an entity isolated from the rest of the gastrointestinal tract. This article focuses on those findings most clinically relevant to cases of canine gastritis in veterinary medicine.

[On the benefits to keep using the asperger diagnosis].

PubMed

Delcommenne, M; Francolini, M; Bon, O L

The purpose of this paper is to examine the possible benefits to keep using the diagnosis of Asperger's syndrome. We first describe the evolution of this entity over time and within nomenclature bases such as the ICD- 10, the CFTMEA and the last versions of DSM. Then, we discuss more precisely the impact of the decision made in the DSM-5 to suppress the Asperger syndrome as a differentiated entity within the pervasive developmental disorders (PDD). This disorder chapter by the way also disappears and is replaced by Autism Spectrum Disorder (ASD). We present here three clinical cases encountered in an outpatient general child psychiatry clinic : 1 case was diagnosed as Asperger syndrome, 1 as infantile autism (early infantile autism) and 1 as another pervasive developmental disorder (psychotic disharmony). The objective was to expose the commonali ties and differences between these three entities. We conclude that keeping using the Asperger diagnosis is important for the clinical management of these clinical situations but also for the individual, his or her family and society at large.

Clinical implications of omics and systems medicine: focus on predictive and individualized treatment.

PubMed

Benson, M

2016-03-01

Many patients with common diseases do not respond to treatment. This is a key challenge to modern health care, which causes both suffering and enormous costs. One important reason for the lack of treatment response is that common diseases are associated with altered interactions between thousands of genes, in combinations that differ between subgroups of patients who do or do not respond to a given treatment. Such subgroups, or even distinct disease entities, have been described recently in asthma, diabetes, autoimmune diseases and cancer. High-throughput techniques (omics) allow identification and characterization of such subgroups or entities. This may have important clinical implications, such as identification of diagnostic markers for individualized medicine, as well as new therapeutic targets for patients who do not respond to existing drugs. For example, whole-genome sequencing may be applied to more accurately guide treatment of neurodevelopmental diseases, or to identify drugs specifically targeting mutated genes in cancer. A study published in 2015 showed that 28% of hepatocellular carcinomas contained mutated genes that potentially could be targeted by drugs already approved by the US Food and Drug Administration. A translational study, which is described in detail, showed how combined omics, computational, functional and clinical studies could identify and validate a novel diagnostic and therapeutic candidate gene in allergy. Another important clinical implication is the identification of potential diagnostic markers and therapeutic targets for predictive and preventative medicine. By combining computational and experimental methods, early disease regulators may be identified and potentially used to predict and treat disease before it becomes symptomatic. Systems medicine is an emerging discipline, which may contribute to such developments through combining omics with computational, functional and clinical studies. The aims of this review are to provide a brief introduction to systems medicine and discuss how it may contribute to the clinical implementation of individualized treatment, using clinically relevant examples. © 2015 The Association for the Publication of the Journal of Internal Medicine.

Structured prediction models for RNN based sequence labeling in clinical text.

PubMed

Jagannatha, Abhyuday N; Yu, Hong

2016-11-01

Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies for structured prediction in order to improve the exact phrase detection of various medical entities.

Structured prediction models for RNN based sequence labeling in clinical text

PubMed Central

Jagannatha, Abhyuday N; Yu, Hong

2016-01-01

Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies1 for structured prediction in order to improve the exact phrase detection of various medical entities. PMID:28004040

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.

[Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Contribution of two new cases].

PubMed

Fernández Fernández, F J; de la Fuente Aguado, J; Pérez Fernández, S; Sopeña Pérez-Argüelles, B; Nodar Germiñas, A; Butrón Vila, M

2005-03-01

The autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome is characterized for clinical, biochemical, immunological, and histological features overlapping those of AIH and PBC, whose pathogenesis and more appropriate treatment are unknown at present. We describe two new patients of this entity, which made debut with cholestasic acute hepatitis accompanied of hypergammaglobulinemia. In the first patient was demonstrated the presence of AMA, ASMA, and anti-LKM1 autoantibodies; and ANA in the second one. The histological findings showed changes suggestive of AIH and PBC. After the start of immunosuppressive treatment, associated to ursodeoxycholic acid in one patient, a successful outcome was observed.

TRPV1 as a key determinant in ciguatera and neurotoxic shellfish poisoning

PubMed Central

Cuypers, Eva; Yanagihara, Angel; Rainier, Jon D.; Tytgat, Jan

2007-01-01

Ciguatera fish poisoning and neurotoxic shellfish poisoning are distinct clinical entities characterized by gastrointestinal and neurological disturbances, following the consumption of certain reef fish and shellfish containing toxic polyether compounds sporadically present in certain toxic marine dinoflagellates. The biotransformation and bioaccumulation of gambierol and brevetoxin, and their congeners, are believed to be involved in the pathogenesis of these “food-chain diseases”, for which no effective treatments are available. Here, we describe for the first time the potent effect of gambierol and brevetoxin on TRPV1 channels, a key player in thermal and pain sensation. Our findings may lead to promising new therapeutic interventions. PMID:17659256

[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.

Pharmacologically, are smokers the same as non-smokers?

PubMed

Bani, Massimo; Andorn, Anne; Heidbreder, Christian

2014-02-01

Growing evidence suggests that there are subpopulations of daily smokers ranging from light infrequent users to heavy daily users. In the present review we will investigate whether these differences can be explained by factors such as social context, responsiveness to environmental cues, personality traits, neurochemical and pharmacogenetic differences. We will also assess how controlled abstinence and free choice smoking paradigms in a human laboratory setting may help identify and characterize these differences and what can be learned from these models to accurately predict clinical efficacy in the later phase testing of new chemical entities for the treatment of smoking dependence. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cervical necrotizing fasciitis of nonodontogenic origin: case report and review of literature.

PubMed

Suárez, Aldo; Vicente, Mario; Tomás, Jose A; Floría, Luis M; Delhom, José; Baquero, Mari C

2014-11-01

Cervical necrotizing fasciitis (CNF) is a potentially fatal infection characterized by generalized necrosis of the cervical fascia that progresses rapidly. The incidence of this entity corresponds to 2.6% of all infections of the head and neck. The most frequent primary origin is dental infection, although other causes exist that should be evaluated.Delay in the diagnosis of this entity may lead to rapid progression and fatal outcome. Patients often present immunosuppression or systemic diseases that predispose them to this pathology. Cervical necrotizing fasciitis is associated with mortality rates of 7% to 20% depending on the extension of the cervical lesion. The highest rates correspond to cases that progress to mediastinitis or septic shock, which are the main and most frequent complications. Early detection and adequate emergency treatment are critical in the management of these patients and may reduce morbimortality and improve survival. The emergency services should be prepared to manage such cases efficiently, through a multidisciplinary treatment by coordinating emergency surgery with critical support and clinical stabilization of patients.We present a case of CNF of non odontogenic origin managed in our hospital.

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.

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

PubMed

Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel

2016-02-25

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Breast Cancer Subtypes: Morphologic and Biologic Characterization

PubMed Central

2016-01-01

Advances in basic science, technology and translational research have created a revolution in breast cancer diagnosis and therapy. Researchers' discoveries of genes defining variability in response to therapy and heterogeneity in clinical presentations and tumor biology are the foundation of the path to personalized medicine. The success of personalized breast cancer care depends on access to pertinent clinical information and risk factors, optimal imaging findings, well-established morphologic features, and traditional and contemporary prognostic/predictive testing. The integration of these entities provides an opportunity to identify patients who can benefit from specific therapies, and demonstrates the link between breast cancer subtypes and their association with different tumor biology. It is critical to recognize specific types of breast cancer in individual patients and design optimal personalized therapy. This article will highlight the roles of morphologic features and established tumor biomarkers on patient outcome. PMID:26756229

¹⁸F-FDG PET-CT usefulness in extra-pancreatic involvement in IgG4 related diseases.

PubMed

Cárdenas-Perilla, R; Monturiol-Duran, J; Simó-Perdigó, M; Barios-Profitós, M; Castell-Conesa, J

2014-01-01

IgG4-related diseases are a group of recently identified entities that include disorders that were previously known by other names, such as Mikulicz disease, Küttner's tumor, Riedel thyroiditis, among others, as well as some new ones described in the last years. These pathologies are a challenge for the medical community in terms of diagnosis and characterization due to their wide spectrum of clinical presentation. Functional imaging can provide a new approach to the comprehension of physiopathology, staging and targeting site of biopsy of IgG4-related diseases. In this clinical note, we describe five patients who underwent ¹⁸F-FDG PET-CT and correlate their findings with previous reports. Copyright © 2013 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Urticaria Multiforme

PubMed Central

Bernardo, Sebastian G.; Kovalerchik, Olga; Ahmad, Moneeb

2013-01-01

Urticaria multiforme is a benign cutaneous hypersensitivity reaction seen in pediatric patients that is characterized by the acute and transient onset of blanchable, annular, polycyclic, erythematous wheals with dusky, ecchymotic centers in association with acral edema. It is most commonly misdiagnosed as erythema multiforme, a serum-sickness-like reaction, or urticarial vasculitis. Since these three diagnoses represent distinct clinical entities with unique prognoses and management strategies, it is important that physicians distinguish urticaria multiforme from its clinical mimics in order to optimize patient care. By performing a thorough history and physical examination, the astute clinician can make the correct diagnosis and develop an appropriate, effective treatment plan while avoiding unnecessary biopsies and laboratory evaluations. The authors report a case of urticaria multiforme in a four-year-old girl in order to emphasize the distinctive morphological manifestations of this rare, albeit unique, disease seen in the pediatric population. PMID:23556035

PTCH1 Germline Mutations and the Basaloid Follicular Hamartoma Values in the Tumor Spectrum of Basal Cell Carcinoma Syndrome (NBCCS).

PubMed

Ponti, Giovanni; Manfredini, Marco; Pastorino, Lorenza; Maccaferri, Monia; Tomasi, Aldo; Pellacani, Giovanni

2018-01-01

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominantly inherited disorder characterized by multiple basal cell carcinomas (BCC), odontogenic tumors and various skeletal anomalies. Basaloid follicular hamartomas (BFHs) constitute rare neoplasms that can be detected in sporadic and familial settings as in the Basaloid Follicular Hamartoma Syndrome (BFHS). Although BFHS shares clinical, histopathological and genetic overlapping with the NBCCS, they are still considered two distinctive entities. The aim of our single-institution study was the analysis of a cohort of PTCH1-mutated patients in order to define clinical and biomolecular relationship between NBCCS and BFHs. In our study we evaluated PTCH1 gene-carrier probands affected by NBCCS to detect the incidence of BFHs and their correlation with this rare syndrome. Among probands we recognized 4 patients with BFHs. We found 15 germline PTCH1 mutations, uniformly distributed across the PTCH1 gene. Six of them had familial history of NBCCS, two of them were novel and have not been described previously. NBCCS and BFHS may be the same genetic entity and not two distinctive syndromes. The inclusion of BFH in the NBCCS cutaneous tumor spectrum might be useful for the recognition of misdiagnosed NBCCS cases that could benefit from tailored surveillance strategies. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Indolent small intestinal CD4+ T-cell lymphoma is a distinct entity with unique biologic and clinical features.

PubMed

Margolskee, Elizabeth; Jobanputra, Vaidehi; Lewis, Suzanne K; Alobeid, Bachir; Green, Peter H R; Bhagat, Govind

2013-01-01

Enteropathy-associated T-cell lymphomas (EATL) are rare and generally aggressive types of peripheral T-cell lymphomas. Rare cases of primary, small intestinal CD4+ T-cell lymphomas with indolent behavior have been described, but are not well characterized. We describe morphologic, phenotypic, genomic and clinical features of 3 cases of indolent primary small intestinal CD4+ T-cell lymphomas. All patients presented with diarrhea and weight loss and were diagnosed with celiac disease refractory to a gluten free diet at referring institutions. Small intestinal biopsies showed crypt hyperplasia, villous atrophy and a dense lamina propria infiltrate of small-sized CD4+ T-cells often with CD7 downregulation or loss. Gastric and colonic involvement was also detected (n = 2 each). Persistent, clonal TCRβ gene rearrangement products were detected at multiple sites. SNP array analysis showed relative genomic stability, early in disease course, and non-recurrent genetic abnormalities, but complex changes were seen at disease transformation (n = 1). Two patients are alive with persistent disease (4.6 and 2.5 years post-diagnosis), despite immunomodulatory therapy; one died due to bowel perforation related to large cell transformation 11 years post-diagnosis. Unique pathobiologic features warrant designation of indolent small intestinal CD4+ T-cell lymphoma as a distinct entity, greater awareness of which would avoid misdiagnosis as EATL or an inflammatory disorder, especially celiac disease.

Keratolysis exfoliativa (dyshidrosis lamellosa sicca): a distinct peeling entity.

PubMed

Chang, Y Y; van der Velden, J; van der Wier, G; Kramer, D; Diercks, G F H; van Geel, M; Coenraads, P J; Zeeuwen, P L J M; Jonkman, M F

2012-11-01

Keratolysis exfoliativa (KE), also known as dyshidrosis lamellosa sicca, is a palmoplantar dermatosis characterized by air-filled blisters and collarette desquamation. It has been regarded as a subtype of dyshidrotic eczema, a fungal infection or a dermatophytid reaction. KE may also resemble acral peeling skin syndrome and localized epidermolysis bullosa simplex. Although KE is a common disorder, it is a rarely reported and is an under-recognized dermatosis. To delineate the characteristic features of KE. We investigated the clinical, immunohistopathological, ultrastructural and molecular features of KE. Patients were included from the clinical records. Additional diagnostic research consisted of mutation analysis of the candidate genes TGM5, KRT5, KRT14, FLG, SPINK6 and SPINK9. A total of 24 patients with KE were identified, six with familial and 18 with sporadic KE. Lesions consisted of air-filled blisters only on palmoplantar skin, followed by collarette and lamellar peeling. Both light microscopy and electron microscopy showed cleavage and partially degraded corneodesmosomes within the stratum corneum, whereas immunofluorescence microscopy showed normal expression of corneodesmosomal components. No mutations were found in TGM5, KRT5/14 and SPINK6/9. There was no clear link with atopy or with FLG mutations. Our study suggests premature corneodesmolysis as the main pathological mechanism of this palmoplantar skin disorder. We conclude that KE appears to be a distinct peeling entity. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

Combined Guillain-Barré syndrome and myasthenia gravis.

PubMed

Hsieh, Meng-Ying; Chan, Oi-Wa; Lin, Jainn-Jim; Lin, Kuang-Lin; Hsia, Shao-Hsuan; Wang, Huei-Shyong; Chiu, Cheng-Hsun

2013-10-01

Guillain-Barré syndrome and myasthenia gravis both lead to muscle weakness but the two combined is uncommon. Detection of these entities can help identify forms of autoimmune neuromuscular diseases that may respond to immunotherapy. This report sought to characterize the clinical features of these two entities when combined. This report is of a case of combined Guillain-Barré syndrome and myasthenia gravis. The clinical features were analyzed and correlated to those published in English literature from 1960 to 2012. Ten reports and 12 cases, including the present case, were reviewed. There were 12 patients (4 women and 8 men), aged 17 to 84 years, with combined Guillain-Barré syndrome and myasthenia gravis. Four had post-infectious Guillain-Barré syndrome followed by the development of myasthenia gravis concurrently or concomitantly within one month. All cases had symptoms of ptosis and areflexia. The other common presentations were limb weakness, oculobulbar weakness, and respiratory involvement. Functional outcome was mentioned in 10 patients and seven had good outcome (Hughes scale ≤ 2). Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing combined Guillain-Barré syndrome and myasthenia gravis. The early recognition of this combination of peripheral nervous and neuro-muscular junction inflammation is important for initial treatment and prognosis. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

New tumor entities in the 4th edition of the World Health Organization classification of head and neck tumors: Nasal cavity, paranasal sinuses and skull base.

PubMed

Thompson, Lester D R; Franchi, Alessandro

2018-03-01

The World Health Organization recently published the 4th edition of the Classification of Head and Neck Tumors, including several new entities, emerging entities, and significant updates to the classification and characterization of tumor and tumor-like lesions, specifically as it relates to nasal cavity, paranasal sinuses, and skull base in this overview. Of note, three new entities (NUT carcinoma, seromucinous hamartoma, biphenotypic sinonasal sarcoma,) were added to this section, while emerging entities (SMARCB1-deficient carcinoma and HPV-related carcinoma with adenoid cystic-like features) and several tumor-like entities (respiratory epithelial adenomatoid hamartoma, chondromesenchymal hamartoma) were included as provisional diagnoses or discussed in the setting of the differential diagnosis. The sinonasal tract houses a significant diversity of entities, but interestingly, the total number of entities has been significantly reduced by excluding tumor types if they did not occur exclusively or predominantly at this site or if they are discussed in detail elsewhere in the book. Refinements to nomenclature and criteria were provided to sinonasal papilloma, borderline soft tissue tumors, and neuroendocrine neoplasms. Overall, the new WHO classification reflects the state of current understanding for many relatively rare neoplasms, with this article highlighting the most significant changes.

Policy enabled information sharing system

DOEpatents

Jorgensen, Craig R.; Nelson, Brian D.; Ratheal, Steve W.

2014-09-02

A technique for dynamically sharing information includes executing a sharing policy indicating when to share a data object responsive to the occurrence of an event. The data object is created by formatting a data file to be shared with a receiving entity. The data object includes a file data portion and a sharing metadata portion. The data object is encrypted and then automatically transmitted to the receiving entity upon occurrence of the event. The sharing metadata portion includes metadata characterizing the data file and referenced in connection with the sharing policy to determine when to automatically transmit the data object to the receiving entity.

Extranodal NK/T Cell Lymphoma, Nasal Type (ENKTL-NT): An Update on Epidemiology, Clinical Presentation, and Natural History in North American and European Cases.

PubMed

Haverkos, Bradley M; Pan, Zenggang; Gru, Alejandro A; Freud, Aharon G; Rabinovitch, Rachel; Xu-Welliver, Meng; Otto, Brad; Barrionuevo, Carlos; Baiocchi, Robert A; Rochford, Rosemary; Porcu, Pierluigi

2016-12-01

Extranodal NK/T cell lymphoma, nasal type (ENKTL-NT) is an aggressive extranodal non-Hodgkin lymphoma most commonly occurring in East Asia and Latin America but with increasing incidence in the United States. Data on epidemiology, disease presentation, and outcome for European and North American ("Western") cases are very limited. We review published landmark clinical studies on ENKTL-NT in the West and report in detail recent data, including our institutional experience. We highlight key observations in its epidemiology, natural history, and trends in clinical management. In the USA, ENKTL-NT is more common among Asian Pacific Islanders (API) and Hispanics compared to non-Hispanic whites. Published studies indicate less heterogeneity in clinical presentation in Western ENKTL-NT compared to Asian patients. While there is variation in age at diagnosis, presence of antecedent lymphoproliferative disorders, and outcomes among racial/ethnic groups, the universal association of ENKTL-NT with EBV and the poor response of this neoplasm to anthracycline-based therapy is consistent across all geographic areas. Data on epidemiology, disease presentation, and clinical outcomes in mature T cell and NK cell (T/NK cell) neoplasms, including ENKTL-NT, in Europe and North America are very limited. As the classification and diagnostic characterization of the currently recognized T/NK cell lymphoma disease entities continue to evolve, gaps and inconsistencies in data reporting across different studies are being recognized. Despite these limitations, several studies from the USA suggest that the incidence of ENKTL-NT is higher in Asian Pacific Islanders (API) and non-white Hispanics and that outcomes may be worse in non-whites. However, the universal association of ENKTL-NT with Epstein-Barr virus (EBV) across all ethnic groups suggests a common pathogenesis. Given the overlap between the entities included in the category of T/NK cell neoplasms, there is a need to further define biological and clinical differences that may affect diagnosis, treatment, and outcome.

Psychomedical care in gender identity dysphoria during adolescence.

PubMed

Sánchez Lorenzo, Isabel; Mora Mesa, Juan José; Oviedo de Lúcas, Olga

In the clinical literature, the term gender dysphoria is used to define the perception of rejection that a person has to the fact of being male or female. In children and adolescents, gender identity dysphoria is a complex clinical entity. The result of entity is variable and uncertain, but in the end only a few will be transsexuals in adulthood. METHODOLOGY: RESULTS AND CONCLUSIONS. Copyright © 2015 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

Osteitis pubis in elite athletes: Diagnostic and therapeutic approach

PubMed Central

Angoules, Antonios G

2015-01-01

Osteitis pubis (OP) is a debilitating overuse syndrome characterizing by pelvic pain and local tenderness over the pubic symphysis commonly encountered in athletes often involved in kicking, twisting and cutting activities in sports such as soccer and rugby and to a lesser degree distance running. It is a common source of groin pain in elite athletes attributable to pubis sympysis instability as the result of microtrauma caused by repetitive muscle strains on pubic bones. Diagnosis is based mainly on detailed sports history and a meticulous clinical examination, although occasionally is difficult to distinguish this nosological entity from other pathologies affecting the involved area which may occur concomitantly in the same patient. Radiologic examinations such as plain radiographs, magnetic resonance imaging and 3 phase bone isotope scanning may be helpful to differentiate from other clinical entities with similar clinical presentation. Most cases respond well to conservative treatment which includes several physical modalities and especially a progressive rehabilitation programmed individualized to each one of patients diagnosed with OP. Local injection therapies have been also been proposed as a non-operative therapeutic option for the efficient management of these patients. In refractory cases, surgical therapeutic strategies are warranted. These include several open or minimally invasive surgical interventions such as arthroscopic or open symphysis curettage, wedge or total resection of pubic sympysis, polypropylene mesh placement and pubic fusion. In this review a critical analysis of OP in elite athletes is performed with special focus on current concepts of diagnosis and management of this source of athletic groin pain. PMID:26495244

Microscopic enteritis: Bucharest consensus

PubMed Central

Rostami, Kamran; Aldulaimi, David; Holmes, Geoffrey; Johnson, Matt W; Robert, Marie; Srivastava, Amitabh; Fléjou, Jean-François; Sanders, David S; Volta, Umberto; Derakhshan, Mohammad H; Going, James J; Becheanu, Gabriel; Catassi, Carlo; Danciu, Mihai; Materacki, Luke; Ghafarzadegan, Kamran; Ishaq, Sauid; Rostami-Nejad, Mohammad; Peña, A Salvador; Bassotti, Gabrio; Marsh, Michael N; Villanacci, Vincenzo

2015-01-01

Microscopic enteritis (ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy. This work recognises a need to characterize disorders with microscopic and submicroscopic features, currently regarded as functional or non-specific entities, to obtain further understanding of their clinical relevance. The consensus working party reviewed statements about the aetiology, diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment. Following the 5th International Course in Digestive Pathology in Bucharest in November 2012, an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME. A five-step agreement scale (from strong agreement to strong disagreement) was used to score 21 statements, independently. There was strong agreement on all statements about ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100% agreement. A statement on the management of ME elicited agreement from the lowest rate (60%) up to 100%. The remaining two categories showed general agreement between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of ME. There was strong agreement on the histological definition of ME. Weaker agreement on management indicates a need for further investigations, better definitions and clinical trials to produce quality guidelines for management. This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy. PMID:25759526

Microscopic enteritis: Bucharest consensus.

PubMed

Rostami, Kamran; Aldulaimi, David; Holmes, Geoffrey; Johnson, Matt W; Robert, Marie; Srivastava, Amitabh; Fléjou, Jean-François; Sanders, David S; Volta, Umberto; Derakhshan, Mohammad H; Going, James J; Becheanu, Gabriel; Catassi, Carlo; Danciu, Mihai; Materacki, Luke; Ghafarzadegan, Kamran; Ishaq, Sauid; Rostami-Nejad, Mohammad; Peña, A Salvador; Bassotti, Gabrio; Marsh, Michael N; Villanacci, Vincenzo

2015-03-07

Microscopic enteritis (ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy. This work recognises a need to characterize disorders with microscopic and submicroscopic features, currently regarded as functional or non-specific entities, to obtain further understanding of their clinical relevance. The consensus working party reviewed statements about the aetiology, diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment. Following the 5(th) International Course in Digestive Pathology in Bucharest in November 2012, an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME. A five-step agreement scale (from strong agreement to strong disagreement) was used to score 21 statements, independently. There was strong agreement on all statements about ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100% agreement. A statement on the management of ME elicited agreement from the lowest rate (60%) up to 100%. The remaining two categories showed general agreement between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of ME. There was strong agreement on the histological definition of ME. Weaker agreement on management indicates a need for further investigations, better definitions and clinical trials to produce quality guidelines for management. This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

Steel syndrome: dislocated hips and radial heads, carpal coalition, scoliosis, short stature, and characteristic facial features.

PubMed

Flynn, John M; Ramirez, Norman; Betz, Randal; Mulcahey, Mary Jane; Pino, Franz; Herrera-Soto, Jose A; Carlo, Simon; Cornier, Alberto S

2010-01-01

A syndrome of children with short stature, bilateral hip dislocations, radial head dislocations, carpal coalitions, scoliosis, and cavus feet in Puerto Rican children, was reported by Steel et al in 1993. The syndrome was described as a unique entity with dismal results after conventional treatment of dislocated hips. The purpose of this study is to reevaluate this patient population with a longer follow-up and delineate the clinical and radiologic features, treatment outcomes, and the genetic characteristics. This is a retrospective cohort study of 32 patients in whom we evaluated the clinical, imaging data, and genetic characteristics. We compare the findings and quality of life in patients with this syndrome who have had attempts at reduction of the hips versus those who did not have the treatment. Congenital hip dislocations were present in 100% of the patients. There was no attempt at reduction in 39% (25/64) of the hips. In the remaining 61% (39/64), the hips were treated with a variety of modalities fraught with complications. Of those treated, 85% (33/39) remain dislocated, the rest of the hips continue subluxated with acetabular dysplasia and pain. The group of hips that were not treated reported fewer complaints and limitation in daily activities compared with the hips that had attempts at reduction. Steel syndrome is a distinct clinical entity characterized by short stature, bilateral hip and radial head dislocation, carpal coalition, scoliosis, cavus feet, and characteristic facial features with dismal results for attempts at reduction of the hips. Prognostic Study Level II.

[Epithelioid hemangioendothelioma: an uncommon liver tumor].

PubMed

Pareja, Eugenia; Cortés, Miriam; Rayon, Miguel; Moya, Angel; Mir, Jose

2010-01-01

We report the case of a female patient who was referred to our unit because of a solid liver tumor, suggestive of metastasis. After biopsy, the patient was diagnosed with epithelioid hemangioendothelioma of the liver. Epithelioid hemangioendothelioma is a rare entity with an unpredictable, potentially fatal, clinical course and outcome. Due to its rarity, this entity should be considered when a solitary hepatic lesion is detected and should be included in the differential diagnosis with liver metastases. We highlight the infrequency of this tumor, its presentation as a solitary hepatic lesion and the indication of surgical treatment. We describe the clinical and pathological characteristics of epithelioid hemangioendothelioma of the liver and report a new case of this entity. The distinct therapeutic options are discussed. Copyright 2010 Elsevier España, S.L. All rights reserved.

Genotype-phenotype analysis of recombinant chromosome 4 syndrome: an array-CGH study and literature review

PubMed Central

2013-01-01

Background Recombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter. To date, 10 cases of recombinant chromosome 4 have been reported. Result We describe the second case in which array-CGH was used to characterize recombinant chromosome 4 syndrome. The patient was a one-year old boy with consistent clinical features. Conventional cytogenetics and FISH documented a recombinant chromosome 4, derived from a paternal pericentric inversion, leading to partial trisomy 4p and partial monosomy of 4q. Array-CGH, performed to further characterize the rearranged chromosome 4 and delineate the breakpoints, documented a small (4.36 Mb) 4q35.1 terminal deletion and a large (23.81 Mb) 4p15.1 terminal duplication. Genotype-phenotype analysis of 10 previously reported cases and the present case indicated relatively consistent clinical features and breakpoints. This consistency was more evident in our case and another characterized by array-CGH, where both showed the common breakpoints of p15.1 and q35.1. A genotype-phenotype correlation study between rec(4), dup(4p), and del(4q) syndromes revealed that urogenital and cardiac defects are probably due to the deletion of 4q whereas the other clinical features are likely due to 4p duplication. Conclusion Our findings support that the clinical features of patients with rec(4) are relatively consistent and specific to the regions of duplication or deletion. Recombinant chromosome 4 syndrome thus appears to be a discrete entity that can be suspected on the basis of clinical features or specific deleted and duplicated chromosomal regions. PMID:23639048

Genotype-phenotype analysis of recombinant chromosome 4 syndrome: an array-CGH study and literature review.

PubMed

Hemmat, Morteza; Hemmat, Omid; Anguiano, Arturo; Boyar, Fatih Z; El Naggar, Mohammed; Wang, Jia-Chi; Wang, Borris T; Sahoo, Trilochan; Owen, Renius; Haddadin, Mary

2013-05-02

Recombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter. To date, 10 cases of recombinant chromosome 4 have been reported. We describe the second case in which array-CGH was used to characterize recombinant chromosome 4 syndrome. The patient was a one-year old boy with consistent clinical features. Conventional cytogenetics and FISH documented a recombinant chromosome 4, derived from a paternal pericentric inversion, leading to partial trisomy 4p and partial monosomy of 4q. Array-CGH, performed to further characterize the rearranged chromosome 4 and delineate the breakpoints, documented a small (4.36 Mb) 4q35.1 terminal deletion and a large (23.81 Mb) 4p15.1 terminal duplication. Genotype-phenotype analysis of 10 previously reported cases and the present case indicated relatively consistent clinical features and breakpoints. This consistency was more evident in our case and another characterized by array-CGH, where both showed the common breakpoints of p15.1 and q35.1. A genotype-phenotype correlation study between rec(4), dup(4p), and del(4q) syndromes revealed that urogenital and cardiac defects are probably due to the deletion of 4q whereas the other clinical features are likely due to 4p duplication. Our findings support that the clinical features of patients with rec(4) are relatively consistent and specific to the regions of duplication or deletion. Recombinant chromosome 4 syndrome thus appears to be a discrete entity that can be suspected on the basis of clinical features or specific deleted and duplicated chromosomal regions.

Acute Hemorrhagic Edema of Infancy: an unusual diagnosis for the general pediatrician

PubMed Central

Cunha, Diego Fontana Siqueira; Darcie, Ana Letícia Fornazieri; Ferronato, Angela Espósito; Hein, Noely; Lo, Denise Swei; Yoshioka, Cristina Ryoka Miyao; Hirose, Maki; Cardoso, Debora Morais; Gilio, Alfredo Elias

2015-01-01

Acute Hemorrhagic Edema of Infancy (AHEI) is a rare leukocytoclastic vasculitis, clinically characterized by the classical triad: palpable purpuric skin lesions, edema and fever, and is commonly misdiagnosed as Henoch-Schönlein purpura. In addition to its sudden onset, AHEI is also characterized by its self-limited course with complete and spontaneous recovery occurring between 1 and 3 weeks. Because of the scarcity of studies on therapy with corticosteroids, the conservative approach is usually recommended. The authors report an unusual case of an one-year-old boy who presented with typical cutaneous rash of AHEI and orchitis, the latter showing complete resolution after less than 24 hours of prednisolone therapy. The authors call attention to this entity mainly as a differential diagnosis of Henoch-Schönlein purpura and to the importance of new studies to establish the benefits of corticosteroid therapy for AHEI. PMID:26558246

Acute Hemorrhagic Edema of Infancy: an unusual diagnosis for the general pediatrician.

PubMed

Cunha, Diego Fontana Siqueira; Darcie, Ana Letícia Fornazieri; Benevides, Gabriel Nuncio; Ferronato, Angela Espósito; Hein, Noely; Lo, Denise Swei; Yoshioka, Cristina Ryoka Miyao; Hirose, Maki; Cardoso, Debora Morais; Gilio, Alfredo Elias

2015-01-01

Acute Hemorrhagic Edema of Infancy (AHEI) is a rare leukocytoclastic vasculitis, clinically characterized by the classical triad: palpable purpuric skin lesions, edema and fever, and is commonly misdiagnosed as Henoch-Schönlein purpura. In addition to its sudden onset, AHEI is also characterized by its self-limited course with complete and spontaneous recovery occurring between 1 and 3 weeks. Because of the scarcity of studies on therapy with corticosteroids, the conservative approach is usually recommended. The authors report an unusual case of an one-year-old boy who presented with typical cutaneous rash of AHEI and orchitis, the latter showing complete resolution after less than 24 hours of prednisolone therapy. The authors call attention to this entity mainly as a differential diagnosis of Henoch-Schönlein purpura and to the importance of new studies to establish the benefits of corticosteroid therapy for AHEI.

Heterogeneity of obsessive-compulsive disorder: a literature review.

PubMed

Lochner, Christine; Stein, Dan J

2003-01-01

Significant advances have been made in characterizing the phenomenology and psychobiology of obsessive-compulsive disorder (OCD) in recent years. In many ways, such advances suggest a conceptualization of OCD as a relatively homogeneous neuropsychiatric entity, underpinned by particular mechanisms that manifest in universal symptoms. Nevertheless, some data have pointed to the heterogeneity of this disorder. A computerized literature search (MEDLINE: 1964-2001) was used to collect studies addressing the heterogeneity of OCD. In addition, reviews of the phenomenology, psychobiology, family studies, and treatment of OCD were examined in an attempt to collate data addressing this issue. There is a growing consensus that some subtypes of OCD are valid and provide a useful means of integrating data on its symptomatology, neurobiology, and treatment response; for example, OCD with comorbid tics is characterized by earlier onset, a particular range of OCD symptoms, and worse response to selective serotonin reuptake inhibitors. The heterogeneity of OCD has important clinical and research implications.

Is the female G-spot truly a distinct anatomic entity?

PubMed

Kilchevsky, Amichai; Vardi, Yoram; Lowenstein, Lior; Gruenwald, Ilan

2012-03-01

The existence of an anatomically distinct female G-spot is controversial. Reports in the public media would lead one to believe the G-spot is a well-characterized entity capable of providing extreme sexual stimulation, yet this is far from the truth. The aim of this article was to provide an overview of the evidence both supporting and refuting the existence of an anatomically distinct female G-spot. PubMed search for articles published between 1950 and 2011 using key words "G-spot," "Grafenberg spot," "vaginal innervation," "female orgasm," "female erogenous zone," and "female ejaculation." Clinical trials, meeting abstracts, case reports, and review articles that were written in English and published in a peer-reviewed journal were selected for analysis. The main outcome measure of this article was to assess any valid objective data in the literature that scientifically evaluates the existence of an anatomically distinct G-spot. The literature cites dozens of trials that have attempted to confirm the existence of a G-spot using surveys, pathologic specimens, various imaging modalities, and biochemical markers. The surveys found that a majority of women believe a G-spot actually exists, although not all of the women who believed in it were able to locate it. Attempts to characterize vaginal innervation have shown some differences in nerve distribution across the vagina, although the findings have not proven to be universally reproducible. Furthermore, radiographic studies have been unable to demonstrate a unique entity, other than the clitoris, whose direct stimulation leads to vaginal orgasm. Objective measures have failed to provide strong and consistent evidence for the existence of an anatomical site that could be related to the famed G-spot. However, reliable reports and anecdotal testimonials of the existence of a highly sensitive area in the distal anterior vaginal wall raise the question of whether enough investigative modalities have been implemented in the search of the G-spot. © 2012 International Society for Sexual Medicine.

Environmental Technology Verification (ETV) Program: Site Characterization and Monitoring Technologies Center

EPA Pesticide Factsheets

The ETV Site Characterization and Monitoring Technology Pilot is composed of EPA, DoD, DOE, other Federal agencies, state regulators, technology evaluation and verification entities, and potential end users of these technologies to facilitate independent..

Seronegative celiac disease: Shedding light on an obscure clinical entity.

PubMed

Volta, Umberto; Caio, Giacomo; Boschetti, Elisa; Giancola, Fiorella; Rhoden, Kerry J; Ruggeri, Eugenio; Paterini, Paola; De Giorgio, Roberto

2016-09-01

Although serological tests are useful for identifying celiac disease, it is well established that a minority of celiacs are seronegative. To define the prevalence and features of seronegative compared to seropositive celiac disease, and to establish whether celiac disease is a common cause of seronegative villous atrophy. Starting from 810 celiac disease diagnoses, seronegative patients were retrospectively characterized for clinical, histological and laboratory findings. Of the 810 patients, fourteen fulfilled the diagnostic criteria for seronegative celiac disease based on antibody negativity, villous atrophy, HLA-DQ2/-DQ8 positivity and clinical/histological improvement after gluten free diet. Compared to seropositive, seronegative celiac disease showed a significantly higher median age at diagnosis and a higher prevalence of classical phenotype (i.e., malabsorption), autoimmune disorders and severe villous atrophy. The most frequent diagnosis in the 31 cases with seronegative flat mucosa was celiac disease (45%), whereas other diagnoses were Giardiasis (20%), common variable immunodeficiency (16%) and autoimmune enteropathy (10%). Although rare seronegative celiac disease can be regarded as the most frequent cause of seronegative villous atrophy being characterized by a high median age at diagnosis; a close association with malabsorption and flat mucosa; and a high prevalence of autoimmune disorders. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Neuropsychological functioning in children with temporal lobe epilepsy and hippocampal atrophy without mesial temporal sclerosis: a distinct clinical entity?

PubMed

Schmidt, Charlotte S M; Lassonde, Maryse; Gagnon, Louise; Sauerwein, Catherine H; Carmant, Lionel; Major, Philippe; Paquette, Natacha; Lepore, Franco; Gallagher, Anne

2015-03-01

Unilateral hippocampal atrophy (HA) is considered as a precursor of mesial temporal sclerosis (MTS) in some patients with temporal lobe epilepsy. However, in other cases, it has been suggested that HA without MTS may constitute a distinct epileptic entity. Hippocampal atrophy without MTS was defined as HA without T2-weighted hyperintensity, loss of internal architecture, or associated lesion seen on the MRI data. To date, no study has focused on the cognitive pattern of children with epilepsy with HA without MTS. The objectives of the present study were to characterize the cognitive profile of these children and to investigate the presence (or the absence) of material-specific memory deficits in these young patients, as found in patients with MTS. Toward this end, 16 young patients with epilepsy with either left or right HA without MTS completed a set of neuropsychological tests, assessing overall intelligence, verbal memory and nonverbal memory, and some aspects of attention and executive functions. Results showed normal intellectual functioning without specific memory deficits in these patients. Furthermore, comparison between patients with left HA and patients with right HA failed to reveal a material-specific lateralized memory pattern. Instead, attention and executive functions were found to be impaired in most patients. These results suggest that HA may constitute a distinct epileptic entity, and this information may help health-care providers initiate appropriate and timely interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

A Novel Approach towards Medical Entity Recognition in Chinese Clinical Text

PubMed Central

Yu, Jian

2017-01-01

Medical entity recognition, a basic task in the language processing of clinical data, has been extensively studied in analyzing admission notes in alphabetic languages such as English. However, much less work has been done on nonstructural texts that are written in Chinese, or in the setting of differentiation of Chinese drug names between traditional Chinese medicine and Western medicine. Here, we propose a novel cascade-type Chinese medication entity recognition approach that aims at integrating the sentence category classifier from a support vector machine and the conditional random field-based medication entity recognition. We hypothesized that this approach could avoid the side effects of abundant negative samples and improve the performance of the named entity recognition from admission notes written in Chinese. Therefore, we applied this approach to a test set of 324 Chinese-written admission notes with manual annotation by medical experts. Our data demonstrated that this approach had a score of 94.2% in precision, 92.8% in recall, and 93.5% in F-measure for the recognition of traditional Chinese medicine drug names and 91.2% in precision, 92.6% in recall, and 91.7% F-measure for the recognition of Western medicine drug names. The differences in F-measure were significant compared with those in the baseline systems. PMID:29065612

Clinical vampirism. A presentation of 3 cases and a re-evaluation of Haigh, the 'acid-bath murderer'.

PubMed

Hemphill, R E; Zabow, T

1983-02-19

Clinical vampirism is named after the mythical vampire, and is a recognizable, although rare, clinical entity characterized by periodic compulsive blood-drinking, affinity with the dead and uncertain identity. It is hypothetically the expression of an inherited archaic myth, the act of taking blood being a ritual that gives temporary relief. From ancient times vampirists have given substance to belief in the existence of supernatural vampires. Four vampirists, including Haigh, the 'acid-bath murderer', are described. From childhood they cut themselves, drank their own, exogenous human or animal blood to relieve a craving, dreamed of blood-shed, associated with the dead, and had a changing identity. They were intelligent, with no family mental or social pathology. Some self-cutters are auto-vampirists; females are not likely to assault others for blood, but males are potentially dangerous. Vampirism may be a cause of unpredictable repeated assault and murder, and should be looked for in violent criminals who are self-mutilators. No specific treatment is known.

Recurrent epistaxis from Kiesselbach area syndrome in patients suffering from hemorrhoids: fact or fiction?

PubMed

Mladina, Ranko; Cavcic, Josip; Subaric, Marin

2002-01-01

It has been found that >90% of patients suffering from recurrent epistaxis from Kiesselbach area syndrome (REKAS) simultaneously suffered from hemorrhoids. To clarify this, the authors decided to investigate in the opposite direction, i.e., to find out whether or not REKAS occurs in patients suffering primarily from hemorrhoids. The study group included 53 randomly selected hospitalized patients with hemorrhoidal disorder (31 males and 22 females: age range 18-57 years). A search for essential clinical signs of REKAS was performed in each patient. Incidence was not high, although all clinical parameters were nearly the same: dilated vessels in Kiesselbach venous plexus (83.01%) and a positive hereditary factor (92.7%). The only missing factor in patients with hemorrhoids was anterior septal deformity, so frequent in REKAS patients. CONCLUSIONS; The authors conclude that REKAS and hemorrhoidal syndrome are separate clinical entities that are characterized by dilated vessels of similar venous plexus and simultaneous appearance in the same patient or close relatives.

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

PEG-modified biopharmaceuticals.

PubMed

Bailon, Pascal; Won, Chee-Youb

2009-01-01

PEGylation is a process in which one or more units of chemically activated polyethylene glycol reacts with a biomolecule, usually a protein, peptide, small molecule or oligonucleotide, creating a putative new molecular entity possessing physicochemical and physiological characteristics that are distinct from its predecessor molecules. In recent years, PEGylation has been used not only as a drug delivery technology but used also as a drug modification technology to transform existing biopharmaceuticals clinically more efficacious than before their PEGylation. PEGylation bestows several useful properties upon the native molecule, resulting in improved pharmacokinetic and pharmacodynamic properties, which in turn enable the native molecule to achieve maximum clinical potency. In addition, PEGylation results in sustained clinical response with minimal dose and less frequency of dosing, leading to improved quality of life via increased patient compliance and reduced cost. During the course of development of various pegylated protein therapeutics, several new insights have been gained. This review article focuses on the approaches, strategies and the utilization of modern PEGylation concepts in the design and development of well-characterized pegylated protein therapeutics.

Identifying Liver Cancer and Its Relations with Diseases, Drugs, and Genes: A Literature-Based Approach

PubMed Central

Song, Min

2016-01-01

In biomedicine, scientific literature is a valuable source for knowledge discovery. Mining knowledge from textual data has become an ever important task as the volume of scientific literature is growing unprecedentedly. In this paper, we propose a framework for examining a certain disease based on existing information provided by scientific literature. Disease-related entities that include diseases, drugs, and genes are systematically extracted and analyzed using a three-level network-based approach. A paper-entity network and an entity co-occurrence network (macro-level) are explored and used to construct six entity specific networks (meso-level). Important diseases, drugs, and genes as well as salient entity relations (micro-level) are identified from these networks. Results obtained from the literature-based literature mining can serve to assist clinical applications. PMID:27195695

77 FR 34958 - Draft Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-12

... the Agency considers your comment on this draft guidance before it begins work on the final version of... the regulated entities under FDA's and OHRP's jurisdiction. The Agencies wish to stress, however, that... other entities involved in the study oversight transfer process. FDA and OHRP will continue to work...

42 CFR 414.902 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... carrier means an entity assigned by CMS to process and pay claims for drugs and biologicals under the CAP... participating CAP physician, in his or her clinical judgment, to require prompt action or attention for purposes... requirements of § 414.906(e) are met. Local carrier means an entity assigned by CMS to process and pay claims...

42 CFR 414.902 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... carrier means an entity assigned by CMS to process and pay claims for drugs and biologicals under the CAP... participating CAP physician, in his or her clinical judgment, to require prompt action or attention for purposes... requirements of § 414.906(e) are met. Local carrier means an entity assigned by CMS to process and pay claims...

42 CFR 414.902 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... carrier means an entity assigned by CMS to process and pay claims for drugs and biologicals under the CAP... participating CAP physician, in his or her clinical judgment, to require prompt action or attention for purposes... requirements of § 414.906(e) are met. Local carrier means an entity assigned by CMS to process and pay claims...

Cystic renal tumors: new entities and novel concepts.

PubMed

Moch, Holger

2010-05-01

Cystic renal neoplasms and renal epithelial stromal tumors are diagnostically challenging and represent some novel tumor entities. In this article, clinical and pathologic features of established and novel entities are discussed. Predominantly cystic renal tumors include cystic nephroma/mixed epithelial and stromal tumor, synovial sarcoma, and multilocular cystic renal cell carcinoma. These entities are own tumor entities of the 2004 WHO classification of renal tumors. Tubulocystic carcinoma and acquired cystic disease-associated renal cell carcinoma are neoplasms with an intrinsically cystic growth pattern. Both tumor types should be included in a future WHO classification as novel entities owing to their characteristic features. Cysts and clear cell renal cell carcinoma frequently coexist within the kidneys of patients with von Hippel-Lindau disease. Sporadic clear cell renal cell carcinomas often contain cysts, usually as a minor component. Some clear cell renal cell carcinomas have prominent cysts, and multilocular cystic renal cell carcinoma is composed almost exclusively of cysts. Recent molecular findings suggest that clear cell renal cancer may develop through cyst-dependent and cyst-independent molecular pathways.

Acute disseminated encephalomyelitis: a case report of effective early immunotherapy

NASA Astrophysics Data System (ADS)

Ritarwan, K.; Ramayani, O. R.; Eyanoer, P.

2018-03-01

Acute disseminated encephalomyelitis (ADEM) is a monophasic acute non-vasculitic inflammatory demyelinating disorder of the central nervous system characterized by diffuse neurologic signs and symptoms coupled with evidence of multifocal lesions of demyelination on neuroimaging. Despite the long-standing recognition of ADEM as a specific entity, no consensus definition of ADEM had been reached until recently. Historically, different definitions of ADEM have been in published cases of pediatric and adult patients, which varied as to whether events required (1) monofocal or multifocal clinical features, (2) a change in mental status, and (3) a documentation of previous infection or immunization. The treatment has been given to the patient such as supportive therapy and high dose corticosteroids.

Pseudo-hemothorax at computed tomography due to residual contrast media.

PubMed

Romero, Matías; Bächler, Pablo

2014-01-01

Pleural effusion is a clinical problem that has many causes, with hemothorax being one of them. Computed tomography readily characterizes pleural fluid with determination of the attenuation value, helping to distinguish hemothorax from other types of effusion. Herein, we report the case of a 67-year-old man with end-stage renal disease in which a high-density pleural effusion due to residual contrast media was misinterpreted as hemothorax. Radiologists should consider the possibility of contrast media retention when interpreting a high-density pleural effusion in patients with end-stage renal disease. Recognition of this entity is crucial to avoid misdiagnosis, which might lead to unnecessary testing or procedures. Copyright © 2014 Elsevier Inc. All rights reserved.

D-Lactic Acidosis in Humans: Review of Update

PubMed Central

Kang, Kyung Pyo; Lee, Sik

2006-01-01

D-Lactic acidosis has been well documented in ruminants. In humans, D-lactic acidosis is very rare, but D-lactic acidosis may be more common than generally believed and should be looked for in a case of metabolic acidosis in which the cause of acidosis is not apparent. The clinical presentation of D-lactic acidosis is characterized by episodes of encephalopathy and metabolic acidosis. The entity should be considered as a diagnosis in a patient who presents with metabolic acidosis accompanied by high anion gap, normal lactate level, negative Acetest, history of short bowel syndrome or malabsorption, and characteristic neurologic manifestations. Low carbohydrate diet, bicarbonate treatment, rehydration, and oral antibiotics would be helpful in controlling symptoms. PMID:24459486

Role of Imaging and Cytogenetics in Evaluation of DiGeorge Syndrome - A Rare Entity in Clinical Practice.

PubMed

Ramachandran, Rajoo; Babu, Sellappan Rajamanickam; Ilanchezhian, Subramanian; Radhakrishnan, Prabhu Radhan

2015-01-01

DiGeorge syndrome is a congenital genetic disorder that affects the endocrine system, mainly the thymus and parathyroid glands. The syndrome produces different symptoms, which vary in severity and character between patients. It manifests with craniofacial dysmorphism and defects in the heart, parathyroid, and thymus. Patients can present with a palatal deformity and nasal speech. This rare entity is caused mainly due to deletion of chromosome 22q11.2. Radiographic evaluation of DiGeorge syndrome is necessary to define aberrant anatomy, evaluate central nervous system, craniofacial abnormalities, musculoskeletal system, and cardiothoracic contents. It also helps in planning surgical procedures and surgical reconstructions. We report a case of DiGeorge syndrome in a 4-month-old neonate and discuss the clinical, imaging, and cytogenetic findings that helped in the diagnosis of this rare entity.

Combat Identification with Sequential Observations, Rejection Option, and Out-of-Library Targets

DTIC Science & Technology

2005-09-01

nature of the entities sharing the battlespace is unknown. Here CID characterizes those entities using information from a variety of sources. The goal...producing high-resolution returns with signif - icantly enhanced target to clutter (and noise) ratios through Doppler filtering and clutter...treat the subject from a natural science perspective. The following 43 subsections on the various model selection techniques are derived from these

Obstructive sleep apnea syndrome: An important piece in the puzzle of cardiovascular risk factors.

