Standards to support information systems integration in anatomic pathology.

PubMed

Daniel, Christel; García Rojo, Marcial; Bourquard, Karima; Henin, Dominique; Schrader, Thomas; Della Mea, Vincenzo; Gilbertson, John; Beckwith, Bruce A

2009-11-01

Integrating anatomic pathology information- text and images-into electronic health care records is a key challenge for enhancing clinical information exchange between anatomic pathologists and clinicians. The aim of the Integrating the Healthcare Enterprise (IHE) international initiative is precisely to ensure interoperability of clinical information systems by using existing widespread industry standards such as Digital Imaging and Communication in Medicine (DICOM) and Health Level Seven (HL7). To define standard-based informatics transactions to integrate anatomic pathology information to the Healthcare Enterprise. We used the methodology of the IHE initiative. Working groups from IHE, HL7, and DICOM, with special interest in anatomic pathology, defined consensual technical solutions to provide end-users with improved access to consistent information across multiple information systems. The IHE anatomic pathology technical framework describes a first integration profile, "Anatomic Pathology Workflow," dedicated to the diagnostic process including basic image acquisition and reporting solutions. This integration profile relies on 10 transactions based on HL7 or DICOM standards. A common specimen model was defined to consistently identify and describe specimens in both HL7 and DICOM transactions. The IHE anatomic pathology working group has defined standard-based informatics transactions to support the basic diagnostic workflow in anatomic pathology laboratories. In further stages, the technical framework will be completed to manage whole-slide images and semantically rich structured reports in the diagnostic workflow and to integrate systems used for patient care and those used for research activities (such as tissue bank databases or tissue microarrayers).

The association of magnetic resonance imaging (MRI)-detected structural pathology of the knee with crepitus in a population-based cohort with knee pain: the MoDEKO study.

PubMed

Crema, M D; Guermazi, A; Sayre, E C; Roemer, F W; Wong, H; Thorne, A; Singer, J; Esdaile, J M; Marra, M D; Kopec, J A; Nicolaou, S; Cibere, J

2011-12-01

Osteoarthritis (OA) is the most common arthropathy of the knee joint(1). Symptoms reported by patients and signs noted during physical examination guide clinicians in identifying subjects with knee OA(2-4). Pain is one of the most important symptoms reported by subjects with knee OA(2,3). Although very common, pain is a non-specific symptom, related to pathology in several structures within the knee joint, and includes synovitis(5), subchondral bone marrow lesions(6), and joint effusion(7). Further, pain is a subjective symptom that cannot be directly measured or assessed during physical examination. Crepitus or crepitation in association with arthritis is defined as a crackling or grinding sound on joint movement with a sensation in the joint. Crepitus may occur with or without pain and is a common finding during physical examination in subjects with knee OA(2-4,8,9). It is not known whether crepitus is related to pathology in various structures within the knee. The aim of our study was to determine the cross-sectional associations of structural pathologies within the knee with crepitus in a population-based cohort with knee pain, using magnetic resonance imaging (MRI). Subjects with knee pain were recruited as a random population sample, with crepitus assessed in each compartment of the knee using a validated and standardized approach during physical examination(10). MRI of the knee was performed to assess cartilage morphology, meniscal morphology, osteophytes, cruciate ligaments, and collateral ligaments. For both compartment-specific and whole-knee analyses, a multiple logistic regression analysis was performed to assess the associations of MRI-detected structural pathology with crepitus, adjusting for potential confounders. Variables were selected by backwards elimination within each compartment and in the overall knee models, and only statistically significant variables remained in the "selected" models; remaining variables in these models are adjusted for each other. An increased risk for compartment-specific crepitus was associated with osteophytes at the patellofemoral (PF) and lateral tibiofemoral (LTF) joints. Crepitus was associated with osteophytes and medial collateral ligament (MCL) pathology at the medial tibiofemoral (MTF) compartment, but cartilage damage was negatively associated with crepitus at this compartment. In the selected whole-knee model, only meniscal tears were associated with an increased risk for general crepitus. Thus, it seems that crepitus may be associated with pathology in several internal structures. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Gynaecomastia as a presenting feature of thyrotoxicosis

PubMed Central

Chan, W; Yeung, V; Chow, C; So, W; Cockram, C

1999-01-01

The association between gynaecomastia and thyrotoxicosis is well recognised. However, the reported frequency of the association is variable, partly depending upon the defining criteria used. Here we report two patients with thyrotoxicosis in whom gynaecomastia was the presenting feature. Both patients had other contributing factors, which are assumed to have predisposed to gynaecomastia. In both patients, the gynaecomastia resolved with successful treatment of the thyrotoxicosis. When gynaecomastia is a presenting, or prominent feature of thyrotoxicosis, the possibility of additional underlying pathology should be considered.