PubMed

Costa, Cátia; Santos, Beatriz; Severino, Davide; Cabanelas, Nuno; Peres, Marisa; Monteiro, Isabel; Leal, Margarida

2015-01-01

The obstructive sleep apnea syndrome (OSA) is a clinical entity characterized by recurring episodes of apnea and/or hypopnea during sleep, due to a total or partial collapse, respectively, of the upper airway. This collapse originates a set of pathophysiological changes that determine the appearance of several cardiovascular complications. OSA contributes for the development of hypertension, heart failure, arrhythmias and coronary heart disease. Nowadays it is recognized to be an important public health problem, taking into account not just its repercussions but also its prevalence, since the main risk factor for the disease is obesity, a growing problem worldwide, both in developed and developing countries. The present review summarizes the current knowledge about OSA, as regards its definition, pathophysiology, clinical manifestations, diagnosis, cardiovascular effects and treatment. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Up-to-date approach to manage keloids and hypertrophic scars: A useful guide

PubMed Central

Arno, Anna I.; Gauglitz, Gerd G.; Barret, Juan P.; Jeschke, Marc G.

2014-01-01

Keloids and hypertrophic scars occur anywhere from 30 to 90% of patients, and are characterized by pathologically excessive dermal fibrosis and aberrant wound healing. Both entities have different clinical and histochemical characteristics, and unfortunately still represent a great challenge for clinicians due to lack of efficacious treatments. Current advances in molecular biology and genetics reveal new preventive and therapeutical options which represent a hope to manage this highly prevalent, chronic and disabling problem, with long-term beneficial outcomes and improvement of quality of life. While we wait for these translational clinical products to be marketed, however, it is imperative to know the basics of the currently existing wide array of strategies to deal with excessive scars: from the classical corticotherapy, to the most recent botulinum toxin and lasers. The main aim of this review paper is to offer a useful up-to-date guideline to prevent and treat keloids and hypertrophic scars. PMID:24767715

Are Traditional Remedies Useful in Management of Fibromyalgia and Chronic Fatigue Syndrome? A Review Study

PubMed Central

Mahjoub, Fatemeh; Salari, Roshanak; Noras, Mohammad Reza; Yousefi, Mahdi

2017-01-01

Fibromyalgia and chronic fatigue syndrome are disorders that often occur simultaneously and are characterized by widespread pain and persistent fatigue. The patients are associated with disability and impairment social and physical functions. There are many remedies in traditional Persian medicine suggested for management of the disease complaints. The aim of this study was to investigate the clinical presentations and pathophysiology of disorders with the basic and principal textbook of traditional Persian medicine written by Avicenna (Canon of Medicine). According to Persian medicine, the term E’aya can be matched by mentioned disorders. Avicenna believed that strenuous activities play an important role in the beginning of some types of fatigue. He classified fatigue into 4 groups, and in each type the clinical symptoms varied. The multifaceted entity of fibromyalgia and chronic fatigue syndrome in Persian medicine and conventional medicine suggests multidisciplinary therapies in management of these disabling disorders. PMID:28597692

Modified endoscopic medial maxillectomy for zygomatic implant salvage.

PubMed

Schwartz, Joseph S; Tajudeen, Bobby A; Adappa, Nithin D; Palmer, James N

2016-01-01

Odontogenic chronic rhinosinusitis (CRS) is an epidemiologically important disease process due, in part, to the increasingly commonplace use of dental restorative procedures such as zygomatic implantation. Traditional management of this clinical entity typically entails extraction of the infected hardware via an open or endoscopic approach. We describe a novel management strategy of odontogenic CRS following bilateral zygomatic implantation for oral rehabilitation that we surgically salvaged via a modified endoscopic medial maxillectomy. We describe the presentation and management of a case of metachronous development of bilateral CRS subsequent to zygomatic implantation. The patient's postoperative course was characterized by marked endoscopic, radiologic, and symptomatic improvement as measured by the 22-item Sino-Nasal Outcome Test. We describe a novel treatment strategy for the management of odontogenic sinusitis resulting from erroneous zygomatic implant placement. Modified endoscopic medial maxillectomy in this clinical context facilitates mucosal normalization of the affected sinus, while permitting preservation of oral function through salvage of the displaced implant.

[Cutaneous lupus erythematosus and skin manifestations in systemic lupus erythematosus].

PubMed

Sticherling, M

2013-06-01

Skin manifestations are frequently observed in lupus erythematosus (LE) and are manifold. Nonspecific and specific symptoms can be differentiated with the latter belonging to the dermatologically well-characterized clinical entities of acute cutaneous, subacute cutaneous, chronic cutaneous as well as intermittent cutaneous LE. These forms are differentially related to systemic LE. Patient history and clinical examinations, laboratory and immunoserological findings as well as organ imaging results determine the time point as well as the intensity of therapy. Apart from cessation of smoking and alcohol consumption as well as stringent UV protection, topical therapy with corticosteroids or calcineurin inhibitors may suffice with limited forms of the disease. In many cases, however, systemic treatment with antimalarial drugs as a basic treatment is mandatory. Several immunosuppressive agents can alternatively be used in conjunction with systemic corticosteroids. Early and effective therapy is important to prevent irreversible scarring of the skin and to avoid internal organ damage.

[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

Bullous lichen planus - a review.

PubMed

Liakopoulou, Angeliki; Rallis, Efstathios

2017-03-31

Bullous lichen planus is a rare variant of lichen planus. It is characterized by vesicles or bullae, which usually develop in the context of pre-existing LP lesions. It is often misdiagnosed and should be differentiated from other subepidermal bullous diseases especially lichen planus pemphigoides. The diagnosis is based on clinical suspicion and is confirmed by histopathology and immunofluoresence. The clinical features of bullous lichen planus include typical lichen planus lesions, accompanied by the formation of bullae on the affected or perilesional skin. This is evident on histology, with alteration of the dermo-epidermal junction and intrabasal bullae as a consequence of extensive inflammation. The histologic features in conjunction with the negative immunofluoresence indicate that bullous lichen planus is a form of "hyper-reactive lichen planus" rather than a distinct entity. There is no standard treatment of bullous lichen planus. Topical and systemic corticosteroids, dapsone and acitretin have been described as effective choices.

Clericuzio-type poikiloderma with neutropenia syndrome in three sibs with mutations in the C16orf57 gene: delineation of the phenotype.

PubMed

Concolino, D; Roversi, G; Muzzi, G L; Sestito, S; Colombo, E A; Volpi, L; Larizza, L; Strisciuglio, P

2010-10-01

We report on three sibs who have autosomal recessive Clericuzio-type poikiloderma neutropenia (PN) syndrome. Recently, this consanguineous family was reported and shown to be informative in identifying the C16orf57 gene as the causative gene for this syndrome. Here we present the clinical data in detail. PN is a distinct and recognizable entity belonging to the group of poikiloderma syndromes among which Rothmund-Thomson is perhaps the best described and understood. PN is characterized by cutaneous poikiloderma, hyperkeratotic nails, generalized hyperkeratosis on palms and soles, neutropenia, short stature, and recurrent pulmonary infections. In order to delineate the phenotype of this rare genodermatosis, the clinical presentation together with the molecular investigations in our patients are reported and compared to those from the literature. Copyright © 2010 Wiley-Liss, Inc.

Novel Development of Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome due to Insulin Therapy.

PubMed

Mainali, Naba Raj; Schmidt, Torrey R; Alweis, Richard; George, David L

2014-01-01

Male, 67 FINAL DIAGNOSIS: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome Symptoms: Bilateral wrist swelling Medication: - Clinical Procedure: - Specialty: Rheumatology. Unusual or unexpected effect of treatment. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is a rare clinical entity characterized by the sudden onset of inflammatory arthritis and marked pitting edema on upper and lower extremities. RS3PE is considered a rheumatic process distinct from rheumatoid arthritis, which may occasionally represent a paraneoplastic syndrome. Herein, we describe a rare case of RS3PE associated with insulin therapy in a patient with no evidence of underlying malignancy. To the best of our knowledge, this is the first case report of RS3PE associated with insulin therapy. Physicians should look at the introduction of drugs as possible triggers for the development of RS3PE.

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

[Xanthoma disseminatum with asymptomatic multisystem involvement].

PubMed

Zinoun, M; Hali, F; Marnissi, F; Lazaar, S; Benchikhi, H

2015-04-01

Xanthogranulomas belong to non-Langerhans histiocytosis of the second group in the Histiocyte Society classification. They comprise a heterogeneous group of rare entities frequently involving cutaneous tropism. Xanthoma disseminatum belongs to this group of non-Langerhans histiocytosis. We report a case of xanthoma disseminatum (XD) in which localized skin and mucous impairment revealed multisystem involvement. A 28-year-old man presented with a two-year history of progressive yellow-orange and infiltrated xanthomatous papulonodular lesions of the face. Lesions of the oral mucosa and genital region were seen, with no functional repercussions. No ophthalmic or other complications were found. Histopathology showed a dense histiocytic infiltrate within the dermis with Touton giant cells, foamy multinucleated giant cells and inflammatory cells, without necrobiosis. Histiocytes were positive for CD68 but negative for CD1a. Gastric and lung involvement was seen and was confirmed at histology. Bone scintigraphy showed suspicious left ulnar hyperfixation suggesting bone involvement. No monoclonal gammopathy or diabetes insipidus was seen. Our patient was treated with corticosteroids 1mg/kg/day and thalidomide 100 mg/day. The outcome was marked by regression and exfiltration of the cutaneous lesions from the second week of treatment, with subsidence continuing at 3 months. This case involves a very rare form of xanthoma disseminatum. The localized facial skin lesions revealed multifocal non-Langerhans histiocytosis that was in fact asymptomatic. The diagnosis of XD was based on clinical, histological and immunohistochemical criteria. Xanthoma disseminatum is a non-Langerhans histiocytic proliferation first described by Montgomery in 1938. This rare entity is characterized by skin and mucous membrane xanthomatosis in which the facial involvement is common, together with diabetes insipidus and normal lipid metabolism. The prognosis is determined by the presence of mucosal xanthomas and visceral involvement. Thus, all xanthogranulomas involving multiple lesions warrant screening for visceral involvement. Diagnosis of this entity can be difficult and is usually based on clinical and histopathological findings. In addition, treatment is complex and non-consensual. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

4p16.1-p15.31 duplication and 4p terminal deletion in a 3-years old Chinese girl: Array-CGH, genotype-phenotype and neurological characterization.

PubMed

Piccione, Maria; Salzano, Emanuela; Vecchio, Davide; Ferrara, Dante; Malacarne, Michela; Pierluigi, Mauro; Ferrara, Ines; Corsello, Giovanni

2015-07-01

Microscopically chromosome rearrangements of the short arm of chromosome 4 include the two known clinical entities: partial trisomy 4p and deletions of the Wolf-Hirschhorn critical regions 1 and 2 (WHSCR-1 and WHSCR-2, respectively), which cause cranio-facial anomalies, congenital malformations and developmental delay/intellectual disability. We report on clinical findings detected in a Chinese patient with a de novo 4p16.1-p15.32 duplication in association with a subtle 4p terminal deletion of 6 Mb in size. This unusual chromosome imbalance resulted in WHS classical phenotype, while clinical manifestations of 4p trisomy were practically absent. This observation suggests the hypothesis that haploinsufficiency of sensitive dosage genes with regulatory function placed in WHS critical region, is more pathogenic than concomitant 4p duplicated segment. Additionally clinical findings in our patient confirm a variable penetrance of major malformations and neurological features in Chinese children despite of WHS critical region's deletion. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Update on Genetic Conditions Affecting the Skin and the Kidneys

PubMed Central

Reimer, Antonia; He, Yinghong; Has, Cristina

2018-01-01

Genetic conditions affecting the skin and kidney are clinically and genetically heterogeneous, and target molecular components present in both organs. The molecular pathology involves defects of cell–matrix adhesion, metabolic or signaling pathways, as well as tumor suppressor genes. This article gives a clinically oriented overview of this group of disorders, highlighting entities which have been recently described, as well as the progress made in understanding well-known entities. The genetic bases as well as molecular cell biological mechanisms are described, with therapeutic applications. PMID:29552546

[Isotretinoin embryopathy: An entity that can be avoided].

PubMed

Cammarata-Scalisi, Francisco; Nieves, Dairelis; Avendaño, Andrea; Lacruz-Rengel, María A; Alviárez, Karelys; Dávila, Francys; Yavuz, Izzet; Callea, Michele

2018-04-01

Isotretinoin is the most effective drug in the treatment of severe recalcitrant nodulocystic acne. However, treatment with this drug is associated with adverse effects, the most severe being teratogenesis. It has been estimated that 40% of pregnancies exposed to isotretinoin present spontaneous abortion and 35% develop embryopathy. We present the case of a newborn with a history of prenatal exposure to isotretinoin, a clinical entity that can be avoided, with severe congenital defects in the central nervous system and important facial dysmorphisms, with unfavorable clinical course. Sociedad Argentina de Pediatría.

Clinics in diagnostic imaging (178). Wünderlich syndrome and pseudoaneurysm.

PubMed

Chung, Raymond; Chawla, Ashish; Peh, Wilfred Cg

2017-06-01

Wünderlich syndrome is a rare entity characterised by spontaneous retroperitoneal haemorrhage with renal origin. We present a case of Wünderlich syndrome secondary to clotting dyscrasia in a 64-year-old woman. The patient experienced a second Wünderlich haemorrhagic event with metachronous pseudoaneurysm formation, which was likely secondary to the large subcapsular haematoma stripping the renal capsule and tearing the cortical arteries. Selective pseudoaneurysm embolisations were successfully performed on both occasions. This clinical entity, its imaging differential diagnoses and management are discussed. Copyright: © Singapore Medical Association.

The clinical entity of remitting seronegative synovitis with pitting edema (RS3PE syndrome).

PubMed

Triplett, L M; Pfister, A K

2001-01-01

Remitting seronegative symmetrical synovitis with pitting edema is a clinical entity distinct from polymyalgia rheumatica arthritis appearing in elderly patients. Distal pitting edema and tenosynovitis of the digitorum tendons are characteristically seen in this disorder. In contrast to polymyalgia rheumatica and rheumatoid arthritis, treatment with low-dose glucocorticoids usually produces a prompt and enduring remission after several months. Follow-up evaluations are necessary not only to assure this diagnosis is posterior, but also to observe for the possible occurrence of associated neoplasms.

Is the common cold a clinical entity or a cultural concept?

PubMed

Eccles, R

2013-03-01

Common cold is the most common infectious disease of mankind and the term is widely used in the clinical literature as though it were a defined clinical syndrome. Clinical studies on this syndrome often use elaborate symptom scoring systems to diagnose a common cold. The symptom scores are based on a study conducted over 50 years ago to retrospectively diagnose experimental cold and this method cannot be applied to diagnosis of common cold in the community. Diagnosis of the common cold by virology is not feasible because of the number of viruses and the variability in the disease states caused by the viruses. Because of the familiarity of subjects with common cold and the variability in symptomatology it seems a more reasonable approach to use self-diagnosis of common cold for clinical research studies and accept that the common cold is a cultural concept and not a clinical entity.

Characterizing autopoiesis in the game of life.

PubMed

Beer, Randall D

2015-01-01

Maturana and Varela's concept of autopoiesis defines the essential organization of living systems and serves as a foundation for their biology of cognition and the enactive approach to cognitive science. As an initial step toward a more formal analysis of autopoiesis, this article investigates its application to the compact, recurrent spatiotemporal patterns that arise in Conway's Game-of-Life cellular automaton. In particular, we demonstrate how such entities can be formulated as self-constructing networks of interdependent processes that maintain their own boundaries. We then characterize the specific organizations of several such entities, suggest a way to simplify the descriptions of these organizations, and briefly consider the transformation of such organizations over time.

Melorheostosis: a rare entity: a case report.

PubMed

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease.

Melorheostosis: a rare entity: a case report

PubMed Central

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease. PMID:25489356

Thoracoscopic treatment of congenital esophageal stenosis in combination with H-type tracheoesophageal fistula.

PubMed

van Poll, Daan; van der Zee, David C

2012-08-01

Congenital esophageal stenosis combined with H-type tracheoesophageal fistula is a rare clinical entity that is often not diagnosed until months or sometimes many years after birth. We present a case of a boy who presented both these entities and was treated by thoracoscopy. Copyright © 2012 Elsevier Inc. All rights reserved.

Overlapping Morphologic and Immunohistochemical Features of Hashimoto Thyroiditis and IgG4-Related Thyroid Disease.

PubMed

Raess, Philipp W; Habashi, Arlette; El Rassi, Edward; Milas, Mira; Sauer, David A; Troxell, Megan L

2015-05-01

Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathologic entity characterized by both IgG4+ plasma cell infiltration and fibrosis in one or more organs, prototypically pancreas or salivary/lacrimal glands. IgG4-RD in the thyroid (IgG4-RTD) is an area of active study, and the relationship between IgG4-RTD and Hashimoto thyroiditis is not fully delineated due to their overlapping histologic features. Retrospective review was performed of all thyroidectomy cases demonstrating lymphocytic inflammation at a single institution over a 4-year period. Approximately half (23/38) of patients had a clinical diagnosis of Hashimoto thyroiditis (HT). Nine of the 38 patients had increased absolute and relative numbers of IgG4+ plasma cells. Patients with a clinical diagnosis of HT had increased lymphoplasmacytic inflammation, but the relative proportion of IgG4+ plasma cells was not increased compared to patients without HT. There was no correlation between IgG4 levels and the amount of fibrosis in patients with or without HT. Patients identified as having the fibrosing variant of HT were not more likely to have increased levels of IgG4+ plasma cells than those without. There is significant morphologic and immunohistochemical overlap between HT and IgG4-RTD. Future studies to identify specific characteristics of IgG4-RTD involving the thyroid are necessary to accurately define this entity.

Spine malformation complex in 3 diverse syndromic entities: Case reports.

PubMed

Kaissi, Ali Al; van Egmond-Fröhlich, Andreas; Ryabykh, Sergey; Ochirov, Polina; Kenis, Vladimir; Hofstaetter, Jochen G; Grill, Franz; Ganger, Rudolf; Kircher, Susanne Gerit

2016-12-01

Clinical and radiographic phenotypic characterizations were the base line tool of diagnosis in 3 syndromic disorders in which congenital cervico-thoracic kyphosis was the major deformity. Directing maximal care toward the radiographic analysis is not only the axial malformation but also toward the appendicular abnormalities was our main concern. We fully documented the diversity of the spine phenotypic malformation complex via the clinical and radiographic phenotypes. We established the diagnosis via phenotypic/genotypic confirmation in 3 diverse syndromic entities namely acampomelic campomelic dysplasia, Larsen syndrome and Morquio syndrome type A (mucopolysaccharidosis type IV A). Surgical interventions have been carried out in the Larsen syndrome and Morquio syndrome type A, resepectively. The earliest the diagnosis is, the better the results are. The necessity to diagnose children in their first year of life has many folds, firstly the management would be in favor of the child's growth and development and secondly, the prognosis could be clearer to the family and the medical staff as well. Our current paper is to sensitize paediatricians, physicians and orthopedic surgeons regarding the necessity to detect the aetiological understanding in every child who manifests a constellation of malformation complex. Scoliosis and kyphosis/kyphoscoliosis are not a diagnosis in themselves. Such deformities are mostly a symptom complex correlated to dozens of types of syndromic associations. The rate curve progression and the final severity of congenital spine tilting are related to 3 factors: (a) the type of vertebral malformation present, (b) the patient's phenotype, and (c) the diagnosis.

Landscape of Innovation for Cardiovascular Pharmaceuticals: From Basic Science to New Molecular Entities.

PubMed

Beierlein, Jennifer M; McNamee, Laura M; Walsh, Michael J; Kaitin, Kenneth I; DiMasi, Joseph A; Ledley, Fred D

2017-07-01

This study examines the complete timelines of translational science for new cardiovascular therapeutics from the initiation of basic research leading to identification of new drug targets through clinical development and US Food and Drug Administration (FDA) approval of new molecular entities (NMEs) based on this research. This work extends previous studies by examining the association between the growth of research on drug targets and approval of NMEs associated with these targets. Drawing on research on innovation in other technology sectors, where technological maturity is an important determinant in the success or failure of new product development, an analytical model was used to characterize the growth of research related to the known targets for all 168 approved cardiovascular therapeutics. Categorizing and mapping the technological maturity of cardiovascular therapeutics reveal that (1) there has been a distinct transition from phenotypic to targeted methods for drug discovery, (2) the durations of clinical and regulatory processes were significantly influenced by changes in FDA practice, and (3) the longest phase of the translational process was the time required for technology to advance from initiation of research to a statistically defined established point of technology maturation (mean, 30.8 years). This work reveals a normative association between metrics of research maturation and approval of new cardiovascular therapeutics and suggests strategies for advancing translational science by accelerating basic and applied research and improving the synchrony between the maturation of this research and drug development initiatives. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

[Updated treatment of peritoneal carcinomas: a review].

PubMed

Deraco, M; Laterza, B; Kusamura, S; Baratti, D

2007-12-01

Peritoneal surface malignancy (PSM) is a clinical entity with an unfavourable prognosis, which characterizes the evolution of neoplastic diseases from the abdominal and/or pelvic organs and could also be the terminal stage of extra-abdominal tumors. Examples of diseases that can spread mainly within the peritoneal cavity are appendiceal tumors, ovarian cancer, colorectal cancer, abdominal sarcomatosis, gastric cancer and peritoneal mesothelioma. The locoregional therapy is defined as the combination of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). The rationale of this combined therapy for PSM is based on the natural history of this clinical entity that remains confined in the peritoneal cavity for most of its natural history. This pattern of spread would seem to indicate the potential usefulness of selectively increasing drug concentration in the tumour-bearing area by direct intraperitoneal chemotherapy instillation. This approach led to these outcomes: the median survival of colorectal carcinoma and ovarian cancer was 32 months; patients with peritoneal mesothelioma showed 57% survival at 5 years, while in patients with appendiceal mucinous tumors and pseudomyxoma peritonei (PMP) the 10 years overall survival was 78%. A significant improvement in survival was associated with hyperthermic intra-peritoneal chemotherapy (HIPEC) in patients with gastric cancer. Considering the constant increasing of diseases treatable with this procedure, more centres should be activated. The establishment of a clear policy and scientific guidelines is mandatory, in order to perform the CRS+HIPEC safely, minimizing treatment-related morbidity and mortality and maximizing the results in terms of survival and quality of life.

[The clinical view through the Archives: the clinical notes of 2009].

PubMed

Samolski, Daniel; Martín Robles, Irene; Castillo Villegas, Diego

2010-12-01

The Clinical Notes published in 2009 serve as a resource to reflect on clinical aspects relevant to different clinical entities. Through this review an attempt is likewise made to bring the reader closer to the clinical reality of our environment. Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.

Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic Brain Injury

PubMed Central

Tsitsopoulos, Parmenion P.; Abu Hamdeh, Sami; Marklund, Niklas

2017-01-01

Traumatic brain injury (TBI) is a multidimensional and highly complex disease commonly resulting in widespread injury to axons, due to rapid inertial acceleration/deceleration forces transmitted to the brain during impact. Axonal injury leads to brain network dysfunction, significantly contributing to cognitive and functional impairments frequently observed in TBI survivors. Diffuse axonal injury (DAI) is a clinical entity suggested by impaired level of consciousness and coma on clinical examination and characterized by widespread injury to the hemispheric white matter tracts, the corpus callosum and the brain stem. The clinical course of DAI is commonly unpredictable and it remains a challenging entity with limited therapeutic options, to date. Although axonal integrity may be disrupted at impact, the majority of axonal pathology evolves over time, resulting from delayed activation of complex intracellular biochemical cascades. Activation of these secondary biochemical pathways may lead to axonal transection, named secondary axotomy, and be responsible for the clinical decline of DAI patients. Advances in the neurocritical care of TBI patients have been achieved by refinements in multimodality monitoring for prevention and early detection of secondary injury factors, which can be applied also to DAI. There is an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial fluid using microdialysis in the evaluation of axonal injury in TBI. These biomarker studies have assessed various axonal and neuroglial markers as well as inflammatory mediators, such as cytokines and chemokines. Moreover, modern neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI patients across all injury severities using magnetic resonance spectroscopy, diffusion tensor imaging, and positron emission tomography. Importantly, serial neuroimaging studies provide evidence for evolving axonal injury. Since axonal injury may be a key risk factor for neurodegeneration and dementias at long-term following TBI, the secondary injury processes may require prolonged monitoring. The aim of the present review is to summarize the clinical short- and long-term monitoring possibilities of axonal injury in TBI. Increased knowledge of the underlying pathophysiology achieved by advanced clinical monitoring raises hope for the development of novel treatment strategies for axonal injury in TBI. PMID:29209266

The mutational profile and infiltration pattern of murine MLH1-/- tumors: concurrences, disparities and cell line establishment for functional analysis.

PubMed

Maletzki, Claudia; Beyrich, Franziska; Hühns, Maja; Klar, Ernst; Linnebacher, Michael

2016-08-16

Mice lines homozygous negative for one of the four DNA mismatch repair (MMR) genes (MLH1, MSH2, PMS2, MSH6) were generated as models for MMR deficient (MMR-D) diseases. Clinically, hereditary forms of MMR-D include Lynch syndrome (characterized by a germline MMR gene defect) and constitutional MMR-D, the biallelic form. MMR-D knockout mice may be representative for both diseases. Here, we aimed at characterizing the MLH1-/- model focusing on tumor-immune microenvironment and identification of coding microsatellite mutations in lymphomas and gastrointestinal tumors (GIT).All tumors showed microsatellite instability (MSI) in non-coding mononucleotide markers. Mutational profiling of 26 coding loci in MSI+ GIT and lymphomas revealed instability in half of the microsatellites, two of them (Rfc3 and Rasal2) shared between both entities. MLH1-/- tumors of both entities displayed a similar phenotype (high CD71, FasL, PD-L1 and CTLA-4 expression). Additional immunofluorescence verified the tumors' natural immunosuppressive character (marked CD11b/CD200R infiltration). Vice versa, CD3+ T cells as well as immune checkpoints molecules were detectable, indicative for an active immune microenvironment. For functional analysis, a permanent cell line from an MLH1-/- GIT was established. The newly developed MLH1-/- A7450 cells exhibit stable in vitro growth, strong invasive potential and heterogeneous drug response. Moreover, four additional MSI target genes (Nktr1, C8a, Taf1b, and Lig4) not recognized in the primary were identified in this cell line.Summing up, molecular and immunological mechanisms of MLH1-/- driven carcinogenesis correlate well with clinical features of MMR-D. MLH1-/- knockout mice combine characteristics of Lynch syndrome and constitutional MMR-D, making them suitable models for preclinical research aiming at MMR-D related diseases.

The mutational profile and infiltration pattern of murine MLH1-/- tumors: concurrences, disparities and cell line establishment for functional analysis

PubMed Central

Hühns, Maja; Klar, Ernst; Linnebacher, Michael

2016-01-01

Mice lines homozygous negative for one of the four DNA mismatch repair (MMR) genes (MLH1, MSH2, PMS2, MSH6) were generated as models for MMR deficient (MMR-D) diseases. Clinically, hereditary forms of MMR-D include Lynch syndrome (characterized by a germline MMR gene defect) and constitutional MMR-D, the biallelic form. MMR-D knockout mice may be representative for both diseases. Here, we aimed at characterizing the MLH1-/- model focusing on tumor-immune microenvironment and identification of coding microsatellite mutations in lymphomas and gastrointestinal tumors (GIT). All tumors showed microsatellite instability (MSI) in non-coding mononucleotide markers. Mutational profiling of 26 coding loci in MSI+ GIT and lymphomas revealed instability in half of the microsatellites, two of them (Rfc3 and Rasal2) shared between both entities. MLH1-/- tumors of both entities displayed a similar phenotype (high CD71, FasL, PD-L1 and CTLA-4 expression). Additional immunofluorescence verified the tumors’ natural immunosuppressive character (marked CD11b/CD200R infiltration). Vice versa, CD3+ T cells as well as immune checkpoints molecules were detectable, indicative for an active immune microenvironment. For functional analysis, a permanent cell line from an MLH1-/- GIT was established. The newly developed MLH1-/- A7450 cells exhibit stable in vitro growth, strong invasive potential and heterogeneous drug response. Moreover, four additional MSI target genes (Nktr1, C8a, Taf1b, and Lig4) not recognized in the primary were identified in this cell line. Summing up, molecular and immunological mechanisms of MLH1-/- driven carcinogenesis correlate well with clinical features of MMR-D. MLH1-/- knockout mice combine characteristics of Lynch syndrome and constitutional MMR-D, making them suitable models for preclinical research aiming at MMR-D related diseases. PMID:27447752

AL Amyloidoma of the Skin/Subcutis: Cutaneous Amyloidosis, Plasma Cell Dyscrasia or a Manifestation of Primary Cutaneous Marginal Zone Lymphoma?

PubMed

Walsh, Noreen M; Lano, Ian Marie; Green, Peter; Gallant, Christopher; Pasternak, Sylvia; Ly, Thai Yen; Requena, Luis; Kutzner, Heinz; Chott, Andreas; Cerroni, Lorenzo

2017-08-01

It is unclear whether AL amyloidoma of the skin/subcutis represents a distinct entity, an indolent precursor of systemic amyloidosis, or a manifestation of cutaneous marginal zone lymphoma (cMZL). We collected 10 cases of cutaneous AL amyloidoma in order to better characterize the clinicopathologic features of this elusive entity (M:F=4:6; median age: 62.5 y, range: 31 to 82 y). Nine patients had a solitary nodule or plaque on the lower extremity (n=7), upper extremity (n=1), or chin (n=1). One patient had an AL amyloidoma on the right thigh and a second lesion on the right arm showing histopathologic features of cMZL without amyloid deposits. Clinical investigations excluded relevant systemic disease in all cases. Microscopically, dermal/subcutaneous deposits of amyloid were associated with sparse to moderate perivascular infiltrates of lymphocytes and monotypic plasma cells (7 with kappa and 3 with lambda light chain restriction). The plasma cells expressed CD56 in one of 9 studied cases. One case was characterized by a t(14;18)(q32;q21)/IGH-MALT1 translocation. Follow-up was available in 8 cases. All remain systemically well after a median time of 86.5 months (range: 40 to 144 mo). Local recurrence of disease was observed in 3 patients. A fourth patient presented with a cMZL without amyloid deposits 8 years after excision of the cutaneous AL amyloidoma. Although our series is small, careful categorization and follow-up of the cases, together with updated information in the literature, show clinical and biological links between AL amyloidomas of the skin/subcutis and cMZL, suggesting that at least a subset of cutaneous AL amyloidoma may represent an unusual manifestation of cMZL (cutaneous mucosa-associated lymphoid tissue lymphomas).

Acute hemorrhagic leukoencephalitis: a critical entity for forensic pathologists to recognize.

PubMed

Lann, Meredith A; Lovell, Mark A; Kleinschmidt-DeMasters, B K

2010-03-01

Acute hemorrhagic leukoencephalopathy (AHLE) is a rare, acute disorder characterized by perivenular demyelination and diffuse hemorrhagic necrosis of the central nervous system. AHLE is thought to represent a hyperacute form of acute disseminated encephalomyelitis. AHLE is associated with a greater morbidity and mortality and, fortunately, is much less common than acute disseminated encephalomyelitis. Since most cases of AHLE result in patient demise, forensic pathologists should be cognizant of this entity and consider it in their differential diagnosis.Here we describe an interesting case of a previously healthy 11-year-old boy who initially complained of vague gastroenteritis-like symptoms while visiting a mountain lake. The boy's symptoms evolved to include severe headache and dizziness, necessitating a visit to a rural emergency department. He presented with focal neurologic findings, and head computed tomography (CT) scan confirmed thalamic edema. Cerebrospinal fluid analysis was suggestive of infectious etiology, and multiple empiric therapies were initiated. He was transferred to our institution, and his clinical status continued to worsen. Given the poor prognosis, the family requested withdrawal of supportive care. On day 14 of symptoms the boy succumbed to his illness. An autopsy was requested to further characterize the proximate cause of death.AHLE often presents with abrupt onset of fever, neck stiffness, seizure, and/or focal neurologic signs several days following a viral illness or vaccination. Thus, AHLE can clinically mimic a direct central nervous system infection or a toxic ingestion. AHLE has a very poor prognosis, with rapid deterioration and death usually occurring within days to one week after onset of symptoms. The cause for AHLE is unclear. An autoimmune pathophysiology is likely, with immune cross-reactivity between myelin basic protein moieties and various infectious agent antigens. Treatment for AHLE is not well-established; some authors describe in recent literature that a combination of immunosuppressant medications and/or therapeutic plasma exchange may be of benefit in treating AHLE.

Neurofibromatosis type 2 (NF 2) or schwannomatosis?--Case report study and diagnostic criteria.

PubMed

Radek, Maciej; Tomasik, Bartłomiej; Wojdyn, Maciej; Snopkowska-Wiaderna, Dorota; Błaszczyk, Maciej; Radek, Andrzej

2016-01-01

Neurofibromatosis type 2 (NF2) and schwannomatosis are entities that may, due to the similarity of clinical symptoms, cause diagnostic difficulties. Incidence rate of both diseases is similar and estimated between 1:25,000 and 1:40,000. The genes associated with the development of the aforementioned disorders are located on chromosome 22 and lay in proxmity. Schwannomatosis is characterized by an incomplete penetrance and the risk of its transmission to the offspring is significantly lower than in the case of NF 2. Schwannomatosis clinical characteristic is similar to the NF2, however vestibular schwannomas are not present. Therefore the imaging studies evaluated by an experienced radiologist play a key role in the diagnostic process. Forty two-year-old female hospitalized three times because of the tumors of the spinal canal was admitted to the Department of Neurosurgery and Peripheral Nerve Surgery in 2008 because of the cervical pain syndrome with concomitant headache. She was diagnosed with a schwannomatosis, recently distinguished, the third form of neurofibromatosis. MRI imaging revealed craniocervical junction tumor. Suboccipital craniectomy with concomitant C1-C2 laminectomy was done in order to remove the lesion. After the surgery the patient did not present any deficits in neurological examination and was discharged from hospital in good general condition. The patient was diagnosed with schwannomatosis, recently established neurofibromatosis entity which may resemble NF2 clinically. In patients after the age of 30, in whom we observe multiple schwannomas without the concomitant hearing impairment, the diagnosis of schwannomatosis is very likely. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

[CLINICAL ENTITIES AND CHARACTERISTICS OF PAIN IN PATIENTS WITH RHEUMATIC DISEASES].

PubMed

Prus, Višnja; Kardum, Željka

Musculoskeletal pain is the most common symptom present in almost all rheumatic diseases. Rheumatic diseases include more than 150 clinical entities. There is no uniform classification of rheumatic diseases. In general, we distinguish inflammatory rheumatic diseases, non-inflammatory degenerative articular diseases, systemic connective tissue diseases, metabolic disorders with articular manifestations, and regional and extended pain syndromes. According to the International Association for the Study of Pain (IASP), pain is defined as an unpleasant sensation associated with tissue damage or reported simultaneously with such damage. Pain has a physical, mental, and social component. In rheumatic diseases the pain is mostly chronic and may severely impair the patient’s general condition. The defining criteria involve a period of more than 3 or 6 months, and according to some definitions more than 6 weeks. In most cases the pain is nociceptive rather than neuropathic. Musculoskeletal pain, especially chronic pain, is a global public health problem because of its prevalence, as well as the frequently associated muslculoskeletal function impairment and development of chronic pain syndrome, which can be considered as a separate clinical entity and requires a biopsychosocial treatment approach.

Evaluating the Influence of the Client Behavior in Cloud Computing.

PubMed

Souza Pardo, Mário Henrique; Centurion, Adriana Molina; Franco Eustáquio, Paulo Sérgio; Carlucci Santana, Regina Helena; Bruschi, Sarita Mazzini; Santana, Marcos José

2016-01-01

This paper proposes a novel approach for the implementation of simulation scenarios, providing a client entity for cloud computing systems. The client entity allows the creation of scenarios in which the client behavior has an influence on the simulation, making the results more realistic. The proposed client entity is based on several characteristics that affect the performance of a cloud computing system, including different modes of submission and their behavior when the waiting time between requests (think time) is considered. The proposed characterization of the client enables the sending of either individual requests or group of Web services to scenarios where the workload takes the form of bursts. The client entity is included in the CloudSim, a framework for modelling and simulation of cloud computing. Experimental results show the influence of the client behavior on the performance of the services executed in a cloud computing system.

Evaluating the Influence of the Client Behavior in Cloud Computing

PubMed Central

Centurion, Adriana Molina; Franco Eustáquio, Paulo Sérgio; Carlucci Santana, Regina Helena; Bruschi, Sarita Mazzini; Santana, Marcos José

2016-01-01

This paper proposes a novel approach for the implementation of simulation scenarios, providing a client entity for cloud computing systems. The client entity allows the creation of scenarios in which the client behavior has an influence on the simulation, making the results more realistic. The proposed client entity is based on several characteristics that affect the performance of a cloud computing system, including different modes of submission and their behavior when the waiting time between requests (think time) is considered. The proposed characterization of the client enables the sending of either individual requests or group of Web services to scenarios where the workload takes the form of bursts. The client entity is included in the CloudSim, a framework for modelling and simulation of cloud computing. Experimental results show the influence of the client behavior on the performance of the services executed in a cloud computing system. PMID:27441559

A case of choking phobia: towards a conceptual approach.

PubMed

Lopes, Rui; Melo, Raquel; Curral, Rosário; Coelho, Rui; Roma-Torres, António

2014-03-01

Choking phobia, also known as phagophobia or swallowing phobia is an uncommon clinical entity that has been underappreciated and is included in the new DSM-5 and upcoming ICD-11 diagnostic category of avoidant/restrictive food intake disorder. Phenomenologically distinct from other eating disorders, it is characterized by the phobic stimulus of swallowing that results in the avoidance of food or drinks, and ultimately to low weight, social withdrawal, anxiety and depression states. Its prevalence and long-term course on the general population still needs to be determined, probably reflecting years of indefiniteness regarding its nosology and by the absence of a clear set of diagnostic criteria. We present a clinical case of choking phobia in a 32-year-old male patient after an episode of choke when eating chicken. An early diagnosis and distinction from other eating disorders is important for proper treatment and fundamental for prognosis. We also make a thorough revision on literature in clinical features, differential diagnosis and treatment approaches, suggesting a conceptual approach for choking phobia as a clinical spectrum settled by different degrees of phobic subtypes, which may depend on a varied number of clinical variables.

Idiopathic thoracic transdural intravertebral spinal cord herniation

PubMed Central

Turel, Mazda K; Wewel, Joshua T; Kerolus, Mena G; O'Toole, John E

2017-01-01

Idiopathic spinal cord herniation is a rare and often missed cause of thoracic myelopathy. The clinical presentation and radiological appearance is inconsistent and commonly confused with a dorsal arachnoid cyst and often is a misdiagnosed entity. While ventral spinal cord herniation through a dural defect has been previously described, intravertebral herniation is a distinct entity and extremely rare. We present the case of a 70-year old man with idiopathic thoracic transdural intravertebral spinal cord herniation and discuss the clinico-radiological presentation, pathophysiology and operative management along with a review the literature of this unusual entity. PMID:29021685

Subependymomas - Characteristics of a "Leave me Alone" Lesion.

PubMed

Kammerer, Sara; Mueller-Eschner, Monika; Lauer, Arne; Luger, Anna-Luisa; Quick-Weller, Johanna; Franz, Kea; Harter, Patrick; Berkefeld, Joachim; Wagner, Marlies

2018-06-18

 Intracranial subependymomas are rare, mostly asymptomatic tumours, which are often found incidentally and therefore did not receive much attention in previous literature. By being classified as benign grade I in the WHO classification of tumours of the central nervous system, they are given a special status compared to the other ependymal tumours. Tumor recurrences are a rarity, spinal "drop metastases" do not occur. While etiological, pathological and therapeutic characteristics have been subject of several publications over the last few decades and have meanwhile been well studied, the imaging characteristics are much less well received.  Retrospective analysis of our relatively large group of 33 patients with subependymoma, including 4 patients with a mixture of subependymomas with ependymal cell fractions in terms of imaging and clinical aspects and with reference to a current literature review.  Subependymomas have typical image morphologic characteristics that differentiate them from tumors of other entities, however, the rare subgroup of histopathological mixtures of subependymomas with ependymal cell fractions has no distinctly different imaging properties.  Knowing the imaging characteristics of subpendymoma and their differential diagnoses is of particular importance in order to be able to decide between the necessity of follow-up controls, an early invasive diagnosis or, depending on the entity, tumor resection.   · Subependymomas have typical imaging characteristics that are clearly distinguishable from other entities.. · Increased incidence in middle/ older aged men, most frequent localization: 4th ventricle.. · Symptomatic subependymomas, often located in lateral ventricles, are usually characterized by hydrocephalus.. · Radiological identification of mixed subependymoma with ependymal cell fractions is not possible.. · Image based differentiation from other entities is important for the procedure.. · Kammerer S, Mueller-Eschner M, Lauer A et al. Subependymomas - Characteristics of a "Leave me Alone" Lesion. Fortschr Röntgenstr 2018; DOI: 10.1055/a-0576-1028. © Georg Thieme Verlag KG Stuttgart · New York.

Early- and late-onset Alzheimer disease: Are they the same entity?

PubMed

Tellechea, P; Pujol, N; Esteve-Belloch, P; Echeveste, B; García-Eulate, M R; Arbizu, J; Riverol, M

2018-05-01

Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Nucleic Acid-Based Nanoconstructs

Cancer.gov

Focuses on the design, synthesis, characterization, and development of spherical nucleic acid constructs as effective nanotherapeutic, single-entity agents for the treatment of glioblastoma multiforme and prostate cancers.

Orthostatic hypotension as an unusual clinical manifestation of pheochromocytoma: a case report.

PubMed

Bortnik, Miriam; Occhetta, Eraldo; Marino, Paolo

2008-08-01

Pheochromocytoma is a rare endocrine tumor which can have a highly variable presentation related to increased catecholamine secretion. We report the case of a 74-year-old man in whom recurrent episodes of syncope due to orthostatic hypotension were the only clinical manifestations of this challenging entity. Diagnosis of pheochromocytoma was achieved by biochemical test samples and computed tomography scans. Surgical excision of the tumor resulted in clinical improvement with normalization of catecholamine concentrations and no more episodes of orthostatic hypotension during a follow-up of 24 months. Although rare, pheochromocytoma may frequently cause disorders of orthostatic tolerance; because of its meaningful implications, screening for this entity should be considered in case of recurrent syncopal episodes due to new-onset orthostatic hypotension.

Spectrum of MRI findings in clinical athletic pubalgia.

PubMed

Zajick, Donald C; Zoga, Adam C; Omar, Imran M; Meyers, William C

2008-03-01

Athletic pubalgia is a frequently encountered syndrome for clinicians who treat active patients participating in a wide variety of athletic endeavors worldwide. Pathologies associated with this clinical scenario span anatomically from the pubic symphysis to the hip and include a myriad of poorly understood and incompletely described musculoskeletal entities, many of which are centered about the pubic symphysis and its tendinous attachments. In this article, we discuss the relevant anatomy and pathophysiology for the most frequently encountered of these disorders, using magnetic resonance (MR) images as a guide. We describe an MR imaging protocol tailored to clinical athletic pubalgia. We then review reproducible MRI patterns of pathology about the pubic symphysis, the rectus abdominis/adductor aponeurosis and the inguinal ring, as well as a group of clinically confounding entities remote from the symphysis but visible by MRI.

Non-thrombocytopenic purpura in familial Mediterranean fever-comorbidity with Henoch-Schönlein purpura or an additional rare manifestation of familial Mediterranean fever?

PubMed

Ben-Chetrit, Eldad; Yazici, Hasan

2016-07-01

Henoch-Schönlein purpura is a relatively common vasculitis mainly affecting children. It is characterized by purpuric skin rash, abdominal cramping, and haematuria. Skin biopsies taken from Henoch-Schönlein purpura lesions disclose perivascular IgA deposits. FMF is an autoinflammatory disease characterized by recurrent attacks of fever lasting 2-3 days which resolve spontaneously. Typical manifestations of the disease are peritonitis, pleuritis, pericarditis, arthritis and erysipelas-like erythema usually affecting the lower limbs. Over the years many reviews emphasized the clinical impression that Henoch-Schönlein purpura is more common among FMF patients than in healthy control population. In this review we summarize these reports and show that sometimes Henoch-Schönlein purpura associated with FMF differs from typical isolated Henoch-Schönlein purpura, and this is also the case with polyarteritis nodosa and SpA associated with FMF. It is suggested that these clinical manifestations (polyarteritis nodosa, Henoch-Schönlein purpura and SpA) should be considered to be associated with FMF as part of what we call FMF rather than as co-existing additional separate clinical entities. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Spontaneous and bilateral avascular necrosis of the navicula: Müller-Weiss disease.

PubMed

Aktaş, Erdem; Ayanoğlu, Tacettin; Hatipoğlu, Yasin; Kanatlı, Ulunay

2016-12-01

Although, trauma, foot deformity (pesplanovalgus), systemic diseases such as diabetes mellitus and lupus, drugs (steroids, antineoplastic) and excessive alcohol consumption have all been accused in the etiology of avascular necrosis of the tarsal bones, spontaneous avascular necrosis of the navicular bone, especially in adults, is a rare entity. In this article, we report a 50-year-old female patient with bilateral, spontaneous avascular necrosis of the navicular bone and related severe talonavicular arthrosis. Clinical and radiological findings were concordant with Müller-Weiss disease, which is a rare disease with complex idiopathic foot condition of the adult tarsal navicular bone characterized by progressive navicular fragmentation and talonavicular joint destruction. The patient was successfully treated with two-staged bilateral talonavicular arthrodesis.

Plasma cell leukemia: update on biology and therapy.

PubMed

Mina, Roberto; D'Agostino, Mattia; Cerrato, Chiara; Gay, Francesca; Palumbo, Antonio

2017-07-01

Plasma cell leukemia (PCL) is a rare, but very aggressive, plasma cell dyscrasia, representing a distinct clinicopathological entity as compared to multiple myeloma (MM), with peculiar biological and clinical features. A hundred times rarer than MM, the disease course is characterized by short remissions and poor survival. PCL is defined by an increased percentage (>20%) and absolute number (>2 × 10 9 /l) of plasma cells in the peripheral blood. PCL is defined as 'primary' when peripheral plasmacytosis is detected at diagnosis, 'secondary' when leukemization occurs in a patient with preexisting MM. Novel agents have revolutionized the outcomes of MM patients and have been introduced also for the treatment of PCL. Here, we provide an update on biology and treatment options for PCL.

Elephantiasis nostras verrucosa complicated with chronic tibial osteomyelitis.

PubMed

Turhan, Egemen; Ege, Ahmet; Keser, Selcuk; Bayar, Ahmet

2008-10-01

Elephantiasis nostras verrucosa represents an infrequent clinical entity with cutaneous changes characterized by dermal fibrosis, hyperkeratotic verrucous and papillamotous lesions resulting from chronic non-filarial lymphedema secondary to infections, surgeries, tumor obstruction, radiation, congestive heart failure, and obesity. Although recurrent streptococcal lymphangitis is believed to play a critical role in the origin of elephantiasis nostras verrucosa, the exact pathogenesis of the disorder is not yet clear. Therapeutic efforts should aim to reduce lymph stasis, which will also lead to improvement of the cutaneous changes but unfortunately there is no specific treatment for advanced cases. In this report, we present a patient who was treated by below knee amputation as a result of elephantiasis nostras verrucosa complicated with chronic tibial osteomyelitis.

Mucobilia in Association With a Biliary Cystadenocarcinoma of the Caudate Duct: A Rare Cause of Malignant Biliary Obstruction

PubMed Central

Chamberlain, Ronald S.

2000-01-01

Mucobilia is a rare condition characterized by the accumulation of abundant mucus within the intra- or extrahepatic biliary tree. A variety of hepatobiliary and pancreatic neoplasms are mucin producing and have been associated with the development of mucobilia including biliary mucinosis, biliary papillomatosis, mucin-producing cholangiocarcinoma (MPCC), or cystic neoplasms of the pancreas or biliary tree (cystadenoma or cystadenocarcinoma). We report the case of 46 year-old male with a biliary cystadenocarcinoma of the caudate lobe which resulted in chronic biliary obstruction and relapsing cholangitis. A review of the literature for both mucobilia and biliary cystadenocarcinoma is provided along with a discussion addressing the clinical presentation, diagnosis, treatment, and prognosis for this rare entity. PMID:10674751

[Melkersson-Rosenthal syndrome. Report of five cases and review of the literature].

PubMed

Ghorbel, Imed Ben; SioudDhrif, Asma; Lamloum, Mounir; Trabelsi, Salem; Habib Houman, Mohammed

2006-12-01

The goal of this work is to report five cases of Melkersson-Rosenthal syndrom with a literature review. It is a rare entity and is characterized in its complete presentation, by the association of reccurent orofacial swelling, peripheral facial palsy and plicated tongue. Incomplete forms are more frequent and more difficult to establish its diagnosis. This latter is based on major and minor clinical and histological critieria sorted in three levels. There is four forms of MRS. The pathogenesis of this syndrome is still unknown; treatment remains random. It is based on topical or systemic steroids with or without cheiloplastic procedure. We must think of MRS in presence of any recurrent peripheral facial palsy and/or chronic facial swelling.

Hand dermatitis/eczema: current management strategy.

PubMed

Sehgal, Virendra N; Srivastava, Govind; Aggarwal, Ashok K; Sharma, Alpna D

2010-07-01

Ever since its inception a couple of centuries ago, hand dermatitis/eczema has been in the reckoning. Idiosyncrasies continued to loom large thereafter, till it acquired its appropriate position. Dermatitis/eczema are synonymous, often used to indicate a polymorphic pattern of the inflammation of the skin, characterized by pruritus, erythema and vesiculation. A spectrum delineated into acute sub-acute and chronic dermatitis of the hands. Pompholyx, recurrent focal palmer peeling, ring, wear and tear and fingertip eczema, apron, discoid eczema, chronic acral dermatitis, gut and patchy papulosquamous eczema are its clinical variants. Occupational dermatitis/eczema may be contributory. Etiological definitions are clinched by detailed history of exogenous and endogenous factors. However, scientific confirmation of the entity is through patch testing by using available antigens.

The unique entity of nodular lymphocyte-predominant Hodgkin lymphoma: current approaches to diagnosis and management.

PubMed

Hawkes, Eliza A; Wotherspoon, Andrew; Cunningham, David

2012-03-01

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare disease constituting only 3-8% of all Hodgkin lymphoma. It has a distinct histological and clinical presentation as well as significantly different natural history compared to the classical form of Hodgkin lymphoma. Presenting most often as early-stage disease, NLPHL is characterized by frequent relapses, but paradoxically an overall good prognosis. The approach to management should therefore reflect this pattern and focus on attaining prolonged remissions, with long-term follow-up paramount. Due to the rarity of the disease, few prospective data exist. Options for treatment include radiotherapy, chemotherapy or combined chemotherapy plus radiotherapy and targeted anti-CD20 antibody therapy, as well as observation in selected patients.

A meta-analysis of HLA peptidome composition in different hematological entities: entity-specific dividing lines and “pan-leukemia” antigens

PubMed Central

Walz, Simon; Schuster, Heiko; Berlin, Claudia; Neidert, Marian Christoph; Schemionek, Mirle; Brümmendorf, Tim H.; Vucinic, Vladan; Niederwieser, Dietger; Kanz, Lothar; Salih, Helmut Rainer; Kohlbacher, Oliver; Weisel, Katja; Rammensee, Hans-Georg; Stevanović, Stefan; Walz, Juliane Sarah

2017-01-01

Hematological malignancies (HM) are highly amenable targets for immunotherapeutic intervention and may be effectively treated by antigen-specific T-cell based treatment. Recent studies demonstrate that physiologically occurring anti-cancer T-cell responses in certain HM entities target broadly presented non-mutated epitopes. HLA ligands are thus implied as prime targets for broadly applicable and antigen-specific off-the-shelf compounds. With the aim of assessing the presence of common targets shared among different HM which may enable addressing a larger patient collective we conducted a meta-analysis of 83 mass spectrometry-based HLA peptidome datasets (comprising 40,361 unique peptide identifications) across four major HM (19 AML, 16 CML, 35 CLL, and 13 MM/MCL samples) and investigated similarities and differences within the HLA presented antigenic landscape. We found the cancer HLA peptidome datasets to cluster specifically along entity and lineage lines, suggesting that the immunopeptidome directly reflects the differences in the underlying (tumor-)biology. In line with these findings, we only detected a small set of entity-spanning antigens, which were predominantly characterized by low presentation frequencies within the different patient cohorts. These findings suggest that design of T-cell immunotherapies for the treatment of HM should ideally be conducted in an entity-specific fashion. PMID:28159928

Clinical translation of handheld optical coherence tomography: practical considerations and recent advancements

NASA Astrophysics Data System (ADS)

Monroy, Guillermo L.; Won, Jungeun; Spillman, Darold R.; Dsouza, Roshan; Boppart, Stephen A.

2017-12-01

Since the inception of optical coherence tomography (OCT), advancements in imaging system design and handheld probes have allowed for numerous advancements in disease diagnostics and characterization of the structural and optical properties of tissue. OCT system developers continue to reduce form factor and cost, while improving imaging performance (speed, resolution, etc.) and flexibility for applicability in a broad range of fields, and nearly every clinical specialty. An extensive array of components to construct customized systems has also become available, with a range of commercial entities that produce high-quality products, from single components to full systems, for clinical and research use. Many advancements in the development of these miniaturized and portable systems can be linked back to a specific challenge in academic research, or a clinical need in medicine or surgery. Handheld OCT systems are discussed and explored for various applications. Handheld systems are discussed in terms of their relative level of portability and form factor, with mention of the supporting technologies and surrounding ecosystem that bolstered their development. Additional insight from our efforts to implement systems in several clinical environments is provided. The trend toward well-designed, efficient, and compact handheld systems paves the way for more widespread adoption of OCT into point-of-care or point-of-procedure applications in both clinical and commercial settings.

Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation

PubMed Central

2011-01-01

Background The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) (OMIM 225400) is a rare inheritable connective tissue disorder characterized by a deficiency of collagen lysyl hydroxylase 1 (LH1; EC 1.14.11.4) due to mutations in PLOD1. Biochemically this results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP) and hydroxylysyl pyridinoline (HP) crosslinks excreted in the urine. Clinically the disorder is characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Severe hypotonia usually leads to delay in gross motor development, whereas cognitive development is reported to be normal. Methods We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome. Results Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial), independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients. Conclusion In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity. PMID:21699693

Toll-like Receptor 2: A Novel Therapeutic Target for Ischemic White Matter Injury and Oligodendrocyte Death

PubMed Central

Choi, Jun Young

2017-01-01

Despite paramount clinical significance of white matter stroke, there is a paucity of researches on the pathomechanism of ischemic white matter damage and accompanying oligodendrocyte (OL) death. Therefore, a large gap exists between clinical needs and laboratory researches in this disease entity. Recent works have started to elucidate cellular and molecular basis of white matter injury under ischemic stress. In this paper, we briefly introduce white matter stroke from a clinical point of view and review pathophysiology of ischemic white matter injury characterized by OL death and demyelination. We present a series of evidence that Toll-like receptor 2 (TLR2), one of the membranous pattern recognition receptors, plays a cell-autonomous protective role in ischemic OL death and ensuing demyelination. Moreover, we also discuss our recent findings that its endogenous ligand, high-mobility group box 1 (HMGB1), is released from dying OLs and exerts autocrine trophic effects on OLs and myelin sheath under ischemic condition. We propose that modulation of TLR2 and its endogenous ligand HMGB1 can be a novel therapeutic target for ischemic white matter disease. PMID:28912641

PLASMA CELL LEUKEMIA

PubMed Central

de Larrea, Carlos Fernandez; Kyle, Robert A.; Durie, Brian GM; Ludwig, Heinz; Usmani, Saad; Vesole, David H.; Hajek, Roman; Miguel, Jésus San; Sezer, Orhan; Sonneveld, Pieter; Kumar, Shaji K.; Mahindra, Anuj; Comenzo, Ray; Palumbo, Antonio; Mazumber, Amitabha; Anderson, Kenneth C.; Richardson, Paul G.; Badros, Ashraf Z.; Caers, Jo; Cavo, Michele; LeLeu, Xavier; Dimopoulos, Meletios A.; Chim, CS; Schots, Rik; Noeul, Amara; Fantl, Dorotea; Mellqvist, Ulf-Henrik; Landgren, Ola; Chanan-Khan, Asher; Moreau, Philippe; Fonseca, Rafael; Merlini, Giampaolo; Lahuerta, JJ; Bladé, Joan; Orlowski, Robert Z.; Shah, Jatin J.

2014-01-01

Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathologic entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥ 20%) and absolute number (≥ 2 × 10 9/L) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be reexamined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem-cell transplantation (HDT/ASCT) if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL. PMID:23288300

Cutaneous metastasis of transitional cell bladder carcinoma: a rare presentation and literature review.

PubMed

Salemis, Nikolaos S; Gakis, Christos; Zografidis, Andreas; Gourgiotis, Stavros

2011-01-01

Cutaneous metastasis from transitional cell bladder carcinoma is a rare clinical entity associated with poor prognosis. We present a case of cutaneous metastasis arising from a transitional cell bladder carcinoma in a male patient who had undergone a radical cystectomy and bilateral ureterostomy 17 months previously. The cutaneous metastasis became evident 3 months before the manifestations of generalized recurrent disease. An awareness of this rare clinical entity and high index of suspicion is needed to rule out metastatic spread in patients with a previous history of transitional cell bladder carcinoma presenting with cutaneous nodules. Definitive diagnosis requires a histological confirmation, but prognosis is generally poor.

Unconsummated marriages: a separate and different clinical entity.

PubMed

Gindin, Leon Roberto; Resnicoff, Diana

2002-01-01

We bring our experience in the treatment of unconsummated marriages (UM). We postulate that it is an independent clinical entity. Since 1991, 199 couples with UM have sought treatment in our center in Buenos Aires. A new approach to this problem is based on an intensive treatment session that lasts a whole day and a pledge to pay only if therapy succeeds. The outcome was a success (97%) with coitus consummation. We make a long-term follow up. The advantages are the brevity of the treatment and lack of desertions. We postulate that UM cannot be approached with an individual perspective or with the usual psychotherapy techniques.

Biological Gene Delivery Vehicles: Beyond Viral Vectors

PubMed Central

Seow, Yiqi; Wood, Matthew J

2009-01-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications. PMID:19277019

Biological gene delivery vehicles: beyond viral vectors.

PubMed

Seow, Yiqi; Wood, Matthew J

2009-05-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications.

Unstable solar lentigo: A defined separate entity.

PubMed

Byrom, Lisa; Barksdale, Sarah; Weedon, David; Muir, Jim

2016-08-01

An unstable solar lentigo is a solar lentigo with areas of melanocytic hyperplasia not extending past the margin of the lesion. They are discrete, macular, pigmented lesions arising on sun-damaged skin and a subset of typical solar lentigos. Clinically they differ from usual solar lentigines in often being solitary or larger and darker than adjacent solar lentigines. These lesions are of clinical importance as they can arise in close proximity to lentigo maligna and in a single lesion there can be demonstrated changes of solar lentigo, unstable solar lentigo and lentigo maligna. These observations led us to conjecture that unstable solar lentigos could be a precursor lesion to lentigo maligna. In this article we examine the possibility that lentigo maligna can arise within a solar lentigo through an intermediate lesion, the unstable solar lentigo. We propose that the histopathological recognition of this entity will allow for future research into its behaviour and thus management. We review difficulties in the diagnosis of single cell predominant melanocytic proliferations and the concept of unstable lentigo in view of the literature and clinical experience supporting the proposal of its recognition as a separate entity. © 2016 The Australasian College of Dermatologists.

Clinical Documents: Attribute-Values Entity Representation, Context, Page Layout And Communication

PubMed Central

Lovis, Christian; Lamb, Alexander; Baud, Robert; Rassinoux, Anne-Marie; Fabry, Paul; Geissbühler, Antoine

2003-01-01

This paper presents how acquisition, storage and communication of clinical documents are implemented at the University Hospitals of Geneva. Careful attention has been given to user-interfaces, in order to support complex layouts, spell checking, templates management with automatic prefilling in order to facilitate acquisition. A dual architecture has been developed for storage using an attributes-values entity unified database and a consolidated, patient-centered, layout-respectful files-based storage, providing both representation power and sinsert (peed of accesses. This architecture allows great flexibility to store a continuum of data types from simple type values up to complex clinical reports. Finally, communication is entirely based on HTTP-XML internally and a HL-7 CDA interface V2 is currently studied for external communication. Some of the problem encountered, mostly concerning the typology of documents and the ontology of clinical attributes are evoked. PMID:14728202

Early descriptions of acromegaly and gigantism and their historical evolution as clinical entities.

PubMed

Mammis, Antonios; Eloy, Jean Anderson; Liu, James K

2010-10-01

Giants have been a subject of fascination throughout history. Whereas descriptions of giants have existed in the lay literature for millennia, the first attempt at a medical description was published by Johannes Wier in 1567. However, it was Pierre Marie, in 1886, who established the term "acromegaly" for the first time and established a distinct clinical diagnosis with clear clinical descriptions in 2 patients with the characteristic presentation. Multiple autopsy findings revealed a consistent correlation between acromegaly and pituitary enlargement. In 1909, Harvey Cushing postulated a “hormone of growth" as the underlying pathophysiological trigger involved in pituitary hypersecretion in patients with acromegaly. This theory was supported by his observations of clinical remission in patients with acromegaly in whom he had performed hypophysectomy. In this paper, the authors present some of the early accounts of acromegaly and gigantism, and describe its historical evolution as a medical and surgical entity.

[Significance of group A streptococcal infections in human pathology].

PubMed

Cvjetković, Dejan; Jovanović, Jovana; Hrnjaković-Cvjetković, Ivana; Aleksić-Dordević, Mirjana; Stefan-Mikić, Sandra

2008-01-01

Group A streptococci is the causative agent in 80 percents of human streptococcal infections. The only member of this group is Streptococcus pyogenes. CLINICALFEATURES OF GAS INFECTIONS: The various clinical entities and related complications caused by pyogenic streptococci are reviewed in the article. Pharyngitis, scarlet fever, skin and soft tissue infections (pyoderma, cellulitis, perianal dermatitis, necrotising fasciitis) and streptococcal toxic shock syndrome are described. The way of setting the diagnosis including epidemiological data, clinical features and the course of illness, laboratory findings and supportive diagnostic methods are represented in the article. The most important clinical entities which should be discussed in differential diagnosis of diseases caused by pyogenic streptococci are listed. The major principles of etiologic treatment through widely accepted strategies related to first choice antibiotics and alternatives are reviewed.

The Abernethy malformation-myriad imaging manifestations of a single entity.

PubMed

Ghuman, Samarjit S; Gupta, Saumya; Buxi, T B S; Rawat, Kishan S; Yadav, Anurag; Mehta, Naimish; Sud, Seema

2016-01-01

Abernethy malformation, also known as congenital extrahepatic portosystemic shunts (CEPS) is a rare clinical entity and manifests with different clinical symptoms. CEPS are abnormalities of vascular development where there is shunting of portal blood into the systemic venous system. Multidetector computed tomography (MDCT) is a fast and effective modality for evaluation of CEPS. CT displays all the information desired by the surgeon as well as the clinician including the anatomy of the splenic and superior mesenteric veins, size and site of the shunt, presence or absence of the portal vein radicles, and helps to plan the therapy and even the follow-up of these patients. Contrast-enhanced magnetic resonance imaging (MRI) has also emerged as a promising tool for the evaluation of liver lesions associated with the malformation. The Radiologist should be aware of the various imaging appearances of this entity including its complications. In this article, we describe the imaging appearances of CEPS, their complications, and their imaging appearances on CT and MRI. We have also described various associated anomalies.

The Abernethy malformation—myriad imaging manifestations of a single entity

PubMed Central

Ghuman, Samarjit S; Gupta, Saumya; Buxi, T B S; Rawat, Kishan S; Yadav, Anurag; Mehta, Naimish; Sud, Seema

2016-01-01

Abernethy malformation, also known as congenital extrahepatic portosystemic shunts (CEPS) is a rare clinical entity and manifests with different clinical symptoms. CEPS are abnormalities of vascular development where there is shunting of portal blood into the systemic venous system. Multidetector computed tomography (MDCT) is a fast and effective modality for evaluation of CEPS. CT displays all the information desired by the surgeon as well as the clinician including the anatomy of the splenic and superior mesenteric veins, size and site of the shunt, presence or absence of the portal vein radicles, and helps to plan the therapy and even the follow-up of these patients. Contrast-enhanced magnetic resonance imaging (MRI) has also emerged as a promising tool for the evaluation of liver lesions associated with the malformation. The Radiologist should be aware of the various imaging appearances of this entity including its complications. In this article, we describe the imaging appearances of CEPS, their complications, and their imaging appearances on CT and MRI. We have also described various associated anomalies. PMID:27857464

Differentiation of pigmented Spitz nevi and Reed nevi by integration of dermatopathologic and dermatoscopic findings

PubMed Central

Bär, Michael; Tschandl, Philipp; Kittler, Harald

2012-01-01

Background: It is unclear whether pigmented Spitz and Reed nevi are distinct morphologic entities or part of the spectrum of Spitz nevi. Methods: In a retrospective observational study we analyzed dermatopathologic slides of 22 cases with clinical and dermatoscopic features indicative of pigmented Spitz or Reed nevus in a blinded fashion according to predefined criteria and subsequently correlated dermatopathologic with clinical and dermatoscopic findings. Results: We differentiated pigmented Spitz and Reed nevus dermatopathologically by their capacity of melanin production and a vertical versus horizontal growth pattern. Based on histopathology 20 nevi (91%) could be reliably diagnosed as Reed nevus (68%, n=15) or as pigmented Spitz nevus (23%, n=5). In two cases (9%, n=2) it was not possible to make a clear distinction from a dermatopathologic point of view. Dermatopathologic-dermatoscopic correlation showed that Reed nevi were characterized by a dermatoscopic pattern of peripheral radial lines or pseudopods (fascicular growth pattern), whereas pigmented Spitz nevi were typified by a pattern consisting of clods (nested growth pattern). “Spitz cells” (large epithelioid melanocytes) were more commonly found in Spitz nevi (100%, n = 5) but were also present in Reed nevi (n=6, 40%). Spindle cells were found in both types of nevi. Conclusions: Pigmented Spitz and Reed nevi can be reliably distinguished based on their dermatopathologic and dermatoscopic patterns. The specific dermatopathologic patterns of pigmented Spitz and Reed nevi correspond well to their dermatoscopic patterns. The presence of “Spitz cells” or spindle cells should not be regarded as the decisive criterion to differentiate between these two entities. PMID:24765545

Neuron-directed autoimmunity in the central nervous system: entities, mechanisms, diagnostic clues, and therapeutic options.

PubMed

Melzer, Nico; Meuth, Sven G; Wiendl, Heinz

2012-06-01

The human central nervous system (CNS) can mistakenly be the target of adaptive cellular and humoral immune responses causing both functional and structural impairment. We here provide an overview of neuron-directed autoimmunity as a novel class of inflammatory CNS disorders, their differential diagnoses, clinical hallmarks, imaging features, characteristic laboratory, electrophysiological, cerebrospinal fluid and neuropathological findings, cellular and molecular disease mechanisms, as well as therapeutic options. A growing number of immune-mediated CNS disorders of both autoimmune and paraneoplastic origin have emerged, in which neurons seem to be the target of the immune response. Antibodies binding to a variety of synaptic and extrasynaptic antigens located on the neuronal surface membrane can define distinct entities. Clinically, these disorders are characterized by subacute CNS-related [and sometimes peripheral nervous system (PNS)-related] symptoms involving a variety of cortical and subcortical gray matter areas, which often reflect the expression pattern and function of the respective target antigen. Antibodies seem to be pathogenic and cause (reversible) disturbance of synaptic transmission and neuronal excitability by selective functional inhibition or crosslinking and internalization of their antigen in the absence of overt cytotoxicity, at least at early disease stages. Whether at later disease stages antibody-mediated cytotoxicity, cytotoxic CD8+ T cells, or other detrimental immune mechanisms contribute to neuronal impairment is unclear at present. Adaptive humoral autoimmunity directed to neuronal cell-surface antigens offers first and unique insights and provokes further investigation into the systemic, cellular, and molecular consequences of immune-mediated disruption of distinct neuronal signaling pathways within the living human CNS.

Current concepts of etiology and treatment of chondromalacia patellae.

PubMed

Bentley, G; Dowd, G

1984-10-01

Chondromalacia patellae is a distinct clinical entity characterized by retropatellar pain that is associated with recognizable changes in the articular cartilage of the posterior surface of the patella. Several factors may be involved in the etiology, such as severe patella alta, trauma, and, in rare cases, abnormal patellar tracking. Clinical symptoms and signs are reliable in only 50% of cases, but measurable quadriceps wasting, palpable patellofemoral crepitus, and effusion are strongly suggestive. Diagnosis must be confirmed by arthroscopy or direct examination of the posterior surface of the patella. Radiologic measurements of patellofemoral relations are of limited value in diagnosis. The initial pathologic finding is usually surface cartilage breakdown. Radioisotope studies show cartilage cell replication which suggests a healing capacity in early cases following treatment that alters the load through the affected cartilage. There is no evidence of progression to patellofemoral osteoarthritis, which is probably a different entity. The treatment should be conservative where possible with isometric quadriceps exercises and simple anti-inflammatory drugs such as aspirin. Operative treatment is indicated for patients with persistent pain and macroscopic involvement of more than half a centimeter of the articular cartilage surface. The simplest effective procedure that avoids quadriceps dysfunction and fibrosis is a distal patellar tendon medial realignment with lateral release and medial reefing of the quadriceps expansion. Patellectomy is indicated in more extensive involvement of the patella of 2 or more centimeters in diameter, but this must be performed only when the patient has excellent quadriceps function before surgery and is motivated to exercise after surgery.

Acute Splenic Sequestration Crisis in Adult Sickle Cell Disease: A Report of 16 Cases.

PubMed

Naymagon, Leonard; Pendurti, Gopichand; Billett, Henny H

2015-01-01

Acute splenic sequestration crisis (ASSC), characterized by rapidly progressive anemia and circulatory compromise in the setting of sudden splenic enlargement, is an uncommon entity among adult sickle cell patients. We reviewed cases of adult ASSC encountered at our institution to generate insight into the recognition, diagnosis, and treatment of the condition. Cases of adult ASSC during a 10-year period were identified retrospectively. Patient charts were reviewed for laboratory and imaging results; demographic data and clinical course were collected and reviewed. Sixteen cases of adult ASSC were identified. Most patients presented with pain crisis; only four of 16 patients presented with abdominal pain. The maximum decreases in hemoglobin (Hb) (42.0%) and platelets (62.1%) occurred at day 2.9, delaying identification and treatment. Hemodynamic instability played a large role in dictating risk stratification. Therapy consisted of transfusion (14/16) and splenectomy (5/16). No recurrences were noted in a mean follow-up time of 5.3 years but review of patients' charts demonstrated that at least one of the patients had two prior episodes. Adult ASSC may present with non specific findings and patients may not deteriorate until several days into a previously uneventful hospital course. Changes in platelet counts may be more reliable markers than changes in Hb level since red cell transfusions may interfere with assessments of the sequestration process. This case series of adult ASSC, the largest reported in the literature to date, highlights common clinical, laboratory, radiological, and pathological features of this uncommon entity and helps to guide recognition, diagnosis, and treatment.

Spine malformation complex in 3 diverse syndromic entities

PubMed Central

Kaissi, Ali Al; van Egmond-Fröhlich, Andreas; Ryabykh, Sergey; Ochirov, Polina; Kenis, Vladimir; Hofstaetter, Jochen G.; Grill, Franz; Ganger, Rudolf; Kircher, Susanne Gerit

2016-01-01

Abstract Rationale: Clinical and radiographic phenotypic characterizations were the base line tool of diagnosis in 3 syndromic disorders in which congenital cervico-thoracic kyphosis was the major deformity. Patients concerns: Directing maximal care toward the radiographic analysis is not only the axial malformation but also toward the appendicular abnormalities was our main concern. We fully documented the diversity of the spine phenotypic malformation complex via the clinical and radiographic phenotypes. Diagnoses: We established the diagnosis via phenotypic/genotypic confirmation in 3 diverse syndromic entities namely acampomelic campomelic dysplasia, Larsen syndrome and Morquio syndrome type A (mucopolysaccharidosis type IV A). Interventions: Surgical interventions have been carried out in the Larsen syndrome and Morquio syndrome type A, resepectively. Outcomes: The earliest the diagnosis is, the better the results are. The necessity to diagnose children in their first year of life has many folds, firstly the management would be in favor of the child's growth and development and secondly, the prognosis could be clearer to the family and the medical staff as well. Our current paper is to sensitize paediatricians, physicians and orthopedic surgeons regarding the necessity to detect the aetiological understanding in every child who manifests a constellation of malformation complex. Lesons: Scoliosis and kyphosis/kyphoscoliosis are not a diagnosis in themselves. Such deformities are mostly a symptom complex correlated to dozens of types of syndromic associations. The rate curve progression and the final severity of congenital spine tilting are related to 3 factors: (a) the type of vertebral malformation present, (b) the patient's phenotype, and (c) the diagnosis. PMID:27977582

A continuous function model for path prediction of entities

NASA Astrophysics Data System (ADS)

Nanda, S.; Pray, R.

2007-04-01

As militaries across the world continue to evolve, the roles of humans in various theatres of operation are being increasingly targeted by military planners for substitution with automation. Forward observation and direction of supporting arms to neutralize threats from dynamic adversaries is one such example. However, contemporary tracking and targeting systems are incapable of serving autonomously for they do not embody the sophisticated algorithms necessary to predict the future positions of adversaries with the accuracy offered by the cognitive and analytical abilities of human operators. The need for these systems to incorporate methods characterizing such intelligence is therefore compelling. In this paper, we present a novel technique to achieve this goal by modeling the path of an entity as a continuous polynomial function of multiple variables expressed as a Taylor series with a finite number of terms. We demonstrate the method for evaluating the coefficient of each term to define this function unambiguously for any given entity, and illustrate its use to determine the entity's position at any point in time in the future.

CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease.

PubMed

Anders, Hans-Joachim; Huber, Tobias B; Isermann, Berend; Schiffer, Mario

2018-06-01

The increasing global prevalence of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has prompted research efforts to tackle the growing epidemic of diabetic kidney disease (DKD; also known as diabetic nephropathy). The limited success of much of this research might in part be due to the fact that not all patients diagnosed with DKD have renal dysfunction as a consequence of their diabetes mellitus. Patients who present with CKD and diabetes mellitus (type 1 or type 2) can have true DKD (wherein CKD is a direct consequence of their diabetes status), nondiabetic kidney disease (NDKD) coincident with diabetes mellitus, or a combination of both DKD and NDKD. Preclinical studies using models that more accurately mimic these three entities might improve the ability of animal models to predict clinical trial outcomes. Moreover, improved insights into the pathomechanisms that are shared by these entities - including sodium-glucose cotransporter 2 (SGLT2) and renin-angiotensin system-driven glomerular hyperfiltration and tubular hyper-reabsorption - as well as those that are unique to individual entities might lead to the identification of new treatment targets. Acknowledging that the clinical entity of CKD plus diabetes mellitus encompasses NDKD as well as DKD could help solve some of the urgent unmet medical needs of patients affected by these conditions.

A Rare Case of Splenic Torsion with Sigmoid Volvulus in a 14-Year-Old Girl.

PubMed

Ahmadi, Hamid; Tehrani, Mahdieh Mohammad Khan

2016-01-01

Wandering spleen is an uncommon entity in adults and has been described only rarely with sigmoid volvulus, that rarely affects children and adolescents. It is usually described in adults.Wandering spleen characterized by the abnormal location of the spleen, caused by incomplete fusion of the four primary splenic ligaments, allowing the spleen to be mobile within the abdomen.The wandering spleen can lead to torsion and subsequent splenic infarction or rupture. Clinical suspicion plus urgent investigation and intervention are important. We present a rare clinical case of acute abdomen due to torsion of wandering spleen and volvulus of sigmoid in a 14-year-old girl presented with painful periumbilical mass. Detorsion of sigmoid occurred while undergoing exploratory laparotomy and splenectomy was performed. The possibility of torsion and its complication like gastric, pancreas tail and colon volvulus should be kept in mind in the differential diagnosis of the acute abdomen to avoid serious complications.

Paroxysmal sympathetic hyperactivity: An entity to keep in mind.

PubMed

Godoy, D A; Panhke, P; Guerrero Suarez, P D; Murillo-Cabezas, F

2017-12-15

Paroxysmal sympathetic hyperactivity (PSH) is a potentially life-threatening neurological emergency secondary to multiple acute acquired brain injuries. It is clinically characterized by the cyclic and simultaneous appearance of signs and symptoms secondary to exacerbated sympathetic discharge. The diagnosis is based on the clinical findings, and high alert rates are required. No widely available and validated homogeneous diagnostic criteria have been established to date. There have been recent consensus attempts to shed light on this obscure phenomenon. Its physiopathology is complex and has not been fully clarified. However, the excitation-inhibition model is the theory that best explains the different aspects of this condition, including the response to treatment with the available drugs. The key therapeutic references are the early recognition of the disorder, avoiding secondary injuries and the triggering of paroxysms. Once sympathetic crises occur, they must peremptorily aborted and prevented. of the later the syndrome is recognized, the poorer the patient outcome. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Distinctive clinical and histological features of Waldenström's macroglobulinemia and splenic marginal zone lymphoma.

PubMed

Arcaini, Luca; Varettoni, Marzia; Boveri, Emanuela; Orlandi, Ester; Rattotti, Sara; Zibellini, Silvia; Merli, Michele; Lucioni, Marco; Rizzi, Silvia; Gotti, Manuel; Morello, Lucia; Pascutto, Cristiana; Paulli, Marco

2011-02-01

We studied 122 patients with Waldenström's macroglobulinemia (WM) and 98 with splenic marginal zone lymphoma (SMZL); 29 SMZL patients (30%) had a serum MC (IgM in 17 patients). SMZL differed from WM for female prevalence, abdominal and superficial adenopathy, spleen and liver involvement, positive HCV. The median MC level was 2.0 g/dL in WM and 0.95 g/dL in SMZL (P<.001). On BM histology, SMZL was characterized by sinusoidal infiltration (70% of cases) and by a more frequent nodular pattern (P<.01) while WM had a higher incidence of interstitial BM localization. After a median follow-up of 5.3 years, median OS was not reached for SMZL and was 12 years for WM (P=.23; 14 years for asymptomatic WM, 8 years for symptomatic WM). In conclusion, despite similar outcomes of these 2 entities, SMZL appears as a disease with distinct clinical features and BM histology and a peculiar association with HCV infection.

Modified endoscopic medial maxillectomy for zygomatic implant salvage

PubMed Central

Tajudeen, Bobby A.; Adappa, Nithin D.; Palmer, James N.

2016-01-01

Objectives: Odontogenic chronic rhinosinusitis (CRS) is an epidemiologically important disease process due, in part, to the increasingly commonplace use of dental restorative procedures such as zygomatic implantation. Traditional management of this clinical entity typically entails extraction of the infected hardware via an open or endoscopic approach. We describe a novel management strategy of odontogenic CRS following bilateral zygomatic implantation for oral rehabilitation that we surgically salvaged via a modified endoscopic medial maxillectomy. Methods: We describe the presentation and management of a case of metachronous development of bilateral CRS subsequent to zygomatic implantation. Results: The patient's postoperative course was characterized by marked endoscopic, radiologic, and symptomatic improvement as measured by the 22-item Sino-Nasal Outcome Test. Conclusion: We describe a novel treatment strategy for the management of odontogenic sinusitis resulting from erroneous zygomatic implant placement. Modified endoscopic medial maxillectomy in this clinical context facilitates mucosal normalization of the affected sinus, while permitting preservation of oral function through salvage of the displaced implant. PMID:28107147

Early wound site seeding in a patient with CNS high-grade neuroepithelial tumor with BCOR alteration: A case report.

PubMed

Kirkman, Matthew A; Pickles, Jessica C; Fairchild, Amy R; Avery, Aimee; Pietsch, Torsten; Jacques, Thomas S; Aquilina, Kristian

2018-05-30

Advances in molecular profiling have facilitated the emergence of newly defined entities of central nervous system tumor, including CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR). Relatively little is known about the clinical behaviour of these newly-characterized tumors. We describe a pediatric male patient with CNS HGNET-BCOR who developed seeding of the tumor into the site of the surgical wound within months of surgery for resection of a residual posterior fossa tumor. This case emphasises three important points. First, CNS HGNET-BCOR can be aggressive tumors that necessitate close clinical and radiological surveillance. Second, surveillance imaging in such cases should incorporate the surgical incision site into the field of view, and this should be closely scrutinised to ensure the timely detection of wound site seeding. Third, wound site seeding may still occur despite the use of meticulous surgical techniques. Copyright © 2018. Published by Elsevier Inc.

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

PubMed

Szyfter, W; Wierzbicka, M

1996-01-01

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

Novel Development of Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome due to Insulin Therapy

PubMed Central

Mainali, Naba Raj; Schmidt, Torrey R.; Alweis, Richard; George, David L.

2014-01-01

Patient: Male, 67 Final Diagnosis: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome Symptoms: Bilateral wrist swelling Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Unusual or unexpected effect of treatment Background: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is a rare clinical entity characterized by the sudden onset of inflammatory arthritis and marked pitting edema on upper and lower extremities. RS3PE is considered a rheumatic process distinct from rheumatoid arthritis, which may occasionally represent a paraneoplastic syndrome. Case Report: Herein, we describe a rare case of RS3PE associated with insulin therapy in a patient with no evidence of underlying malignancy. Conclusions: To the best of our knowledge, this is the first case report of RS3PE associated with insulin therapy. Physicians should look at the introduction of drugs as possible triggers for the development of RS3PE. PMID:24696753

Clinical toxicology: a tropical Australian perspective.

PubMed

Currie, B J

2000-02-01

Tropical Australia has an amazing diversity of venomous fauna, from "the world's most venomous creature," the multi-tentacled (chirodropid) box jellyfish Chironex fleckeri, to aggressive spiders whose venom remains to be characterized. All genera of highly venomous Australasian elapid snakes are present, except for tiger snakes. Most notable is the taipan (Oxyuranus scutellatus), with the most efficient "snap-release" biting mechanism of any snake and venom components causing the full constellation of clinical envenoming features: coagulopathy from fibrinogen depletion (procoagulant), neurotoxicity (predominantly presynaptic neurotoxin) and rhabdomyolysis (myotoxin). Brown snakes (Pseudonaja textilis and P. nuchalis) now account for most snake bite fatalities in Australia, as a result of severe coagulopathy and a poorly defined early scenario of collapse, postulated to be caused by profound hypotension caused by transient myocardial dysfunction associated with prothrombin activation. Other venomous entities include paralyzing ticks, the blue-ringed octopus, stone fish and other marine animals with venomous spines, paralyzing cone shells, and a wide range of jellyfish including Carukia barnesi and possibly other four-tentacled (carybdeid) box jellyfish causing the Irukandji syndrome.

Clinical characteristics indicating adenomyosis at the time of hysterectomy: a retrospective study in 291 patients.

PubMed

Taran, F Andrei; Wallwiener, Markus; Kabashi, Drita; Rothmund, Ralf; Rall, Katharina; Kraemer, Bernhard; Brucker, Sara Y

2012-06-01

To better characterize adenomyosis as a disease entity. We retrospectively reviewed the medical records of women undergoing hysterectomy with a histologic diagnosis of adenomyosis, adenomyosis and leiomyomas, and leiomyomas alone. The study included 291 women: 38 with adenomyosis alone, 56 with adenomyosis and leiomyomas, and 197 with leiomyomas alone. In univariate analysis, women with adenomyosis were younger (p = 0.018) and had lower uterine weights (p < 0.001) and more disease-specific symptoms (p = 0.008). In multinomial logistic regression analysis, a lower uterine weight (OR 0.99, CI 95% 0.99-1.0), pelvic pain (OR 4.8, CI 95% 1.5-15.2), a history of smoking (OR 2.6, CI 95% 1.1-6.5) and at least one delivery (OR 4.3, CI 95% 1.5-12.3) were associated with a greater likelihood of having adenomyosis but not leiomyomas alone. Women undergoing hysterectomy with adenomyosis alone have different clinical characteristics from women with adenomyosis and leiomyomas and from those with only leiomyomas.

Spontaneous Rectus Sheath Hematoma: an Overview of 4-Year Single Center Experience.

PubMed

Aktürk, Okan Murat; Kayılıoğlu, Selami Ilgaz; Aydoğan, İhsan; Dinç, Tolga; Yildiz, Baris; Cete, Mükerrem; Erdoğan, Ahmet; Coşkun, Faruk

2015-12-01

Rectus sheath hematoma is a clinical entity characterized by the presence of blood within rectus abdominis muscle sheath. The aim of this study was to analyze clinical characteristics, diagnostic approach, treatment strategy, and outcomes of patients with rectus sheath hematoma. Patients diagnosed and treated for spontaneous rectus sheath hematoma between March 2010 and March 2014 were included in the study. A total of 10 patients were diagnosed as spontaneous rectus sheath hematoma. The mean age was 66.5 ± 16.9 years, and the mean hospital stay was 4.4 ± 1.8 days. There was no mortality. Six patients were using anticoagulant or antiplatelet agents. Eight patients recovered after conservative treatment. Two patients underwent surgery. Spontaneous rectus sheath hematoma is associated with anticoagulant therapy. Cases with abdominal pain and a non-pulsatile abdominal mass particularly in elderly women should be kept in mind. Treatment is mostly based on supportive care to preserve hemodynamic stability.

[Posterior reversible encephalopathy syndrome induced by a cough and cold drug containing pseudoephedrine].

PubMed

Ebbo, M; Benarous, L; Thomas, G; Jourde, N; Genot, S; Bernit, E; Veit, V; Harlé, J-R; Schleinitz, N

2010-06-01

Posterior reversible encephalopathy syndrome is a clinico-radiological entity characterized by neurologic symptoms in association with usually reversible bilateral posterior hemispheric oedema on neuroimaging. Many pathological conditions and treatments have been associated with this syndrome. We report a 19-year-old woman, followed-up for hypocomplementemic urticarial vasculitis, who presented with a posterior reversible encephalopathy syndrome induced by the intake of an over-the-counter cold remedy containing pseudoephedrine. Clinical manifestations and radiological abnormalities resolved after anti-hypertensive therapy and withdrawal of sympathomimetic drug. The diagnosis of posterior reversible encephalopathy syndrome should be considered in patients with compatible clinical and radiological presentation because of its potential reversibility with an appropriate management. Intake of drugs, including over-the-counter cough and cold drugs, should be looked for in the history as well as autoimmune disorders. Copyright 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Up-to-date approach to manage keloids and hypertrophic scars: a useful guide.

PubMed

Arno, Anna I; Gauglitz, Gerd G; Barret, Juan P; Jeschke, Marc G

2014-11-01

Keloids and hypertrophic scars occur anywhere from 30 to 90% of patients, and are characterized by pathologically excessive dermal fibrosis and aberrant wound healing. Both entities have different clinical and histochemical characteristics, and unfortunately still represent a great challenge for clinicians due to lack of efficacious treatments. Current advances in molecular biology and genetics reveal new preventive and therapeutical options which represent a hope to manage this highly prevalent, chronic and disabling problem, with long-term beneficial outcomes and improvement of quality of life. While we wait for these translational clinical products to be marketed, however, it is imperative to know the basics of the currently existing wide array of strategies to deal with excessive scars: from the classical corticotherapy, to the most recent botulinum toxin and lasers. The main aim of this review paper is to offer a useful up-to-date guideline to prevent and treat keloids and hypertrophic scars. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

A Weibull characterization for tensile fracture of multicomponent brittle fibers

NASA Technical Reports Server (NTRS)

Barrows, R. G.

1977-01-01

A statistical characterization for multicomponent brittle fibers in presented. The method, which is an extension of usual Weibull distribution procedures, statistically considers the components making up a fiber (e.g., substrate, sheath, and surface) as separate entities and taken together as in a fiber. Tensile data for silicon carbide fiber and for an experimental carbon-boron alloy fiber are evaluated in terms of the proposed multicomponent Weibull characterization.

Characterizing autism spectrum disorders by key biochemical pathways.

PubMed

Subramanian, Megha; Timmerman, Christina K; Schwartz, Joshua L; Pham, Daniel L; Meffert, Mollie K

2015-01-01

The genetic and phenotypic heterogeneity of autism spectrum disorders (ASD) presents a substantial challenge for diagnosis, classification, research, and treatment. Investigations into the underlying molecular etiology of ASD have often yielded mixed and at times opposing findings. Defining the molecular and biochemical underpinnings of heterogeneity in ASD is crucial to our understanding of the pathophysiological development of the disorder, and has the potential to assist in diagnosis and the rational design of clinical trials. In this review, we propose that genetically diverse forms of ASD may be usefully parsed into entities resulting from converse patterns of growth regulation at the molecular level, which lead to the correlates of general synaptic and neural overgrowth or undergrowth. Abnormal brain growth during development is a characteristic feature that has been observed both in children with autism and in mouse models of autism. We review evidence from syndromic and non-syndromic ASD to suggest that entities currently classified as autism may fundamentally differ by underlying pro- or anti-growth abnormalities in key biochemical pathways, giving rise to either excessive or reduced synaptic connectivity in affected brain regions. We posit that this classification strategy has the potential not only to aid research efforts, but also to ultimately facilitate early diagnosis and direct appropriate therapeutic interventions.

Multifocal systemic tuberculosis: the many faces of an old nemesis.

PubMed

Al-Tawfiq, Jaffar A

2007-04-01

Tuberculosis continues to be a major health problem, where an estimated 7-8 million new cases are diagnosed each year. Multifocal tuberculosis is characterized by the presence of large multifocal tuberculous areas in the same or different organs. Difficulty in diagnosis of multifocal tuberculosis and consideration of other diseases may lead to a delay in diagnosing this entity. Here the clinical features and characteristics of three patients with multifocal systemic tuberculosis are described. During the period of 1999-2005, a total of 128 confirmed cases of tuberculosis were identified. Three (2.3%) patients had multifocal systemic tuberculosis. The first case had involvement of the lung, psoas muscle, and the vertebral bodies. The second patient had multiple brain lesions with mediastinal and retroperitoneal lymphadenopathy. The third patient had multiple brain lesions, lymphadenopathy, and colonic lesions initially mimicking a metastatic disease. Mycobacterium tuberculosis was grown from pleural fluid in one patient and from lymph node biopsies in another patient. The third patient had histopathologic evidence of tuberculosis. All patients received standard anti-tuberculous treatment, resulting in a full recovery in two patients, while the third patient had residual weakness. Multifocal systemic tuberculosis may pose a diagnostic challenge and may occur in immunocompetent hosts, in whom this entity generally has a good outcome.

Characterizing autism spectrum disorders by key biochemical pathways

PubMed Central

Subramanian, Megha; Timmerman, Christina K.; Schwartz, Joshua L.; Pham, Daniel L.; Meffert, Mollie K.

2015-01-01

The genetic and phenotypic heterogeneity of autism spectrum disorders (ASD) presents a substantial challenge for diagnosis, classification, research, and treatment. Investigations into the underlying molecular etiology of ASD have often yielded mixed and at times opposing findings. Defining the molecular and biochemical underpinnings of heterogeneity in ASD is crucial to our understanding of the pathophysiological development of the disorder, and has the potential to assist in diagnosis and the rational design of clinical trials. In this review, we propose that genetically diverse forms of ASD may be usefully parsed into entities resulting from converse patterns of growth regulation at the molecular level, which lead to the correlates of general synaptic and neural overgrowth or undergrowth. Abnormal brain growth during development is a characteristic feature that has been observed both in children with autism and in mouse models of autism. We review evidence from syndromic and non-syndromic ASD to suggest that entities currently classified as autism may fundamentally differ by underlying pro- or anti-growth abnormalities in key biochemical pathways, giving rise to either excessive or reduced synaptic connectivity in affected brain regions. We posit that this classification strategy has the potential not only to aid research efforts, but also to ultimately facilitate early diagnosis and direct appropriate therapeutic interventions. PMID:26483618

Myopericytoma of skin and soft tissues: clinicopathologic and immunohistochemical study of 54 cases.

PubMed

Mentzel, Thomas; Dei Tos, Angelo P; Sapi, Zoltan; Kutzner, Heinz

2006-01-01

Perivascular neoplasms comprise traditionally glomus tumor and hemangiopericytoma (HPC). Whereas glomus tumor represents a well-defined entity, the existence of HPC as a separate entity has been questioned because a number of neoplasms of different lines of differentiation are characterized by a HPC-like vascular growth pattern. Myopericytoma represents a recently delineated entity showing a HPC-like vascular pattern. A large series of myopericytoma of skin and soft tissues has been analyzed to further characterize the clinicopathologic spectrum of this entity. Fifty-four cases of myopericytoma of skin and soft tissues were retrieved and the histology reviewed. Immunohistochemical stainings using alpha-smooth muscle actin (ASMA), desmin, and h-caldesmon antibodies were performed, and clinical data and follow-up information were obtained from referring pathologists. Thirty-four patients were male and 18 were female (gender was unknown in 2 cases). Patient age ranged from 13 to 87 years (median, 52 years). The lower extremities were most commonly affected (26 cases) followed by the upper extremities (16 cases), the head and neck region (4 cases), and the trunk (2 cases); exact location was unknown in 5 cases. In 20 cases, the neoplasms were confined to the dermis, in 6 cases an extension into the subcutis was seen, and 24 as well as 4 cases arose in subcutaneous and deep soft tissue, respectively. Two cases were multicentric; and in 1 of these patients, multiple anatomic regions were involved. Histologically, in all cases, numerous thin-walled vessels and a concentric, perivascular arrangement of ovoid, plump spindled to round myoid tumor cells was seen. However, a broad morphologic spectrum ranging from hypocellular, fibroma-like (3 cases), myofibroma-like (2 cases), angioleiomyoma-like (12 cases), and HPC-like neoplasms (13 cases) to classic myopericytomas (14 cases) and immature, cellular lesions (2 cases) was noted. In addition, 2 neoplasms with focal glomoid features, 5 intravascular, and 1 malignant myopericytomas were found. Prominent cytologic atypia and increased proliferative activity (>3 mitoses/10 high power fields) was seen in 4 and 2 cases, respectively. Immunohistochemically, all cases tested stained positively for ASMA. In addition, 29 of 32 cases tested stained positively for h-caldesmon, whereas desmin was only focally positive in 3 of 33 cases. Follow-up information was available in 46 cases (range, 7-168 months; median, 48 months). Despite marginal or incomplete excision in 23 of 46 cases, only 2 neoplasms (1 malignant and 1 intravascular myopericytoma) recurred locally (within 1 and 4 years, respectively). Despite overlapping morphologic features to angioleiomyoma and myofibroma, myopericytoma represents a distinct perivascular, myoid neoplasm of skin and soft tissues, characterized by a broad morphologic spectrum of concentrically, perivascularly growing myoid tumor cells that stain positively for ASMA and often for h-caldesmon, whereas desmin is usually negative. Most cases of myopericytoma behave in a benign fashion, but local recurrences and rarely metastases may occur in atypical and malignant neoplasms.

Staphylococcus aureus, phagocyte NADPH oxidase and chronic granulomatous disease.

PubMed

Buvelot, Helene; Posfay-Barbe, Klara M; Linder, Patrick; Schrenzel, Jacques; Krause, Karl-Heinz

2017-03-01

Dysfunction of phagocytes is a relevant risk factor for staphylococcal infection. The most common hereditary phagocyte dysfunction is chronic granulomatous disease (CGD), characterized by impaired generation of reactive oxygen species (ROS) due to loss of function mutations within the phagocyte NADPH oxidase NOX2. Phagocytes ROS generation is fundamental to eliminate pathogens and to regulate the inflammatory response to infection. CGD is characterized by recurrent and severe bacterial and fungal infections, with Staphylococcus aureus as the most frequent pathogen, and skin and lung abscesses as the most common clinical entities. Staphylococcus aureus infection may occur in virtually any human host, presumably because of the many virulence factors of the bacterium. However, in the presence of functional NOX2, staphylococcal infections remain rare and are mainly linked to breaches of the skin barrier. In contrast, in patients with CGD, S. aureus readily survives and frequently causes clinically apparent disease. Astonishingly, little is known why S. aureus, which possesses a wide range of antioxidant enzymes (e.g. catalase, SOD), is particularly sensitive to control through NOX2. In this review, we will evaluate the discovery of CGD and our present knowledge of the role of NOX2 in S. aureus infection. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clinical Studies with Epothilones

NASA Astrophysics Data System (ADS)

Altmann, Karl-Heinz

As indicated in previous chapters, epothilone research so far has delivered seven new chemical entities that have been advanced to clinical trials in humans (Fig. 1). However, the amount of clinical data publicly available at this time strongly varies between individual compounds, depending on their development stage, but also on the general publication policy of the developing company. The compound that has been most comprehensively characterized in the clinical literature is ixabepilone (BMS-247550), for which trial results have been described in a number of articles in peer-reviewed journals and which has been granted FDA approval for two clinical indications on Oct. 16, 2007. For all other compounds, most of the information on clinical trials is available only in abstract form. In all these cases it remains uncertain, whether the content of these abstracts fully reflects the content of the subsequent (poster or oral) presentations at the corresponding meeting; in fact, it seems likely that additional data will have been included in the actual meeting presentations that may not have been available at the time of abstract submission. As this is unknown to the author, such additional information cannot be considered in this chapter, which is solely based on information documented in accessible abstracts or journal publications. It should also be kept in mind that the interpretation of data from ongoing clinical trials or forward looking statements based on data from completed trials are always preliminary in character.

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.

High Resolution Imaging of Viscoelastic Properties of Intracranial Tumours by Multi-Frequency Magnetic Resonance Elastography.

PubMed

Reiss-Zimmermann, M; Streitberger, K-J; Sack, I; Braun, J; Arlt, F; Fritzsch, D; Hoffmann, K-T

2015-12-01

In recent years Magnetic Resonance Elastography (MRE) emerged into a clinically applicable imaging technique. It has been shown that MRE is capable of measuring global changes of the viscoelastic properties of cerebral tissue. The purpose of our study was to evaluate a spatially resolved three-dimensional multi-frequent MRE (3DMMRE) for assessment of the viscoelastic properties of intracranial tumours. A total of 27 patients (63 ± 13 years) were included. All examinations were performed on a 3.0 T scanner, using a modified phase-contrast echo planar imaging sequence. We used 7 vibration frequencies in the low acoustic range with a temporal resolution of 8 dynamics per wave cycle. Post-processing included multi-frequency dual elasto-visco (MDEV) inversion to generate high-resolution maps of the magnitude |G*| and the phase angle φ of the complex valued shear modulus. The tumour entities included in this study were: glioblastoma (n = 11), anaplastic astrocytoma (n = 3), meningioma (n = 7), cerebral metastasis (n = 5) and intracerebral abscess formation (n = 1). Primary brain tumours and cerebral metastases were not distinguishable in terms of |G*| and φ. Glioblastoma presented the largest range of |G*| values and a trend was delineable that glioblastoma were slightly softer than WHO grade III tumours. In terms of φ, meningiomas were clearly distinguishable from all other entities. In this pilot study, while analysing the viscoelastic constants of various intracranial tumour entities with an improved spatial resolution, it was possible to characterize intracranial tumours by their mechanical properties. We were able to clearly delineate meningiomas from intraaxial tumours, while for the latter group an overlap remains in viscoelastic terms.

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.

An ontology model for nursing narratives with natural language generation technology.

PubMed

Min, Yul Ha; Park, Hyeoun-Ae; Jeon, Eunjoo; Lee, Joo Yun; Jo, Soo Jung

2013-01-01

The purpose of this study was to develop an ontology model to generate nursing narratives as natural as human language from the entity-attribute-value triplets of a detailed clinical model using natural language generation technology. The model was based on the types of information and documentation time of the information along the nursing process. The typesof information are data characterizing the patient status, inferences made by the nurse from the patient data, and nursing actions selected by the nurse to change the patient status. This information was linked to the nursing process based on the time of documentation. We describe a case study illustrating the application of this model in an acute-care setting. The proposed model provides a strategy for designing an electronic nursing record system.

Cancer-associated fibroblasts as target and tool in cancer therapeutics and diagnostics.

PubMed

De Vlieghere, Elly; Verset, Laurine; Demetter, Pieter; Bracke, Marc; De Wever, Olivier

2015-10-01

Cancer-associated fibroblasts (CAFs) are drivers of tumour progression and are considered as a target and a tool in cancer diagnostic and therapeutic applications. An increased abundance of CAFs or CAF signatures are recognized as a bad prognostic marker in several cancer types. Tumour-environment biomimetics strongly improve our understanding of the communication between CAFs, cancer cells and other host cells. Several experimental drugs targeting CAFs are in clinical trials for multiple tumour entities; alternatively, CAFs can be exploited as a tool to characterize the functionality of circulating tumour cells or to capture them as a tool to prevent metastasis. The continuous interaction between tissue engineers, biomaterial experts and cancer researchers creates the possibility to biomimic the tumour-environment and provides new opportunities in cancer diagnostics and management.

A rare cause of acute flaccid paralysis: Human coronaviruses

PubMed Central

Turgay, Cokyaman; Emine, Tekin; Ozlem, Koken; Muhammet, S. Paksu; Haydar, A. Tasdemir

2015-01-01

Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian–Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co-infection by the real-time polymerase chain reaction, has been reported for the first time. PMID:26557177

A rare cause of acute flaccid paralysis: Human coronaviruses.

PubMed

Turgay, Cokyaman; Emine, Tekin; Ozlem, Koken; Muhammet, S Paksu; Haydar, A Tasdemir

2015-01-01

Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian-Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co-infection by the real-time polymerase chain reaction, has been reported for the first time.

Exercise Related Leg Pain (ERLP): a Review of The Literature

PubMed Central

2007-01-01

Exercise related leg pain (ERLP) is a regional pain syndrome described as pain between the knee and ankle which occurs with exercise. Indiscriminant use of terminology such as “shin splints” has resulted in ongoing confusion regarding the pathoanatomic entities associated with this pain syndrome. Each of the pathoanatomic entities – medial tibial stress syndrome, chronic exertional compartment syndrome, tibial and fibular stress fractures, tendinopathy, nerve entrapment, and vascular pathology – which manifest as ERLP are each described in terms of relevant anatomy, epidemiology, clinical presentation, associated pathomechanics, and intervention strategies. Evidence regarding risk factors for ERLP general and specific pathoanatomic entities are presented in the context of models of sports injury prevention. PMID:21522213

A critical appraisal of the mild axonal peripheral neuropathy of late neurologic Lyme disease

PubMed Central

Wormser, Gary P.; Strle, Franc; Shapiro, Eugene D.; Dattwyler, Raymond J.; Auwaerter, Paul G.

2018-01-01

In older studies, a chronic distal symmetric sensory neuropathy was reported as a relatively common manifestation of late Lyme disease in the United States. However, the original papers describing this entity had notable inconsistencies and certain inexplicable findings, such as reports that this condition developed in patients despite prior antibiotic treatment known to be highly effective for other manifestations of Lyme disease. More recent literature suggests that this entity is seen rarely, if at all. A chronic distal symmetric sensory neuropathy as a manifestation of late Lyme disease in North America should be regarded as controversial and in need of rigorous validation studies before acceptance as a documented clinical entity. PMID:27914746

An unusual case of primary spontaneous tension pneumothorax in a jamaican female.

PubMed

Johnson, M; French, S; Cornwall, D

2014-06-01

Spontaneous pneumothorax is a well-recognized entity with a classical presentation of acute onset chest pain and shortness of breath. It may be complicated by the development of a tension pneumothorax or a haemopneumothorax. We report an interesting case of a spontaneous tension haemopneumothorax which presented atypically and was diagnosed on computed tomography (CT) scan of the chest. The clinical and pathophysiological characteristics and treatment of this unusual entity is discussed.

Unilateral RS3PE in a Patient of Seronegative Rheumatoid Arthritis.

PubMed

Varshney, Ankur Nandan; Kumar, Nilesh; Tiwari, Ashutosh; Anand, Ravi; Prasad, Sashi Ranjan; Anand, Arvind; Mishra, Abhinandan; Singh, N K

2013-01-01

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare but well-reported clinical entity. It is classically described as symmetrical involvement of both upper extremities. Asymmetrical involvement had also been reported, but unilateral presentation is very rare. We hereby report a case of unilateral RS3PE in a patient of seronegative rheumatoid arthritis which was initially misdiagnosed as cellulitis and was given high dose antibiotics without any significant improvement. Later a rheumatologic consultation leads to a prompt diagnosis, and treatment with steroids leads to dramatic reversal of symptoms. This case demonstrates the rare presentation of this rare clinical entity and highlights the necessity of awareness regarding unilateral disease to clinicians.

A Challenging Case of Primary Breast Hodgkin's Lymphoma

PubMed Central

ZARNESCU, Narcis Octavian; ILIESIU, Andreea; PROCOP, Alexandru; TAMPA, Mircea; MATEI, Clara; SAJIN, Maria; COSTACHE, Mariana; DUMITRU, Adrian; LAZAROIU, Anca Mihaela

2015-01-01

Primary breast lymphoma (PBL) is a rare entity accounting for less than 1% of all breast malignancies. Diagnostic criteria for primary Hodgkin's lymphoma of the breast are: the presence of sufficient tissue for diagnosis, close interaction between mammary tissue and lymphomatous infiltrate and no evidence or prior diagnosis of widespread lymphoma. Our case illustrates an unusual presentation of Hodgkin's lymphoma of the breast: clinically as inflammatory breast cancer and core biopsy as granulomatous mastitis, the final diagnosis requiring surgical biopsy. Current information regarding this entity is scant, mainly build upon its rarity. In this paper we assess the clinical presentation, the step-by-step diagnosis, the treatment and the importance of immunohistochemistry in this uncommon condition. PMID:26225149

A Challenging Case of Primary Breast Hodgkin's Lymphoma.

PubMed

Zarnescu, Narcis Octavian; Iliesiu, Andreea; Procop, Alexandru; Tampa, Mircea; Matei, Clara; Sajin, Maria; Costache, Mariana; Dumitru, Adrian; Lazaroiu, Anca Mihaela

2015-03-01

Primary breast lymphoma (PBL) is a rare entity accounting for less than 1% of all breast malignancies. Diagnostic criteria for primary Hodgkin's lymphoma of the breast are: the presence of sufficient tissue for diagnosis, close interaction between mammary tissue and lymphomatous infiltrate and no evidence or prior diagnosis of widespread lymphoma. Our case illustrates an unusual presentation of Hodgkin's lymphoma of the breast: clinically as inflammatory breast cancer and core biopsy as granulomatous mastitis, the final diagnosis requiring surgical biopsy. Current information regarding this entity is scant, mainly build upon its rarity. In this paper we assess the clinical presentation, the step-by-step diagnosis, the treatment and the importance of immunohistochemistry in this uncommon condition.

Leiomyoma of the anal canal: report of two cases.

PubMed

Witz, M; Bernheim, J; Griffel, B; Dinbar, A

1986-10-01

Leiomyoma of the rectum and anal canal is an unusual clinical entity. Generally, it does not produce any clinical signs and in most cases it is discovered incidentally in the course of routine rectal examination. The clinical presentation, diagnosis, and surgical treatment are described in two presented cases of anal canal leiomyoma.

Vestibular Migraine: Clinical Challenges and Opportunities for Multidisciplinarity

PubMed Central

Luís, Leonel; Gonçalves, Freire; Pavão Martins, Isabel

2016-01-01

Migraine and vertigo are two very prevalent conditions in general population. The coexistence of both in the same subject is a significant clinical challenge, since it is not always possible to understand whether they are causally related or associated by chance, requiring different diagnostic and therapeutic approaches. In this review we analyze and summarize the actual knowledge about vestibular migraine (VM), focusing on the new concepts proposed by the International Classification of Headache Disorders 3-beta and by the Bárány Society and also addressing the former concepts, which are still present in clinical practice. We conclude that clinical studies using a multidisciplinary approach are crucial in this field, since different specialists observe the same pathology with different eyes. Clinical presentation of VM is variable in what concerns vestibular symptoms temporal relation with migraine headache, as well as in their accompanying manifestations. Biomarkers, either genomics or functional, and molecular imaging techniques will be helpful to clarify many aspects of the complexity of this entity, helping to define to what extent can VM be considered a separate and independent clinical entity. PMID:28082766

Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue: new entities and new variants of old entities recorded during the last 25 years. Part XII: appendix.

PubMed

Bisceglia, M; Spagnolo, D; Galliani, C; Fisher, C; Suster, S; Kazakov, D V; Cooper, K; Michal, M

2006-08-01

In an eleven part series published in Pathologica, we have presented various tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue (ST), which emerged as new entities or as variants of established entities during the last quarter of a century. Detailed clinicomorphological and differential diagnostic features of approximately sixty entities were chosen on the basis of their clinical significance and morphologic distinctiveness. The series included fibrous and myofibroblastic tumors (e.g. solitary fibrous tumor, high grade classic and pigmented dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor and myofibrosarcomas), fibromyxoid and fibrohistiocytic neoplasms (e.g., Evans' tumor, phosphaturic mesenchymal tumor, inflammatory myxohyaline tumor), special adipocytic/vascular/and smooth muscle lesions (e.g., chondroid lipoma, Dabska's tumor, ST hemangioblastoma, lipoleiomyosarcoma), epithelioid mesenchymal malignancies of diverse lineages (e.g., epithelioid liposarcoma, proximal-type epithelioid sarcoma, neuroendocrine extraskeletal chondromyxoid sarcoma), ST Ewing's tumor and peripheral nerve sheath tumors (perineuriomas and pigmented and rosetting tumors of the schwannoma/neurofibroma group), extranodal dendritic or histiocytic proliferative processes (follicular dendritic cell sarcoma, Rosai-Dorfman disease, Castleman's disease, and plexiform xanthomatous tumor), and tumors with myoepithelial differentiation. The section devoted to selected pseudotumoral entities considered representatives of the hamartoma group (neural fibrolipomatous hamartoma, ectopic hamartomatous thymoma, rudimentary meningocele), metabolic diseases (amyloid tumor, nephrogenic fibrosing dermopathy, tophaceous pseudogout, pseudoinfiltrative parathyromatosis), stromal tissue reactions to trauma (fibroosseous pseudotumors of digits) and infections (bacillary angiomatosis), and normal organs (glomus coccygeum). To conclude the descriptive phase, supplementary material has now been collected and appended in an attempt to provide a quick digest of essential knowledge both for comparison and differential diagnosis. The data have been tailored to synthesize diverse sources, integrating clinical elements and references to articles that previously appeared in Part I ("Introduction"), Part II ("The List and Review of New Entities") and Parts III to XI ("Excerpta"). At the very least we hope this final part ("Appendix") will provide the reader with a useful tabular organization of ST lesions and a reference resource.

Parkin disease: a clinicopathologic entity?

PubMed

Doherty, Karen M; Silveira-Moriyama, Laura; Parkkinen, Laura; Healy, Daniel G; Farrell, Michael; Mencacci, Niccolo E; Ahmed, Zeshan; Brett, Francesca M; Hardy, John; Quinn, Niall; Counihan, Timothy J; Lynch, Timothy; Fox, Zoe V; Revesz, Tamas; Lees, Andrew J; Holton, Janice L

2013-05-01

Mutations in the gene encoding parkin (PARK2) are the most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic reports suggest that homozygous and compound heterozygous parkin mutations are characterized by severe substantia nigra pars compacta neuronal loss. To investigate whether parkin-linked parkinsonism is a different clinicopathologic entity to Parkinson disease (PD). We describe the clinical, genetic, and neuropathologic findings of 5 unrelated cases of parkin disease and compare them with 5 pathologically confirmed PD cases and 4 control subjects. The PD control cases and normal control subjects were matched first for age at death then disease duration (PD only) for comparison. Presenting signs in the parkin disease cases were hand or leg tremor often combined with dystonia. Mean age at onset was 34 years; all cases were compound heterozygous for mutations of parkin. Freezing of gait, postural deformity, and motor fluctuations were common late features. No patients had any evidence of cognitive impairment or dementia. Neuronal counts in the substantia nigra pars compacta revealed that neuronal loss in the parkin cases was as severe as that seen in PD, but relative preservation of the dorsal tier was seen in comparison with PD (P = .04). Mild neuronal loss was identified in the locus coeruleus and dorsal motor nucleus of the vagus, but not in the nucleus basalis of Meynert, raphe nucleus, or other brain regions. Sparse Lewy bodies were identified in 2 cases (brainstem and cortex). These findings support the notion that parkin disease is characterized by a more restricted morphologic abnormality than is found in PD, with predominantly ventral nigral degeneration and absent or rare Lewy bodies.

Motivation and Organizational Principles for Anatomical Knowledge Representation

PubMed Central

Rosse, Cornelius; Mejino, José L.; Modayur, Bharath R.; Jakobovits, Rex; Hinshaw, Kevin P.; Brinkley, James F.

1998-01-01

Abstract Objective: Conceptualization of the physical objects and spaces that constitute the human body at the macroscopic level of organization, specified as a machine-parseable ontology that, in its human-readable form, is comprehensible to both expert and novice users of anatomical information. Design: Conceived as an anatomical enhancement of the UMLS Semantic Network and Metathesaurus, the anatomical ontology was formulated by specifying defining attributes and differentia for classes and subclasses of physical anatomical entities based on their partitive and spatial relationships. The validity of the classification was assessed by instantiating the ontology for the thorax. Several transitive relationships were used for symbolically modeling aspects of the physical organization of the thorax. Results: By declaring Organ as the macroscopic organizational unit of the body, and defining the entities that constitute organs and higher level entities constituted by organs, all anatomical entities could be assigned to one of three top level classes (Anatomical structure, Anatomical spatial entity and Body substance). The ontology accommodates both the systemic and regional (topographical) views of anatomy, as well as diverse clinical naming conventions of anatomical entities. Conclusions: The ontology formulated for the thorax is extendible to microscopic and cellular levels, as well as to other body parts, in that its classes subsume essentially all anatomical entities that constitute the body. Explicit definitions of these entities and their relationships provide the first requirement for standards in anatomical concept representation. Conceived from an anatomical viewpoint, the ontology can be generalized and mapped to other biomedical domains and problem solving tasks that require anatomical knowledge. PMID:9452983

Transforming to a computerized system for nursing care: organizational success within Magnet idealism.

PubMed

Lindgren, Carolyn L; Elie, Leslie G; Vidal, Elizabeth C; Vasserman, Alex

2010-01-01

In reaching the goal for standardized, quality care, a not-for-profit healthcare system consisting of seven institutional entities is transforming nursing practice guidelines, patient care workflow, and patient documents into electronic, online, real-time modalities for use across departments and all healthcare delivery entities of the system. Organizational structure and a strategic plan were developed for the 2-year Clinical Transformation Project. The Siemens Patient Care Document System was adopted and adapted to the hospitals' documentation and information needs. Two fast-track sessions of more than 100 nurses and representatives from other health disciplines were held to standardize assessments, histories, care protocols, and interdisciplinary plans of care for the top 10 diagnostic regulatory groups. Education needs of the users were addressed. After the first year, a productive, functional system is evidenced. For example, the bar-coded Medication Administration Check System is in full use on the clinical units of one of the hospitals, and the other institutional entities are at substantial stages of implementation of Patient Care Documentation System. The project requires significant allocation of personnel and financial resources for a highly functional informatics system that will transform clinical care. The project exemplifies four of the Magnet ideals and serves as a model for others who may be deciding about launching a similar endeavor.

PROGRESS IN ACUTE MYELOID LEUKEMIA

PubMed Central

Kadia, Tapan M.; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M.

2014-01-01

Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

Primitive myxoid mesenchymal tumor of infancy in a preterm infant.

PubMed

Lam, Joseph; Lara-Corrales, Irene; Cammisuli, Salvatore; Somers, Gino R; Pope, Elena

2010-01-01

Primitive myxoid mesenchymal tumor of infancy is a recently recognized entity that has been added to the differential diagnosis of myxoid tumors of the soft tissue. Few cases have been reported of this entity in the literature, but none presenting in a preterm infant. We present the case and clinical course of a preterm boy with a primitive myxoid mesenchymal tumor of infancy that occurred following excision of a congenital juvenile xanthogranuloma. © 2010 Wiley Periodicals, Inc.

A database of natural products and chemical entities from marine habitat

PubMed Central

Babu, Padavala Ajay; Puppala, Suma Sree; Aswini, Satyavarapu Lakshmi; Vani, Metta Ramya; Kumar, Chinta Narasimha; Prasanna, Tallapragada

2008-01-01

Marine compound database consists of marine natural products and chemical entities, collected from various literature sources, which are known to possess bioactivity against human diseases. The database is constructed using html code. The 12 categories of 182 compounds are provided with the source, compound name, 2-dimensional structure, bioactivity and clinical trial information. The database is freely available online and can be accessed at http://www.progenebio.in/mcdb/index.htm PMID:19238254

Breast implant-associated, ALK-negative, T-cell, anaplastic, large-cell lymphoma: establishment and characterization of a model cell line (TLBR-1) for this newly emerging clinical entity.

PubMed

Lechner, Melissa G; Lade, Stephen; Liebertz, Daniel J; Prince, H Miles; Brody, Garry S; Webster, Howard R; Epstein, Alan L

2011-04-01

Primary lymphomas of the breast are very rare (0.2-1.5% of breast malignancies) and the vast majority (95%) are of B-cell origin. Recently, 40 cases of clinically indolent anaplastic large-cell kinase (ALK)-negative, T-cell, anaplastic, non-Hodgkin lymphomas (T-ALCL) have been reported worldwide. A tumor biopsy specimen from a patient in this series was obtained for characterization. By using a human stromal feeder layer and IL-2, a novel cell line, TLBR-1, was established from this biopsy and investigated by using cytogenetics and various biomolecular methods. Immunoperoxidase staining of the tumor biopsy showed a CD30/CD8/CD4 coexpressing T-cell population that was epithelial membrane antigen (EMA)(+) and perforin(+) . Multiplex polymerase chain reaction (PCR) of TCRγ genes showed monoclonality that suggested a T-cell origin, yet pan-T markers CD2/5/7, anaplastic large-cell kinase (ALK)-1, pancytokeratins, CD20, CD56, and Epstein-Barr virus (EBV) by in situ hybridization (ISH) were negative. TLBR-1 is IL-2 dependent, has a relatively long doubling time (55 hours), and displays different cellular shapes in culture. Cytogenetic analysis of tumor and TLBR-1 cells confirmed a highly anaplastic cell population with a modal number of 47 chromosomes lacking t(2;5). PCR screens for EBV and human T-lymphotropic virus types 1 and 2 (HTLV-1/2) were negative. Fluorescence-activated cell-sorting (FACS) analysis showed strong positivity for CD4/8, CD30, CD71, and CD26 expression, and antigen presentation (HLA-DR(+) CD80(+) CD86(+) ), IL-2 signaling (CD25(+) CD122(+) ), and NK (CD56(+) ) markers, and Western blots demonstrated strong Notch1 expression. Severe combined immunodeficiency (SCID) mouse TLBR-1 heterotransplants recapitulated the histology and marker characteristics of the original tumor. TLBR-1, a novel ALK-negative, T-cell, anaplastic, large-cell lymphoma, closely resembles the original biopsy and represents an important tool for studying this newly recognized disease entity. Copyright © 2010 American Cancer Society.

Breast Implant-Associated, ALK-Negative, T-Cell, Anaplastic, Large-Cell Lymphoma: Establishment and Characterization of a Model Cell Line (TLBR-1) for This Newly Emerging Clinical Entity

PubMed Central

Lechner, Melissa G.; Lade, Stephen; Liebertz, Daniel J.; Prince, H. Miles; Brody, Garry S.; Webster, Howard R.; Epstein, Alan L.

2014-01-01

BACKGROUND Primary lymphomas of the breast are very rare (0.2–1.5% of breast malignancies) and the vast majority (95%) are of B-cell origin. Recently, 40 cases of clinically indolent anaplastic large-cell kinase (ALK)-negative, T-cell, anaplastic, non-Hodgkin lymphomas (T-ALCL) have been reported worldwide. METHODS A tumor biopsy specimen from a patient in this series was obtained for characterization. By using a human stromal feeder layer and IL-2, a novel cell line, TLBR-1, was established from this biopsy and investigated by using cytogenetics and various biomolecular methods. RESULTS Immunoperoxidase staining of the tumor biopsy showed a CD30/CD8/CD4 coexpressing T-cell population that was epithelial membrane antigen (EMA)+ and perforin+. Multiplex polymerase chain reaction (PCR) of TCRγ genes showed monoclonality that suggested a T-cell origin, yet pan-T markers CD2/5/7, anaplastic large-cell kinase (ALK)-1, pancytokeratins, CD20, CD56, and Epstein-Barr virus (EBV) by in situ hybridization (ISH) were negative. TLBR-1 is IL-2 dependent, has a relatively long doubling time (55 hours), and displays different cellular shapes in culture. Cytogenetic analysis of tumor and TLBR-1 cells confirmed a highly anaplastic cell population with a modal number of 47 chromosomes lacking t(2;5). PCR screens for EBV and human T-lymphotropic virus types 1 and 2 (HTLV-1/2) were negative. Fluorescence-activated cell-sorting (FACS) analysis showed strong positivity for CD4/8, CD30, CD71, and CD26 expression, and antigen presentation (HLA-DR+CD80+CD86+), IL-2 signaling (CD25+CD122+), and NK (CD56+) markers, and Western blots demonstrated strong Notch1 expression. Severe combined immunodeficiency (SCID) mouse TLBR-1 heterotransplants recapitulated the histology and marker characteristics of the original tumor. CONCLUSIONS TLBR-1, a novel ALK-negative, T-cell, anaplastic, large-cell lymphoma, closely resembles the original biopsy and represents an important tool for studying this newly recognized disease entity. PMID:21425149

Exploring performance issues for a clinical database organized using an entity-attribute-value representation.

PubMed

Chen, R S; Nadkarni, P; Marenco, L; Levin, F; Erdos, J; Miller, P L

2000-01-01

The entity-attribute-value representation with classes and relationships (EAV/CR) provides a flexible and simple database schema to store heterogeneous biomedical data. In certain circumstances, however, the EAV/CR model is known to retrieve data less efficiently than conventionally based database schemas. To perform a pilot study that systematically quantifies performance differences for database queries directed at real-world microbiology data modeled with EAV/CR and conventional representations, and to explore the relative merits of different EAV/CR query implementation strategies. Clinical microbiology data obtained over a ten-year period were stored using both database models. Query execution times were compared for four clinically oriented attribute-centered and entity-centered queries operating under varying conditions of database size and system memory. The performance characteristics of three different EAV/CR query strategies were also examined. Performance was similar for entity-centered queries in the two database models. Performance in the EAV/CR model was approximately three to five times less efficient than its conventional counterpart for attribute-centered queries. The differences in query efficiency became slightly greater as database size increased, although they were reduced with the addition of system memory. The authors found that EAV/CR queries formulated using multiple, simple SQL statements executed in batch were more efficient than single, large SQL statements. This paper describes a pilot project to explore issues in and compare query performance for EAV/CR and conventional database representations. Although attribute-centered queries were less efficient in the EAV/CR model, these inefficiencies may be addressable, at least in part, by the use of more powerful hardware or more memory, or both.

On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions.

PubMed

Oronoz, Maite; Gojenola, Koldo; Pérez, Alicia; de Ilarraza, Arantza Díaz; Casillas, Arantza

2015-08-01

The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Familial Kleine-Levin Syndrome: A Specific Entity?

PubMed Central

Nguyen, Quang Tuan Remy; Groos, Elisabeth; Leclair-Visonneau, Laurène; Monaca-Charley, Christelle; Rico, Tom; Farber, Neal; Mignot, Emmanuel; Arnulf, Isabelle

2016-01-01

Study Objectives: Kleine-Levin syndrome (KLS) is a rare, mostly sporadic disorder, characterized by intermittent episodes of hypersomnia plus cognitive and behavior disorders. Although its cause is unknown, multiplex families have been described. We contrasted the clinical and biological features of familial versus sporadic KLS. Methods: Two samples of patients with KLS from the United States and France (n = 260) were studied using clinical interviews and human leukocyte antigen (HLA) genotyping. A multiplex family contained two or more first- or second-degree affected relatives (familial cases). Results: Twenty-one patients from 10 multiplex families (siblings: n = 12, including two pairs of monozygotic twins; parent-child: n = 4; cousins: n = 2; uncle-nephews: n = 3) and 239 patients with sporadic KLS were identified, yielding to 4% multiplex families and 8% familial cases. The simplex and multiplex families did not differ for autoimmune, neurological, and psychiatric disorders. Age, sex ratio, ethnicity, HLA typing, karyotyping, disease course, frequency, and duration of KLS episodes did not differ between groups. Episodes were less frequent in familial versus sporadic KLS (2.3 ± 1.8/y versus 3.8 ± 3.7/y, P = 0.004). Menses triggered more frequently KLS onset in the nine girls with familial KLS (relative risk, RR = 4.12, P = 0.03), but not subsequent episodes. Familial cases had less disinhibited speech (RR = 3.44, P = 0.049), less combined hypophagia/hyperphagia (RR = 4.38, P = 0.006), more abrupt termination of episodes (RR = 1.45, P = 0.04) and less postepisode insomnia (RR = 2.16, P = 0.008). There was similar HLA DQB1 distribution in familial versus sporadic cases and no abnormal karyotypes. Conclusion: Familial KLS is mostly present in the same generation, and is clinically similar to but slightly less severe than sporadic KLS. Citation: Nguyen QT, Groos E, Leclair-Visonneau L, Monaca-Charley C, Rico T, Farber N, Mignot E, Arnulf I. Familial Kleine-Levin syndrome: a specific entity? SLEEP 2016;39(8):1535–1542. PMID:27253765

Compulsive buying: an overlooked entity.

PubMed

Basu, Bishnupriya; Basu, Saikat; Basu, Jharna

2011-08-01

Compulsive buying is an under-recognised entity among Indian psychiatrists. A Medline search, hand searching of journals and direct communications with lead investigators in compulsive buying have generated numerous studies. Overseas data indicate a community prevalence between 1% and 8% . The phenomenon can be an independent entity or appears as a comorbidity with another axis I or axis II disorder. A degree of suspicion on part of clinician regarding its possible presence is the key to its detection. A few rating instruments are available to quantify the morbidity and screening for compulsive buying. Management involves pharmacotherapy with SSRIs, psychotherapy, self-help groups and self-help books. Epidemiological and clinical studies on compulsive buying should be undertaken by Indian psychiatrists to provide better services for people suffering from compulsive buying.

Scalp Metastasis as the First Sign of Small-Cell Lung Cancer: Management and Literature Review

PubMed Central

Salemis, Nikolaos S.; Veloudis, Georgios; Spiliopoulos, Kyriakos; Nakos, Georgios; Vrizidis, Nikolaos; Gourgiotis, Stavros

2014-01-01

Cutaneous metastasis from primary visceral malignancy is a relatively uncommon clinical entity, with a reported incidence ranging from 0.22% to 10% among various series. However, the presence of cutaneous metastasis as the first sign of a clinically silent visceral cancer is exceedingly rare. We describe here a case of an asymptomatic male patient who presented with a solitary scalp metastasis as the initial manifestation of an underlying small-cell lung cancer. Diagnostic evaluation revealed advanced disease. We conclude that the possibility of metastatic skin disease should always be considered in the differential diagnosis in patients with a history of smoking or lung cancer presenting with cutaneous nodules. Physicians should be aware of this rare clinical entity, and appropriate investigation should be arranged for early diagnosis and initiation of the appropriate treatment. The prognosis for most patients remains poor. PMID:25058760

Scalp metastasis as the first sign of small-cell lung cancer: management and literature review.

PubMed

Salemis, Nikolaos S; Veloudis, Georgios; Spiliopoulos, Kyriakos; Nakos, Georgios; Vrizidis, Nikolaos; Gourgiotis, Stavros

2014-01-01

Cutaneous metastasis from primary visceral malignancy is a relatively uncommon clinical entity, with a reported incidence ranging from 0.22% to 10% among various series. However, the presence of cutaneous metastasis as the first sign of a clinically silent visceral cancer is exceedingly rare. We describe here a case of an asymptomatic male patient who presented with a solitary scalp metastasis as the initial manifestation of an underlying small-cell lung cancer. Diagnostic evaluation revealed advanced disease. We conclude that the possibility of metastatic skin disease should always be considered in the differential diagnosis in patients with a history of smoking or lung cancer presenting with cutaneous nodules. Physicians should be aware of this rare clinical entity, and appropriate investigation should be arranged for early diagnosis and initiation of the appropriate treatment. The prognosis for most patients remains poor.

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) in adults-a case report and literature review.

PubMed

Yuan, Junliang; Yang, Shuna; Wang, Shuangkun; Qin, Wei; Yang, Lei; Hu, Wenli

2017-05-25

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is a rare clinico-radiological entity characterized by the magnetic resonance imaging (MRI) finding of a reversible lesion in the corpus callosum, sometimes involved the symmetrical white matters. Many cases of child-onset MERS with various causes have been reported. However, adult-onset MERS is relatively rare. The clinical characteristics and pathophysiologiccal mechanisms of adult-onset MERS are not well understood. We reviewed the literature on adult-onset MERS in order to describe the characteristics of MERS in adults and to provide experiences for clinician. We reported a case of adult-onset MERS with acute urinary retension and performed literature search from PubMed and web of science databases to identify other adult-onset MERS reports from Januarary 2004 to March 2016. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed on selection process. And then we summarized the clinico-radiological features of adult-onset MERS. Twenty-nine adult-onset MERS cases were reviewed from available literature including the case we have. 86.2% of the cases (25/29) were reported in Asia, especially in Japan. Ages varied between 18 and 59 years old with a 12:17 female-to-male ratio. The major cause was infection by virus or bacteria. Fever and headache were the most common clinical manifestation, and acute urinary retention was observed in 6 patients. All patients recovered completely within a month. Adult-onset MERS is an entity with a broad clinico-radiological spectrum because of the various diseases and conditions. There are similar characteristics between MERS in adults and children, also some differences.

A pathophysiologic approach for subacute encephalopathy with seizures in alcoholics (SESA) syndrome.

PubMed

Choi, Jun Yong; Kwon, Jiwon; Bae, Eun-Kee

2014-09-01

Subacute encephalopathy with seizures in alcoholics (SESA) syndrome is a unique disease entity characterized by typical clinical and electroencephalographic (EEG) features in the setting of chronic alcoholism. We present two patients with distinctive serial MRI and EEG findings which suggest a clue to the underlying pathophysiologic mechanisms of SESA syndrome. Two patients with chronic alcoholism and alcoholic liver cirrhosis presented with generalized seizures and confused mental status. Brain MRI demonstrated restricted diffusion, increased T2-weighted signal intensity, and hyperperfusion in the presumed seizure focus and nearby posterior regions of the cerebral hemispheres. EEG showed periodic lateralized epileptiform discharges which were prominent in the posterior regions of the cerebral hemispheres ipsilateral to the side of brain MRI abnormalities. Even after patients clinically improved, these brain abnormalities persisted with progressive atrophic changes on follow-up brain MRI. These patients had not only the distinguishing clinical and EEG features of SESA syndrome, but also showed novel brain MRI abnormalities. These changes on MRI displayed characteristics of seizure-related changes. The posterior dominance of abnormalities on MRI and EEG suggests that the pathophysiologic mechanisms of SESA syndrome may share those of posterior reversible encephalopathy syndrome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genomewide search and genetic localization of a second gene associated with autosomal dominant branchio-oto-renal syndrome: clinical and genetic implications.

PubMed Central

Kumar, S; Deffenbacher, K; Marres, H A; Cremers, C W; Kimberling, W J

2000-01-01

Branchio-oto-renal (BOR) syndrome is characterized by ear malformations, cervical fistulas, hearing loss, and renal anomalies. It is an autosomal dominant disorder with variable clinical manifestations. The most common features of BOR syndrome are branchial, hearing, and renal anomalies. However, many affected subjects have been observed with branchial-cleft anomalies and hearing loss but without renal anomalies, a condition called "branchio-otic" (BO) syndrome. It is logical to question whether the BOR and BO syndromes are allelic or whether they represent distinct genetic entities. We identified a very large extended family whose members had branchial and hearing anomalies associated with commissural lip pits that segregated in an autosomal dominant fashion. Using a genomewide search strategy, we identified genetic linkage, with a maximum LOD score of 4.81 at recombination fraction 0, between the BO phenotype and polymorphic marker D1S2757 in the genetic region of chromosome 1q31. This is the first report of linkage for a second gene associated with BOR syndrome. The findings have important clinical implications and will provide insight into the genetic basis of BOR syndrome. PMID:10762556

Advances in the molecular genetics of gliomas - implications for classification and therapy.

PubMed

Reifenberger, Guido; Wirsching, Hans-Georg; Knobbe-Thomsen, Christiane B; Weller, Michael

2017-07-01

Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine glioma classification, to improve prediction of patient outcomes, and to guide individualized treatment. Thus, the WHO Classification of Tumours of the Central Nervous System was revised in 2016 to incorporate molecular biomarkers - together with classic histological features - in an integrated diagnosis, in order to define distinct glioma entities as precisely as possible. This paradigm shift is markedly changing how glioma is diagnosed, and has important implications for future clinical trials and patient management in daily practice. Herein, we highlight the developments in our understanding of the molecular genetics of gliomas, and review the current landscape of clinically relevant molecular biomarkers for use in classification of the disease subtypes. Novel approaches to the genetic characterization of gliomas based on large-scale DNA-methylation profiling and next-generation sequencing are also discussed. In addition, we illustrate how advances in the molecular genetics of gliomas can promote the development and clinical translation of novel pathogenesis-based therapeutic approaches, thereby paving the way towards precision medicine in neuro-oncology.

Advances in sarcoma diagnostics and treatment

PubMed Central

Dancsok, Amanda R; Asleh-Aburaya, Karama; Nielsen, Torsten O

2017-01-01

The heterogeneity of sarcomas with regard to molecular genesis, histology, clinical characteristics, and response to treatment makes management of these rare yet diverse neoplasms particularly challenging. This review encompasses recent developments in sarcoma diagnostics and treatment, including cytotoxic, targeted, epigenetic, and immune therapy agents. In the past year, groups internationally explored the impact of adding mandatory molecular testing to histological diagnosis, reporting some changes in diagnosis and/or management; however, the impact on outcomes could not be adequately assessed. Transcriptome sequencing techniques have brought forward new diagnostic tools for identifying fusions and/or characterizing unclassified entities. Next-generation sequencing and advanced molecular techniques were also applied to identify potential targets for directed and epigenetic therapy, where preclinical studies reported results for agents active within the receptor tyrosine kinase, mTOR, Notch, Wnt, Hedgehog, Hsp90, and MDM2 signaling networks. At the level of clinical practice, modest developments were seen for some sarcoma subtypes in conventional chemotherapy and in therapies targeting the pathways activated by various receptor tyrosine kinases. In the burgeoning field of immune therapy, sarcoma work is in its infancy; however, elaborate protocols for immune stimulation are being explored, and checkpoint blockade agents advance from preclinical models to clinical studies. PMID:27732970

Broadening the diagnosis of bipolar disorder: benefits vs. risks

PubMed Central

STRAKOWSKI, STEPHEN M.; FLECK, DAVID E.; MAJ, MARIO

2011-01-01

There is considerable debate over whether bipolar and related disorders that share common signs and symptoms, but are currently defined as distinct clinical entities in DSM-IV and ICD-10, may be better characterized as falling within a more broadly defined “bipolar spectrum”. With a spectrum view in mind, the possibility of broadening the diagnosis of bipolar disorder has been proposed. This paper discusses some of the rationale for an expanded diagnostic scheme from both clinical and research perspectives in light of potential drawbacks. The ultimate goal of broadening the diagnosis of bipolar disorder is to help identify a common etiopathogenesis for these conditions to better guide treatment. To help achieve this goal, bipolar researchers have increasingly expanded their patient populations to identify objective biological or endophenotypic markers that transcend phenomenological observation. Although this approach has and will likely continue to produce beneficial results, the upcoming DSM-IV and ICD-10 revisions will place increasing scrutiny on psychiatry’s diagnostic classification systems and pressure to re-evaluate our conceptions of bipolar disorder. However, until research findings can provide consistent and converging evidence as to the validity of a broader diagnostic conception, clinical expansion to a dimensional bipolar spectrum should be considered with caution. PMID:21991268

POLG1 mutations and stroke like episodes: a distinct clinical entity rather than an atypical MELAS syndrome.

PubMed

Cheldi, Antonella; Ronchi, Dario; Bordoni, Andreina; Bordo, Bianca; Lanfranconi, Silvia; Bellotti, Maria Grazia; Corti, Stefania; Lucchini, Valeria; Sciacco, Monica; Moggio, Maurizio; Baron, Pierluigi; Comi, Giacomo Pietro; Colombo, Antonio; Bersano, Anna

2013-01-15

POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy. We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum. The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations.

Unilateral RS3PE in a Patient of Seronegative Rheumatoid Arthritis

PubMed Central

Varshney, Ankur Nandan; Kumar, Nilesh; Tiwari, Ashutosh; Anand, Ravi; Prasad, Sashi Ranjan; Anand, Arvind; Mishra, Abhinandan; Singh, N. K.

2013-01-01

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare but well-reported clinical entity. It is classically described as symmetrical involvement of both upper extremities. Asymmetrical involvement had also been reported, but unilateral presentation is very rare. We hereby report a case of unilateral RS3PE in a patient of seronegative rheumatoid arthritis which was initially misdiagnosed as cellulitis and was given high dose antibiotics without any significant improvement. Later a rheumatologic consultation leads to a prompt diagnosis, and treatment with steroids leads to dramatic reversal of symptoms. This case demonstrates the rare presentation of this rare clinical entity and highlights the necessity of awareness regarding unilateral disease to clinicians. PMID:23662237

Clinical features of autoimmune hepatitis with acute presentation: a Japanese nationwide survey.

PubMed

Joshita, Satoru; Yoshizawa, Kaname; Umemura, Takeji; Ohira, Hiromasa; Takahashi, Atsushi; Harada, Kenichi; Hiep, Nguyen Canh; Tsuneyama, Koichi; Kage, Masayoshi; Nakano, Masayuki; Kang, Jong-Hon; Koike, Kazuhiko; Zeniya, Mikio; Yasunaka, Tetsuya; Takaki, Akinobu; Torimura, Takuji; Abe, Masanori; Yokosuka, Osamu; Tanaka, Atsushi; Takikawa, Hajime

2018-02-23

Autoimmune hepatitis (AIH) is characterized by progressive inflammation and necrosis of hepatocytes and eventually leads to a variety of phenotypes, including acute liver dysfunction, chronic progressive liver disease, and fulminant hepatic failure. Although the precise mechanisms of AIH are unknown, environmental factors may trigger disease onset in genetically predisposed individuals. Patients with the recently established entity of AIH with acute presentation often display atypical clinical features that mimic those of acute hepatitis forms even though AIH is categorized as a chronic liver disease. The aim of this study was to identify the precise clinical features of AIH with acute presentation. Eighty-six AIH patients with acute presentation were retrospectively enrolled from facilities across Japan and analyzed for clinical features, histopathological findings, and disease outcomes. Seventy-five patients were female and 11 were male. Patient age ranged from adolescent to over 80 years old, with a median age of 55 years. Median alanine transaminase (ALT) was 776 U/L and median immunoglobulin G (IgG) was 1671 mg/dL. There were no significant differences between genders in terms of ALT (P = 0.27) or IgG (P = 0.51). The number of patients without and with histopathological fibrosis was 29 and 57, respectively. The patients with fibrosis were significantly older than those without (P = 0.015), but no other differences in clinical or histopathological findings were observed. Moreover, antinuclear antibody (ANA)-positive (defined as × 40, N = 63) and -negative (N = 23) patients showed no significant differences in clinical or histopathological findings or disease outcomes. Twenty-five patients experienced disease relapse and two patients died during the study period. ALP ≥ 500 U/L [odds ratio (OR) 3.20; 95% confidence interval (CI) 1.12-9.10; P < 0.030] and GGT ≥ 200 U/L (OR 2.98; 95% CI 1.01-8.77; P = 0.047) were identified as independent risk factors of disease relapse. AIH with acute presentation is a newly recognized disease entity for which diagnostic hallmarks, such as ALT, fibrosis, and ANA, are needed. Further investigation is also required on the mechanisms of this disorder. Clinicians should be mindful of disease relapse during patient care.

Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma

PubMed Central

Roncalli, Massimo; Sciarra, Amedeo; Tommaso, Luca Di

2016-01-01

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed. PMID:27189732

[Distal hereditary motor neuropathy].

PubMed

Devic, P; Petiot, P

2011-11-01

Distal hereditary motor neuropathy (dHMN), also known as spinal muscular atrophy, represents a group of clinically and genetically heterogeneous diseases caused by degenerations of spinal motor neurons and leading to distal muscle weakness and wasting. Nerve conduction studies reveal a pure motor axonopathy and needle examination shows chronic denervation. dHMN were initially subdivided into seven subtypes according to mode of inheritance, age at onset, and clinical evolution. Recent studies have shown that these subtypes are still heterogeneous at the molecular genetic level and novel clinical and genetic entities have been characterized. To date, mutations in 11 different genes have been identified for autosomal-dominant, autosomal-recessive, and X-linked recessive dHMN. Most of the genes encode protein involved in housekeeping functions, endosomal trafficking, axonal transport, translation synthesis, RNA processing, oxidative stress response and apoptosis. The pathophysiological mechanisms underlying dHMN seem to be related to the "length-dependent" death of motor neurons of the anterior horn of the spinal cord, likely because their large axons have higher metabolic requirements for maintenance. dHMN remain heterogeneous at the clinical and molecular genetic level. The molecular pathomechanisms explaining why mutations in these ubiquitously expressed housekeeping genes result in the selective involvement of spinal motor neurons remain to be unravelled. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Cytomorphology of unusual infectious entities in the Pap test

PubMed Central

Khalbuss, Walid E.; Michelow, Pam; Benedict, Cynthia; Monaco, Sara E.; Pantanowitz, Liron

2012-01-01

Rare entities in the Pap test, including neoplastic and non-neoplastic conditions, pose challenges due to their infrequent occurrence in the daily practice of cytology. Furthermore, these conditions give rise to important diagnostic pitfalls. Infections such as tuberculosis cervicitis may be erroneously diagnosed as carcinoma, whereas others, such as schistosomiasis, are associated with squamous cell carcinoma. These cases include granuloma inguinale (donovanosis), tuberculosis, coccidioidomycosis, schistosomiasis, taeniasis, and molluscum contagiosum diagnosed in Pap tests. Granuloma inguinale shows histiocytes that contain intracytoplasmic bacteria (Donovan bodies). Tuberculosis is characterized by necrotizing granulomatous inflammation with Langhans-multinucleated giant cells. Coccidioidomycosis may show large intact or ruptured fungal spherules associated with endospores. Schistosoma haematobium is diagnosed by finding characteristic ova with a terminal spine. Molluscum contagiosum is characterized by the appearance of squamous cells with molluscum bodies. This article reviews the cytomorphology of selected rare infections and focuses on their cytomorphology, differential diagnosis, and role of ancillary diagnostic studies. PMID:22919422

Machine learning to parse breast pathology reports in Chinese.

PubMed

Tang, Rong; Ouyang, Lizhi; Li, Clara; He, Yue; Griffin, Molly; Taghian, Alphonse; Smith, Barbara; Yala, Adam; Barzilay, Regina; Hughes, Kevin

2018-06-01

Large structured databases of pathology findings are valuable in deriving new clinical insights. However, they are labor intensive to create and generally require manual annotation. There has been some work in the bioinformatics community to support automating this work via machine learning in English. Our contribution is to provide an automated approach to construct such structured databases in Chinese, and to set the stage for extraction from other languages. We collected 2104 de-identified Chinese benign and malignant breast pathology reports from Hunan Cancer Hospital. Physicians with native Chinese proficiency reviewed the reports and annotated a variety of binary and numerical pathologic entities. After excluding 78 cases with a bilateral lesion in the same report, 1216 cases were used as a training set for the algorithm, which was then refined by 405 development cases. The Natural language processing algorithm was tested by using the remaining 405 cases to evaluate the machine learning outcome. The model was used to extract 13 binary entities and 8 numerical entities. When compared to physicians with native Chinese proficiency, the model showed a per-entity accuracy from 91 to 100% for all common diagnoses on the test set. The overall accuracy of binary entities was 98% and of numerical entities was 95%. In a per-report evaluation for binary entities with more than 100 training cases, 85% of all the testing reports were completely correct and 11% had an error in 1 out of 22 entities. We have demonstrated that Chinese breast pathology reports can be automatically parsed into structured data using standard machine learning approaches. The results of our study demonstrate that techniques effective in parsing English reports can be scaled to other languages.

Towards an Obesity-Cancer Knowledge Base: Biomedical Entity Identification and Relation Detection

PubMed Central

Lossio-Ventura, Juan Antonio; Hogan, William; Modave, François; Hicks, Amanda; Hanna, Josh; Guo, Yi; He, Zhe; Bian, Jiang

2017-01-01

Obesity is associated with increased risks of various types of cancer, as well as a wide range of other chronic diseases. On the other hand, access to health information activates patient participation, and improve their health outcomes. However, existing online information on obesity and its relationship to cancer is heterogeneous ranging from pre-clinical models and case studies to mere hypothesis-based scientific arguments. A formal knowledge representation (i.e., a semantic knowledge base) would help better organizing and delivering quality health information related to obesity and cancer that consumers need. Nevertheless, current ontologies describing obesity, cancer and related entities are not designed to guide automatic knowledge base construction from heterogeneous information sources. Thus, in this paper, we present methods for named-entity recognition (NER) to extract biomedical entities from scholarly articles and for detecting if two biomedical entities are related, with the long term goal of building a obesity-cancer knowledge base. We leverage both linguistic and statistical approaches in the NER task, which supersedes the state-of-the-art results. Further, based on statistical features extracted from the sentences, our method for relation detection obtains an accuracy of 99.3% and a f-measure of 0.993. PMID:28503356

Globulomaxillary cysts--do they really exist?

PubMed

Dammer, U; Driemel, O; Mohren, W; Giedl, C; Reichert, T E

2014-01-01

The so-called "globulomaxillary cyst", described as a fissural cyst, caused by entrapped epithelium between the nasal and maxillary process, is no longer considered for its own entity. Nevertheless, cystic lesions, which correspond to the previous image of globulomaxillary cysts, do still occur in daily practice. This raises the question to which entities pathological processes in this particular region actually belong to. In a retrospective study, 17 cases (12 men and 5 women, 12-59 years old) of primarily diagnosed globulomaxillary cysts are analysed according to clinical, radiological and histological aspects, catamnestic processed and assigned to a new entity. The results are compared with the international literature and draws conclusions on the diagnostic and therapeutic procedure. Seven lateral periodontal cysts, four radicular cysts, two keratocystic odontogenic tumours, one adenomatoid odontogenic tumour, one periapical granuloma, one residual cyst and one undefined jaw cyst were determined. According to the results of our study and the data from the international literature, the entity globulomaxillary cyst is no longer justified.

Light-triggered self-assembly of triarylamine-based nanospheres

NASA Astrophysics Data System (ADS)

Moulin, Emilie; Niess, Frédéric; Fuks, Gad; Jouault, Nicolas; Buhler, Eric; Giuseppone, Nicolas

2012-10-01

Tailored triarylamine units modified with terpyridine ligands were coordinated to Zn2+ ions and characterized as discrete dimeric entities. Interestingly, when these complexes were subsequently irradiated with simple visible light in chloroform, they readily self-assembled into monodisperse spheres with a mean diameter of 160 nm.Tailored triarylamine units modified with terpyridine ligands were coordinated to Zn2+ ions and characterized as discrete dimeric entities. Interestingly, when these complexes were subsequently irradiated with simple visible light in chloroform, they readily self-assembled into monodisperse spheres with a mean diameter of 160 nm. Electronic supplementary information (ESI) available: Synthetic procedures and products' characterization (2-4 and 6-9). 1H NMR titration of compound 6 by Zn(OTf)2 to form complex 7. Kinetic measurements by UV-Vis-NIR spectroscopy. Transmission electron microscopy imaging for complexes 8 and 9. UV-Vis-NIR for an Fe2+ analogue of complex 7. Dynamic light scattering and time autocorrelation function for self-assembly of complexes 7-9. Copies of 1H and 13C NMR spectra for compounds 2-4 and 6. See DOI: 10.1039/c2nr32168h

Coexistence of autoimmune polyglandular syndrome type 2 and diabetes insipidus in pregnancy.

PubMed

Krysiak, Robert; Samborek, Malgorzata

2011-11-01

Autoimmune polyglandular syndromes are rarely diagnosed conditions characterized by the association of at least 2 organ-specific autoimmune disorders. Very few cases of these syndromes have been described during pregnancy. The authors report a case of a patient diagnosed with autoimmune thyroiditis and a history of HELLP (hemolysis, elevated liver enzymes and low platelet) syndrome in a prior pregnancy. After increasing the levothyroxine dose, she developed Addisonian crisis. Normalization of adrenal cortex function resulted in the appearance of diabetes insipidus. This report shows that pregnancy may influence the course of preexisting endocrine disorders and lead to their unmasking. Although the risk of the development of autoimmune polyglandular syndromes during pregnancy is small, they may pose a serious health problem. The possible presence of these clinical entities should be considered in every woman with 1 or more endocrine disturbances.

Vogt-Koyanagi-Harada disease: inquiry into the genesis of a disease name in the historical context of Switzerland and Japan.

PubMed

Herbort, Carl P; Mochizuki, Manabu

2007-01-01

To delineate the historical steps associated with the genesis of the name and the definition of Vogt-Koyanagi-Harada (VKH) disease. A bibliographical review of the major publications that were relevant to the original development of the name of the clinical entity known today as Vogt-Koyanagi-Harada disease, in the historical context of the early 20th century. Three distinct time periods can be considered to be important in terms of providing a historical perspective on VKH disease. Given that the cutaneous manifestations of VKH disease are so characteristic, these could not have been missed even before the actual clinical entity of VKH was recognized in the early 20th century. Indeed, several authors, including the Arabic doctor Mohammad-al-Ghâfiqî in the 12th century as well as Jacobi, Nettelship and Tay in the 19th century, described poliosis, neuralgias and hearing disorders. Many of these cases were probably due to sympathetic ophthalmia, but some were clearly VKH cases. The second phase is characterized by the surge of articles that appeared early in the 20th century that defined the disease more precisely. A number of these authors subsequently became associated with the disease name, the first being Alfred Vogt from Switzerland, followed by Japanese researchers. Yoshizo Koyanagi was in fact not the first Japanese author to describe the disease; this honor goes to the first Japanese Professor of Ophthalmology at the University of Tokyo, Dr. Jujiro Komoto, who published in a German language journal, Klinische Monatsblätter für Augenheilkunde in 1911. Yoshizo Koyanagi published his first report in the Nippon Ganka Gakkai Zasshi 3 years later, in 1914, but it was a much later article, one published in 1929, that definitively associated his name with the disease. In this review article, Koyanagi reported 16 cases, of which six were his own cases, that beautifully illustrate the natural course of the disease. In this same time period, Einosuke Harada, in an article published in Nippon Ganka Gakkai Zasshi in 1926 that was based on several case studies, comprehensively described a syndrome that included (1) a prodromal phase of malaise and meningeal irritation; (2) bilateral uveitis of diverse intensity; (3) bilateral retinal detachments spontaneously resolving; (4) integumentary changes; (5) lymphocytosis of the spinal fluid; (6) dysacousia. It is now accepted that Vogt-Koyanagi disease and the syndrome described by Harada are one entity with a diverse clinical spectrum bearing the universally accepted name of Vogt-Koyanagi-Harada disease. The third phase and most recent phase is characterized by the rapid progress made in terms of knowledge of the physiopathology of the disease, primarily due to the development of immunological methods. The evidence accumulated to date clearly points towards an autoimmune Th1 disease directed against proteins associated with choroidal melanin. Other analytical techniques, such as indocyanine green angiography, have enabled researchers to monitor more closely the primary lesional process at the level of the choroid, and standardized diagnostic criteria have been generated in the recent past. Those who earn scientific merit in clinical medicine are the ones who are able to visualize an overview based on the synthesis of 'new' medical facts that have been made available, usually reported singly by several, unassociated authors concomitantly. This is certainly the case for Yoshizo Koyanagi and Einosuke Harada. Conversely, Alfred Vogt was primarily lucky in that he encountered and subsequently precisely described the first case in the literature.

Partial uniparental isodisomy of chromosome 16 unmasks a deleterious biallelic mutation in IFT140 that causes Mainzer-Saldino syndrome.

PubMed

Helm, Benjamin M; Willer, Jason R; Sadeghpour, Azita; Golzio, Christelle; Crouch, Eric; Vergano, Samantha Schrier; Katsanis, Nicholas; Davis, Erica E

2017-07-19

The ciliopathies represent an umbrella group of >50 clinical entities that share both clinical features and molecular etiology underscored by structural and functional defects of the primary cilium. Despite the advances in gene discovery, this group of entities continues to pose a diagnostic challenge, in part due to significant genetic and phenotypic heterogeneity and variability. We consulted a pediatric case from asymptomatic, non-consanguineous parents who presented as a suspected ciliopathy due to a constellation of retinal, renal, and skeletal findings. Although clinical panel sequencing of genes implicated in nephrotic syndromes yielded no likely causal mutation, an oligo-SNP microarray identified a ~20-Mb region of homozygosity, with no altered gene dosage, on chromosome 16p13. Intersection of the proband's phenotypes with known disease genes within the homozygous region yielded a single candidate, IFT140, encoding a retrograde intraflagellar transport protein implicated previously in several ciliopathies, including the phenotypically overlapping Mainzer-Saldino syndrome (MZSDS). Sanger sequencing yielded a maternally inherited homozygous c.634G>A; p.Gly212Arg mutation altering the exon 6 splice donor site. Functional studies in cells from the proband showed that the locus produced two transcripts: a majority message containing a mis-splicing event that caused a premature termination codon and a minority message homozygous for the p.Gly212Arg allele. Zebrafish in vivo complementation studies of the latter transcript demonstrated a loss of function effect. Finally, we conducted post-hoc trio-based whole exome sequencing studies to (a) test the possibility of other causal loci in the proband and (b) explain the Mendelian error of segregation for the IFT140 mutation. We show that the proband harbors a chromosome 16 maternal heterodisomy, with segmental isodisomy at 16p13, likely due to a meiosis I error in the maternal gamete. Using clinical phenotyping combined with research-based genetic and functional studies, we have characterized a recurrent IFT140 mutation in the proband; together, these data are consistent with MZSDS. Additionally, we report a rare instance of a uniparental isodisomy unmasking a deleterious mutation to cause a ciliary disorder.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland.

PubMed

Seethala, Raja R; Stenman, Göran

2017-03-01

The salivary gland section in the 4th edition of the World Health Organization classification of head and neck tumors features the description and inclusion of several entities, the most significant of which is represented by (mammary analogue) secretory carcinoma. This entity was extracted mainly from acinic cell carcinoma based on recapitulation of breast secretory carcinoma and a shared ETV6-NTRK3 gene fusion. Also new is the subsection of "Other epithelial lesions," for which key entities include sclerosing polycystic adenosis and intercalated duct hyperplasia. Many entities have been compressed into their broader categories given clinical and morphologic similarities, or transitioned to a different grouping as was the case with low-grade cribriform cystadenocarcinoma reclassified as intraductal carcinoma (with the applied qualifier of low-grade). Specific grade has been removed from the names of the salivary gland entities such as polymorphous adenocarcinoma, providing pathologists flexibility in assigning grade and allowing for recognition of a broader spectrum within an entity. Cribriform adenocarcinoma of (minor) salivary gland origin continues to be divisive in terms of whether it should be recognized as a distinct category. This chapter also features new key concepts such as high-grade transformation. The new paradigm of translocations and gene fusions being common in salivary gland tumors is featured heavily in this chapter.

A critical approach to the definition of Darwinian units of selection.

PubMed

Rinkevich, B

2000-12-01

What are the biological units of selection? In fact, the notion of "unit of selection" (UOS) is blurred by ambiguity and controversy. To further evaluate the biological entities that are the objects of natural selection, three novel conceptual criteria (holism, minimalism, functionalism) are critically applied; they reveal, in addition to the self-evident case of the "individual," at least six distinct types of UOSs. These UOSs do not always have a defined structural organization; they can be parts of a living organism, a cohesive group of conspecifics, a multiunit entity, a totipotent cell, a DNA fragment, or a whole organism. UOS types diversify by amalgamation or parcelation processes of apparent entities. Therefore, previous attempts to characterize the UOSs solely on some morphological levels (gene, individual, group) without applying stringent criteria have failed to cope with the structural variations of natural phenomena and have led to the ambiguity of terms used.

The use of supernatural entities in moral conversations as a cultural-psychological attractor.

PubMed

Tófalvy, Tamás; Viciana, Hugo

2009-06-01

Social behavior in most human societies is characterized by the following of moral rules explicitly justified by religious belief systems. These systems constitute the diverse domain of human sacred values. Supernatural entities as founders or warranty of moral principles may be seen as a form of "conversation stoppers," considerations that can be dropped into a moral decision process in order to prevent endlessly reconsidering and endlessly asking for further justification. In this article we offer a general naturalistic framework toward answering the question of why supernatural entities are so attractive in moral argumentation. We present an explanatory model based on the phenomena of multiple channels of moral reasoning, the suspension of epistemic vigilance, and relevance assumptions through the attractiveness of the sacred, moral dumbfounding, and the expression of social coalitionary commitment. Thus, in light of much of current cognitive theory, sacred values make sense as basins in the evolutionary landscape of human morality.

Intracellular production of hydrogels and synthetic RNA granules by multivalent molecular interactions

NASA Astrophysics Data System (ADS)

Nakamura, Hideki; Lee, Albert A.; Afshar, Ali Sobhi; Watanabe, Shigeki; Rho, Elmer; Razavi, Shiva; Suarez, Allister; Lin, Yu-Chun; Tanigawa, Makoto; Huang, Brian; Derose, Robert; Bobb, Diana; Hong, William; Gabelli, Sandra B.; Goutsias, John; Inoue, Takanari

2018-01-01

Some protein components of intracellular non-membrane-bound entities, such as RNA granules, are known to form hydrogels in vitro. The physico-chemical properties and functional role of these intracellular hydrogels are difficult to study, primarily due to technical challenges in probing these materials in situ. Here, we present iPOLYMER, a strategy for a rapid induction of protein-based hydrogels inside living cells that explores the chemically inducible dimerization paradigm. Biochemical and biophysical characterizations aided by computational modelling show that the polymer network formed in the cytosol resembles a physiological hydrogel-like entity that acts as a size-dependent molecular sieve. We functionalize these polymers with RNA-binding motifs that sequester polyadenine-containing nucleotides to synthetically mimic RNA granules. These results show that iPOLYMER can be used to synthetically reconstitute the nucleation of biologically functional entities, including RNA granules in intact cells.

Risk Modeling of Interdependent Complex Systems of Systems: Theory and Practice.

PubMed

Haimes, Yacov Y

2018-01-01

The emergence of the complexity characterizing our systems of systems (SoS) requires a reevaluation of the way we model, assess, manage, communicate, and analyze the risk thereto. Current models for risk analysis of emergent complex SoS are insufficient because too often they rely on the same risk functions and models used for single systems. These models commonly fail to incorporate the complexity derived from the networks of interdependencies and interconnectedness (I-I) characterizing SoS. There is a need to reevaluate currently practiced risk analysis to respond to this reality by examining, and thus comprehending, what makes emergent SoS complex. The key to evaluating the risk to SoS lies in understanding the genesis of characterizing I-I of systems manifested through shared states and other essential entities within and among the systems that constitute SoS. The term "essential entities" includes shared decisions, resources, functions, policies, decisionmakers, stakeholders, organizational setups, and others. This undertaking can be accomplished by building on state-space theory, which is fundamental to systems engineering and process control. This article presents a theoretical and analytical framework for modeling the risk to SoS with two case studies performed with the MITRE Corporation and demonstrates the pivotal contributions made by shared states and other essential entities to modeling and analysis of the risk to complex SoS. A third case study highlights the multifarious representations of SoS, which require harmonizing the risk analysis process currently applied to single systems when applied to complex SoS. © 2017 Society for Risk Analysis.

42 CFR 55a.102 - Who is eligible to apply for a Black Lung clinics grant?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Who is eligible to apply for a Black Lung clinics... SERVICES GRANTS PROGRAM GRANTS FOR BLACK LUNG CLINICS General Provisions § 55a.102 Who is eligible to apply for a Black Lung clinics grant? Any State or public or private entity may apply for a grant under this...

42 CFR 55a.102 - Who is eligible to apply for a Black Lung clinics grant?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Who is eligible to apply for a Black Lung clinics... SERVICES GRANTS PROGRAM GRANTS FOR BLACK LUNG CLINICS General Provisions § 55a.102 Who is eligible to apply for a Black Lung clinics grant? Any State or public or private entity may apply for a grant under this...

[Pain disorders in traumatized individuals - neurophysiology and clinical presentation].

PubMed

Egloff, N; Hirschi, A; von Känel, R

2012-01-18

This overview portrays the salient physiological mechanisms being involved in the clinical manifestation of chronic pain in traumatized patients. A «hypermnesia-hyperarousal-model» is purported to support the neurophysiologic plausibility of the trauma-pain-relationship. We discuss seven characteristic clinical pain entities which alone or in combination can be found in patients with a previous psychological trauma.

Round cell sarcomas beyond Ewing: emerging entities.

PubMed

Antonescu, Cristina

2014-01-01

Primitive small blue round cell tumours (SBRCT) of childhood and young adults have been problematic to diagnose and classify. Diagnosis is also complicated in cases with atypical morphology, aberrant immunoprofiles and unusual clinical presentations. Even with the increased use of ancillary techniques in archival material, such as immunohistochemistry and molecular/genetic methods, a proportion of these tumours cannot be subclassified into specific histological types. A subset of tumours resembling microscopically the Ewing sarcoma family of tumours (EFT), being composed of primitive small round cells and occurring in paediatric or young adult age groups, remain unclassified, being negative for EWSR1, SS18(SYT), DDIT3(CHOP) and FOXO1(FKHR) gene rearrangements by FISH/RT-PCR. A small number of cases sharing the undifferentiated EFT appearance have been characterized recently carrying BCOR-CCNB3 or CIC-DUX4 fusions. However, based on the somewhat limited number of cases, it remains unclear if these newly defined genetic entities belong to any of the pre-existing clinicopathological disorders or represent altogether novel conditions. This review presents the latest molecular findings related to these SBRCTs, beyond the common EWSR1-ETS fusions. Specific attention has been paid to morphological features not associated typically with classic EFT, and the value of ancillary tests that can be applied when dealing with EWSR1-negative SBRCTs is discussed. © 2013 John Wiley & Sons Ltd.

A distinct variant of papillary thyroid carcinoma indicating familial adenomatous polyposis (FAP): a case report and brief review.

PubMed

Liyanapathirana, Nishantha; Seneviratne, Sanjeewa Anuruddha; Samarasekera, Dharmabandhu Nandadeva

2015-12-17

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited intestinal polyposis syndrome with an incidence of about 1/8300 births and accounts for about 1% of all colorectal cancers. It has a spectrum of extra-intestinal manifestations including thyroid carcinoma which occur in 1-2% of affected. The cribriform morular variant (CMV) is a rare but distinct histological subtype of papillary thyroid carcinoma (PTC) associated with FAP. Most of the reported cases describe the above entity in the background of well-established FAP. We report a case where both entities presenting simultaneously in a previously undiagnosed patient with FAP without a family history of polyposis. A 24 year old Asian female presented to the surgical clinic with a goitre of eight months duration and recent onset of altered bowel habits with features of anaemia. She was previously healthy and there was no family history of adenomatous polyposis, colorectal carcinoma or thyroid neoplasms. Colonoscopy revealed large bowel polyposis and fine needle aspiration of thyroid revealed a smear suspicious for malignancy. She underwent total thyroidectomy which revealed CMV PTC. Histology was characterized by a prominent cribriform pattern of growth with interspersed cell clusters arranged as morules along with papillary structures which are the key features of this subtype. Diagnosis of CMV warrants ruling out of underlying FAP, irrespective of family history or gastrointestinal symptoms.

Cholesterol embolism: still an unrecognized entity with a high mortality rate.

PubMed

Jucgla, Anna; Moreso, Francesc; Muniesa, Cristina; Moreno, Abelardo; Vidaller, Antonio

2006-11-01

Cholesterol embolism (CE) is an increasingly common but often underdiagnosed medical problem. The recognition of clinical manifestations of CE is the first step toward a correct diagnosis. Our aim was to characterize the features of CE and the risk factors for fatal outcome. Clinical records of patients with clinical and histopathologic diagnoses of CE seen from January 1993 through March 2003 were reviewed. Twenty-six male patients were identified. Mean age was 64 years (range, 48-88 years). All patients had two or more risk factors for atherosclerosis. All but one patient had preexisting symptomatic atherosclerotic disease. At least one precipitating factor was identified in 23 patients (88%). Diagnosis of CE at admission was made in 9 patients only (35%). Cutaneous lesions (88%) and renal failure (73%) were the most common clinical findings. Complications (dialysis, acute pulmonary edema, amputation, or gastrointestinal surgery) were present in 21 patients (81%), and 15 patients died (58%). Previous chronic renal failure was the only variable associated with mortality (relative risk: 4.54, 95% confidence interval 1.26-16.6; P = .02). The results were obtained from patients admitted to a university hospital. This fact may have selected a higher proportion of severe cases. CE was frequently misdiagnosed. Skin lesions were the most common clinical findings and skin biopsy provided histologic confirmation in most of the patients. Chronic renal failure was the only factor related to death.

Determining similarity of scientific entities in annotation datasets

PubMed Central

Palma, Guillermo; Vidal, Maria-Esther; Haag, Eric; Raschid, Louiqa; Thor, Andreas

2015-01-01

Linked Open Data initiatives have made available a diversity of scientific collections where scientists have annotated entities in the datasets with controlled vocabulary terms from ontologies. Annotations encode scientific knowledge, which is captured in annotation datasets. Determining relatedness between annotated entities becomes a building block for pattern mining, e.g. identifying drug–drug relationships may depend on the similarity of the targets that interact with each drug. A diversity of similarity measures has been proposed in the literature to compute relatedness between a pair of entities. Each measure exploits some knowledge including the name, function, relationships with other entities, taxonomic neighborhood and semantic knowledge. We propose a novel general-purpose annotation similarity measure called ‘AnnSim’ that measures the relatedness between two entities based on the similarity of their annotations. We model AnnSim as a 1–1 maximum weight bipartite match and exploit properties of existing solvers to provide an efficient solution. We empirically study the performance of AnnSim on real-world datasets of drugs and disease associations from clinical trials and relationships between drugs and (genomic) targets. Using baselines that include a variety of measures, we identify where AnnSim can provide a deeper understanding of the semantics underlying the relatedness of a pair of entities or where it could lead to predicting new links or identifying potential novel patterns. Although AnnSim does not exploit knowledge or properties of a particular domain, its performance compares well with a variety of state-of-the-art domain-specific measures. Database URL: http://www.yeastgenome.org/ PMID:25725057

Determining similarity of scientific entities in annotation datasets.

PubMed

Palma, Guillermo; Vidal, Maria-Esther; Haag, Eric; Raschid, Louiqa; Thor, Andreas

2015-01-01

Linked Open Data initiatives have made available a diversity of scientific collections where scientists have annotated entities in the datasets with controlled vocabulary terms from ontologies. Annotations encode scientific knowledge, which is captured in annotation datasets. Determining relatedness between annotated entities becomes a building block for pattern mining, e.g. identifying drug-drug relationships may depend on the similarity of the targets that interact with each drug. A diversity of similarity measures has been proposed in the literature to compute relatedness between a pair of entities. Each measure exploits some knowledge including the name, function, relationships with other entities, taxonomic neighborhood and semantic knowledge. We propose a novel general-purpose annotation similarity measure called 'AnnSim' that measures the relatedness between two entities based on the similarity of their annotations. We model AnnSim as a 1-1 maximum weight bipartite match and exploit properties of existing solvers to provide an efficient solution. We empirically study the performance of AnnSim on real-world datasets of drugs and disease associations from clinical trials and relationships between drugs and (genomic) targets. Using baselines that include a variety of measures, we identify where AnnSim can provide a deeper understanding of the semantics underlying the relatedness of a pair of entities or where it could lead to predicting new links or identifying potential novel patterns. Although AnnSim does not exploit knowledge or properties of a particular domain, its performance compares well with a variety of state-of-the-art domain-specific measures. Database URL: http://www.yeastgenome.org/ © The Author(s) 2015. Published by Oxford University Press.

Masked Proportional Routing

NASA Technical Reports Server (NTRS)

Wolpert, David

2004-01-01

Masked proportional routing is an improved procedure for choosing links between adjacent nodes of a network for the purpose of transporting an entity from a source node ("A") to a destination node ("B"). The entity could be, for example, a physical object to be shipped, in which case the nodes would represent waypoints and the links would represent roads or other paths between waypoints. For another example, the entity could be a message or packet of data to be transmitted from A to B, in which case the nodes could be computer-controlled switching stations and the links could be communication channels between the stations. In yet another example, an entity could represent a workpiece while links and nodes could represent, respectively, manufacturing processes and stages in the progress of the workpiece towards a finished product. More generally, the nodes could represent states of an entity and the links could represent allowed transitions of the entity. The purpose of masked proportional routing and of related prior routing procedures is to schedule transitions of entities from their initial states ("A") to their final states ("B") in such a manner as to minimize a cost or to attain some other measure of optimality or efficiency. Masked proportional routing follows a distributed (in the sense of decentralized) approach to probabilistically or deterministically choosing the links. It was developed to satisfy a need for a routing procedure that 1. Does not always choose the same link(s), even for two instances characterized by identical estimated values of associated cost functions; 2. Enables a graceful transition from one set of links to another set of links as the circumstances of operation of the network change over time; 3. Is preferably amenable to separate optimization of different portions of the network; 4. Is preferably usable in a network in which some of the routing decisions are made by one or more other procedure(s); 5. Preferably does not cause an entity to visit the same node twice; and 6. Preferably can be modified so that separate entities moving from A to B do not arrive out of order.

Non compaction cardiomyopathy: Review of a controversial entity.

PubMed

Lorca, Rebeca; Rozado, José; Martín, María

2018-05-11

Non-compaction cardiomyopathy is a heterogeneous and complex entity concerning which there are still many doubts to be resolved. While the American Heart Association includes it among genetic cardiomyopathies, the European Society of Cardiology treats it as an unclassified cardiomyopathy. It may present in a sporadic or familial form, isolated or associated with other heart diseases, affecting only the left ventricle or both and can sometimes appear as a mixed phenotype in patients with other cardiomyopathies. Different forms of clinical presentation are also associated with its different morphological manifestations, and even non-compaction of the left ventricle may be triggered by other physiological or pathological processes. The purpose of this review is an update of this entity and its controversies. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

[Kikuchi-Fujimoto's disease and connective tissue disease: a report of three cases].

PubMed

Frikha, F; Marzouk, S; Frigui, M; Jallouli, M; Kechaou, M; Kaddour, N; Boudawara, T; Jlidi, R; Bahloul, Z

2008-02-01

Kikuchi-Fujimoto's disease or histiocytic necrotizing lymphadenitis, clinicopathological entity of unknown aetiology, is a rare and benign cause of cervical lymphadenopathies. It can be associated with various auto-immune diseases especially systemic lupus erythematous (SLE) or with some infectious agents. This report describes a survey of three patients who developed Kikuchi's lymphadenitis occurring concomitantly with connective tissue disease: LES in two cases and non determined connective tissue disease in the other case. Comparing the clinical, histopathological and evolutionary findings to the literature allows to identify the main features of this self-limiting disorder: occurrence in young women; clinical presentation with cervical lymphadenopathy in a context of fever and asthenia. The definite diagnosis is usually made through histopathological examination of a lymph node biopsy. Disease course is generally favourable with spontaneous resolution within few weeks. It may be improved with corticosteroid treatment in patients with systemic involvement. Prognosis is related to the associated disease. Kikuchi-Fujimoto's disease is a rare and benign cause of cervical lymphadenopathy that could resemble lymphoma, tuberculosis and may be associated with a characterized systemic disease.

Coincidence of tuberous sclerosis and systemic lupus erythematosus-a case report.

PubMed

Carrasco Cubero, Carmen; Bejarano Moguel, Verónica; Fernández Gil, M Ángeles; Álvarez Vega, Jose Luis

2016-01-01

Tuberous sclerosis, also called Bourneville Pringle disease, is a phakomatosis with potential dermal, nerve, kidney and lung damage. It is characterized by the development of benign proliferations in many organs, which result in different clinical manifestations. It is associated with the mutation of two genes: TSC1 (hamartin) and TSC2 (tuberin), with the change in the functionality of the complex target of rapamycin (mTOR). MTOR activation signal has been recently described in systemic lupus erythematosus (SLE) and its inhibition could be beneficial in patients with lupus nephritis. We report the case of a patient who began with clinical manifestations of tuberous sclerosis complex (TSC) 30 years after the onset of SLE with severe renal disease (tipe IV nephritis) who improved after treatment with iv pulses of cyclophosphamide. We found only two similar cases in the literature, and hence considered the coexistence of these two entities of great interest. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

[Clinical Phenomenology of Autoimmune Encephalitis].

PubMed

Holle, J F; Jessen, F; Kuhn, J

2016-05-01

Antibody-associated disorders of the central nervous system constitute a heterogeneous group of disorders that can be roughly divided into two categories: Classic paraneoplastic syndromes associated with so-called well-characterized antibodies (paraneoplastic neurological disorders, PND) and autoimmune disorders with antibodies to membrane-bound or synaptic antigens (autoimmune encephalitis, AE). The discovery of autoimmune encephalitis has led to a paradigm shift in diagnosis and therapy as well as a reclassification of some neuropsychiatric syndromes that were previously classified as idiopathic or simply covered with descriptive terms.In this review article, especially clinical aspects of autoimmune encephalitis will be discussed, as there has been a rapid increase in knowledge in this regard within the past decade; increasingly overlap syndromes and associations with other disease entities have been detected. In addition to general aspects, characteristics of anti-NMDAR-, anti-LGI1-, anti-GABAA and GABABR, anti-AMPAR-, anti-CASPR2-, anti-mGluR, anti-GlycinR-, anti-GAD, anti- DPPX- and anti-D2 R encephalitis and the anti-IgLON5 encephalopathy will be presented. © Georg Thieme Verlag KG Stuttgart · New York.

[Drug rash with eosinophilia and systemic symptoms syndrome induced by carbamazepine: Case report].

PubMed

Marín, Jorge Alonso; Ortega, Mayra Alexandra; Sánchez, Isaura Pilar; Pacheco, José Armando

2017-06-01

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity reaction associated with a variety of drugs, mainly anticonvulsants, which is characterized by systemic symptoms and erythematous lesions, common to other toxicodermas. It is an uncommon clinical entity that requires a high suspicion by clinical staff given its varied initial presentation, and the fact that symptoms can overlap with those of other adverse cutaneous reactions to drugs. Without early diagnosis and appropriate treatment, mortality increases.We report the case of a 22-year-old patient with impaired neurodevelopment who received treatment with carbamazepine. Two months later he presented with general symptoms and skin erythematous lesions that began on his trunk. The patient received outpatient care with antihistamines and antipyretics without an appropriate response. His case progressed with increased skin lesions and systemic symptoms that met the diagnostic criteria for DRESS syndrome. He was hospitalized and received medical treatment according to recommended guidelines. The patient's condition improved as his symptoms and associated complications resolved. He was discharged with gradual clearing of the steroid therapy.

Combined pulmonary fibrosis and emphysema: The many aspects of a cohabitation contract.

PubMed

Papaioannou, Andriana I; Kostikas, Konstantinos; Manali, Effrosyni D; Papadaki, Georgia; Roussou, Aneza; Kolilekas, Likurgos; Borie, Raphaël; Bouros, Demosthenis; Papiris, Spyridon A

2016-08-01

Combined pulmonary fibrosis and emphysema (CPFE) is a clinical entity characterized by the coexistence of upper lobe emphysema and lower lobe fibrosis. Patients with this condition experience severe dyspnea and impaired gas exchange with preserved lung volumes. The diagnosis of the CPFE syndrome is based on HRCT imaging, showing the coexistence of emphysema and pulmonary fibrosis both in varying extent and locations within the lung parenchyma. Individual genetic background seem to predispose to the development of the disease. The risk of the development of pulmonary hypertension in patients with CPFE is high and related to poor prognosis. CPFE patients also present a high risk of lung cancer. Mortality is significant in patients with CPFE and median survival is reported between 2.1 and 8.5 years. Currently, no specific recommendations are available regarding the management of patients with CPFE. In this review we provide information on the existing knowledge on CPFE regarding the pathophysiology, clinical manifestations, imaging, complications, possible therapeutic interventions and prognosis of the disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic linkage of familial granulomatous inflammatory arthritis, skin rash, and uveitis to chromosome 16

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

Tromp, G.; Kuivaniemi, H.; Ala-Kokko, L.

1996-11-01

Blau syndrome (MIM 186580), first described in a large, three-generation kindred, is an autosomal, dominantly inherited disease characterized by multiorgan, tissue-specific inflammation. Its clinical phenotype includes granulomatous arthritis, skin rash, and uveitis and probably represents a subtype of a group of clinical entities referred to as {open_quotes}familial granulomatosis.{close_quotes} It is the sole human model with recognizably Mendelian inheritance for a variety of multisystem inflammatory diseases affecting a significant percentage of the population. A genomewide search for the Blau susceptibility locus was undertaken after karyotypic analysis revealed no abnormalities. Sixty-two of the 74-member pedigree were genotyped with dinucleotide-repeat markers. Linkage analysismore » was performed under dominant model of inheritance with reduced penetrance. The marker D16S298 gave a maximum LOD score of 3.75 at {theta} = .04, with two-point analysis. LOD scores for flanking markers were consistent and placed the Blau susceptibility locus within the 16p12-q21 interval. 46 refs., 3 figs., 3 tabs.« less

Drug-induced lupus erythematosus.

PubMed

Marzano, A V; Tavecchio, S; Menicanti, C; Crosti, C

2014-06-01

Drug-induced lupus erythematosus (DI-LE) is defined as an entity characterized by clinical manifestations and immunopathological serum findings similar to those of idiopathic lupus but which is temporally related to drug exposure and resolves after withdrawal of the implicated drug. Similarly to idiopathic lupus, DI-LE can be divided into systemic LE, subacute cutaneous LE (SCLE), chronic cutaneous LE (CCLE) and cutaneous LE tumidus. DI-SCLE is the most frequent variant of drug-induced cutaneous LE and presents mainly with annular-polycyclic lesions; the clinical picture is often widespread, with involvement of the lower legs that are usually spared in idiopathic SCLE. ANA and anti-Ro/SSA antibodies are typically present, whereas antihistone antibodies are uncommonly found. We have recently addressed the question whether DI-SCLE differs significantly from its idiopathic counterpart by virtue of clinical features and, based on our findings, we have suggested that the frequent occurrence of malar rash and bullous, erythema multiforme-like and vasculitic manifestations can be regarded as the hallmark of DI-SCLE. In contrast, the histology is not a useful diagnostic criterion for DI-SCLE, considering that the typical pattern of lichenoid interface dermatitis is seen only in the early stage of disease and tissue eosinophilia does not represent a differentiating histopathological feature. DI-CCLE and DI-LE tumidus, albeit possibly misdiagnosed, are rarely observed and are characterized by classic discoid lesions and erythematous-oedematous plaques on sun exposed areas, respectively. Management of DI-LE is based on the discontinuation of the offending drug; topical and/or systemic corticosteroids and other immunomodulating/immunosuppressive agents should be reserved for resistant cases.

[Amyloidosis maculosa: diagnosis in primary care].

PubMed

Toribio da Pena, S R; Olmos, O; Borbujo, J; Bastos Amigo, J A; Jiménez-Sánchez, F; Alonso, A

1990-01-01

Amyloidosis maculosa is a clinical entity with low incidence factor in our medium, which basically affects middle-aged women. The lesion is characterised by the presence of poorly defined, hyperpigmented, brownish or greyish maculae that converge and focus basically on the upper back and shoulders, usually accompanied by pruritus. Three patients were erroneously catalogued for years as having pityriasis versicolor. Two of these patients presented a typical clinical amyloidosis maculosa, and the third presented a less common manifestation of the disease: a single, well-defined lesion in the subscapular region. We believe that the approach to the diagnosis of pityriasis versicolor with hyperpigmented lesions that do not respond to specific treatment should be revised. Although amyloidosis maculosa has a low incidence in our medium, it is an entity which should not be discarded in these cases.

Primary rhabdomyosarcoma of the pineal gland.

PubMed

Lau, Steven K M; Cykowski, Matthew D; Desai, Shiv; Cao, Ying; Fuller, Gregory N; Bruner, Janet; Okazaki, Ian

2015-05-01

To report a case of primary rhabdomyosarcoma (RMS) of the pineal gland in an adult, as well as review the literature on this rare entity. The case is compared with previous reports of similar entities, with emphasis on this patient's characteristics and clinical presentation, investigations, and management. Diagnosis of primary RMS of the pineal gland was based on the presence of strap cells and multinucleated myotube-like structures, as well as tumor cell expression of skeletal muscle markers consistent with myogenic differentiation. Multimodality treatment was initiated based on pediatric protocols. Unfortunately, the disease progressed on treatment, and the patient survived only 5 months from diagnosis. Pineal RMS is a rare disease with poor prognosis. Optimal management is unknown but likely to involve aggressive multimodality therapy. Copyright© by the American Society for Clinical Pathology.

Complex posttraumatic stress disorder: The need to consolidate a distinct clinical syndrome or to reevaluate features of psychiatric disorders following interpersonal trauma?

PubMed

Giourou, Evangelia; Skokou, Maria; Andrew, Stuart P; Alexopoulou, Konstantina; Gourzis, Philippos; Jelastopulu, Eleni

2018-03-22

Complex posttraumatic stress disorder (Complex PTSD) has been recently proposed as a distinct clinical entity in the WHO International Classification of Diseases, 11 th version, due to be published, two decades after its first initiation. It is described as an enhanced version of the current definition of PTSD, with clinical features of PTSD plus three additional clusters of symptoms namely emotional dysregulation, negative self-cognitions and interpersonal hardship, thus resembling the clinical features commonly encountered in borderline personality disorder (BPD). Complex PTSD is related to complex trauma which is defined by its threatening and entrapping context, generally interpersonal in nature. In this manuscript, we review the current findings related to traumatic events predisposing the above-mentioned disorders as well as the biological correlates surrounding them, along with their clinical features. Furthermore, we suggest that besides the present distinct clinical diagnoses (PTSD; Complex PTSD; BPD), there is a cluster of these comorbid disorders, that follow a continuum of trauma and biological severity on a spectrum of common or similar clinical features and should be treated as such. More studies are needed to confirm or reject this hypothesis, particularly in clinical terms and how they correlate to clinical entities' biological background, endorsing a shift from the phenomenologically only classification of psychiatric disorders towards a more biologically validated classification.

Clinical and Demographic Characteristics Related to Onset

PubMed Central

Norris, Scott A; Jinnah, H A; Espay, Alberto J.; Klein, Christine; Brüggemann, Norbert; Barbano, Richard L.; Malaty, Irene; Rodriguez, Ramon L.; Vidailhet, Marie; Roze, Emmanuel; Reich, Stephen G.; Berman, Brian D.; LeDoux, Mark S.; Richardson, Sarah Pirio; Agarwal, Pinky; Mari, Zoltan; Ondo, William; Shih, Ludy C; Fox, Susan; Berardelli, Alfredo; Testa, Claudia M; Chang, Florence CF; Troung, Daniel; Nahab, Fatta; Xie, Tao; Hallett, Mark; Rosen, Ami R; Wright, Laura J; Perlmutter, JS

2016-01-01

Background Clinical characteristics of isolated, idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. Objectives To characterize clinical characteristics and demographics of isolated, idiopathic cervical dystonia in the largest standardized, multicenter cohort. Methods The Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe and Australia recruited 1477 participants with focal (60.7%) or segmental (39.3%) cervical dystonia on examination. Clinical and demographic characteristics were evaluated in terms of the body region of dystonia onset and spread. Results Site of dystonia onset was: a) focal neck only (78.5%), b) focal onset elsewhere with later segmental spread to neck (13.3%), and c) segmental onset with initial neck involvement (8.2%).Frequency of spread from focal cervical to segmental dystonia (22.8%) was consistent with prior reports, but frequency of segmental onset with initial neck involvement was substantially higher than 3% previously reported. Cervical dystonia with focal neck onset, more than other subtypes, is associated with spread and tremor of any type. Sensory tricks were less frequent in cervical dystonia with segmental components, and segmental cervical onset occurred at an older age. Conclusions Subgroups had modest but significant differences in the clinical characteristics that may represent different clinical entities or pathophysiologic subtypes. These findings are critical for design and implementation of studies to describe, treat, or modify disease progression in idiopathic isolated cervical dystonia. PMID:27753188

45 CFR 60.12 - Reporting adverse actions taken against clinical privileges.

Code of Federal Regulations, 2014 CFR

2014-10-01

... privileges of a physician or dentist for a period longer than 30 days, (ii) Acceptance of the surrender of clinical privileges or any restriction of such privileges by a physician or dentist: (A) While the physician or dentist is under investigation by the health care entity relating to possible incompetence or...

45 CFR 60.12 - Reporting adverse actions taken against clinical privileges.

Code of Federal Regulations, 2013 CFR

2013-10-01

... privileges of a physician or dentist for a period longer than 30 days, (ii) Acceptance of the surrender of clinical privileges or any restriction of such privileges by a physician or dentist: (A) While the physician or dentist is under investigation by the health care entity relating to possible incompetence or...

Is undifferentiated spondyloarthritis a discrete entity? A debate.

PubMed

Deodhar, Atul; Miossec, Pierre; Baraliakos, Xenofon

2018-01-01

The concept of undifferentiated spondyloarthritis has been introduced recently to describe a clinical setting where the classical features of spondyloarthritis (SpA) are not fully present. Whether this is a discrete entity was the basis of a debate during the 4th International Congress on Controversies in Rheumatology & Autoimmunity held in Bologna, Italy 9-11 March 2017. The pro and con aspects of the debate are presented. The implications of the debate are important ranging from diagnostic aspects to consequences for the society and the payers. Copyright © 2017 Elsevier B.V. All rights reserved.

Gastric Volvulus: A Rare Entity Case Report and Literature Review

PubMed Central

Akhtar, Aisha; Sheikh, Abdul Ahad E; Sheikh, Abu Baker; Perisetti, Abhilash

2018-01-01

Gastric volvulus is a rare entity defined as an abnormal rotation of the stomach around itself. It is a diagnosis of exclusion; the clinical index of suspicion is always low and is mostly diagnosed on imaging or on the surgery table. When it occurs, it is an emergency due to the risk of strangulation and consequent gangrene of the stomach. Mesentero-axial (MA) gastric volvuli constitute one-third of all cases. Here, we are present an interesting case of acute MA gastric volvulus diagnosed with imaging and treated subsequently. PMID:29755908

Lenticular fibroxanthomatous nodule.

PubMed

Lee, Seok J; Ling, Jun X; Aaberg, Thomas M; Grossniklaus, Hans E

2003-02-01

To describe two patients with unique lenticular nodular proliferations. Observational case reports. The clinical histories and pathologic findings of two patients with lenticular nodular proliferations were reviewed. One patient with persistent hyperplastic primary vitreous and another patient with trauma developed lenticular nodular proliferations. The nodules were vascularized collections of foamy histiocytes, multinucleated cells, lens capsule, and lens epithelium that had undergone fibrous metaplasia. The lesions were classified as lenticular fibroxanthomatous nodules. A lenticular fibroxanthomatous nodule is a unique clinicopathologic entity that should be differentiated from Soemmerring ring, Elschnig pearl, and other simulating entities such as juvenile xanthogranuloma.

Current approach in the diagnosis and management of posterior uveitis

PubMed Central

Sudharshan, S; Ganesh, Sudha K; Biswas, Jyotrimay

2010-01-01

Posterior uveitic entities are varied entities that are infective or non-infective in etiology. They can affect the adjacent structures such as the retina, vitreous, optic nerve head and retinal blood vessels. Thorough clinical evaluation gives a clue to the diagnosis while ancillary investigations and laboratory tests assist in confirming the diagnosis. Newer evolving techniques in the investigations and management have increased the diagnostic yield. In case of diagnostic dilemma, intraocular fluid evaluation for polymerase chain testing for the genome and antibody testing against the causative agent provide greater diagnostic ability. PMID:20029144

The A to Z of healthcare data breaches.

PubMed

Kobus, Theodore J

2012-01-01

There currently exists a myriad of privacy laws that impact a healthcare entity, including more than 47 notification laws that require notification when a data breach occurs, as well as the breach notification requirements of the Health Information Technology for Economic and Clinical Health Act. Given the plethora of issues a healthcare entity faces, there are certain principles that can be built into an organization's philosophy that will comply with the law and help protect it from reputational harm. © 2012 American Society for Healthcare Risk Management of the American Hospital Association.

Modeling Clinical Information Needs in the Context of a Specific Patient

PubMed Central

Price, Susan L.

2000-01-01

Investigators have tried various approaches to link clinical information directly to information sources that may contain answers to clinical questions. Developing a model of clinical information needs that may arise in the context of viewing information about a specific patient is a preliminary step to finding an efficient, useful solution to the information retrieval problem. This poster illustrates a method of modeling clinical information needs in the context of a specific patient that that is adapted from entity-relationship models used in database design.

POLG1 mutations and stroke like episodes: a distinct clinical entity rather than an atypical MELAS syndrome

PubMed Central

2013-01-01

Background POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy. Case presentation We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum. Conclusion The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations. PMID:23324391

Motor palsies of cranial nerves (excluding VII) after vaccination: reports to the US Vaccine Adverse Event Reporting System.

PubMed

Woo, Emily Jane; Winiecki, Scott K; Ou, Alan C

2014-01-01

We reviewed cranial nerve palsies, other than VII, that have been reported to the US Vaccine Adverse Event Reporting System (VAERS). We examined patterns for differences in vaccine types, seriousness, age, and clinical characteristics. We identified 68 reports of cranial nerve palsies, most commonly involving the oculomotor (III), trochlear (IV), and abducens (VI) nerves. Isolated cranial nerve palsies, as well as palsies occurring as part of a broader clinical entity, were reported. Forty reports (59%) were classified as serious, suggesting that a cranial nerve palsy may sometimes be the harbinger of a broader and more ominous clinical entity, such as a stroke or encephalomyelitis. There was no conspicuous clustering of live vs. inactivated vaccines. The patient age range spanned the spectrum from infants to the elderly. Independent data may help to clarify whether, when, and to what extent the rates of cranial nerve palsies following particular vaccines may exceed background levels.

Clinically distinct presentations of copper deficiency myeloneuropathy and cytopenias in a patient using excessive zinc-containing denture adhesive.

PubMed

Cathcart, Sahara J; Sofronescu, Alina G

2017-08-01

While copper deficiency has long been known to cause cytopenias, copper deficiency myeloneuropathy is a more recently described entity. Here, we present the case of two clinically distinct presentations of acquired copper deficiency syndromes secondary to excessive use of zinc-containing denture adhesive over five years: myeloneuropathy and severe macrocytic anemia and neutropenia. Extensive laboratory testing and histologic evaluation of the liver and bone marrow, were necessary to rule out other disease processes and establish the diagnosis of copper deficiency. The initial presentation consisted of a myelopathy involving the posterior columns. Serum and urine copper were significantly decreased, and serum zinc was elevated. On second presentation (five years later), multiple hematological abnormalities were detected. Serum copper was again decreased, while serum zinc was elevated. Zinc overload is a preventable cause of copper deficiency syndromes. This rare entity presented herein highlights the importance of patient, as well as provider, education. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

A Dimensional Bus model for integrating clinical and research data.

PubMed

Wade, Ted D; Hum, Richard C; Murphy, James R

2011-12-01

Many clinical research data integration platforms rely on the Entity-Attribute-Value model because of its flexibility, even though it presents problems in query formulation and execution time. The authors sought more balance in these traits. Borrowing concepts from Entity-Attribute-Value and from enterprise data warehousing, the authors designed an alternative called the Dimensional Bus model and used it to integrate electronic medical record, sponsored study, and biorepository data. Each type of observational collection has its own table, and the structure of these tables varies to suit the source data. The observational tables are linked to the Bus, which holds provenance information and links to various classificatory dimensions that amplify the meaning of the data or facilitate its query and exposure management. The authors implemented a Bus-based clinical research data repository with a query system that flexibly manages data access and confidentiality, facilitates catalog search, and readily formulates and compiles complex queries. The design provides a workable way to manage and query mixed schemas in a data warehouse.

Cryptogenia multifocal ulcerous stenosing enteritis: an entity on its own as a cause of abdominal pain, iron deficiency anemia and protein-losing enteropathy.

PubMed

Guisado Vasco, P; Fraile Rodríguez, G

2014-01-01

We studied a patient with edema secondary to protein losing enteropathy, and recurrent bouts of bloating and abdominal pain secondary to intestinal subocclusion episodes. After the clinical study, the patient was diagnosed of cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), that is a rare disease, probably caused by mutations in the gene PLA2G4A, and characterized by multiple short stenosis of the small bowel with superficial ulcers, which do not exceed the submucosa layer. Inflammatory bowel disease (Chron's disease), intestinal tuberculosis and intestinal ulcers secondary to non-steroidal anti-inflammatory drugs are the main differential diagnosis. To sum up, physicians should included CMUSE in the differential diagnosis of recurrent abdominal pain, iron deficiency anaemia, occult intestinal bleeding, edema and protein losing enteropathy. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Acute impairment of regional myocardial glucose uptake in the apical ballooning (takotsubo) syndrome.

PubMed

Bybee, Kevin A; Murphy, Joseph; Prasad, Abhiram; Wright, R Scott; Lerman, Amir; Rihal, Charanjit S; Chareonthaitawee, Panithaya

2006-01-01

Apical ballooning syndrome (ABS) is a poorly understood clinical entity characterized by acute, transient systolic dysfunction of the left ventricular (LV) apex in the absence of epicardial coronary artery disease and commonly associated with acute emotional stress. We report abnormal regional myocardial perfusion and glucose uptake in 4 consecutive ABS patients studied using positron emission tomography with 13N-ammonia and 18F-fluorodeoxyglucose within 72 hours of presentation with ABS. All patients were postmenopausal females, 3 of whom had a major recent life stress event. Coronary angiography revealed no or minimal obstructive epicardial coronary artery disease. All patients exhibited reduced glucose uptake in the mid-LV and apical myocardial segments, which was out of proportion to perfusion abnormalities in half of the cases. In all 4 patients, affected regions subsequently recovered regional LV systolic function within 6 weeks.

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.

Triple-negative breast cancer--current status and future directions.

PubMed

Gluz, O; Liedtke, C; Gottschalk, N; Pusztai, L; Nitz, U; Harbeck, N

2009-12-01

Triple-negative breast cancer (TNBC) is defined by a lack of expression of both estrogen and progesterone receptor as well as human epidermal growth factor receptor 2. It is characterized by distinct molecular, histological and clinical features including a particularly unfavorable prognosis despite increased sensitivity to standard cytotoxic chemotherapy regimens. TNBC is highly though not completely concordant with various definitions of basal-like breast cancer (BLBC) defined by high-throughput gene expression analyses. The lack in complete concordance may in part be explained by both BLBC and TNBC comprising entities that in themselves are heterogeneous. Numerous efforts are currently being undertaken to improve prognosis for patients with TNBC. They comprise both optimization of choice and scheduling of common cytotoxic agents (i.e. addition of platinum salts or dose intensification strategies) and introduction of novel agents (i.e. poly-ADP-ribose-polymerase-1 inhibitors, agents targeting the epidermal growth factor receptor, multityrosine kinase inhibitors or antiangiogenic agents).

[Practical update of Tsaktubo syndrome].

PubMed

Núñez-Gil, Iván J; Mejía-Rentería, Hernán D; Martínez-Losas, Pedro

2016-03-04

Takotsubo syndrome, apical ballooning or «broken heart» syndrome, is a growing diagnostic entity which clinically mimics an acute coronary syndrome. Included into the stress cardiomyopathy group of cardiopathies, this condition is characterized by the absence of potentially responsible coronary lesions, while displaying a transient abnormal ventricular motion, usually affecting various coronary territories. It is generally observed in postmenopausal women and frequently seen in the presence of a stressful situation, both physical and emotional. With a prevalence of 1.2% among patients undergoing a cardiac catheterization with a suspected diagnosis of acute coronary syndromes, Takotsubo syndrome usually has a good prognosis. However, complications can occur in the acute phase, generally heart failure, which can even lead to death. In this review we discuss the latest available information on this disease and present it in a practical and useful way for the attending physician. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Emergent processes in cognitive-emotional interactions

PubMed Central

Pessoa, Luiz

2010-01-01

Emotion and cognition have been viewed as largely separate entities in the brain. Within this framework, significant progress has been made in understanding specific aspects of behavior. Research in the past two decades, however, has started to paint a different picture of brain organization, one in which network interactions are key to understanding complex behaviors. From both basic and clinical perspectives, the characterization of cognitive-emotional interactions constitutes a fundamental issue in the investigation of the mind and brain. This review will highlight the interactive and integrative potential that exists in the brain to bring together the cognitive and emotional domains. First, anatomical evidence will be provided, focusing on structures such as hypothalamus, basal forebrain, amygdala, cingulate cortex, orbitofrontal cortex, and insula. Data on functional interactions will then be discussed, followed by a discussion of a dual competition framework, which describes cognitive-emotional interactions in terms of perceptual and cognitive competition mechanisms. PMID:21319489

Coexistence of amelanotic melanoma and liposarcoma.

PubMed

Jeong, Taek Jo; Lee, Eun Ju; Haw, Sik; Shin, Min Kyung; Haw, Choong Rim

2009-11-01

An amelanotic malignant melanoma is characterized by little or no pigment. It is frequently misdiagnosed because it is a rare entity in general, and because of its unusual clinical features. Liposarcoma is one of the most common adult soft tissue sarcomas. We encountered a case of amelanotic melanoma with a concurrent liposarcoma. A 68-year-old man presented with a single, 1.5x1.5 cm round erythematous, eroded nodule on the left heel. A biopsy specimen showed atypical, pleomorphic tumor cells with little melanin pigment. The tumor cells were positive for S-100, HMB-45 and negative for cytokeratins. These findings were consistent with amelanotic melanoma. On positron emission tomography/computed tomography (PET/CT), a hypermetabolic lesion was found in the left buttock. This lesion was excised and diagnosed as a well-differentiated liposarcoma. An association between sarcomas and other primary malignancies has been reported. However, an association between melanoma and liposarcoma is rare.

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.

Emphysematous cystitis occurred in the case treated with steroid for autoimmune hepatitis.

PubMed

Yoshino, Tateki; Ohara, Shinya; Moriyama, Hiroyuki

2013-01-01

Emphysematous cystitis is a rare clinically entity, more commonly seen in diabetic, immunocompromised patients, which was characterized by air within the bladder wall and lumen. A 83-year-old woman was introduced to our department with fever elevation and abnormal findings of computed tomography (CT). She took orally prednisolone for autoimmune hepatitis. Pelvic CT revealed diffuse air throughout the bladder wall. Urinalysis showed combined hematuria and pyuria. Escherichia coli was detected in blood culture. Abnormal findings of complete blood count and laboratory examination included an elevated WBC count (12,200/μL), C-reactive protein (11.7 mg/dL), and creatinine (1.07 mg/dL). Cystoscopy confirmed diffuse submucosal emphysema throughout. On the basis of diagnosis with emphysematous cystitis, she was treated with antibiotics based on the results of blood culture and indwelling Foley catheter. After treatment, the improvement of inflammatory findings and submucosal emphysema on cystoscopy and CT were achieved.

Current Evaluation of the Millennium Phytomedicine— Ginseng (II): Collected Chemical Entities, Modern Pharmacology, and Clinical Applications Emanated from Traditional Chinese Medicine

PubMed Central

Jia, Lee; Zhao, Yuqing; Liang, Xing-Jie

2009-01-01

This review, a sequel to part 1 in the series, collects about 107 chemical entities separated from the roots, leaves and flower buds of Panax ginseng, quinquefolius and notoginseng, and categorizes these entities into about 18 groups based on their structural similarity. The bioactivities of these chemical entities are described. The ‘Yin and Yang’ theory and the fundamentals of the ‘five elements’ applied to the traditional Chinese medicine (TCM) are concisely introduced to help readers understand how ginseng balances the dynamic equilibrium of human physiological processes from the TCM perspectives. This paper concerns the observation and experimental investigation of biological activities of ginseng used in the TCM of past and present cultures. The current biological findings of ginseng and its medical applications are narrated and critically discussed, including 1) its antihyperglycemic effect that may benefit type II diabetics; in vitro and in vivo studies demonstrated protection of ginseng on beta-cells and obese diabetic mouse models. The related clinical trial results are stated. 2) its aphrodisiac effect and cardiovascular effect that partially attribute to ginseng’s bioactivity on nitric oxide (NO); 3) its cognitive effect and neuropharmacological effect that are intensively tested in various rat models using purified ginsenosides and show a hope to treat Parkinson’s disease (PD); 4) its uses as an adjuvant or immunotherapeutic agent to enhance immune activity, appetite and life quality of cancer patients during their chemotherapy and radiation. Although the apoptotic effect of ginsenosides, especially Rh2, Rg3 and Compound K, on various tumor cells has been shown via different pathways, their clinical effectiveness remains to be tested. This paper also updates the antioxidant, anti-inflammatory, anti-apoptotic and immune-stimulatory activities of ginseng, its ingredients and commercial products, as well as common side effects of ginseng mainly due to its overdose, and its pharmacokinetics. PMID:19689273

Current evaluation of the millennium phytomedicine- ginseng (II): Collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine.

PubMed

Jia, Lee; Zhao, Yuqing; Liang, Xing-Jie

2009-01-01

This review, a sequel to part 1 in the series, collects about 107 chemical entities separated from the roots, leaves and flower buds of Panax ginseng, quinquefolius and notoginseng, and categorizes these entities into about 18 groups based on their structural similarity. The bioactivities of these chemical entities are described. The 'Yin and Yang' theory and the fundamentals of the 'five elements' applied to the traditional Chinese medicine (TCM) are concisely introduced to help readers understand how ginseng balances the dynamic equilibrium of human physiological processes from the TCM perspectives. This paper concerns the observation and experimental investigation of biological activities of ginseng used in the TCM of past and present cultures. The current biological findings of ginseng and its medical applications are narrated and critically discussed, including 1) its antihyperglycemic effect that may benefit type II diabetics; in vitro and in vivo studies demonstrated protection of ginseng on beta-cells and obese diabetic mouse models. The related clinical trial results are stated. 2) its aphrodisiac effect and cardiovascular effect that partially attribute to ginseng's bioactivity on nitric oxide (NO); 3) its cognitive effect and neuropharmacological effect that are intensively tested in various rat models using purified ginsenosides and show a hope to treat Parkinson's disease (PD); 4) its uses as an adjuvant or immunotherapeutic agent to enhance immune activity, appetite and life quality of cancer patients during their chemotherapy and radiation. Although the apoptotic effect of ginsenosides, especially Rh2, Rg3 and Compound K, on various tumor cells has been shown via different pathways, their clinical effectiveness remains to be tested. This paper also updates the antioxidant, anti-inflammatory, anti-apoptotic and immune-stimulatory activities of ginseng, its ingredients and commercial products, as well as common side effects of ginseng mainly due to its overdose, and its pharmacokinetics.

ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

PubMed Central

Hayreh, Sohan Singh

2011-01-01

The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual acuity improvement during the first 7 days differs significantly (p<0.001) among the 4 types of CRAO; among them, in eyes with initial visual acuity of counting finger or worse, visual acuity improved, remained stable or deteriorated in nonarteritic CRAO in 22%, 66% and 12% respectively; in nonarteritic CRAO with cilioretinal artery sparing in 67%, 33% and none respectively; and in transient nonarteritic CRAO in 82%, 18% and none respectively. Arteritic CRAO shows no change. Recent studies have shown that administration of local intra-arterial thrombolytic agent not only has no beneficial effect but also can be harmful. Prevalent multiple misconceptions on CRAO are discussed. Branch retinal artery occlusion Pathogeneses, clinical features and management of various types of BRAO are discussed at length. The natural history of visual acuity outcome shows a final visual acuity of 20/40 or better in 89% of permanent BRAO cases, 100% of transient BRAO and 100% of nonarteritic CLRAO alone. Cotton wools spots These are common, non-specific acute focal retinal ischemic lesions, seen in many retinopathies. Their pathogenesis and clinical features are discussed in detail. Amaurosis fugax Its pathogenesis, clinical features and management are described. PMID:21620994

Chronic lingual papulosis: new, independent entity or "mature" form of transient lingual papillitis?

PubMed

Bouquot, Jerry E; Adibi, Shawn S; Sanchez, Maga

2012-01-01

Several acute, usually pediatric variants of edematous, symptomatic fungiform lingual papillitis have been reported since the 1990s, most notably transient lingual papillitis (TLP); but no chronic forms have been mentioned. Is there a chronic counterpart, akin to the older palatal examples of inflammatory papillary hyperplasia? The objective of this study was to clinicopathologically characterize a previously unreported entity with clustered, chronic fibrous papules (nonsyndromic) of the tongue. Cases were collected from clinics in 2 dental schools. Five women and 4 men were identified with multiple, moderately firm, slightly pedunculated, normally colored masses clustered at the tip of the tongue (n = 4), covering the dorsal surface (n = 4) or on the lateral border (n = 1); 2 showed several erythematous or edematous papules (similar to TLP) admixed with fibrous papules. Patient ages ranged from 31 to 62 years (average 49) and all lesions had been present for many years. All lesions were asymptomatic except for the lateral border lesion, which presented with a burning sensation and mild tenderness (disappeared with antifungal medication). Five cases were associated with mouth breathing or a tongue-thrust habit; 4 were associated with geographic tongue or fissured tongue. Four papules were biopsied. All were composed of dense, avascular fibrous tissue with no or very few inflammatory cells; one showed focal mild neovascularity and edema. The lesion appeared to represent altered filiform papillae, more so than fungiform papillae. Chronic lingual papulosis (CLP) is an innocuous entity represented by focal or diffuse enlargement of numerous lingual papillae, primarily the filiform papillae. It appears to usually have an adult onset and most likely represents papillary reaction to very low-grade, chronic irritation or desiccation. Some cases with childhood onset, however, seem to be variations of normal anatomy. No treatment or biopsy is required, but a number of systemic disorders and syndromes must be ruled out before applying the CLP diagnosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Balancing exploration and exploitation in transferring research into practice: a comparison of five knowledge translation entity archetypes

PubMed Central

2013-01-01

Background Translating knowledge from research into clinical practice has emerged as a practice of increasing importance. This has led to the creation of new organizational entities designed to bridge knowledge between research and practice. Within the UK, the Collaborations for Leadership in Applied Health Research and Care (CLAHRC) have been introduced to ensure that emphasis is placed in ensuring research is more effectively translated and implemented in clinical practice. Knowledge translation (KT) can be accomplished in various ways and is affected by the structures, activities, and coordination practices of organizations. We draw on concepts in the innovation literature—namely exploration, exploitation, and ambidexterity—to examine these structures and activities as well as the ensuing tensions between research and implementation. Methods Using a qualitative research approach, the study was based on 106 semi-structured, in-depth interviews with the directors, theme leads and managers, key professionals involved in research and implementation in nine CLAHRCs. Data was also collected from intensive focus group workshops. Results In this article we develop five archetypes for organizing KT. The results show how the various CLAHRC entities work through partnerships to create explorative research and deliver exploitative implementation. The different archetypes highlight a range of structures that can achieve ambidextrous balance as they organize activity and coordinate practice on a continuum of exploration and exploitation. Conclusion This work suggests that KT entities aim to reach their goals through a balance between exploration and exploitation in the support of generating new research and ensuring knowledge implementation. We highlight different organizational archetypes that support various ways to maintain ambidexterity, where both exploration and exploitation are supported in an attempt to narrow the knowledge gaps. The KT entity archetypes offer insights on strategies in structuring collaboration to facilitate an effective balance of exploration and exploitation learning in the KT process. PMID:24007259

Balancing exploration and exploitation in transferring research into practice: a comparison of five knowledge translation entity archetypes.

PubMed

Oborn, Eivor; Barrett, Michael; Prince, Karl; Racko, Girts

2013-09-05

Translating knowledge from research into clinical practice has emerged as a practice of increasing importance. This has led to the creation of new organizational entities designed to bridge knowledge between research and practice. Within the UK, the Collaborations for Leadership in Applied Health Research and Care (CLAHRC) have been introduced to ensure that emphasis is placed in ensuring research is more effectively translated and implemented in clinical practice. Knowledge translation (KT) can be accomplished in various ways and is affected by the structures, activities, and coordination practices of organizations. We draw on concepts in the innovation literature--namely exploration, exploitation, and ambidexterity--to examine these structures and activities as well as the ensuing tensions between research and implementation. Using a qualitative research approach, the study was based on 106 semi-structured, in-depth interviews with the directors, theme leads and managers, key professionals involved in research and implementation in nine CLAHRCs. Data was also collected from intensive focus group workshops. In this article we develop five archetypes for organizing KT. The results show how the various CLAHRC entities work through partnerships to create explorative research and deliver exploitative implementation. The different archetypes highlight a range of structures that can achieve ambidextrous balance as they organize activity and coordinate practice on a continuum of exploration and exploitation. This work suggests that KT entities aim to reach their goals through a balance between exploration and exploitation in the support of generating new research and ensuring knowledge implementation. We highlight different organizational archetypes that support various ways to maintain ambidexterity, where both exploration and exploitation are supported in an attempt to narrow the knowledge gaps. The KT entity archetypes offer insights on strategies in structuring collaboration to facilitate an effective balance of exploration and exploitation learning in the KT process.

Information and organization in public health institutes: an ontology-based modeling of the entities in the reception-analysis-report phases.

PubMed

Pozza, Giandomenico; Borgo, Stefano; Oltramari, Alessandro; Contalbrigo, Laura; Marangon, Stefano

2016-09-08

Ontologies are widely used both in the life sciences and in the management of public and private companies. Typically, the different offices in an organization develop their own models and related ontologies to capture specific tasks and goals. Although there might be an overall coordination, the use of distinct ontologies can jeopardize the integration of data across the organization since data sharing and reusability are sensitive to modeling choices. The paper provides a study of the entities that are typically found at the reception, analysis and report phases in public institutes in the life science domain. Ontological considerations and techniques are introduced and their implementation exemplified by studying the Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), a public veterinarian institute with different geographical locations and several laboratories. Different modeling issues are discussed like the identification and characterization of the main entities in these phases; the classification of the (types of) data; the clarification of the contexts and the roles of the involved entities. The study is based on a foundational ontology and shows how it can be extended to a comprehensive and coherent framework comprising the different institute's roles, processes and data. In particular, it shows how to use notions lying at the borderline between ontology and applications, like that of knowledge object. The paper aims to help the modeler to understand the core viewpoint of the organization and to improve data transparency. The study shows that the entities at play can be analyzed within a single ontological perspective allowing us to isolate a single ontological framework for the whole organization. This facilitates the development of coherent representations of the entities and related data, and fosters the use of integrated software for data management and reasoning across the company.

Overgrowth syndromes with vascular anomalies.

PubMed

Blei, Francine

2015-04-01

Overgrowth syndromes with vascular anomalies encompass entities with a vascular anomaly as the predominant feature vs those syndromes with predominant somatic overgrowth and a vascular anomaly as a more minor component. The focus of this article is to categorize these syndromes phenotypically, including updated clinical criteria, radiologic features, evaluation, management issues, pathophysiology, and genetic information. A literature review was conducted in PubMed using key words "overgrowth syndromes and vascular anomalies" as well as specific literature reviews for each entity and supportive genetic information (e.g., somatic mosaicism). Additional searches in OMIM and Gene Reviews were conducted for each syndrome. Disease entities were categorized by predominant clinical features, known genetic information, and putative affected signaling pathway. Overgrowth syndromes with vascular anomalies are a heterogeneous group of disorders, often with variable clinical expression, due to germline or somatic mutations. Overgrowth can be focal (e.g., macrocephaly) or generalized, often asymmetrically (and/or mosaically) distributed. All germ layers may be affected, and the abnormalities may be progressive. Patients with overgrowth syndromes may be at an increased risk for malignancies. Practitioners should be attentive to patients having syndromes with overgrowth and vascular defects. These patients require proactive evaluation, referral to appropriate specialists, and in some cases, early monitoring for potential malignancies. Progress in identifying vascular anomaly-related overgrowth syndromes and their genetic etiology has been robust in the past decade and is contributing to genetically based prenatal diagnosis and new therapies targeting the putative causative genetic mutations. Copyright © 2015 Mosby, Inc. All rights reserved.

Cyclooxygenase inhibitors: From pharmacology to clinical read-outs.

PubMed

Patrignani, Paola; Patrono, Carlo

2015-04-01

Acetylsalicylic acid (aspirin) is a prototypic cyclooxygenase (COX) inhibitor. It was synthesized serendipitously from a natural compound, i.e., salicylic acid, with known analgesic activity. This chemical modification, obtained for the first time in an industrial environment in 1897, endowed aspirin with the unique capacity of acetylating and inactivating permanently COX-isozymes. Traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) were developed to mimic the pharmacological effects of aspirin, using aspirin-sensitive experimental models of pain and inflammation as the template for screening new chemical entities. Among the tNSAIDs, some were endowed with moderate COX- selectivity (e.g., diclofenac), but no studies of sufficient size and duration were performed to show any clinically relevant difference between different members of the class. Similarly, no serious attempts were made to unravel the mechanisms involved in the shared therapeutic and toxic effects of tNSAIDs until the discovery of COX-2. This led to characterizing their main therapeutic effects as being COX-2-dependent and their gastrointestinal (GI) toxicity as being COX-1-dependent, and provided a rationale for developing a new class of selective COX-2 inhibitors, the coxibs. This review will discuss the clinical pharmacology of tNSAIDs and coxibs, and the clinical read-outs of COX-isozyme inhibition. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance." Copyright © 2014 Elsevier B.V. All rights reserved.

Geometry and mechanics of two-dimensional defects in amorphous materials

PubMed Central

Moshe, Michael; Levin, Ido; Aharoni, Hillel; Kupferman, Raz; Sharon, Eran

2015-01-01

We study the geometry of defects in amorphous materials and their elastic interactions. Defects are defined and characterized by deviations of the material’s intrinsic metric from a Euclidian metric. This characterization makes possible the identification of localized defects in amorphous materials, the formulation of a corresponding elastic problem, and its solution in various cases of physical interest. We present a multipole expansion that covers a large family of localized 2D defects. The dipole term, which represents a dislocation, is studied analytically and experimentally. Quadrupoles and higher multipoles correspond to fundamental strain-carrying entities. The interactions between those entities, as well as their interaction with external stress fields, are fundamental to the inelastic behavior of solids. We develop analytical tools to study those interactions. The model, methods, and results presented in this work are all relevant to the study of systems that involve a distribution of localized sources of strain. Examples are plasticity in amorphous materials and mechanical interactions between cells on a flexible substrate. PMID:26261331

Person- and place-selective neural substrates for entity-specific semantic access.

PubMed

Fairhall, Scott L; Anzellotti, Stefano; Ubaldi, Silvia; Caramazza, Alfonso

2014-07-01

Object-category has a pronounced effect on the representation of objects in higher level visual cortex. However, the influence of category on semantic/conceptual processes is less well characterized. In the present study, we conduct 2 fMRI experiments to investigate the semantic processing of information specific to individual people and places (entities). First, during picture presentation, we determined which brain regions show category-selective increases during access to entity-specific semantic information (i.e., nationality) in comparison to general-category discrimination (person vs. place). In the second experiment, we presented either words or pictures to assess the independence of entity-specific category-selective semantic representations from the processes used to access those representations. Convergent results from these 2 experiments show that brain regions exhibiting a category-selective increase during entity-specific semantic access are the same as those that show a supramodal (word/picture) category-selective response during the same task. These responses were different from classical "perceptual" category-selective responses and were evident in the medial precuneus for people and in the retrosplenial complex as well as anterior/superior sections of the transverse occipital sulcus and parahippocampal gyrus for places. These results reveal the pervasive influence of object-category in cortical organization, which extends to aspects of semantic knowledge arbitrarily related to physical/perceptual properties. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

CLOVES syndrome: review of a PIK3CA-related overgrowth spectrum (PROS).

PubMed

Martinez-Lopez, A; Blasco-Morente, G; Perez-Lopez, I; Herrera-Garcia, J D; Luque-Valenzuela, M; Sanchez-Cano, D; Lopez-Gutierrez, J C; Ruiz-Villaverde, R; Tercedor-Sanchez, J

2017-01-01

Overgrowth syndromes are characterized by global or localized disproportionate growth associated with other anomalies, including vascular malformations and neurological and/or visceral disorders. CLOVES (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal naevi, Scoliosis/Skeletal and spinal anomalies) is an overgrowth syndrome caused by mosaic activating mutation in gene PIK3CA, which gives rise to abnormal PI3K-AKT-mTOR pathway activation. These mutations are responsible for the clinical manifestations of the syndrome, which include low- and high-flow vascular malformations, thoracic lipomatous hyperplasia, asymmetric growth, and visceral and neurological disorders. These common anomalies are illustrated with figures from two personal cases. Identification of the clinical and genetic characteristics of CLOVES syndrome is crucial for the differential diagnosis with other overgrowth syndromes, such as Proteus or Klippel-Trenaunay (K-T) syndromes, and for the therapeutic management of the different anomalies. In this context, a new entity comprising different syndromes with phenotypic mutations in PIK3CA has been proposed, designated PIK3CA-related overgrowth spectrum (PROS), with the aim of facilitating clinical management and establishing appropriate genetic study criteria. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Primary and persistent negative symptoms: Concepts, assessments and neurobiological bases.

PubMed

Mucci, Armida; Merlotti, Eleonora; Üçok, Alp; Aleman, André; Galderisi, Silvana

2017-08-01

Primary and persistent negative symptoms (PPNS) represent an unmet need in the care of people with schizophrenia. They have an unfavourable impact on real-life functioning and do not respond to available treatments. Underlying etiopathogenetic mechanisms of PPNS are still unknown. The presence of primary and enduring negative symptoms characterizes deficit schizophrenia (DS), proposed as a separate disease entity with respect to non-deficit schizophrenia (NDS). More recently, to reduce the heterogeneity of negative symptoms by using criteria easily applicable in the context of clinical trials, the concept of persistent negative symptoms (PNS) was developed. Both PNS and DS constructs include enduring negative symptoms (at least 6months for PNS and 12months for DS) that do not respond to available treatments. PNS exclude secondary negative symptoms based on a cross-sectional evaluation of severity thresholds on commonly used rating scales for positive symptoms, depression and extrapyramidal side effects; the DS diagnosis, instead, excludes all potential sources of secondary negative symptoms based on a clinical longitudinal assessment. In this paper we review the evolution of concepts and assessment modalities relevant to PPNS, data on prevalence of DS and PNS, as well as studies on clinical, neuropsychological, brain imaging electrophysiological and psychosocial functioning aspects of DS and PNS. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical and laboratory features of children with community-acquired pneumonia are associated with distinct radiographic presentations.

PubMed

Falup-Pecurariu, Oana G; Diez-Domingo, Javier; Esposito, Susanna; Finn, Adam; Rodrigues, Fernanda; Spoulou, Vana; Syrogiannopoulos, George A; Usonis, Vytautas; Greenberg, David

2018-07-01

Chest radiographs from children with community-acquired pneumonia (CAP) were categorized into three distinct presentations and each presentation was correlated to clinical and laboratory findings. Children < 59 months with CAP presenting to pediatric emergency rooms during two years were enrolled prospectively in eight centers across Europe. Clinical and laboratory data were documented and radiographs obtained from patients. Of the 1107 enrolled patients, radiographs were characterized as 74.9% alveolar CAP, 8.9% non-alveolar CAP, and 16.3% clinical CAP. Alveolar CAP patients had significantly higher rates of fever (90.7%), vomiting (27.6%), and abdominal pain (18.6%), while non-alveolar CAP patients presented more with cough (96.9%). A model using independent parameters that characterize alveolar, non-alveolar, and clinical CAP demonstrated that alveolar CAP patients were significantly older (OR = 1.02) and had significantly lower oxygen saturation than non-alveolar CAP patients (OR = 0.54). Alveolar CAP patients had significantly higher mean WBC (17,760 ± 8539.68 cells/mm 3 ) and ANC (11.5 ± 7.5 cells/mm 3 ) than patients categorized as non-alveolar CAP (WBC 15,160 ± 5996 cells/mm 3 , ANC 9.2 ± 5.1 cells/mm 3 ) and clinical CAP (WBC 13,180 ± 5892, ANC 7.3 ± 4.7). Alveolar CAP, non-alveolar CAP, and clinical CAP are distinct entities differing not only by chest radiographic appearance but also in clinical and laboratory characteristics. Alveolar CAP has unique characteristics, which suggest association with bacterial etiology. Trial number 3075 (Soroka Hospital, Israel) What is Known: • Community-acquired pneumonia in children is diagnosed based on clinical and radiological definitions. • Radiological criteria were standardized by WHO-SICR and have been utilized in vaccine studies. What is New: • Correlation between the WHO-SICR radiological definitions and clinical and laboratory parameters has not been studied. • Using the WHO-SICR radiological definitions for alveolar community-acquired pneumonia (CAP) and non-alveolar CAP and the study definition for clinical CAP, it was found that the groups are distinct, differing clinically and in laboratory parameters.

Breast lesions of uncertain malignant nature and limited metastatic potential: Proposals to improve their recognition and clinical management

PubMed Central

Rakha, Emad A.; Badve, Sunil; Eusebi, Vincenzo; Reis-Filho, Jorge S.; Fox, Stephen B.; Dabbs, David J.; Decker, Thomas; Hodi, Zsolt; Ichihara, Shu; Lee, Andrew HS.; Palacios, José; Richardson, Andrea L.; Vincent-Salomon, Anne; Schmitt, Fernando C.; Tan, Puay-Hoon; Tse, Gary M.; Ellis, Ian O.

2016-01-01

Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are traditionally classified into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey-zone between benign and malignant as their behaviour cannot be predicted reliably. Defined pathological categorisation of such lesions is challenging and for some entities is recognised to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over-treatment or under-treatment. The rarity of these lesions makes acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification, behaviour and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions remain of uncertain malignant nature such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of 1) breast lesions of uncertain malignant nature and 2) breast lesions of limited metastatic potential, are proposed with details of which histological entities could be included in each category, and their management implications are discussed. PMID:26348644

A review of sub acute subdural hematoma (SASDH) with our institutional experience and its management by double barrel technique (DbT): A novel technique.

PubMed

Tripathy, Soubhagya R; Swarnakar, Pankaj K; Mishra, Sanjib; Mishra, Sudhanshu S; Dhir, Manmath K; Behera, Sanjay K; Nath, Pratap C; Jena, Somnath P; Mohanta, Itibrata; Das, Deepak; Satapathy, Mani C; Rout, Sitansu K; Behera, Bikash R; Parida, Deepak K; Rath, Tanushree S

2016-01-01

Subacute subdural hematoma (SASDH) is an entity which is yet to capture the popular imagination among the neurosurgeons. Its management is often equated clinically to that of the chronic subdural hematoma (CSDH). However, their neurological deterioration is usually rapid, which seems to align them with acute subdural hematoma (ASDH). We proceed for their epidemiological evaluation. The advantages of a novel "double barrel technique (DbT)" over the conventional burrhole drainage are also presented. This retrospective study was conducted on all the patients having clinical and radiological evidence of SASDH, admitted to a tertiary care referral institute, during the period August 2013 to December 2015. Postoperatively, patients were followed-up for 3-24 months. 46.87% of the patients belonged to the 35-54 year age group with a male predominance (3.6:1); 68.7% had a history of alcohol abuse, whereas aspirin users were 25%. 87.5% cases were unilateral, 18.75% were hemispheric, and 46.87% were present on the left side. Altered consciousness (100%) followed by headache (37.5%) were the most common presenting clinical features. SASDH is an uncommon neurosurgical entity (0.89% of traumatic brain injury cases in our study) and mimics both CSDH as well as ASDH. The true incidence of SASDH may have been underestimated due to its clinical imitation with CSDH. This study in a South Asian nation also provides the epidemiological data of this rare neurosurgical entity. Outcome of surgery is good; our retrospective study confirms that "DbT" is an adequate and safe treatment. However, a better designed, randomized control trial will be needed to reinforce our findings.

Prurigo, pruritic folliculitis, and atopic eruption of pregnancy: Facts and controversies.

PubMed

Roth, Maria Magdalena; Cristodor, Patricia; Kroumpouzos, George

2016-01-01

Prurigo (PP) and pruritic folliculitis of pregnancy (PFP) are poorly characterized entities. Traditionally classified under specific dermatoses of pregnancy, they were reclassified under a new umbrella entity, atopic eruption of pregnancy (AEP), which also includes atopic dermatitis (AD) that can worsen or present for the first time in pregnancy. Still, several aspects of AEP have not been adequately elucidated. It needs to be clarified whether it is the intrinsic ("nonallergic" or "atopiform dermatitis") or extrinsic (immunoglobulin E-associated) AD that is affected by pregnancy. Future studies need to examine the postpartum prognosis of AD that develops for the first time during gestation. A revision of diagnostic criteria of AEP will allow a more accurate estimate of its prevalence, as well as clarification of the relationship between AD and specific dermatoses, such as PP and PFP. In this context, this review discusses the history, epidemiologic data, clinicopathologic features, and management of these entities. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of toceranib, piroxicam and thalidomide with or without hypofractionated radiation therapy on clinical outcome in dogs with inflammatory mammary carcinoma.

PubMed

Rossi, F; Sabattini, S; Vascellari, M; Marconato, L

2018-05-27

In dogs, inflammatory mammary carcinoma is a clinicopathological entity characterized by rapid progression and aggressive behavior from onset of disease. Reported median survival time is short, with no effective treatment options. The aims of this prospective, noncontrolled clinical trial were to investigate outcome variables and safety profile of toceranib, thalidomide and piroxicam with or without hypofractionated radiation therapy in dogs with measurable histologically confirmed inflammatory mammary carcinoma that underwent a complete staging. Eighteen dogs were enrolled: 14 received medical treatment, and 4 were treated with hypofractionated radiation therapy and medical therapy. Overall, median time to progression was 34 days and median survival time was 109 days. In dogs treated with medical therapy, overall response rate was 21%, and clinical benefit rate (CBR) was 64%; median time to progression was 28 days and median survival time was 59 days. In dogs receiving medical therapy and undergoing radiation therapy, overall response rate and clinical benefit rate were 100%, with significantly longer time to progression (156 days) and survival time (180 days). Overall, treatment was well tolerated, with mild gastrointestinal and dermatological adverse events. Although the optimal treatment to this disease remains uncertain, the current approach consisting of systemic anti-angiogenic drugs with or without hypofractionated radiation therapy, provided clinical benefit in a significant proportion of dogs and should, therefore, be further explored. © 2018 John Wiley & Sons Ltd.

An ontologically founded architecture for information systems in clinical and epidemiological research.

PubMed

Uciteli, Alexandr; Groß, Silvia; Kireyev, Sergej; Herre, Heinrich

2011-08-09

This paper presents an ontologically founded basic architecture for information systems, which are intended to capture, represent, and maintain metadata for various domains of clinical and epidemiological research. Clinical trials exhibit an important basis for clinical research, and the accurate specification of metadata and their documentation and application in clinical and epidemiological study projects represents a significant expense in the project preparation and has a relevant impact on the value and quality of these studies.An ontological foundation of an information system provides a semantic framework for the precise specification of those entities which are presented in this system. This semantic framework should be grounded, according to our approach, on a suitable top-level ontology. Such an ontological foundation leads to a deeper understanding of the entities of the domain under consideration, and provides a common unifying semantic basis, which supports the integration of data and the interoperability between different information systems.The intended information systems will be applied to the field of clinical and epidemiological research and will provide, depending on the application context, a variety of functionalities. In the present paper, we focus on a basic architecture which might be common to all such information systems. The research, set forth in this paper, is included in a broader framework of clinical research and continues the work of the IMISE on these topics.

Genetics Home Reference: L1 syndrome

MedlinePlus

... X-linked hydrocephalus: evidence for closely related clinical entities of unknown molecular bases. Acta Neuropathol. 2013 Sep; ... F. Three cases with L1 syndrome and two novel mutations in the L1CAM gene. Eur J Pediatr. ...

Hyperkinetic Impulse Disorder in Children's Behavior Problems

ERIC Educational Resources Information Center

Laufer, Maurice W.; Denhoff, Eric; Solomons, Gerald

2011-01-01

A very common cause of children's behavior disorder disturbance is an entity described as the hyperkinetic impulse disorder. This is characterized by hyperactivity, short attention span and poor powers of concentration, irritability, impulsiveness, variability, and poor schoolwork. The existence of this complexity may lead to many psychological…

All That Glitters Yellow Is Not Gold: Presentation and Pathophysiology of Bile Cast Nephropathy.

PubMed

Pitlick, Mitchell; Rastogi, Prerna

2017-10-01

Acute kidney injury (AKI) often manifests in patients with liver disease because of a prerenal cause and presents as acute tubular necrosis or hepatorenal syndrome. Distinguishing between these entities is important for prognosis and treatment. Some patients may develop AKI related to their underlying liver disease: for example, membranoproliferative glomerulonephritis or IgA nephropathy. Bile cast nephropathy is an often ignored differential diagnosis of AKI in the setting of obstructive jaundice. It is characterized by the presence of bile casts in renal tubules, which can possibly cause tubular injury through obstructive and direct toxic effects. Thus, AKI in patients with liver disease may have a structural component in addition to a functional one. In this study, we describe 2 patients with severe hyperbilirubinemia who developed AKI and underwent a kidney biopsy that revealed bile casts in tubular lumens, consistent with bile cast nephropathy. One patient was treated aggressively for alcoholic hepatitis and required hemodialysis for AKI. The second patient was treated conservatively for drug-induced liver injury and did not require dialysis. Both patients saw a reduction in their bilirubin and creatinine toward baseline. Bile cast nephropathy is an important pathological entity that may account for the renal dysfunction in some patients with liver disease. It requires kidney biopsy for diagnosis and may often be overlooked given the scarcity of kidney biopsy in this particular clinical setting. The etiology is multifactorial, and it is often difficult to predict without the aid of a renal biopsy.

HGNET-BCOR Tumors of the Cerebellum: Clinicopathologic and Molecular Characterization of 3 Cases.

PubMed

Appay, Romain; Macagno, Nicolas; Padovani, Laetitia; Korshunov, Andrey; Kool, Marcel; André, Nicolas; Scavarda, Didier; Pietsch, Torsten; Figarella-Branger, Dominique

2017-09-01

The central nervous system (CNS) high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR) is a recently described molecular entity. We report 3 new CNS HGNET-BCOR cases sharing common clinical presentation and pathologic features. The 3 cases concerned children aged 3 to 7 years who presented with a voluminous mass of the cerebellum. Pathologic features included proliferation of uniform spindle to ovoid cells with fine chromatin associated with a rich arborizing capillary network. Methylation profiling classified these cases as CNS HGNET-BCOR tumors. Polymerase chain reaction analysis confirmed the presence of internal tandem duplications in the C-terminus of BCOR (BCOR-ITD), a characteristic of these tumors, in all 3 cases. Immunohistochemistry showed a strong nuclear BCOR expression. In 2 cases, local recurrence occurred within 6 months. The third case, a patient who received a craniospinal irradiation after total surgical removal followed by a metronomics maintenance with irinotecan, temozolomide, and itraconazole, is still free of disease 14 months after diagnosis. In summary, CNS HGNET-BCOR represents a rare tumor occurring in young patients with dismal prognosis. BCOR nuclear immunoreactivity is highly suggestive of a BCOR-ITD. Whether CNS HGNET-BCOR should be classified among the category of "embryonal tumors" or within the category of "mesenchymal, nonmeningothelial tumors" remains to be clarified. Because CNS HGNET-BCOR share pathologic features and characteristic BCOR-ITD with clear cell sarcoma of the kidney, these tumors may represent local variants of the same entity.

Posterior reversible encephalopathy syndrome in IgA vasculitis: Neuroimaging of a 14-year-old child.

PubMed

Arslan, Harun; Yavuz, Alpaslan; Arslan, Ayşe; Aycan, Abdurrahman

IgA vasculitis (IgAV) is a leukocytoclastic vasculitis and characterized by involvement of small vessels in skin, gastrointestinal system, joints, kidneys, and less frequently other organs. It is the commonest vasculitis in childhood and etiology is not completely known. Neurological manifestations of IgAV are very rare and usually seen in patients with severe hypertension or as an uncommon feature such as peripheral neuropathy. Posterior reversible encephalopathy syndrome (PRES) is a clinic-radiologic entity characterized with temporary vasogenic edema developing typically in posterior circulation of the brain and has been reported as a rare manifestation of IgAV. In this paper, a PRES case of 14-year-old male with IgAV is reported and etiopathogenesis was discussed with literature. Diagnosis was made by magnetic resonance imaging because of the existence of neurological symptoms (headache and visual loss) during the course of disease. His radiological findings have resolved with therapy. Although neurological involvement is a rare manifestation in IgAV, we recommend magnetic resonance imaging in such patients for diagnosis and evaluation of complications. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

Isolation, Analysis and Antimicrobial Activity of the Acidic Fractions of Mastic, Kurdica, Mutica and Cabolica Gums from Genus Pistacia

PubMed Central

Sharifi, Mohammad Sharif; Hazell, Stuart Loyd

2012-01-01

The chemical entities of Mastic, Kurdica, Mutica and Cabolica gums from genus Pistacia have been isolated and characterised by GC-Mass Spectrometry, High Performance Liquid Chromatography and Column Chromatography. These chemical entities were screened for anti-microbial activities against nine strains of Helicobacter pylori and some other Gram-negative and Gram-positive bacteria. The most bioactive components were structurally analysed. These components mimic steroid compounds, in particular, the known antibiotic Fusidic acid. Some of these chemical entities have produced promising data that could lead to the development of a novel class of antimicrobial agents that may have application in the treatment of infectious disease. Kill kinetics have been also performed, and the produced data were evaluated by Generalized Multiplicative Analysis Of Variance (GEMANOVA) for the bactericidal and bacteriostatic activities which can be clinically significant. The isolated components were all bactericidal. PMID:22980113

Cryptogenic stroke. A non-diagnosis.

PubMed

Gutiérrez-Zúñiga, Raquel; Fuentes, Blanca; Díez-Tejedor, Exuperio

2018-04-30

The term cryptogenic stroke refers to a stroke for which there is no specific attributable cause after a comprehensive evaluation. However, there are differences between the diagnostic criteria of etiological classifications used in clinical practice. An improvement in diagnostic tools such advances in monitoring for atrial fibrillation, advances in vascular imaging and evidence regarding the implication of patent foramen oval on the risk of stroke specially in young patients are reducing the proportion of stroke patients without etiological diagnosis. We carried out a critical review of the current concept of cryptogenic stroke, as a non-diagnosis, avoiding the simplification of it and reviewing the different entities that could fall under this diagnosis and reviewing the different entities that could fall under this diagnosis; and therefore avoid the same treatment for differents entities with uncertains results. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Primary disorders of the lymphatic vessels--a unified concept.

PubMed

Levine, C

1989-03-01

Congenital defects of lymphatics constitute a spectrum of disorders that may manifest with a variety of clinical presentations including lymphedema, chylous effusions, lymphangiomatous malformations with cystic masses and localized gigantism, and intestinal lymphangiectasia with malabsorption. These entities constitute a relatively rare group of disorders, the origin of which remains somewhat controversial, but in some it appears to be due to early lymphatic obstruction. Five cases are described, which demonstrate the anatomical pathology of these entities. A classification and description of the defects is also presented. An attempt is made to present a unified theory of origin for this seemingly diverse group of diseases. While these entities may be challenging from a diagnostic and therapeutic standpoint, a wide variety of imaging modalities, which includes lymphography, computed tomography scanning, and ultrasound, may be used to diagnose the extent and internal structural characteristics of the abnormalities.

The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system.

PubMed

Mihm, Bernhard; Bergmann, Markus; Brück, Wolfgang; Probst-Cousin, Stefan

2014-06-01

To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14-positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8-positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process. © 2013 Japanese Society of Neuropathology.

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.

Systemic sclerosis complicated with localized scleroderma-like lesions induced by Köbner phenomenon.

PubMed

Saigusa, Ryosuke; Asano, Yoshihide; Yamashita, Takashi; Takahashi, Takehiro; Nakamura, Kouki; Miura, Shunsuke; Ichimura, Yohei; Toyama, Tetsuo; Taniguchi, Takashi; Sumida, Hayakazu; Tamaki, Zenshiro; Miyazaki, Miki; Yoshizaki, Ayumi; Sato, Shinichi

2018-03-01

Scleroderma is a chronic disease of unknown etiology characterized by skin fibrosis and is divided into two clinical entities: systemic sclerosis (SSc) and localized scleroderma (LSc). In general, LSc is rarely complicated with SSc, but a certain portion of SSc patients manifests bilateral symmetric LSc-like lesions on the trunk and extremities. We investigated SSc patients with LSc-like lesions to clarify the underlying pathophysiology. Nine SSc cases complicated with LSc-like lesions were clinically and histologically characterized. SSc patients with LSc-like lesions exhibited multiple progressive hyper- and/or hypo-pigmented plaques with mild sclerosis symmetrically distributed on the trunk and extremities, especially abdominal region. In histological assessment, epidermal IL-1α expression was elevated in both forearms and LSc-like lesions of these patients to a greater extent than in forearms of control patients (SSc patients without LSc-like lesions). Of note, the infiltration and degranulation of mast cells were evident throughout the dermis of LSc-like lesions, while detectable to a lesser extent in forearms of SSc patients with LSc-like lesions and control patients. The epidermis of SSc patients with LSc-like lesions seems to possess an inflammatory phenotype, leading to the activation of mast cells in the dermis of mechanically stressed skin. Köbner phenomenon may be involved in the induction of LSc-like lesions in a certain subset of SSc. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Anti-TIF1-γ antibody and cancer-associated myositis: A clinicohistopathologic study.

PubMed

Hida, Ayumi; Yamashita, Takenari; Hosono, Yuji; Inoue, Manami; Kaida, Kenichi; Kadoya, Masato; Miwa, Yusuke; Yajima, Nobuyuki; Maezawa, Reika; Arai, Satoko; Kurasawa, Kazuhiro; Ito, Kazuhiro; Shimada, Hiroyuki; Iwanami, Tomoko; Sonoo, Masahiro; Hatanaka, Yuki; Murayama, Shigeo; Uchibori, Ayumi; Chiba, Atsuro; Aizawa, Hitoshi; Momoo, Takayuki; Nakae, Yoshiharu; Sakurai, Yasuhisa; Shiio, Yasushi; Hashida, Hideji; Yoshizawa, Toshihiro; Sakiyama, Yoshio; Oda, Aya; Inoue, Kiyoharu; Takeuchi, Sousuke; Iwata, Nobue K; Date, Hidetoshi; Masuda, Naoki; Mikata, Takashi; Motoyoshi, Yasufumi; Uesaka, Yoshikazu; Maeda, Meiko Hashimoto; Nakashima, Ran; Tsuji, Shoji; Kwak, Shin; Mimori, Tsuneyo; Shimizu, Jun

2016-07-19

We aimed to analyze the clinical and histopathologic features of cancer-associated myositis (CAM) in relation to anti-transcriptional intermediary factor 1 γ antibody (anti-TIF1-γ-Ab), a marker of cancer association. We retrospectively studied 349 patients with idiopathic inflammatory myopathies (IIMs), including 284 patients with pretreatment biopsy samples available. For the classification of IIMs, the European Neuromuscular Center criteria were applied. Patients with CAM with (anti-TIF1-γ-Ab[+] CAM) and without anti-TIF1-γ-Ab (anti-TIF1-γ-Ab[-] CAM) were compared with patients with IIM without cancers within and beyond 3 years of myositis diagnosis. Cancer was detected in 75 patients, of whom 36 (48%) were positive for anti-TIF1-γ-Ab. In anti-TIF1-γ-Ab(+) patients with CAM, cancers were detected within 1 year of myositis diagnosis in 35 (97%) and before 1 year of myositis diagnosis in 1. All the anti-TIF1-γ-Ab(+) patients with CAM satisfied the dermatomyositis (DM) criteria, including 2 possible DM sine dermatitis cases, and were characterized histologically by the presence of perifascicular atrophy, vacuolated fibers (VFs), and dense C5b-9 deposits on capillaries (dC5b-9). In contrast, 39 anti-TIF1-γ-Ab(-) patients with CAM were classified into various subgroups, and characterized by a higher frequency of necrotizing autoimmune myopathy (NAM). Notably, all 7 patients with CAM classified into the NAM subgroup were anti-TIF1-γ-Ab(-) and exhibited no dC5b-9 or VFs. CAM includes clinicohistopathologically heterogeneous disease entities. Among CAM entities, anti-TIF1-γ-Ab(+) CAM has characteristically shown a close temporal association with cancer detection and the histopathologic findings of dC5b-9 and VFs, and CAM with NAM is a subset of anti-TIF1-γ-Ab(-) CAM. © 2016 American Academy of Neurology.

Primary extraskeletal myxoid chondrosarcoma of pulmonary arteries: a rare mimic of acute pulmonary thromboembolism.

PubMed

Gadabanahalli, Karthik; Belaval, Vinay V; Bhat, Venkatraman; Gorur, Imran M

2015-04-01

Primary extraskeletal myxoid chondrosarcoma of the pulmonary arteries is a very rare entity. Multimodality imaging reports on this entity are few. Myxoid chondrosarcoma is characterized by chondroid and neurogenic differentiation in extraskeletal locations. These tumours represent fewer than 2.5% of all soft-tissue sarcomas, and are most commonly found in the lower extremities, limb girdles, distal extremities and trunk. We report an unusual case of a 31-year old man with histopathologically proven extraskeletal myxoid chondrosarcoma of the pulmonary arteries mimicking acute pulmonary thromboembolism. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Moore-Federman syndrome and acromicric dysplasia: are they the same entity?

PubMed Central

Winter, R M; Patton, M A; Challener, J; Mueller, R F; Baraitser, M

1989-01-01

Four unrelated patients are reported with short stature, stiffness of the joints, short fingers, inability to make a fist, and thickened skin on the forearms. Investigations have failed to show a lysosomal storage disorder and radiographs show non-specific changes with a delayed carpal bone age. The clinical features in the four children are very similar to the recently described acromicric dysplasia. There are also similarities to Moore-Federman syndrome which has only been described in one family. The case is made that acromicric dysplasia and Moore-Federman syndrome are the same entity. Images PMID:2732993

Politics and Graduate Medical Education in Internal Medicine: A Dynamic Landscape.

PubMed

Wardrop, Richard M; Berkowitz, Lee R

2017-02-01

The promotion of change and growth within medical education is oftentimes the result of a complex mix of societal, cultural and economic forces. Graduate medical education in internal medicine is not immune to these forces. Several entities and organizations can be identified as having a major influence on internal medicine training and graduate medical education as a whole. We have reviewed how this is effectively accomplished through these entities and organizations. The result is a constantly changing and dynamic landscape for internal medicine training. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Breast cancer - one term, many entities?

PubMed

Bertos, Nicholas R; Park, Morag

2011-10-01

Breast cancer, rather than constituting a monolithic entity, comprises heterogeneous tumors with different clinical characteristics, disease courses, and responses to specific treatments. Tumor-intrinsic features, including classical histological and immunopathological classifications as well as more recently described molecular subtypes, separate breast tumors into multiple groups. Tumor-extrinsic features, including microenvironmental configuration, also have prognostic significance and further expand the list of tumor-defining variables. A better understanding of the features underlying heterogeneity, as well as of the mechanisms and consequences of their interactions, is essential to improve targeting of existing therapies and to develop novel agents addressing specific combinations of features.

Product-related research: how research can contribute to successful life-cycle management.

PubMed

Sandner, Peter; Ziegelbauer, Karl

2008-05-01

Declining productivity with decreasing new molecular entity output combined with increased R&D spending is one of the key challenges for the entire pharmaceutical industry. In order to offset decreasing new molecular entity output, life-cycle management activities for established drugs become more and more important to maintain or even expand clinical indication and market opportunities. Life-cycle management covers a whole range of activities from strategic pricing to a next generation product launch. In this communication, we review how research organizations can contribute to successful life-cycle management strategies using phosphodiesterase 5 inhibitors as an example.

Surfer's myelopathy: case report and review.

PubMed

Karabegovic, Amna; Strachan-Jackman, Shirley; Carr, David

2011-09-01

Nontraumatic spinal cord injury from surfing is a new entity first described in 2004 and likely of ischemic etiology. We report the case of a 25-year-old man who presented to the emergency department with a 2-week history of lower extremity weakness after surfing in Indonesia. The patient reported developing low back pain, lower extremity weakness, sensory changes, and urinary retention shortly after his first surfing lesson. The patient was subsequently diagnosed with surfer's myelopathy. The purpose of this report is to review the clinical presentation, etiology, risk factors, and management of this increasingly described entity.

Inflammatory myoglandular polyp--a rare but distinct type of colorectal polyps.

PubMed

Becheanu, Gabriel; Stamm, Bernhard

2003-01-01

The aim of this paper was to report another example of a rare type of colorectal polyps, the inflammatory myoglandular polyp, and to reaffirm this type of polyp as a distinct entity. This solitary pedunculated polyp was detected after a single episode of rectal bleeding. It was situated in the sigmoid colon, measured 2.5 cm in greatest diameter, and was composed almost exclusively of smooth muscles and hyperplastic glands. The patient had neither chronic colitis nor diverticula. Clinical presentation, localization, and histology give this type of polyp a unique appearance and justify its designation as a separate entity.

A new autosomal dominant syndrome of distinctive face showing ptosis and prominent eyes associated with cleft palate, ear anomalies, and learning disability.

PubMed

Tyshchenko, N; Neuhann, T M; Gerlach, E; Hahn, G; Heisch, K; Rump, A; Schrock, E; Tinschert, S; Hackmann, K

2011-09-01

We report on three patients from two families with apparently a novel clinical entity. The main features of which include unusual craniofacial dysmorphism with ptosis, prominent eyes, flat midface, Cupid's bow configuration of the upper lip, low-set, posteriorly rotated small ears, as well as conductive hearing loss, cleft palate, heart defect, and mild developmental delay. We suggest that this entity is an autosomal dominant disorder given the occurrence in a mother and daughter as well as in an unrelated boy. Copyright © 2011 Wiley-Liss, Inc.

The Mobile Team of Parasitology-Mycology, a medical entity for educational purposes to serve sick patients.

PubMed

Desoubeaux, G; Simon, E G; Perrotin, D; Chandenier, J

2014-06-01

The Mobile Team of Parasitology-Mycology is a movable entity of the Parasitology-Mycology laboratory of Tours University Hospital, France. In contrast to the usual prerogatives of biomedical laboratories, the Mobile Team of Parasitology-Mycology is requested to intervene directly at bedside in various clinical departments, or even outside the hospital facility. Although its actions are of course primarily devoted to specialized diagnostic and therapeutic purposes, the Mobile Team also plays an important educational role in the medical training of undergraduate or graduate students. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Characterization of low-abundance species in the active pharmaceutical ingredient of CIGB-300: A clinical-grade anticancer synthetic peptide.

PubMed

Garay, Hilda; Espinosa, Luis Ariel; Perera, Yasser; Sánchez, Aniel; Diago, David; Perea, Silvio E; Besada, Vladimir; Reyes, Osvaldo; González, Luis Javier

2018-04-20

CIGB-300 is a first-in-class synthetic peptide-based drug of 25 amino acids currently undergoing clinical trials in cancer patients. It contains an amidated disulfide cyclic undecapeptide fused to the TAT cell-penetrating peptide through a beta-alanine spacer. CIGB-300 inhibits the CK2-mediated phosphorylation leading to apoptosis of tumor cells in vitro, and in vivo in cancer patients. Despite the clinical development of CIGB-300, the characterization of peptide-related impurities present in the active pharmaceutical ingredient has not been reported earlier. In the decision tree of ICHQ3A(R2) guidelines, the daily doses intake, the abundance, and the identity of the peptide-related species are pivotal nodes that define actions to be taken (reporting, identification, and qualification). For this, purity was first assessed by reverse-phase chromatography (>97%) and low-abundance impurities (≤0.27%) were collected and identified by mass spectrometry. Most of the impurities were generated during peptide synthesis, the spontaneous air oxidation of the reduced peptide, and the lyophilization step. The most abundant impurity, with no biological activity, was the full-length peptide containing Met 17 transformed into a sulfoxide residue. Interestingly, parallel and antiparallel dimers of CIGB-300 linked by 2 intermolecular disulfide bonds exhibited a higher antiproliferative activity than the CIGB-300 monomer. Likewise, very low abundance trimers and tetramers of CIGB-300 linked by disulfide bonds (≤0.01%) were also detected. Here we describe for the first time the presence of active dimeric species whose feasibility as novel CIGB-300 derived entities merits further investigation. Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.

A clinical analysis of two indolent lymphoma entities: mantle cell lymphoma and marginal zone lymphoma (including the mucosa-associated lymphoid tissue and monocytoid B-cell subcategories): a Southwest Oncology Group study.

PubMed

Fisher, R I; Dahlberg, S; Nathwani, B N; Banks, P M; Miller, T P; Grogan, T M

1995-02-15

The objectives of this study were (1) to determine the clinical presentation and natural history associated with two newly recognized pathologic entities termed mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), including the mucosa-associated lymphoid tissue (MALT) and monocytoid B-cell subcategories, and (2) to determine whether these entities differ clinically from the other relatively indolent non-Hodgkin's lymphomas with which they have been previously classified. We reviewed the conventional pathology and clinical course of 376 patients who had no prior therapy; had stage III/IV disease; were classified as Working Formulation categories A, B, C, D, or E; and received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) on Southwest Oncology Group (SWOG) studies no. 7204, 7426, or 7713. All slides were reviewed by the three pathologists who reached a consensus diagnosis. Age, sex, performance status, bone marrow and/or gastrointestinal involvement, failure-free survival, and overall survival were compared among all the categories. We found that (1) MCL and MZL each represent approximately 10% of stage III or IV patients previously classified as Working Formulation categories A through E and treated with CHOP on SWOG clinical trials; (2) the failure-free survival and overall survival of patients with MZL is the same as that of patients with Working Formulation categories A through E, but the failure-free survival and overall survival of the monocytoid B-cell patients were higher than that of the MALT lymphoma patients (P = .009 and .007, respectively); and (3) the failure-free survival and overall survival of patients with MCL is significantly worse than that of patients with Working Formulation categories A through E (P = .0002 and .0001, respectively). In conclusion, patients with advanced stage MALT lymphomas may have a more aggressive course than previously recognized. Patients with MCL do not have an indolent lymphoma and are candidates for innovative therapy.

Clinical features and course of refractory anemia with ring sideroblasts associated with marked thrombocytosis

PubMed Central

Broseus, Julien; Florensa, Lourdes; Zipperer, Esther; Schnittger, Susanne; Malcovati, Luca; Richebourg, Steven; Lippert, Eric; Cermak, Jaroslav; Evans, Jyoti; Mounier, Morgane; Raya, José Maria; Bailly, François; Gattermann, Norbert; Haferlach, Torsten; Garand, Richard; Allou, Kaoutar; Besses, Carlos; Germing, Ulrich; Haferlach, Claudia; Travaglino, Erica; Luno, Elisa; Pinan, Maria Angeles; Arenillas, Leonor; Rozman, Maria; Perez Sirvent, Maria Luz; Favre, Bernardine; Guy, Julien; Alonso, Esther; Ahwij, Nuhri; Jerez, Andrés; Hermouet, Sylvie; Maynadié, Marc; Cazzola, Mario; Girodon, François

2012-01-01

Background Refractory anemia with ring sideroblasts associated with marked thrombocytosis was proposed as a provisional entity in the 2001 World Health Organization classification of myeloid neoplasms and also in the 2008 version, but its existence as a single entity is contested. We wish to define the clinical features of this rare myelodysplastic/myeloproliferative neoplasm and to compare its clinical outcome with that of refractory anemia with ring sideroblasts and essential thrombocythemia. Design and Methods We conducted a collaborative retrospective study across Europe. Our database included 200 patients diagnosed with refractory anemia with ring sideroblasts and marked thrombocytosis. For each of these patients, each patient diagnosed with refractory anemia with ring sideroblasts was matched for age and sex. At the same time, a cohort of 454 patients with essential thrombocythemia was used to compare outcomes of the two diseases. Results In patients with refractory anemia with ring sideroblasts and marked thrombocytosis, depending on the Janus Kinase 2 V617F mutational status (positive or negative) or platelet threshold (over or below 600×109/L), no difference in survival was noted. However, these patients had shorter overall survival and leukemia-free survival with a lower risk of thrombotic complications than did patients with essential thrombocythemia (P<0.001) but better survival (P<0.001) and a higher risk of thrombosis (P=0.039) than patients with refractory anemia with ring sideroblasts. Conclusions The clinical course of refractory anemia with ring sideroblasts and marked thrombocytosis is better than that of refractory anemia with ring sideroblasts and worse than that of essential thrombocythemia. The higher risk of thrombotic events in this disorder suggests that anti-platelet therapy might be considered in this subset of patients. From a clinical point of view, it appears to be important to consider refractory anemia with ring sideroblasts and marked thrombocytosis as a distinct entity. PMID:22532522

Tuberculous pseudotumor of the liver

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

Dhekne, R.D.; Moore, W.H.; Long, S.E.

1987-10-01

Tuberculosis of the liver in association with generalized miliary tuberculosis is not an uncommon clinical entity. A solitary tuberculous liver abscess, however, is rare. Two such cases, in which there was no clinical evidence of extrahepatic tuberculosis, are reported. The similarities between this condition and other causes of hepatic lesions are discussed, with particular emphasis placed on the imaging patterns of various diagnostic imaging procedures.

Granulomatous lobular mastitis.

PubMed

Miliauskas, J R; Pieterse, A S; Williams, R S

1995-02-01

Two cases of benign lobular granulomatous mastitis, both clinically felt to be carcinoma, are reported. One patient was cured by local excision of the mass while the other was cured by oral prednisolone, demonstrating the variable ways to treat this entity. The clinical and histological features were similar to those noted in previous reports. Immunological studies revealed predominantly stromal T lymphocytes and only duct intra-epithelial T lymphocytes.

Age-related monoclonal gammapathies: clinical lessons from the aging C57BL mouse.

PubMed

Radl, J

1990-07-01

In this article the long-held notion that benign monoclonal gammapathy (BMG) is a premalignant stage in the development of multiple myeloma (MM) is attacked. Jiri Radl argues that clinical and experimental observations indicate that they are separate entities which may be distinguished in the laboratory and which should be managed in radically different ways.

A retrospective clinico-pathological study comparing lichen planus pigmentosus with ashy dermatosis.

PubMed

Cheng, Hui Mei; Chuah, Sai Yee; Gan, Emily Yiping; Jhingan, Anjali; Thng, Steven Tien Guan

2018-04-10

Controversy persists as to whether lichen planus pigmentosus and ashy dermatosis are separate clinical entities. This study was conducted to examine the clinicopathological features and treatment outcome of the two conditions. A retrospective medical chart review of all patients who were diagnosed with lichen planus pigmentosus or ashy dermatosis was conducted. The information collected included the participants' age at onset, site of onset, duration of disease, presence of precipitating factors, distribution of disease, pigmentation and presence of symptoms. In patients from whom a biopsy was taken the histopathological reports were included. Altogether 26 patients with ashy dermatosis and 29 with lichen planus pigmentosus were included in the study. Compared with ashy dermatosis, lichen planus pigmentosus had a more localised distribution with a preponderance for facial involvement, compared with the truncal preponderance in ashy dermatosis. Ashy dermatosis tended to have a more stable clinical course than lichen planus pigmentosus, which was more likely to wax and wane. The utility of histopathology in differentiating between the two conditions is low. Ashy dermatosis and lichen planus pigmentosus, as defined in this study, appear to be two separate clinical entities with distinguishable clinical features and natural histories. © 2018 The Australasian College of Dermatologists.

The SAPHO syndrome: a clinical and imaging study.

PubMed

Sallés, Meritxell; Olivé, Alejandro; Perez-Andres, Ricard; Holgado, Susana; Mateo, Lourdes; Riera, Elena; Tena, Xavier

2011-02-01

The purpose of this study is to describe the clinical and radiological manifestations of patients with the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Retrospective study (1984-2007) was performed in a single center. All patients with the SAPHO syndrome were included. Fifty-two patients were included: 26 male, mean age at diagnosis is 42±12 years. Ostearticular involvement was present before cutaneous involvement in 59.6% of patients and concomitantly in 23.5%. Anterior chest pain was the commonest clinical manifestation, it was present in 38 patients (73%), followed by peripheral arthritis in 17 patients (32%), and sacroliliac pain in 14 patients (26.9%). Cutaneous involvement was present in 33 patients (63.5%). HLA B27 antigen was present in eight patients (17.7%). Bone scintigraphy showed an increased uptake in 42 patients (93.3%). The location of the uptake was mainly in sternoclavicular and manubriosternal joints. CT scan was performed in all "hot joints" showing sclerosis, erosions, hyperostosis, and soft tissue involvement. Refractory patients were treated mainly with pamidronate. Although SAPHO syndrome is an entity that share features that fit into a variety of established disease categories, the present study has a homogenous clinical and radiological pattern that gives support to believe that the SAPHO syndrome is an isolated clinical entity.

EPAct 2005: A Roadmap for Open Access

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

Morrison, Jay A.

After nine years of negotiation characterized by significant philosophical swings, Congress came together in the middle to support a moderate vision of open access intended primarily to enable load-serving entities to obtain the transmission service they need to meet the long-term needs of their consumers reliably and economically.

Complex Landscape Terms in Seri

ERIC Educational Resources Information Center

O'Meara, Carolyn; Bohnemeyer, Jurgen

2008-01-01

The nominal lexicon of Seri is characterized by a prevalence of analytical descriptive terms. We explore the consequences of this typological trait in the landscape domain. The complex landscape terms of Seri classify geographic entities in terms of their material make-up and spatial properties such as shape, orientation, and merological…

78 FR 49714 - Amendment to Standards and Practices for All Appropriate Inquiries

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-15

... specific aspects of this rule, contact Rachel Lentz, Office of Brownfields and Land Revitalization (5105T... addition, any entity conducting a site characterization or assessment on a property with a brownfields... state, local and Tribal governments that receive brownfields site assessment grants. A summary of the...

Characterizing "Adversity" of Pathology Findings in Nonclinical Toxicity Studies: Results from the 4th ESTP International Expert Workshop.

EPA Science Inventory

The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment in the toxicologic pathology community regarding how nonclinical adversity is det...

ESTROGENIC RESPONSES TO XENOBIOTICS IN CHANNEL CATFISH (ICTALURUS PUNCTATUS) (R823450)

EPA Science Inventory

Abstract

Several environmentally relevant contaminants are characterized as xenoestrogens by virtue of their ability to induce responses similar to 17-estradiol (E2). T...

76 FR 13448 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-11

... concerning a final regulation, REG-209365-89 (T.D. 9013), Limitations on Passive Activity Losses and Credits... . SUPPLEMENTARY INFORMATION: Title: Limitation on Passive Activity Losses and Credits--Treatment of Self-Charged... with owners of interests in the entity re-characterized as passive activity gross income. The IRS will...

Metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract. Management and literature review.

PubMed

Salemis, Nikolaos S; Seretis, Charalambos; Seretis, Fotios; Christofyllakis, Charalambos; Karalis, Georgios

2014-01-01

Multifocal soft tissue sarcoma is a rare clinical entity occurring in 1% of patients with extremity soft tissue sarcoma and in 4.5% of patients with liposarcoma. Multifocal disease may arise either synchronously or metachronously and has been associated with poor prognosis. Herein, we have described a rare case of metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract that developed 14 months after the resection of a myxoid buttock liposarcoma. Diagnostic evaluation and management of the patient are discussed along with a review of the relevant literature. We conclude that multifocal myxoid liposarcoma is a rare clinical entity that usually represents metastatic disease with poor prognosis. A thorough imaging and careful physical examination are essential in the preoperative evaluation and postoperative follow-up of patients with myxoid extremity liposarcomas, as these tumors are known to have a tendency to spread toward extrapulmonary sites, frequently without pulmonary metastases.

Metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract. Management and literature review

PubMed Central

Salemis, Nikolaos S.; Seretis, Charalambos; Seretis, Fotios; Christofyllakis, Charalambos; Karalis, Georgios

2014-01-01

Multifocal soft tissue sarcoma is a rare clinical entity occurring in 1% of patients with extremity soft tissue sarcoma and in 4.5% of patients with liposarcoma. Multifocal disease may arise either synchronously or metachronously and has been associated with poor prognosis. Herein, we have described a rare case of metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract that developed 14 months after the resection of a myxoid buttock liposarcoma. Diagnostic evaluation and management of the patient are discussed along with a review of the relevant literature. We conclude that multifocal myxoid liposarcoma is a rare clinical entity that usually represents metastatic disease with poor prognosis. A thorough imaging and careful physical examination are essential in the preoperative evaluation and postoperative follow-up of patients with myxoid extremity liposarcomas, as these tumors are known to have a tendency to spread toward extrapulmonary sites, frequently without pulmonary metastases. PMID:24678225

Palisaded Neutrophilic and Granulomatous Dermatitis/Interstitial Granulomatous Dermatitis Overlap: A Striking Clinical and Histologic Presentation With "Burning Rope Sign" and Subsequent Mirror-Image Contralateral Recurrence.

PubMed

Kern, Malan; Shiver, Mallory B; Addis, Kristen M; Gardner, Jerad M

2017-09-01

Palisaded neutrophilic and granulomatous dermatitis and interstitial granulomatous dermatitis are uncommon granulomatous dermatoses that often arise in association with rheumatoid arthritis. These 2 entities have overlapping features and may exist on a spectrum. We report an intriguing case of a 53-year-old man with advanced rheumatoid arthritis who presented with a large indurated painful truncal plaque with a palpable cord in addition to a papulonodular eruption on his dorsal hands. Furthermore, our patient had a recurrence in a near-identical mirror-image pattern on the contralateral trunk. The constellation of clinical and histopathological findings in our patient further suggests that palisaded neutrophilic and granulomatous dermatitis and interstitial granulomatous dermatitis exist as overlapping disease entities on a continuum. In addition, we propose that recurrence of skin findings may be indicative of the severity of the underlying systemic disease process.

Nontraumatic head and neck injuries: a clinical approach. Part 2.

PubMed

Brea Álvarez, B; Esteban García, L; Tuñón Gómez, M; Cepeda Ibarra, Y

Nontraumatic emergencies of the head and neck represent a challenge in the field of neuroradiology for two reasons. As explained in the first part of this update, these entities affect an area where the thorax joins the cranial cavity and can thus compromise both structures; second, they are uncommon, so they are not well known. Maintaining the same approach as in the first part, focusing on the clinical presentations in the emergency department rather than on the anatomic regions affected, we will study the entities that present with two patterns: those that present with a combination of cervical numbness, dysphagia, and dyspnea and those that present with acute sensory deficits. In the latter group, we will specifically focus on visual deficits, because this is the most common symptom that calls for urgent imaging studies. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

[Pneumomediastinum, giant subcutaneous emphysema and pneumoperitoneum revealed by jaw pain. Uncommon physiopathology of pneumomediastinum].

PubMed

Le Loch, J-B; Freymond, N; Khettab, F; Pacheco, Y; Devouassoux, G

2008-02-01

Spontaneous pneumomediastinum is a rare entity, predominantly described in young man. The association of acute dyspnea, chest pains and subcutaneous emphysema is usually reported. We report the observation of a pneumomediastinum, fortuitously discovered in front of an isolated giant subcutaneous emphysema in a 59 year old man. The recent clinical history was only marked by the presence of intense and acute dental pains. Associated with a pneumoperitoneum, a retro-pneumoperitoneum, this clinical presentation is uncommon and differs from previous published case reports. Despite a complete evaluation of classical risk factors, its origin remains uncertain. However, the presence of huge dental injuries led to consider such local origin, facilitating air diffusion. This case report allows to reconsider spontaneous pneumomediastinum entity and to propose additional physiopathological mechanisms. This original description underlines the interest to systematically perform dental examination in the presence of unexplained pneumomediastinum.

Clinical features of hidradenitis suppurativa and Crohn disease: what do these two entities have in common?

PubMed

Vilarrasa Rull, E; González Lama, Y

2016-09-01

Hidradenitis suppurativa (HS) and Crohn disease (CD) are chronic, recurrent inflammatory diseases. They share certain clinical characteristics and flares are common in both. Both entities are usually diagnosed between the second and third decades of life and share risk factors such as smoking and overweight. In CD, as in HS, acute untreated episodes of inflammation can lead to sequels such as abscesses, fistulas and stenosis. Consequently, early management is of the utmost importance. Some patients have both diseases. The estimated prevalence of SH in CD patients is 12.4%-17.9%, while the prevalence of CD in HS patients is around 3%. The presence of HS in patients with inflammatory bowel disease (IBD) is associated with an earlier onset of IBD and with more frequent need for anti-TNF-alpha therapy and surgical resection. Copyright © 2016 Elsevier España, S.L.U. y AEDV. All rights reserved.

Clinical benchmarking for the office practitioner enabled by the online health record

PubMed Central

Ricciardi, TN; Masarie, FE; Landholt, T; Middleton, B

2000-01-01

Payer organizations, regulatory entities, and delivery networks are placing increasing pressure on physicians to report aggregate information about their patients and practice of medicine. Historically, clinicians have been ill-equipped to respond to these pressures when their practices have relied upon payer records for clinical information management. Key Industry Drivers: Physicians need specific information from their practices for the purposes of contract management, preventive care, office productivity, and utilization reviews. Value Statement: Clinical data captured at the point of care can support reporting requirements, and supplement or replace laboriously-collected data derived from billing and other administrative systems. Information from the Online Health Record can empower the individual physician to assess what is going on in their practice of medicine, as opposed to being "profiled" by an external entity. We created a secure web-based system that provides access to a clinical data mart, to allow online benchmarking for the individual or office practitioner. Providers used a web-enabled documentation system to document the clinical facts of the encounter. A nightly set of routines extracts data from the online chart into the clinical data mart built in a relational database. The system uses a clinical vocabulary server to map provider-entered strings to normalized clinical concepts. The system loads chart data into a dimensional data model, to simplify data representation and ensure fast query performance. Providers can access their own profiles from a secure web browser. PMID:11080030

EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes

PubMed Central

van Dongen, J J M; Lhermitte, L; Böttcher, S; Almeida, J; van der Velden, V H J; Flores-Montero, J; Rawstron, A; Asnafi, V; Lécrevisse, Q; Lucio, P; Mejstrikova, E; Szczepański, T; Kalina, T; de Tute, R; Brüggemann, M; Sedek, L; Cullen, M; Langerak, A W; Mendonça, A; Macintyre, E; Martin-Ayuso, M; Hrusak, O; Vidriales, M B; Orfao, A

2012-01-01

Most consensus leukemia & lymphoma antibody panels consist of lists of markers based on expert opinions, but they have not been validated. Here we present the validated EuroFlow 8-color antibody panels for immunophenotyping of hematological malignancies. The single-tube screening panels and multi-tube classification panels fit into the EuroFlow diagnostic algorithm with entries defined by clinical and laboratory parameters. The panels were constructed in 2–7 sequential design–evaluation–redesign rounds, using novel Infinicyt software tools for multivariate data analysis. Two groups of markers are combined in each 8-color tube: (i) backbone markers to identify distinct cell populations in a sample, and (ii) markers for characterization of specific cell populations. In multi-tube panels, the backbone markers were optimally placed at the same fluorochrome position in every tube, to provide identical multidimensional localization of the target cell population(s). The characterization markers were positioned according to the diagnostic utility of the combined markers. Each proposed antibody combination was tested against reference databases of normal and malignant cells from healthy subjects and WHO-based disease entities, respectively. The EuroFlow studies resulted in validated and flexible 8-color antibody panels for multidimensional identification and characterization of normal and aberrant cells, optimally suited for immunophenotypic screening and classification of hematological malignancies. PMID:22552007

Multiple Natural Hazards Assessment and Comparison to Planned Land Use in an Andean Touristic Site within the Riskscape Central Chile

NASA Astrophysics Data System (ADS)

Braun, Andreas; Jaque Castillo, Edilia

2017-04-01

The Andes of central Chile are a natural environment characterized by multiple natural hazards (mass movements, volcanic hazards, seismic hazards, snow avalanches to name a few). The totality of these hazards, according to the notion of Müller-Mahn et al. an in relation to vulnerable entities, spans a riskscape. Spatial planning should take this riskscape into account in order to ensure a save an resilient regional development. However, as frequently observed in developing or newly developed countries, such precaution measures are only hardly realized. Spatial planing tends to be reactive to private inversion, opportunistic and frequently clientelistic. This results in spatial structures whose future development is vulnerable to natural disasters. The contribution analyses these circumstances within a riskscape in central Chile. Within the VIII. Region, close to the volcanic complex Nevados de Chillan, a touristic development around a Hotel for winter sports is established. However, the place is affected by a multitude of natural hazards. The contribution, on the basis of primary and secondary data, first provides hazard maps for several natural hazards. Secondly, the individual hazard maps are merged to an overall hazard map. This overall hazard map is related to the vulnerable entities to span a riskscape. The vulnerable entities are settlements, but also tourist infrastructures. Then, the contribution compares how a precautions spatial planning could have avoided putting vulnerable entities at risk, which spatial structure - especially regarding tourism - is actually found and which challenges for spatial development do exist. It reveals that the most important tourist infrastructures are found particularly at places, characterized by a high overall hazard. Furthermore, it will show that alternatives at economically equally attractive sites, but with a much smaller overall hazard, would have existed. It concludes by discussing possible reasons for this by considering the Chilean planning system.

Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.

PubMed

Martinelli, Simone; Krumbach, Oliver H F; Pantaleoni, Francesca; Coppola, Simona; Amin, Ehsan; Pannone, Luca; Nouri, Kazem; Farina, Luciapia; Dvorsky, Radovan; Lepri, Francesca; Buchholzer, Marcel; Konopatzki, Raphael; Walsh, Laurence; Payne, Katelyn; Pierpont, Mary Ella; Vergano, Samantha Schrier; Langley, Katherine G; Larsen, Douglas; Farwell, Kelly D; Tang, Sha; Mroske, Cameron; Gallotta, Ivan; Di Schiavi, Elia; Della Monica, Matteo; Lugli, Licia; Rossi, Cesare; Seri, Marco; Cocchi, Guido; Henderson, Lindsay; Baskin, Berivan; Alders, Mariëlle; Mendoza-Londono, Roberto; Dupuis, Lucie; Nickerson, Deborah A; Chong, Jessica X; Meeks, Naomi; Brown, Kathleen; Causey, Tahnee; Cho, Megan T; Demuth, Stephanie; Digilio, Maria Cristina; Gelb, Bruce D; Bamshad, Michael J; Zenker, Martin; Ahmadian, Mohammad Reza; Hennekam, Raoul C; Tartaglia, Marco; Mirzaa, Ghayda M

2018-01-17

Exome sequencing has markedly enhanced the discovery of genes implicated in Mendelian disorders, particularly for individuals in whom a known clinical entity could not be assigned. This has led to the recognition that phenotypic heterogeneity resulting from allelic mutations occurs more commonly than previously appreciated. Here, we report that missense variants in CDC42, a gene encoding a small GTPase functioning as an intracellular signaling node, underlie a clinically heterogeneous group of phenotypes characterized by variable growth dysregulation, facial dysmorphism, and neurodevelopmental, immunological, and hematological anomalies, including a phenotype resembling Noonan syndrome, a developmental disorder caused by dysregulated RAS signaling. In silico, in vitro, and in vivo analyses demonstrate that mutations variably perturb CDC42 function by altering the switch between the active and inactive states of the GTPase and/or affecting CDC42 interaction with effectors, and differentially disturb cellular and developmental processes. These findings reveal the remarkably variable impact that dominantly acting CDC42 mutations have on cell function and development, creating challenges in syndrome definition, and exemplify the importance of functional profiling for syndrome recognition and delineation. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Examination of MMPI-2-RF Substantive Scales as Indicators of Acute Suicidal Affective Disturbance Components.

PubMed

Rogers, Megan L; Anestis, Joye C; Harrop, Tiffany M; Schneider, Matthew; Bender, Theodore W; Ringer, Fallon B; Joiner, Thomas E

2017-01-01

A new suicide-specific diagnostic entity, acute suicidal affective disturbance (ASAD), was recently proposed to fill a void in the nomenclature. Although several studies have examined the reliability, validity, and potential clinical utility of ASAD, no studies have examined personality indicators of ASAD. This study sought to examine the association between personality and psychopathology factors, as assessed by the Minnesota Multiphasic Personality Inventory-2-Revised Form (MMPI-2-RF), and constructs that comprise ASAD in a sample of 554 psychiatric outpatients who completed all measures prior to their intake appointments. A smaller subset of patients (N = 58) also completed a measure designed to assess lifetime ASAD symptoms. Results indicated that ASAD symptoms were associated with traits characterized by emotional turmoil and atypical cognitive processes. Further, suicide-related criteria that comprise ASAD were related to low positive emotionality and hopelessness, whereas the overarousal criteria were associated with somatic symptoms and an inability to tolerate frustration and stress. These findings expand on previous research that examines the convergent and discriminant validity of ASAD and could inform clinical treatment by providing insight into personality traits that might be associated with acute suicide risk.

Distributed Data Networks That Support Public Health Information Needs.

PubMed

Tabano, David C; Cole, Elizabeth; Holve, Erin; Davidson, Arthur J

Data networks, consisting of pooled electronic health data assets from health care providers serving different patient populations, promote data sharing, population and disease monitoring, and methods to assess interventions. Better understanding of data networks, and their capacity to support public health objectives, will help foster partnerships, expand resources, and grow learning health systems. We conducted semistructured interviews with 16 key informants across the United States, identified as network stakeholders based on their respective experience in advancing health information technology and network functionality. Key informants were asked about their experience with and infrastructure used to develop data networks, including each network's utility to identify and characterize populations, usage, and sustainability. Among 11 identified data networks representing hundreds of thousands of patients, key informants described aggregated health care clinical data contributing to population health measures. Key informant interview responses were thematically grouped to illustrate how networks support public health, including (1) infrastructure and information sharing; (2) population health measures; and (3) network sustainability. Collaboration between clinical data networks and public health entities presents an opportunity to leverage infrastructure investments to support public health. Data networks can provide resources to enhance population health information and infrastructure.

Scalp eschar and neck lymphadenopathy after tick bite: an emerging syndrome with multiple causes.

PubMed

Dubourg, G; Socolovschi, C; Del Giudice, P; Fournier, P E; Raoult, D

2014-08-01

The clinical and epidemiological features of 56 patients with scalp eschar associated with neck lymphadenopathy after a tick bite (SENLAT) syndrome were evaluated at the National French Rickettsial Center. Eschar swabs, crusts, and biopsies as well as ticks and blood samples were acquired for molecular and serological assays. SENLAT predominantly affects children (p < 0.05), followed by 40- to 70-year-olds, and it is found mostly in women (p < 0.05). The seasonal distribution has two peaks: one in the spring (55%) and one in the autumn (30%). The etiological agent was identified in 18 cases, which include Rickettsia slovaca in 13 cases with incidences of two co-infections with Rickettsia raoultii and one case caused by Rickettsia sibirica mongolitimonae. Other possible agents that were found in attached ticks were Candidatus R. rioja, Coxiella burnetii, and Borrelia burgdorferi. The tick vector was Dermacentor marginatus in almost all cases, with the exception of one case, in which Ixodes ricinus was identified as the vector. Our findings show that SENLAT is a clinical entity characterized as a local infection controlled by the immune system and is neither pathogen- nor vector-specific.

[Fat embolism syndrome following injuries and limb fractures].

PubMed

Volpin, Gershon; Gorski, Albert; Shtarker, Haim; Makhoul, Nicola

2010-05-01

Fat embolism syndrome is a clinical entity characterized by varying degrees of cerebral dysfunction, pulmonary changes and petechial rash that usually develop within 24-48 hours in a small percentage of victims after trauma and Long bone fractures. Deterioration can occur within a few hours Leading to unconsciousness or acute respiratory insufficiency, similar to adult respiratory distress syndrome (ARDS). The pathophysiology is still not clearly understood and there are two theories--the mechanical and biochemical cascade of events. It seems that the most significant diagnostic sign is hypoxemia with relatively normaL values of PaCO2 leading to development of radiographic "snow-like appearance" of the Lungs, resulting from the typical interstitial lung edema. Treatment consists of early fracture fixation, volume replacement, respiratory support and analgesia carefully managed since some of the patients may develop acute respiratory distress. The role of steroids and other drugs is still under debate. The vast majority of patients may heal without any complications, while 5%-10% of the patients may develop some neurological complications manifesting as behavior disturbances. The aim of this review is to update the clinical and pathophysiological aspects of fat embolism syndrome and to describe the various aspects of prevention and treatment.

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.

Advances in understanding the pathogenesis of HLH.

PubMed

Usmani, G Naheed; Woda, Bruce A; Newburger, Peter E

2013-06-01

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder resulting from immune dysfunction reflecting either primary immune deficiency or acquired failure of normal immune homeostasis. Familial HLH includes autosomal recessive and X-linked disorders characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines, secondary to defects in genes encoding proteins involved in granule-dependent cytolytic pathways. In older children and adults, HLH is associated more often with infections, malignancies, autoimmune diseases, and acquired immune deficiencies. HLH, macrophage activation syndrome, sepsis, and systemic inflammatory response syndrome are different clinical entities that probably represent a common immunopathological state, termed cytokine storm. These conditions may be clinically indistinguishable; all include massive inflammatory response, elevated serum cytokine levels, multi-organ involvement, haemophagocytic macrophages, and often death. Tissues of haematopoietic and lymphoid function are directly involved; other organs are secondarily damaged by circulating cytokines and chemokines. Haemophagocytic disorders are now increasingly diagnosed in the context of severe inflammatory reactions to viruses, malignancies and systemic connective tissue diseases. Many of these cases may reflect underlying genetic predispositions to HLH. The detection of gene defects has contributed considerably to our understanding of HLH, but the mechanisms leading to acquired HLH have yet to be fully determined. © 2013 John Wiley & Sons Ltd.

A case of severe thrombotic thrombocytopenic purpura with concomitant Legionella pneumonia: review of pathogenesis and treatment.

PubMed

Talebi, Tony; Fernandez-Castro, Gustavo; Montero, Alberto J; Stefanovic, Alexandra; Lian, Eric

2011-09-01

Thrombotic thrombocytopenia purpura (TTP) is a severe multisystem disorder characterized by fever, microangiopathic hemolytic anemia, thrombocytopenia, neurologic symptoms, and impaired renal function. Platelet counts are usually diminished, whereas the bone marrow shows a large number of megakaryocytes indicating peripheral destruction and consumption of platelets. Coagulation studies in patients with TTP are normal or slightly elevated, which helps differentiate this entity from disseminated intravascular coagulation. The peripheral smear shows an abundance of schistocytes, reticulocytes, and, at times, nucleated red blood cells. Serum lactate dehydrogenase and indirect bilirubin are elevated as a result of mechanical destruction of red blood cells. Legionella pneumophila has been identified as a relatively common cause of both community-acquired and hospital-acquired pneumonia. An association between Legionella and TTP has only been cited once in the literature. Here we present a case of severe TTP with concurrent Legionella infection. Our patient presented with the classic clinical findings of TTP and an ADAMTS13 level of less than 5% associated with an inhibitor. After a 3-week treatment course with plasma exchange, steroids, and antibiotics, he had complete clinical recovery and his ADAMTS13 level increased to greater than 75%. (C) 2011 Lippincott Williams & Wilkins, Inc.

Reversible cerebral vasospasm, multilobular intracerebral hemorrhages, and nonaneurysmal subarachnoid hemorrhage: review of possible interrelationships.

PubMed

Hantson, Philippe; Forget, Patrice

2010-06-01

"Reversible cerebral vasoconstriction syndrome" (RCVS) is a recently described entity that is mainly characterized by the association of severe ("thunderclap") headaches with or without additional neurological symptoms and diffuse, multifocal, segmental narrowings involving large and medium-sized cerebral arteries. By definition, angiographic abnormalities disappear within 3 months. The clinical course is usually benign, with a higher prevalence in young women. RCVS is idiopathic in the majority of the cases. However, recent papers have outlined the role of precipitating factors, including the use of vasoactive substances. Some patients, nevertheless, have a more severe clinical course with transient or permanent ischemic events. Hemorrhagic complications appear to have been underestimated. They are usually restricted to circumscribed cortical subarachnoid hemorrhage, in the absence of any ruptured cerebral aneurysm. This limited bleeding is unlikely at the origin of the diffuse vasoconstriction. The finding of an unruptured cerebral aneurysm in RCVS patients is probably incidental. An overlap is possible between RCVS and other syndromes such as posterior reversible encephalopathy syndrome. There is no standardized treatment regimen for RCVS patients. It appears rational to further investigate the efficacy and safety of the calcium-channel antagonist nimodipine.

The development of biomarkers to reduce attrition rate in drug discovery focused on oncology and central nervous system.

PubMed

Safavi, Maliheh; Sabourian, Reyhaneh; Abdollahi, Mohammad

2016-10-01

The task of discovery and development of novel therapeutic agents remains an expensive, uncertain, time-consuming, competitive, and inefficient enterprise. Due to a steady increase in the cost and time of drug development and the considerable amount of resources required, a predictive tool is needed for assessing the safety and efficacy of a new chemical entity. This study is focused on the high attrition rate in discovery and development of oncology and central nervous system (CNS) medicines, because the failure rate of these medicines is higher than others. Some approaches valuable in reducing attrition rates are proposed and the judicious use of biomarkers is discussed. Unlike the significant progress made in identifying and characterizing novel mechanisms of disease processes and targeted therapies, the process of novel drug development is associated with an unacceptably high attrition rate. The application of clinically qualified predictive biomarkers holds great promise for further development of therapeutic targets, improved survival, and ultimately personalized medicine sets for patients. Decisions such as candidate selection, development risks, dose ranging, early proof of concept/principle, and patient stratification are based on the measurements of biologically and/or clinically validated biomarkers.

If You Build It, They Will Come: How to Establish an Academic Innovation Enterprise.

PubMed

Srimathveeravalli, Govindarajan; Balesh, Elie; Cheng, Christopher P; Chen, David

2017-06-01

The rapid growth of minimally invasive, image-guided intervention has redefined the procedural management of multiple disease entities. The process of innovation which has characterized the growth of interventional radiology can be best described as "needs-based," whereby practicing interventionalists identify unmet clinical needs and subsequently invent solutions to achieve desired technical and clinical outcomes. Historically, catheters and other percutaneous devices were developed with rudimentary manufacturing techniques and subsequently translated to patients with relatively little regulatory oversight. Since then, the resources required and financial costs of interventional technology development have grown exponentially. Fortunately, advances in software development, new methods of rapid prototyping, and commoditization of hardware components have made in-house engineering feasible once again. This has created an opportunity for academic medical centers to translate their research into testable prototypes in humans sooner and at reduced costs, and academic interventional radiology divisions are now leveraging these developments to create collaborative centers of innovation. This article describes five such organizational formats for collaboration and innovation in the academic setting, describing the structure, opportunities, requirements, and caveats of each model. Copyright © 2017 Elsevier Inc. All rights reserved.

Boric acid ingestion clinically mimicking toxic epidermal necrolysis.

PubMed

Webb, David V; Stowman, Anne M; Patterson, James W

2013-11-01

The ingestion of large amounts of boric acid, a component of household insecticides, is a rare occurrence, characterized by a diffuse desquamative skin eruption, neutropenia, thrombocytopenia, delirium, acute renal failure and prolonged ileus. A 56-year-old male with a history of multiple previous suicide attempts was witnessed ingesting household roach killer and 4 days later presented to the hospital with lethargy, stiffness and a diffuse erythematous and desquamative eruption with bullous formation. He subsequently developed erythema of both palms as well as alopecia totalis. Histopathology from a right arm shave biopsy revealed a mostly intact epidermis with subtle vacuolar alteration of the basal layer, scattered intraepidermal apoptotic keratinocytes, parakeratosis with alternating layers of orthokeratosis and considerable superficial exfoliation; accompanying dermal changes included vasodilatation and mild perivascular inflammation. This report describes the cutaneous and systemic complications in a rare case of boric acid ingestion. There is little published material on the symptoms and histopathology following boric acid ingestion, but knowledge of this entity is important, both to differentiate it from other causes of desquamative skin rashes and to allow the initiation of appropriate clinical care. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Small bowel perforation secondary to metastatic non-small cell lung cancer. A rare entity with a dismal prognosis.

PubMed

Salemis, Nikolaos S; Nikou, Efstathios; Liatsos, Christos; Gakis, Christos; Karagkiouzis, Grigorios; Gourgiotis, Stavros

2012-09-01

The incidence of gastrointestinal metastases from lung cancer is higher than previously thought as they have been reported in 2-14% of the cases in autopsy studies. However, clinically significant metastases are rare. Small bowel perforation secondary to metastatic non-small cell lung cancer is a very rare clinical entity. The aim of this study is to describe a case of ileal perforation in a patient with intestinal metastases of a non-small cell lung cancer, along with a review of the literature. A 57-year-old male with a history of non-small cell lung cancer was referred to our emergency department with signs and symptoms of acute surgical abdomen. A computed tomography scan demonstrated dilated small bowel loops, liver deposits, and signs of perforation of an intra-abdominal hollow viscus. Emergency exploratory laparotomy revealed diffuse purulent peritonitis and a perforated ileal tumor. A segmental small bowel resection and primary anastomosis were performed. Histological and immunohistochemical findings were consistent with a metastatic non-small cell lung carcinoma. Additional evaluation revealed widespread metastatic disease. Unfortunately, despite adjuvant treatment, the patient died of progressive disease 2 months after surgery. Small bowel perforation due to metastatic non-small cell lung cancer is a very rare clinical entity. The possibility of small bowel metastases should be kept in mind in patients with lung cancer presenting with an acute abdomen. Intestinal perforation occurs in advanced stages and is usually a sign of widespread disease. Aggressive surgery can provide effective palliation and may improve short-term survival. The prognosis is however dismal.

Epstein-Barr virus-positive nodal T/NK-cell lymphoma: an analysis of 15 cases with distinct clinicopathological features.

PubMed

Jeon, Yoon Kyung; Kim, Jo-Heon; Sung, Ji-Youn; Han, Jae Ho; Ko, Young-Hyeh

2015-07-01

Nodal peripheral T-cell lymphoma, not otherwise specified, is a heterogeneous entity with variable biologic behavior. We analyze the clinicopathological features of 15 patients with Epstein-Barr virus-positive (EBV+) nodal T/NK-cell lymphoma, including 9 males and 6 females, with a median age of 64 years. All patients presented with multiple lymphadenopathy with common B symptoms (80%, 12/15) at an advanced Ann Arbor stage (III, IV) (87%, 13/15). The International Prognostic Index was high or high/intermediate in 87% (13/15) of patients, and the prognostic index for peripheral T-cell lymphoma was group 3 or 4 in 73% (11/15). Spleen and liver involvement was observed in 73% (11/15) and 60% (9/15) of patients, respectively. In contrast, extranodal involvement was infrequent, with no more than 1 site in 71% (10/15) of patients. Moreover, none had nasal lesions, and only 1 had mucocutaneous involvement. The cell lineage of EBV+ tumor cells was determined to be T cell in all except 1 patient, who was NK-cell lineage. Cytotoxic molecules were expressed in all cases, and 64% (9/14) of patients expressed the αβT-cell receptor. Moreover, most patients (67%, 10/15) showed CD8 positivity, with 2 of them being CD4CD8 double positive; the others were CD4 positive (n = 2) or CD4CD8 double negative (n = 3). The clinical course was very aggressive, with a median survival time of 3.5 months, and 10 patients died within 6 months of diagnosis. Taken together, our data demonstrate that EBV+ nodal T/NK-cell lymphoma is a distinct clinicopathological entity characterized by cytotoxic molecule expression, a frequent CD8-positive αβT-cell lineage, and a very aggressive clinical behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical and Neuroradiological Spectrum of Metronidazole Induced Encephalopathy: Our Experience and the Review of Literature

PubMed Central

Panwar, Ajay; Pandit, Alak; Das, Susanta Kumar; Joshi, Bhushan

2016-01-01

Metronidazole is an antimicrobial agent mainly used in the treatment of several protozoal and anaerobic infections, additionally, is often used in hepatic encephalopathy and Crohn disease. Apart from peripheral neuropathy, metronidazole can also cause symptoms of central nervous system dysfunction like ataxic gait, dysarthria, seizures, and encephalopathy which may result from both short term and chronic use of this drug and is collectively termed as “metronidazole induced encephalopathy”(MIE). Neuroimaging forms the backbone in clinching the diagnosis of this uncommon entity, especially in cases where there is high index of suspicion of intoxication. Although typical sites of involvement include cerebellum, brain stem and corpus callosum, however, lesions of other sites have also been reported. Once diagnosed, resolution of findings on Magnetic Resonance Imaging (MRI) of the Brain along with clinical improvement remains the mainstay of monitoring. Here we review the key clinical features and MRI findings of MIE as reported in medical literature. We also analyze implication of use of this drug in special situations like hepatic encephalopathy and brain abscess and discuss our experience regarding this entity. PMID:27504340

Oral dyskinesia: a clinical overview.

PubMed

Blanchet, Pierre J; Rompré, Pierre H; Lavigne, Gilles J; Lamarche, Claude

2005-01-01

Dentists may be the first health care professionals to recognize unusual and abnormal oral movements collectively termed oral dyskinesias. The aims of this clinical overview are to raise the dental community's awareness about this important and complex topic and describe the clinical features and management of the main entities. A MEDLINE search of the different entities reported in the English and French literature was conducted. The main findings of a field study on oral dyskinesia were also reviewed. Involuntary movement disorders are often drug related. In other cases, excessive oral movements may occur at any age in relation to various neuropsychiatric conditions. Orofacial dystonia apparently triggered by dental procedures has also been reported. Edentulousness has been associated with oral stereotypes. In a survey of 352 edentulous elderly individuals attending daycare centers, only 7% displayed visible oral sterotypes, and ill-fitting dentures were suggested as a possible triggering factor for the majority. A multidisciplinary evaluation is desirable in the care of individuals with oral dyskinesia and in the selection of those who may benefit from a prosthodontic approach. A good knowledge of potentially offending drugs may allow avoidance of unnecessary procedures.

Auto immune hemolytic anemia in a child precipitated by chicken pox.

PubMed

Billoo, Samina Shamim; Jamalvi, Syed Waseem

2008-05-01

Auto Immune Hemolytic Anemia (AIHA) is a rare entity in children. We report a case of an adolescent girl with AIHA, which was precipitated by chicken pox. Clinical course over 3 years, till remission is described.

The Endpoint Hypothesis: A Topological-Cognitive Assessment of Geographic Scale Movement Patterns

NASA Astrophysics Data System (ADS)

Klippel, Alexander; Li, Rui

Movement patterns of individual entities at the geographic scale are becoming a prominent research focus in spatial sciences. One pertinent question is how cognitive and formal characterizations of movement patterns relate. In other words, are (mostly qualitative) formal characterizations cognitively adequate? This article experimentally evaluates movement patterns that can be characterized as paths through a conceptual neighborhood graph, that is, two extended spatial entities changing their topological relationship gradually. The central questions addressed are: (a) Do humans naturally use topology to create cognitive equivalent classes, that is, is topology the basis for categorizing movement patterns spatially? (b) Are ‘all’ topological relations equally salient, and (c) does language influence categorization. The first two questions are addressed using a modification of the endpoint hypothesis stating that: movement patterns are distinguished by the topological relation they end in. The third question addresses whether language has an influence on the classification of movement patterns, that is, whether there is a difference between linguistic and non-linguistic category construction. In contrast to our previous findings we were able to document the importance of topology for conceptualizing movement patterns but also reveal differences in the cognitive saliency of topological relations. The latter aspect calls for a weighted conceptual neighborhood graph to cognitively adequately model human conceptualization processes.

The fourth branchial complex anomaly: a rare clinical entity.

PubMed

Patel, Alpen B; Hinni, Michael L

2011-01-01

Fourth branchial pouch anomalies are rare congenital disorders of the neck and are a consequence of abnormal development of the branchial apparatus during embryogenesis. Failure to appropriately recognize these anomalies may result in misdiagnosis, insufficient treatment, and continued recurrence. Here, we present an unique presentation of two cases, describe their diagnosis, clinical course, and management, and review the literature regarding these interesting anomalies.

The Fourth Branchial Complex Anomaly: A Rare Clinical Entity

PubMed Central

Patel, Alpen B.; Hinni, Michael L.

2011-01-01

Fourth branchial pouch anomalies are rare congenital disorders of the neck and are a consequence of abnormal development of the branchial apparatus during embryogenesis. Failure to appropriately recognize these anomalies may result in misdiagnosis, insufficient treatment, and continued recurrence. Here, we present an unique presentation of two cases, describe their diagnosis, clinical course, and management, and review the literature regarding these interesting anomalies. PMID:22937376

EPIRUS-NET: A Wireless Health Telematics Network in Greece

DTIC Science & Technology

2001-10-25

has also to be made. The system is represented of three basic layers: the database layer, the middleware and the Hospital Daily Progress Anamnesis ... Anamnesis . The Encounter entry is uniquely identified by the incremental ID, IID, attribute. Each encounter entry is associated with a clinical...the main entities of the system (Hospital, Patient, Anamnesis , Encounter, Clinical Examination, Daily Progress, Examination, Release Ticket), along

Participation of racial/ethnic groups in clinical trials and race-related labeling: a review of new molecular entities approved 1995-1999.

PubMed Central

Evelyn, B.; Toigo, T.; Banks, D.; Pohl, D.; Gray, K.; Robins, B.; Ernat, J.

2001-01-01

Few recent data are available from formal evaluations of approved new drug applications to address perceptions that racial and ethnic groups are under-represented in clinical trials of new drugs. This study reviews racial and ethnic group participation in clinical trials and race-related labeling for new molecular entities approved during a five-year period by the Food and Drug Administration's (FDA) Center for Drug Evaluation and Research (CDER). This was a retrospective review of FDA medical officers' reviews of clinical trial protocols and product labeling for 185 new molecular entities (NME's) approved by CDER between January 1,1995, and December 31, 1999. Enrollment data were obtained from the reviews and tabulated according to race/ethnicity. The approved product labeling was searched for statements related to product testing in various racial/ethnic groups. All data were compiled and analyzed using Microsoft Access. This study quantifies the participation of racial/ethnic groups in clinical trials by year and therapeutic category. Additionally, the study categorizes labeling based on the types of effects described as related to race/ethnicity. Racial and ethnic groups appear to participate in clinical trials to varying degrees. African Americans participated in trials to the greatest extent; however, their participation steadily declined from 12% in 1995 to 6% in 1999. Among trials known to be conducted only in the U.S., African-American participation is comparable to their representation in the U.S. population. In all cases, participants designated as Hispanic appear to be far below their representation in the population. Some differences in participation for all racial and ethnic groups are seen when comparisons from year-to-year or among drug classes are made. Labeling for 45% (84/185) of the products contained some statement about race, although in only 8% (15/185) were differences related to race described. Fifty percent (50%) of the effects were pharmacokinetic, 39% were efficacy, and 11% were safety. One product label recommended a change in dosage based on racial differences. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 PMID:11798060

Building a comprehensive syntactic and semantic corpus of Chinese clinical texts.

PubMed

He, Bin; Dong, Bin; Guan, Yi; Yang, Jinfeng; Jiang, Zhipeng; Yu, Qiubin; Cheng, Jianyi; Qu, Chunyan

2017-05-01

To build a comprehensive corpus covering syntactic and semantic annotations of Chinese clinical texts with corresponding annotation guidelines and methods as well as to develop tools trained on the annotated corpus, which supplies baselines for research on Chinese texts in the clinical domain. An iterative annotation method was proposed to train annotators and to develop annotation guidelines. Then, by using annotation quality assurance measures, a comprehensive corpus was built, containing annotations of part-of-speech (POS) tags, syntactic tags, entities, assertions, and relations. Inter-annotator agreement (IAA) was calculated to evaluate the annotation quality and a Chinese clinical text processing and information extraction system (CCTPIES) was developed based on our annotated corpus. The syntactic corpus consists of 138 Chinese clinical documents with 47,426 tokens and 2612 full parsing trees, while the semantic corpus includes 992 documents that annotated 39,511 entities with their assertions and 7693 relations. IAA evaluation shows that this comprehensive corpus is of good quality, and the system modules are effective. The annotated corpus makes a considerable contribution to natural language processing (NLP) research into Chinese texts in the clinical domain. However, this corpus has a number of limitations. Some additional types of clinical text should be introduced to improve corpus coverage and active learning methods should be utilized to promote annotation efficiency. In this study, several annotation guidelines and an annotation method for Chinese clinical texts were proposed, and a comprehensive corpus with its NLP modules were constructed, providing a foundation for further study of applying NLP techniques to Chinese texts in the clinical domain. Copyright © 2017. Published by Elsevier Inc.

Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus

PubMed Central

Chong, Vui Heng

2013-01-01

Heterotopic gastric mucosa of the proximal esophagus (HGMPE), also referred to as “inlet patch” or “cervical inlet patch”, is a salmon colored patch that is usually located just distal to the upper esophageal sphincter. HGMPE is uncommon with endoscopic studies reporting a prevalence ranging from less than one percent to 18%. Most HGMPE are asymptomatic and are detected incidentally during endoscopy for evaluations of other gastrointestinal complaints. Most consider HGMPE as clinically irrelevant entity. The clinical significance of HGMPE is mainly acid related or neoplastic transformation. The reported prevalence of laryngopharyngeal reflux symptoms varies from less than 20% to as high as 73.1%. However, most of these symptoms are mild. Clinically significant acid related complications such as bleeding, ulcerations, structure and fistulization have been reported. Although rare, dysplastic changes and malignancies in association with HGMPE have also been reported. Associations with Barrett’s esophagus have also been reported but the findings so far have been conflicting. There are still many areas that are unknown or not well understood and these include the natural history of HGMPE, risk factors for complications, role of Helicobacter pylori infection and factors associated with malignant transformations. Follow-up may need to be considered for patients with complications of HGMPE and surveillance if biopsies show intestinal metaplasia or dysplastic changes. Despite the overall low incidence of clinically relevant manifestations reported in the literature, HGMPE is a clinically significant entity but further researches are required to better understand its clinical significance. PMID:23372354

Infectious and autoantibody-associated encephalitis: clinical features and long-term outcome.

PubMed

Pillai, Sekhar C; Hacohen, Yael; Tantsis, Esther; Prelog, Kristina; Merheb, Vera; Kesson, Alison; Barnes, Elizabeth; Gill, Deepak; Webster, Richard; Menezes, Manoj; Ardern-Holmes, Simone; Gupta, Sachin; Procopis, Peter; Troedson, Christopher; Antony, Jayne; Ouvrier, Robert A; Polfrit, Yann; Davies, Nicholas W S; Waters, Patrick; Lang, Bethan; Lim, Ming J; Brilot, Fabienne; Vincent, Angela; Dale, Russell C

2015-04-01

Pediatric encephalitis has a wide range of etiologies, clinical presentations, and outcomes. This study seeks to classify and characterize infectious, immune-mediated/autoantibody-associated and unknown forms of encephalitis, including relative frequencies, clinical and radiologic phenotypes, and long-term outcome. By using consensus definitions and a retrospective single-center cohort of 164 Australian children, we performed clinical and radiologic phenotyping blinded to etiology and outcomes, and we tested archived acute sera for autoantibodies to N-methyl-D-aspartate receptor, voltage-gated potassium channel complex, and other neuronal antigens. Through telephone interviews, we defined outcomes by using the Liverpool Outcome Score (for encephalitis). An infectious encephalitis occurred in 30%, infection-associated encephalopathy in 8%, immune-mediated/autoantibody-associated encephalitis in 34%, and unknown encephalitis in 28%. In descending order of frequency, the larger subgroups were acute disseminated encephalomyelitis (21%), enterovirus (12%), Mycoplasma pneumoniae (7%), N-methyl-D-aspartate receptor antibody (6%), herpes simplex virus (5%), and voltage-gated potassium channel complex antibody (4%). Movement disorders, psychiatric symptoms, agitation, speech dysfunction, cerebrospinal fluid oligoclonal bands, MRI limbic encephalitis, and clinical relapse were more common in patients with autoantibodies. An abnormal outcome occurred in 49% of patients after a median follow-up of 5.8 years. Herpes simplex virus and unknown forms had the worst outcomes. According to our multivariate analysis, an abnormal outcome was more common in patients with status epilepticus, magnetic resonance diffusion restriction, and ICU admission. We have defined clinical and radiologic phenotypes of infectious and immune-mediated/autoantibody-associated encephalitis. In this resource-rich cohort, immune-mediated/autoantibody-associated etiologies are common, and the recognition and treatment of these entities should be a clinical priority. Copyright © 2015 by the American Academy of Pediatrics.

Personalized Medicine: how to Switch from the Concept to the Integration into the Clinical Development Plan to Obtain Marketing Authorization.

PubMed

Becquemont, Laurent; Bordet, Régis; Cellier, Dominic

2012-01-01

One of the challenges of the coming years is to personalize medicine in order to provide each patient with an individualized treatment plan. The three objectives of personalized medicine are to refine diagnosis, rationalize treatment and engage patients in a preventive approach. Personalization can be characterized by various descriptors whether related to the field, biology, imaging, type of lesion of the entity to be treated, comorbidity factors, coprescriptions or the environment As part of personalized medicine focused on biological markers including genetics or genomics, the integration of the clinical development plan to obtain marketing authorization may be segmented in 3 stages with a known descriptor identified before clinical development, a known descriptor discovered during clinical development or a known descriptor known after clinical development. For each stage, it is important to clearly define the technical optimization elements, to specify the expectations and objectives, to examine the methodological aspects of each clinical development phase and finally to consider the fast changing regulatory requirements in view of the few registered therapeutics complying with the definition of personalized medicine as well as the significant technological breakthroughs according to the screened and selected biomarkers. These considerations should be integrated in view of the time required for clinical development from early phase to MA, i.e. more than 10 years. Moreover, business models related to the economic environment should be taken into account when deciding whether or not to retain a biomarker allowing the selection of target populations in a general population. © 2012 Société Française de Pharmacologie et de Thérapeutique.

Validation of the Hirst-Type Spore Trap for Simultaneous Monitoring of Prokaryotic and Eukaryotic Biodiversities in Urban Air Samples by Next-Generation Sequencing.

PubMed

Núñez, Andrés; Amo de Paz, Guillermo; Ferencova, Zuzana; Rastrojo, Alberto; Guantes, Raúl; García, Ana M; Alcamí, Antonio; Gutiérrez-Bustillo, A Montserrat; Moreno, Diego A

2017-07-01

Pollen, fungi, and bacteria are the main microscopic biological entities present in outdoor air, causing allergy symptoms and disease transmission and having a significant role in atmosphere dynamics. Despite their relevance, a method for monitoring simultaneously these biological particles in metropolitan environments has not yet been developed. Here, we assessed the use of the Hirst-type spore trap to characterize the global airborne biota by high-throughput DNA sequencing, selecting regions of the 16S rRNA gene and internal transcribed spacer for the taxonomic assignment. We showed that aerobiological communities are well represented by this approach. The operational taxonomic units (OTUs) of two traps working synchronically compiled >87% of the total relative abundance for bacterial diversity collected in each sampler, >89% for fungi, and >97% for pollen. We found a good correspondence between traditional characterization by microscopy and genetic identification, obtaining more-accurate taxonomic assignments and detecting a greater diversity using the latter. We also demonstrated that DNA sequencing accurately detects differences in biodiversity between samples. We concluded that high-throughput DNA sequencing applied to aerobiological samples obtained with Hirst spore traps provides reliable results and can be easily implemented for monitoring prokaryotic and eukaryotic entities present in the air of urban areas. IMPORTANCE Detection, monitoring, and characterization of the wide diversity of biological entities present in the air are difficult tasks that require time and expertise in different disciplines. We have evaluated the use of the Hirst spore trap (an instrument broadly employed in aerobiological studies) to detect and identify these organisms by DNA-based analyses. Our results showed a consistent collection of DNA and a good concordance with traditional methods for identification, suggesting that these devices can be used as a tool for continuous monitoring of the airborne biodiversity, improving taxonomic resolution and characterization together. They are also suitable for acquiring novel DNA amplicon-based information in order to gain a better understanding of the biological particles present in a scarcely known environment such as the air. Copyright © 2017 American Society for Microbiology.

Validation of the Hirst-Type Spore Trap for Simultaneous Monitoring of Prokaryotic and Eukaryotic Biodiversities in Urban Air Samples by Next-Generation Sequencing

PubMed Central

Núñez, Andrés; Amo de Paz, Guillermo; Ferencova, Zuzana; Rastrojo, Alberto; Guantes, Raúl; García, Ana M.; Alcamí, Antonio; Gutiérrez-Bustillo, A. Montserrat

2017-01-01

ABSTRACT Pollen, fungi, and bacteria are the main microscopic biological entities present in outdoor air, causing allergy symptoms and disease transmission and having a significant role in atmosphere dynamics. Despite their relevance, a method for monitoring simultaneously these biological particles in metropolitan environments has not yet been developed. Here, we assessed the use of the Hirst-type spore trap to characterize the global airborne biota by high-throughput DNA sequencing, selecting regions of the 16S rRNA gene and internal transcribed spacer for the taxonomic assignment. We showed that aerobiological communities are well represented by this approach. The operational taxonomic units (OTUs) of two traps working synchronically compiled >87% of the total relative abundance for bacterial diversity collected in each sampler, >89% for fungi, and >97% for pollen. We found a good correspondence between traditional characterization by microscopy and genetic identification, obtaining more-accurate taxonomic assignments and detecting a greater diversity using the latter. We also demonstrated that DNA sequencing accurately detects differences in biodiversity between samples. We concluded that high-throughput DNA sequencing applied to aerobiological samples obtained with Hirst spore traps provides reliable results and can be easily implemented for monitoring prokaryotic and eukaryotic entities present in the air of urban areas. IMPORTANCE Detection, monitoring, and characterization of the wide diversity of biological entities present in the air are difficult tasks that require time and expertise in different disciplines. We have evaluated the use of the Hirst spore trap (an instrument broadly employed in aerobiological studies) to detect and identify these organisms by DNA-based analyses. Our results showed a consistent collection of DNA and a good concordance with traditional methods for identification, suggesting that these devices can be used as a tool for continuous monitoring of the airborne biodiversity, improving taxonomic resolution and characterization together. They are also suitable for acquiring novel DNA amplicon-based information in order to gain a better understanding of the biological particles present in a scarcely known environment such as the air. PMID:28455334

Comparative symptomatology of burnout and depression.

PubMed

Bianchi, Renzo; Boffy, Claire; Hingray, Coraline; Truchot, Didier; Laurent, Eric

2013-06-01

The link between burnout and depression remains unclear. In this study, we compared depressive symptoms in 46 burned-out workers, 46 outpatients experiencing a major depressive episode, and 453 burnout-free workers to test the distinctiveness of burnout as a clinical entity. Participants with burnout and major depressive episode reported similar, severe levels of overall depressive symptoms. The between-syndrome overlap was further verified for eight of the nine major depressive episode diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.). Our findings do not support the view hypothesizing that burnout and depression are separate entities and question the nosological added value of the burnout construct.

MRI findings in acute hyperammonemic encephalopathy resulting from decompensated chronic liver disease.

PubMed

Sureka, Jyoti; Jakkani, Ravi Kanth; Panwar, Sanuj

2012-06-01

Hyperammonemic encephalopathy is a type of metabolic encephalopathy with diversified etiology. Hyperammonemia is the end result of several metabolic disorders such as congenital deficiencies of urea cycle enzymes, hepatic encephalopathy, Reye's syndrome and other toxic encephalopathies. Non-specific clinical presentation poses a great challenge in early diagnosis of this entity. Irrespective of the underlying etiology, hyperammonemia causes a distinctive pattern of brain parenchymal injury. The cingulate gyrus and insular cortex are more vulnerable to this type of toxic insult. Characteristic magnetic resonance imaging findings in combination with laboratory parameters can help to differentiate this entity from other metabolic encephalopathy and thus aiding in early diagnosis and treatment.

Politics, culture, and the legitimacy of disease: the case of Buerger's disease.

PubMed

Lockwood, Stephen J; Bresler, Scott C; Granter, Scott R

2016-09-01

Thromboangiitis obliterans (TAO) or Buerger's disease is a rare form of vasculitis with distinctive clinical and pathological features that carries significant morbidity, often leading to amputation, and is strongly associated with tobacco smoking. Despite its distinctive clinicopathological characteristics, the existence of TAO as an entity sui generis was challenged for many years as it languished in relative obscurity. Then, as societal attitudes towards smoking changed, TAO not only became accepted as a disease entity, it quite literally became a poster child to illustrate the ills of smoking. Herein, we examine the history of TAO to illustrate the power of societal attitudes and politics in shaping medicine.

Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum.

PubMed

Schee, Jie Ping; Viswanathan, Shanthi

2018-05-01

We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.

Case Report: A giant but silent adrenal pheochromocytoma – a rare entity

PubMed Central

Munakomi, Sunil; Rajbanshi, Saroj; Adhikary, Prof Shailesh

2016-01-01

Herein we report a rare entity of a giant adrenal pheochromocytoma in a fifty-year-old male presenting with a vague abdominal pain. A computerised tomogram of the abdomen revealed a well-defined  left supraadrenal giant lesion with no evidence of invasion to surrounding structures.The patient underwent surgical excision without any untoward postoperative events. Histopathological study revealed a benign pheochromocytoma. This report highlights the importance of acknowledging the fact that sometimes a giant adrenal pheochromocytoma can present with paucity of clinical  signs and symptoms.Thorough investigations and a multidisciplinary team approach may lead  to a better outcome in these patients. PMID:27785358

[Predictive factors of depression in adolescents at school: the role of implicit theories of intelligence].

PubMed

Da Fonseca, D; Cury, F; Rufo, M; Poinso, F

2007-10-01

The aim of this study was to complete the identification of predictive factors of depression during adolescence. For some authors, depression is characterized by a style of attribution, which consists essentially in attributing most of the negative outcomes to internal, stable, and uncontrollable factors. It seems that these attributions depend essentially on the type of their beliefs and in particular, those concerning the nature of intelligence. These beliefs called "implicit theories of intelligence", are the entity theory of intelligence and the incremental theory of intelligence. The entity theory of intelligence corresponds to the belief according to which intelligence is the expression of a relatively stable, fixed, and noncontrollable feature, and which we cannot change. In contrast, the incremental theory corresponds to the belief according to which intelligence is a controllable quality, which we can develop through effort and work. Several studies have demonstrated that the adolescents who consider intelligence as a malleable quality explain their bad results by internal, unstable, and controllable factors. Conversely, students who consider intelligence as a fixed capacity tend to strongly attribute their failure to internal, stable, and uncontrollable factors. We have consequently formulated the hypothesis according to which the entity theory should be a predictive factor of depression. We have also tested the fact that anxiety should be a mediating factor within the relation between the entity theory and depression. The sample was composed of 424 adolescents. Using different questionnaires, we measured implicit theories of the intelligence (TIDI), self-esteem (EES), anxiety (STAI-Form Y-B) and depression (CDI). Multiple regression analyses demonstrated that the entity theory of intelligence positively predicts depression. Self-esteem negatively predicts anxiety and depression. Moreover, anxiety is a mediator of the relation between self-esteem and depression, on one hand, and the relation between the entity theory of intelligence and depression, on the other. Finally, the effect of the entity theory of intelligence appears to be modulated by the level of self-esteem. This study explains the mechanisms by which the implicit theories of intelligence engender anxiety and depression. Furthermore, this approach provides interesting perspectives in the prevention and management of adolescents presenting depression.

Spatial Statistical Model and Optimal Survey Design for Rapid Geophysical Characterization of UXO Sites

DTIC Science & Technology

2003-07-01

4, Gnanadesikan , 1977). An entity whose measured features fall into one of the regions is classified accordingly. For the approaches we discuss here... Gnanadesikan , R. 1977. Methods for Statistical Data Analysis of Multivariate Observations. John Wiley & Sons, New York. Hassig, N. L., O’Brien, R. F

76 FR 33969 - Marketing Order Regulating the Handling of Spearmint Oil Produced in the Far West; Revision of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-10

... small entities. The Far West spearmint oil industry is characterized by producers whose farming operations generally involve more than one commodity, and whose income from farming operations is not... cultural practice in the production of spearmint oil for weed, insect, and disease control. To remain...

Brief Report: Acrocallosal Syndrome and Autism

ERIC Educational Resources Information Center

Steiner, Carlos Eduardo; Guerreiro, Marilisa Mantovani; Marques-de-Faria, Antonia Paula

2004-01-01

The authors describe a boy presenting with acrocallosal syndrome and autism. Clinical features included craniofacial dysmorphisms, polydactyly, and mental retardation, besides behavioral symptoms compatible with autism. Neuroimaging revealed hypoplasia of the corpus callosum and cerebellar abnormalities. The role of this entity and other…

The emergence of overweight as a disease entity: measuring up normality.

PubMed

Jutel, Annemarie

2006-11-01

As Charles Rosenberg [(2002). The tyranny of diagnosis. The Milbank Quarterly, 80, 237-260] has recently written, clinical diagnosis contributes to imposing structure on cultural reality in a manner which is not unproblematic. A social power resides in the process of naming diseases-one, which legitimises concerns, explains reality, naturalises deviance and imposes status. But clinical entities are not static, as both the concerns of society, and the technological ability of practitioners change (what Rosenberg refers to as the "iatrogenesis of nosology"), so too do the range of labels available for identifying disease. In this paper, I argue that being "overweight," once predominantly an adjectival descriptor of corpulence, a physical sign or a symptom, and even, in some cultures, a sign of wealth and status, is undergoing the transformation to disease entity. I suggest that evidence of this is present in both the frequency and the way in which the term is being used by the media, the medical establishment and the laity. I argue that this change stems from the convergence of two particular phenomena. The first is the belief in the neutrality of quantification, and the objectivity that measurement brings to qualitative description. The second is the importance attributed to normative appearance in health. I discuss some of the implications of this evolution and its impact on health practices, including the exploitation of this purported disease state for commercial benefit.

Clinical and histopathologic study of benign lichenoid keratosis on the face.

PubMed

Kim, Han Su; Park, Eun Joo; Kwon, In Ho; Kim, Kwang Ho; Kim, Kwang Joong

2013-10-01

Benign lichenoid keratosis is a cutaneous entity that consists of a nonpruritic papule or slightly indurated plaque that is histologically characterized by a band-like inflammatory infiltrate with interface involvement. The purpose of this study was to investigate the clinical and histopathologic features of benign lichenoid keratosis localized on the face. Fourteen benign lichenoid keratosis patients diagnosed clinically and histopathologically in our clinic during the 10-year period from 2002 to 2012 were studied. Thirteen female and 1 male patients were included. The mean age at diagnosis was 46.5 years. The color of most of the lesions was brown (10 cases, 71%). The cheek was the most commonly involved area (10 cases, 71%). All of the lesions were single. There were 9 (64%) flat lesion cases and 5 (36%) raised lesion cases. Most patients denied having any symptoms; 3 had mild pruritus. The histopathological findings indicated that all the cases exhibited lichenoid inflammatory infiltrate obscuring the dermal-epidermal junction and vacuolar alteration of basal cell layer. The lesions showed focal parakeratosis (79%), melanophages (79%), hyperkeratosis (71%), and necrotic keratinocytes (71%). Solar elastosis (50%) and acanthosis (43%) were also seen frequently. Diagnosis of benign lichenoid keratosis should be made by a combination of clinical manifestations and histopathological findings. In particular, benign lichenoid keratosis should be considered if a middle-aged patient presents a solitary asymptomatic brown lesion on the face. We think benign lichenoid keratosis may be a specific disorder rather than the inflammatory stage of regressing solar lentigines, large cell acanthoma or reticulated seborrheic keratosis.

The epidemiology of molluscum contagiosum in children.

PubMed

Dohil, Magdalene A; Lin, Peggy; Lee, James; Lucky, Anne W; Paller, Amy S; Eichenfield, Lawrence F

2006-01-01

Molluscum contagiosum (MC) is a viral disorder of the skin and mucous membranes characterized by discrete single or multiple, flesh-colored papules. Although MC as a clinical entity is well defined and commonly observed, few data regarding its epidemiology in the pediatric population exist. Our purpose was to collect epidemiologic data on children with MC with regard to age, gender, ethnicity, degree of involvement, relation to pre-existing atopic dermatitis (AD), and immune status. A retrospective chart review was conducted. All subjects were seen at 3 tertiary pediatric dermatology referral centers with two of the sites based at a Children's Hospital. A total of 302 patient charts with the Current Procedural Terminology code diagnosis of MC seen over a 6- to 8-month period were reviewed. Approximately 80% of the patients were younger than 8 years old. The majority of patients (63%) had more than 15 lesions. All but one patient were otherwise healthy, as determined by history and clinical examination. Approximately 24% of the patients presented with a history of previous or active coexistent AD. However, children with AD were at risk for an increased number of lesions. These data provide valuable updated information on the demographics and clinical presentation of MC in pediatric patients in the United States. Limitations include that this was a retrospective study with a population limited to tertiary pediatric dermatology referral centers.

Myeloproliferative Neoplasms in Children.

PubMed

Hofmann, Inga

2015-09-01

Myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic stem cell disorders characterized by aberrant proliferation of one or more myeloid lineages often with increased immature cells in the peripheral blood. The three classical BCR-ABL-negative MPNs are: 1) polycythemia vera (PV), 2) essential thrombocythemia (ET), and 3) primary myelofibrosis (PMF), which are typically disorders of older adults and are exceedingly rare in children. The diagnostic criteria for MPNs remain largely defined by clinical, laboratory and histopathology assessments in adults, but they have been applied to the pediatric population. The discovery of the JAK2 V617F mutation, and more recently, MPL and CALR mutations, are major landmarks in the understanding of MPNs. Nevertheless, they rarely occur in children, posing a significant diagnostic challenge given the lack of an objective, clonal marker. Therefore, in pediatric patients, the diagnosis must rely heavily on clinical and laboratory factors, and exclusion of secondary disorders to make an accurate diagnosis of MPN. This review focuses on the clinical presentation, diagnostic work up, differential diagnosis, treatment and prognosis of the classical BCR-ABL-negative MPNs (PV, ET and PMF) in children and highlights key differences to the adult diseases. Particular attention will be given to pediatric PMF, as it is the only disorder of this group that is observed in infants and young children, and in many ways appears to be a unique entity compared to adult PMF.

Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family.

PubMed

Sólia-Nasser, L; de Aquino, S-N; Paranaíba, L-M R; Gomes, A; Dos-Santos-Neto, P; Coletta, R-D; Cardoso, A-F; Frota, A-C; Martelli-Júnior, H

2016-05-01

The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1.

D’Andrea’s disease (angiomegaly): a currently well-defined nosological entitys.

PubMed

Taurone, S; Spoletini, M; Di Matteo, F M; Mele, R; Tromba, L; Grippaudo, F R; Minni, A; Artico, M

2017-01-01

In 1997 D’Andrea et al. described a new nosological entity the characteristics of which consisted of lengthening, dilation and tortuosity of blood vessels, arteries or veins, less prominent, but also less circumscribed than an aneurysm. This condition does not necessarily imply specific aneurysm formation although aneurysms at multiple sites are a frequent observation. The term used by authors for angiomegaly of the venous system was venomegaly and the analogous condition of the arterial system was termed arteriomegaly. Although tortuosity and dilation of arteries and veins have been widely reported, suggesting a systemic disorder which affects the structural integrity of all vessels, most papers dealing with this intriguing condition did not describe any alterations in the components of vessel walls. In the present paper, the authors describe a well-defined condition, D’Andrea’s Disease (or DD, in this article), analyzing its salient morphological and clinical features and clarifying this pathological condition as a distinct and now well-defined nosological entity.

Characterization of lymphocyte populations in nonspecific interstitial pneumonia*

PubMed Central

Keogh, Karina A; Limper, Andrew H

2005-01-01

Study objectives Nonspecific interstitial pneumonia (NSIP) has been identified as a distinct entity with a more favorable prognosis and better response to immunosuppressive therapies than usual interstitial pneumonia (UIP). However the inflammatory profile of NSIP has not been characterized. Design Using immunohistochemistry techniques on open lung biopsy specimens, the infiltrate in NSIP was characterized in terms of T and B cells, and macrophages, and the T cell population further identified as either CD4 (helper) or CD8 (suppressor-cytotoxic) T cells. The extent of Th1 and Th2 cytokine producing cells was determined and compared to specimens from patients with UIP. Results In ten NSIP tissue samples 41.4 ± 4% of mononuclear cells expressed CD3, 24.7 ± 1.8% CD4, 19.1 ± 2% CD8, 27.4 ± 3.9% CD20, and 14.3 ± 1.6% had CD68 expression. Mononuclear cells expressed INFγ 21.9 ± 1.9% of the time and IL-4 in 3.0 ± 1%. In contrast, biopsies from eight patients with UIP demonstrated substantially less cellular staining for either cytokine (INFγ; 4.6 ± 1.7% and IL-4; 0.6 ± 0.3%). Significant populations of CD20 positive B-cells were also identified. Conclusion The lymphocytic infiltrate in NSIP is characterized by an elevated CD4/CD8 T-cell ratio, and is predominantly of Th1 type, with additional populations rich in B-cells. Such features are consistent with the favorable clinical course observed in patients with NSIP compared to UIP. PMID:16287509

42 CFR 2a.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

...-RESEARCH SUBJECTS § 2a.2 Definitions. (a) Secretary means the Secretary of Health and Human Services and... subdivision or agency, business trust, partnership, association, or other legal entity. (c) Research means... includes, but is not limited to, behavioral science studies, surveys, evaluations, and clinical...

42 CFR 2a.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-RESEARCH SUBJECTS § 2a.2 Definitions. (a) Secretary means the Secretary of Health and Human Services and... subdivision or agency, business trust, partnership, association, or other legal entity. (c) Research means... includes, but is not limited to, behavioral science studies, surveys, evaluations, and clinical...

42 CFR 2a.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

...-RESEARCH SUBJECTS § 2a.2 Definitions. (a) Secretary means the Secretary of Health and Human Services and... subdivision or agency, business trust, partnership, association, or other legal entity. (c) Research means... includes, but is not limited to, behavioral science studies, surveys, evaluations, and clinical...

42 CFR 2a.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-RESEARCH SUBJECTS § 2a.2 Definitions. (a) Secretary means the Secretary of Health and Human Services and... subdivision or agency, business trust, partnership, association, or other legal entity. (c) Research means... includes, but is not limited to, behavioral science studies, surveys, evaluations, and clinical...

42 CFR 2a.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

...-RESEARCH SUBJECTS § 2a.2 Definitions. (a) Secretary means the Secretary of Health and Human Services and... subdivision or agency, business trust, partnership, association, or other legal entity. (c) Research means... includes, but is not limited to, behavioral science studies, surveys, evaluations, and clinical...

Efficient Execution Methods of Pivoting for Bulk Extraction of Entity-Attribute-Value-Modeled Data

PubMed Central

Luo, Gang; Frey, Lewis J.

2017-01-01

Entity-attribute-value (EAV) tables are widely used to store data in electronic medical records and clinical study data management systems. Before they can be used by various analytical (e.g., data mining and machine learning) programs, EAV-modeled data usually must be transformed into conventional relational table format through pivot operations. This time-consuming and resource-intensive process is often performed repeatedly on a regular basis, e.g., to provide a daily refresh of the content in a clinical data warehouse. Thus, it would be beneficial to make pivot operations as efficient as possible. In this paper, we present three techniques for improving the efficiency of pivot operations: 1) filtering out EAV tuples related to unneeded clinical parameters early on; 2) supporting pivoting across multiple EAV tables; and 3) conducting multi-query optimization. We demonstrate the effectiveness of our techniques through implementation. We show that our optimized execution method of pivoting using these techniques significantly outperforms the current basic execution method of pivoting. Our techniques can be used to build a data extraction tool to simplify the specification of and improve the efficiency of extracting data from the EAV tables in electronic medical records and clinical study data management systems. PMID:25608318

Contact dermatitis in saffron workers: clinical profile and identification of contact sensitizers in a saffron-cultivating area of Kashmir Valley of North India.

PubMed

Hassan, Iffat; Kamili, Afifa; Rasool, Farhan; Nehvi, Firdous; Rather, Parvaiz; Yasmin, Salwee; Pampori, Rafiq A; Jabeen, Yasmeen; Yaseen, Atiya; Bashir, Safia; Naaz, Saima

2015-01-01

Saffron, a bulbous perennial plant belonging to Iridaceae family, is the most expensive cultivated herb that is widely used for industrial and nonindustrial purposes. However, besides its attractive and valuable properties, contact dermatitis due to saffron is an uncommon reported entity. The aims of this study were to determine the clinical pattern patch-testing profile of contact dermatitis in saffron workers and to identify the most common allergens/sensitizers. One hundred ten saffron workers were patch-tested with 39 allergens, which included Indian standard series antigens, plant series antigens, and extracts from different parts of saffron flower. The allergens in Indian standard series accounted for 52.44% of positive reactions. Plant series and different parts of saffron accounted for 47.56% of the positive reactions. Among those patients with positive responses to the supplemental saffron allergens, 83.3% were of present or past relevance. The data observed in the present study confirm that the saffron dermatitis is a distinct clinical entity with characteristic clinical presentation and has a strong significance as an occupational allergen in those handling this plant. Patch testing with different parts of saffron flower has a role to play in finding out the etiological cause.

Combination nucleoside/nucleotide reverse transcriptase inhibitors for treatment of HIV infection.

PubMed

Akanbi, Maxwell O; Scarsi, Kimberly K; Scarci, Kimberly; Taiwo, Babafemi; Murphy, Robert L

2012-01-01

The combination of two nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) and a third agent from another antiretroviral class is currently recommended for initial antiretroviral therapy. In general, N(t)RTIs remain relevant in subsequent regimens. There are currently six nucleoside reverse transcriptase inhibitors and one nucleotide reverse transcriptase inhibitor drug entities available, and several formulations that include two or more N(t)RTIs in a fixed-dose combination. These entities have heterogeneous pharmacological and clinical properties. Accordingly, toxicity, pill burden, dosing frequency, potential drug-drug interaction, preexisting antiretroviral drug resistance and comorbid conditions should be considered when constructing a regimen. This approach is critical in order to optimize virologic efficacy and clinical outcomes. This article reviews N(t)RTI combinations used in the treatment of HIV-infected adults. The pharmacological properties of each N(t)RTI, and the clinical trials that have influenced treatment guidelines are discussed. It is likely that N(t)RTIs will continue to dominate the global landscape of HIV treatment and prevention, despite emerging interest in N(t)RTI-free combination therapy. Clinical domains where only few alternatives to N(t)RTIs exist include treatment of HIV/HBV coinfection and HIV-2. There is a need for novel N(t)RTIs with enhanced safety and resistance profiles compared with current N(t)RTIs.

Papillary tumor of the pineal region: two case studies and a review of the literature.

PubMed

Rickard, Kyle A; Parker, John R; Vitaz, Todd W; Plaga, Alexis R; Wagner, Stephanie; Parker, Joseph C

2011-01-01

Papillary tumor of the pineal region (PTPR) is a newly recognized distinct entity in the 2007 World Health Organization nomenclature. This tumor is characterized by epithelial-appearing areas with papillary features and more densely cellular areas that often display ependymal-like differentiation. Ultrastructurally, this rare neuroepithelial tumor possesses neuroendocrine, secretory, and ependymal organelles that likely originate from the subcommissural organ (SCO) near the aqueduct of Sylvius. To date, approximately fifty-seven described cases worldwide have been recognized, with ages ranging from 5 years to 66 years (mean age=32 years). Clinical presentation most often includes headache and obstructive hydrocephalus. The tumor, which is well circumscribed, may be cystic and radiographically is often considered to be consistent with the findings of a pineocytoma. Microscopic evaluation often demonstrates a lesion with papillary areas lined by epithelioid tumor cells with eosinophilic cytoplasm and more cellular areas with cells exhibiting clear or vacuolated cytoplasm. Perivascular and true rosettes may be identified. Distinctive immunohistochemical features including reactivity for keratins (AE1/AE3, CAM 5.2, CK18) and only focal GFAP staining help distinguish this neoplasm from an ependymoma. The relative paucity of data compiled for this tumor makes giving an accurate diagnosis and prognosis a daunting task. We discuss two additional cases of PTPR that presented to us within a three-month span in order to more fully elucidate the possible presentations of this rare entity. Furthermore, we examine now 59 reported cases of PTPR in order to review the current diagnostic and treatment modalities in addition to exploring emerging research encompassing this unusual neoplasm.

c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).

PubMed

Gehringer, Matthias; Muth, Felix; Koch, Pierre; Laufer, Stefan A

2015-01-01

c-Jun N-terminal kinases (JNKs) are involved in the emergence and progression of diverse pathologies such as neurodegenerative, cardiovascular and metabolic disorders as well as inflammation and cancer. In recent years, several highly selective pan-JNK inhibitors have been characterized and three chemical entities targeting JNKs have been investigated in clinical trials. This review summarizes patents claiming inhibitors of all JNK isoforms published between 2010 and 2014. Although primarily focusing on the patent literature, relevant peer-reviewed publications related to the covered patents have also been included. Moreover, key patents claiming novel applications of previously published chemical entities are reviewed. The article highlights a total of 28 patents from nine pharmaceutical companies and academic research groups. Although some selective pan-JNK inhibitors with reasonable in vivo profiles are now available, little is known about the isoform selectivity required for each particular indication and the development of isoform-selective JNK inhibitors still represents a challenge in JNK drug discovery. Moreover, isoform-selective tool compounds are a prerequisite to a comprehensive understanding of the biology of each JNK isoform. Potential approaches towards such compounds include the design of type-II and type-I(1)/2 binders, which are absent in the current JNK inhibitor portfolios, as well as the design of novel allosteric inhibitors. Furthermore, covalent inhibition, which already led to the first high-quality probe for JNKs, might be further exploited for gaining selectivity and in vivo efficacy. With regard to a potential therapeutic application, the recently proposed concept of covalent reversible inhibitors is expected to be attractive.

The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms.

PubMed

Matutes, E

2018-05-01

Over the last decade, there has been a significant body of information regarding the biology of the lymphoid neoplasms. This clearly supports the need for updating the 2008 WHO (World Health Organization) classification of haematopoietic and lymphoid tumours. The 2017 WHO classification is not a new edition but an update and revision of the 4th edition. New provisional entities but not new definitive entities are included, and novel molecular data in most of the entities and changes in the nomenclature in few of them have been incorporated. In the context of the mature T- and NK-cell neoplasms, the most relevant updates concern to: 1-dysregulation of the JAK/STAT pathway due to gene mutations which are common to various aggressive and indolent neoplasms; 2-incorporation of new molecular players that are relevant to the pathogenesis of these neoplasms and/or have prognostic implications; 3-inclusion of new provisional entities within the subgroups of anaplastic, primarily intestinal and cutaneous lymphomas such as breast implant-associated anaplastic large cell lymphoma, indolent T-cell lymphoproliferative disorder of the gastrointestinal tract and primary cutaneous acral CD8 + T-cell lymphoma; 4-identification of poor prognostic subtypes of peripheral T-cell lymphomas not otherwise specified (PTCL, NOS) characterized by overexpression of certain genes and of a subgroup PTCL, NOS with a T follicular phenotype that now is included together with angioimmunoblastic T-cell lymphoma under the umbrella of lymphomas with a T follicular helper phenotype; and 5-refinement on the designation and definition of already established entities. A review of the major changes will be outlined. © 2018 John Wiley & Sons Ltd.

Characterization of Departures from Regulatory Requirements Identified During Inspections Conducted by the US Federal Select Agent Program, 2014-15.

PubMed

Bjork, Adam; Sosin, Daniel M

We studied departures from regulatory requirements identified on US Federal Select Agent Program (FSAP) inspections to increase transparency regarding biosafety and security risk at FSAP-regulated entities and identify areas for programmatic improvement. Regulatory departures from inspections led by Centers for Disease Control and Prevention inspectors during 2014-15 were grouped into "biosafety," "security," and "other" observation categories and assigned a risk level and score reflecting perceived severity. The resulting 2,267 biosafety (n = 1,153) and security (n = 1,114) observations from 296 inspections were analyzed by frequency and risk across entity and inspection characteristics. The greatest proportion of biosafety observations involved equipment and facilities (28%), and the greatest proportion of security observations involved access restrictions (33%). The greatest proportion of higher-risk observations for biosafety were containment issues and for security were inventory discrepancies. Commercial entities had the highest median cumulative risk score per inspection (17), followed by private (13), academic (10), federal government (10), and nonfederal government (8). Maximum containment (BSL-4) inspections had higher median biosafety risk per inspection (13) than other inspections (5) and lower security risk (0 vs 4). Unannounced inspections had proportionally more upper risk level observations than announced (biosafety, 21% vs 12%; security, 18% vs 7%). Possessors of select agents had higher median biosafety risk per inspection (6) than nonpossessors (4) and more upper risk level security observations (10% vs 0%). Programmatic changes to balance resources according to entity risk may strengthen FSAP oversight. Varying inspection methods by select agent possession and entity type, and conducting more unannounced inspections, may be beneficial.

The spectrum of canine cutaneous perivascular wall tumors: morphologic, phenotypic and clinical characterization.

PubMed

Avallone, G; Helmbold, P; Caniatti, M; Stefanello, D; Nayak, R C; Roccabianca, P

2007-09-01

Perivascular wall tumors (PWTs) are defined as neoplasms deriving from mural cells of blood vessels, excluding the endothelial lining. The spectrum of human cutaneous PWT includes glomus tumor, hemangiopericytoma (HEP), myopericytoma, angioleiomyoma/sarcoma, angiomyofibroblastoma, and angiofibroma. The purpose of this study was to revise clinical presentation, cytology, histopathology, and immunohistology of canine cutaneous PWT with cytology typical of canine HEP. Diagnosis was established on the basis of vascular growth patterns (staghorn, placentoid, perivascular whorling, bundles from media) and immunohistology, including 7 smooth muscle markers and the cell membrane ganglioside of unknown origin recognized by the antibody 3G5 (CMG-3G5). Twenty cases were included. Ages ranged from 6 to 13 years; 12 dogs were males and 8 were females, and there was a prevalence of crossbreeds. Tumors arose from a single site with preferential acral location (10/20). Cytology revealed moderate to high cellularity in all cases, cohesive groups of cells (19/20), capillaries (18/20), and bi- to multinucleated cells (18/20). Six myopericytomas, 5 angioleiomyomas, 2 angioleiomyosarcomas, 2 HEP, 1 angiofibroma, and 1 adventitial tumor were identified. A definitive diagnosis was not possible in 3 cases. Smoothelin, heavy caldesmon, desmin, myosin, calponin, and CMG-3G5 were the most valuable markers to differentially diagnose canine PWT. Similar to reports in humans, canine HEP embodied a spectrum of neoplastic entities arising from different vascular mural cells. Before canine PWTs are assimilated into one prognostic category, a consistent classification and characterization of their biology is necessary. As proposed in humans, HEP should also be considered a diagnosis of exclusion in dogs.

Clinical and genetic characterization of an autosomal dominant nephropathy.

PubMed

Parvari, R; Shnaider, A; Basok, A; Katchko, L; Borochovich, Z; Kanis, A; Landau, D

2001-03-15

Autosomal dominant familial nephropathies with adult onset, no macroscopic cysts, and progressive deterioration include medullary cystic disease (ADMCKD) as well as other less specific entities. We studied a kindred of Jewish ancestry in which 15 members (both male and female) have suffered from chronic renal failure. The first evidence of renal involvement was observed between 18 and 38 years. It included hypertension followed by progressive renal insufficiency. No polyuria, anemia, gout, hematuria, nor proteinuria were seen. An average of 4.5 years elapsed from diagnosis to end-stage renal disease. Renal pathology at early stages of the disease showed extensive tubulointerstitial fibrosis and global glomerulosclerosis. Linkage analysis was performed at the two known loci of ADMCKD, on Chromosomes 1 and 16. Linkage to the chromosome 16 locus was excluded. However, linkage to the chromosome 1q21 locus of ADMCKD was established with a maximum two-point LOD score of 3.82 to D1S394. The disease interval could be narrowed to about 9 cM/7.4 Mb between D1S1156 and D1S2635. Multiple-point linkage analysis revealed a maximum LOD of 4.21, with a broad peak from markers D1S2858 and D1S2624. This report establishes linkage between a familial nephropathy characterized by hypertension and progressive renal failure to the locus described for ADMCKD, a disease classically associated with macroscopic corticomedullary cysts, salt-losing tubulointerstitial nephropathy, and anemia. This finding broadens the clinical spectrum of ADMCKD positioned on chromosome 1q21 locus. Copyright 2001 Wiley-Liss. Inc.

A comprehensive comparison between pediatric and adult patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome.

PubMed

Rigante, Donato; Vitale, Antonio; Natale, Marco Francesco; Lopalco, Giuseppe; Andreozzi, Laura; Frediani, Bruno; D'Errico, Francesca; Iannone, Florenzo; Cantarini, Luca

2017-02-01

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome is a mysterious disorder characterized by periodically recurrent fevers, oropharyngeal inflammation, and adenitis, which mainly affects children, though in very recent times, it has been also recognized in adulthood. We enrolled 115 unrelated pediatric and adult patients with history of periodic fevers who fulfilled the current diagnostic criteria for PFAPA syndrome in three Italian referral centers and highlighted differences between children and adults. Eighty-five children and 30 adults were evaluated: the frequency of flares was significantly higher in pediatric cases, while febrile attack duration was significantly longer in adults. Clockwork periodicity of fever and recurrent pharyngitis were more frequently observed in childhood, but no differences were identified for aphthosis and cervical adenopathy. Conversely, joint symptoms, myalgia, headache, fatigue, ocular signs, and rashes were more common in adults. The simultaneous occurrence of two or three cardinal PFAPA signs did not show any statistical difference between the groups, while the occurrence of only one cardinal manifestation was more frequent in adults. Corticosteroids were effective in 98.82 % of children and 88.2 % of adults. Tonsillectomy was rarely performed, resulting effective in only two patients. Our data illustrate the clinical overlap between pediatric and adult cases of PFAPA syndrome. Adults are characterized by a wider repertoire of inflammatory signs, suggesting that onset in adulthood might leave the disease misdiagnosed. Clinicians, not only pediatricians, should take into account this clinical entity in every patient of whatever age suffering from recurrent fevers of unknown origin.

[Non-neoplastic enlargement of salivary glands: clinico-histologic analysis].

PubMed

González Guevara, Martha Beatriz; Torres Tejero, Marco Antonio; Martínez Mata, Guillermo

2005-01-01

We carried out a retrospective study on non-neoplastic enlargement of the salivary glands at the Oral Histopathology Diagnostic Center of the Autonomous Metropolitan University at Xochimilco (UAM-Xochimilco) in Mexico during a period of 24 years (1979-2003). From 5,625 biopsies received and analyzed, a total of 461 (8.2%) were non-neoplastic enlargement of the salivary glands; for each case, we registered demographic data as well as clinic characteristics. These lesions were characterized as a heterogeneous group of pathologic entities among which we included local, obstructive, infectious, and immunopathologic lesions. The most frequent lesion was the extravasation cyst in 341 (74%) cases, followed by chronic sialoadenitis and Sjögren's syndrome with 54 (11.7%) and 41 (8.8%) cases, respectively, and at a lesser percentage mucous retention cyst, sialosis, benign lymphoepithelial lesions and those related with sialolytes. Females were affected more frequently; mean age was second to third life decades. These lesions were most frequently localized on inferior labial mucosa.

Acute and chronic pancreatitis: surgical management.

PubMed

Dzakovic, Alexander; Superina, Riccardo

2012-08-01

Pancreatitis is becoming increasingly prevalent in children, posing new challenges to pediatric health care providers. Although some general adult treatment paradigms are applicable in the pediatric population, diagnostic workup and surgical management of acute and chronic pancreatitis have to be tailored to anatomic and pathophysiological entities peculiar to children. Nonbiliary causes of acute pancreatitis in children are generally managed nonoperatively with hydration, close biochemical and clinical observation, and early initiation of enteral feeds. Surgical intervention including cholecystectomy or endoscopic retrograde cholangiopancreatography is often required in acute biliary pancreatitis, whereas infected pancreatic necrosis remains a rare absolute indication for pancreatic debridement and drainage via open, laparoscopic, or interventional radiologic procedure. Chronic pancreatitis is characterized by painful irreversible changes of the parenchyma and ducts, which may result in or be caused by inadequate ductal drainage. A variety of surgical procedures providing drainage, denervation, resection, or a combination thereof are well established to relieve pain and preserve pancreatic function. Copyright © 2012. Published by Elsevier Inc.

Usefulness of a Simple Immunohistochemical Staining Technique to Differentiate Anti-p200 Pemphigoid From Other Autoimmune Blistering Diseases: A Report of 2 Cases.

PubMed

García-Díez, I; Martínez-Escala, M E; Ishii, N; Hashimoto, T; Mascaró Galy, J M; Pujol, R M; Herrero-González, J E

Anti-p200 pemphigoid is a rare autoimmune subepidermal blistering disease characterized by the presence of circulating immunoglobulin G antibodies directed against laminin gamma-1, a 200-kDa protein located in the lamina lucida of the basement membrane. We review the clinical, histopathological and immunological characteristics of the first 2 cases described in Spain. Anti-p200 pemphigoid shares histopathological and immunopathological findings with epidermolysis bullosa acquisita, the main entity in the differential diagnosis. However, its management follows the same guidelines as those used for bullous pemphigoid. The diagnosis is confirmed by immunoblotting, which is a complex technique available in few centers. We propose the immunohistochemical detection of collagen type IV on the floor of the blister, combined with standard immunofluorescence techniques, as a simple, accessible alternative to differentiate anti-p200 pemphigoid from epidermolysis bullosa acquisita. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Self-healing juvenile cutaneous mucinosis: cases highlighting subcutaneous/fascial involvement.

PubMed

Nagaraj, Lavanya V; Fangman, William; White, Wain L; Woosley, John T; Prose, Neil; Selim, M Angelica; Morrell, Dean S

2006-12-01

Self-healing juvenile cutaneous mucinosis is a rare disease affecting young people characterized by transient cutaneous lesions and sometimes mild inflammatory symptoms. The deep dermal and subcutaneous features of this disorder have not yet been well described. The purpose of our study was to present 3 cases of self-healing juvenile cutaneous mucinosis in which the histopathologic features caused diagnostic confusion between this disorder and proliferative fasciitis. The study includes clinical and histologic findings of 3 patients, complemented by a literature review. The histologic descriptions of nodular lesions in self-healing juvenile cutaneous mucinosis reveal features of proliferative fasciitis, including a myxoid stroma and gangliocyte-like giant cells. Self-healing juvenile cutaneous mucinosis is a rare condition and has not been frequently reported in medical literature. Our findings are based on the pathologic features of 3 patients. Our findings further elucidate the histologic features of self-healing juvenile cutaneous mucinosis and expand the differential diagnosis for entities in which gangliocyte-like giant cells are noted.

Biofilms in Endodontics-Current Status and Future Directions.

PubMed

Neelakantan, Prasanna; Romero, Monica; Vera, Jorge; Daood, Umer; Khan, Asad U; Yan, Aixin; Cheung, Gary Shun Pan

2017-08-11

Microbiota are found in highly organized and complex entities, known as biofilms, the characteristics of which are fundamentally different from microbes in planktonic suspensions. Root canal infections are biofilm mediated. The complexity and variability of the root canal system, together with the multi-species nature of biofilms, make disinfection of this system extremely challenging. Microbial persistence appears to be the most important factor for failure of root canal treatment and this could further have an impact on pain and quality of life. Biofilm removal is accomplished by a chemo-mechanical process, using specific instruments and disinfecting chemicals in the form of irrigants and/or intracanal medicaments. Endodontic research has focused on the characterization of root canal biofilms and the clinical methods to disrupt the biofilms in addition to achieving microbial killing. In this narrative review, we discuss the role of microbial biofilms in endodontics and review the literature on the role of root canal disinfectants and disinfectant-activating methods on biofilm removal.

CMML AND aCML: NOVEL PATHOGENETIC LESIONS

PubMed Central

Muramatsu, Hideki; Makishima, Hideki; Maciejewski, Jaroslaw P.

2012-01-01

Summary Chronic myelomonocytic leukemia (CMML) and atypical chronic myeloid leukemia (aCML) are distinct, yet related, entities of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) characterized by morphologic dysplasia with accumulation of monocytes or neutrophils, respectively. Our understanding of the molecular pathogenesis of CMML and aCML has advanced, mainly due to the application of novel technologies such as array-based karyotyping or next generation sequencing. In addition to previously known recurrent aberrations, somatic uniparental disomy affecting chromosomes 3, 4, 7, and 11 frequently occurs in CMML. Novel somatic mutations of genes, including those associated with proliferation signaling (CBL, RAS, RUNX1, JAK2 (V617F)) and with modification of epigenetic status (TET2, ASXL1, UTX, EZH2) have been found. Various combinations of mutations suggest a multistep pathogenesis and may account for clinical heterogeneity. The prognostic and diagnostic significance of these molecular lesions, in particular their value as biomarkers of response or resistance to specific therapies, while uncertain now is likely to be clarified as large systematic studies come to completion. PMID:22289493