Keywords: gynaecomastia; thyrotoxicosis; sex hormone PMID:10715765

Diagnostic accuracy of transabdominal ultrasonography for gallbladder polyps: systematic review.

PubMed

Martin, Erin; Gill, Richdeep; Debru, Estifanos

2018-06-01

Previous research has shown variable but generally poor accuracy of transabdominal ultrasonography in the diagnosis of gallbladder polyps. We performed a systematic review of the literature with the aim of helping surgeons interpret and apply these findings in the preoperative assessment and counselling of their patients. We searched PubMed, MEDLINE and the Cochrane database using the keywords "gallbladder," "polyp," "ultrasound," "pathology" and "diagnosis" for English-language articles published after 1990 with the full-text article available through our institutional subscriptions. Polyps were defined as immobile features that on transabdominal ultrasonography appear to arise from the mucosa and that lack an acoustic shadow, and pseudopolyps were defined as features such as inflammation, hyperplasia, cholesterolosis and adenomyomatosis that convey no risk of malignant transformation. The search returned 1816 articles, which were narrowed down to 14 primary sources involving 15 497 (range 23-13 703) patients who had preoperative transabdominal ultrasonography, underwent cholecystectomy and had postoperative pathology results available. Among the 1259 patients in whom a gallbladder polyp was diagnosed on ultrasonography, 188 polyps were confirmed as true polyps on pathologic examination, and 81 of these were found to be malignant. Of the 14 238 patients for whom a polyp was not seen on ultrasonography, 38 had a true polyp on pathologic examination, none of which were malignant. For true gallbladder polyps, transabdominal ultrasonography had a sensitivity of 83.1%, specificity of 96.3%, positive predictive value of 14.9% (7.0% for malignant polyps) and negative predictive value of 99.7%. Transabdominal ultrasonography has a high false-positive rate (85.1%) for the diagnosis of gallbladder polyps. Further study of alternative imaging modalities and reevaluation of existing management guidelines are warranted.

Which ante mortem clinical features predict progressive supranuclear palsy pathology?

PubMed

Respondek, Gesine; Kurz, Carolin; Arzberger, Thomas; Compta, Yaroslau; Englund, Elisabet; Ferguson, Leslie W; Gelpi, Ellen; Giese, Armin; Irwin, David J; Meissner, Wassilios G; Nilsson, Christer; Pantelyat, Alexander; Rajput, Alex; van Swieten, John C; Troakes, Claire; Josephs, Keith A; Lang, Anthony E; Mollenhauer, Brit; Müller, Ulrich; Whitwell, Jennifer L; Antonini, Angelo; Bhatia, Kailash P; Bordelon, Yvette; Corvol, Jean-Christophe; Colosimo, Carlo; Dodel, Richard; Grossman, Murray; Kassubek, Jan; Krismer, Florian; Levin, Johannes; Lorenzl, Stefan; Morris, Huw; Nestor, Peter; Oertel, Wolfgang H; Rabinovici, Gil D; Rowe, James B; van Eimeren, Thilo; Wenning, Gregor K; Boxer, Adam; Golbe, Lawrence I; Litvan, Irene; Stamelou, Maria; Höglinger, Günter U

2017-07-01

Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Brain injury, neuroinflammation and Alzheimer's disease.

PubMed

Breunig, Joshua J; Guillot-Sestier, Marie-Victoire; Town, Terrence

2013-01-01

With as many as 300,000 United States troops in Iraq and Afghanistan having suffered head injuries (Miller, 2012), traumatic brain injury (TBI) has garnered much recent attention. While the cause and severity of these injuries is variable, severe cases can lead to lifelong disability or even death. While aging is the greatest risk factor for Alzheimer's disease (AD), it is now becoming clear that a history of TBI predisposes the individual to AD later in life (Sivanandam and Thakur, 2012). In this review article, we begin by defining hallmark pathological features of AD and the various forms of TBI. Putative mechanisms underlying the risk relationship between these two neurological disorders are then critically considered. Such mechanisms include precipitation and 'spreading' of cerebral amyloid pathology and the role of neuroinflammation. The combined problems of TBI and AD represent significant burdens to public health. A thorough, mechanistic understanding of the precise relationship between TBI and AD is of utmost importance in order to illuminate new therapeutic targets. Mechanistic investigations and the development of preclinical therapeutics are reliant upon a clearer understanding of these human diseases and accurate modeling of pathological hallmarks in animal systems.

Entrustable Professional Activities for Pathology

PubMed Central

Domen, Ronald E.; Conran, Richard M.; Hoffman, Robert D.; Post, Miriam D.; Brissette, Mark D.; Raciti, Patricia M.; Cohen, David A.; Roberts, Cory A.; Rojiani, Amyn M.; Kong, Christina S.; Peterson, Jo Elle G.; Johnson, Kristen; Plath, Sue; Powell, Suzanne Zein-Eldin

2017-01-01

Competency-based medical education has evolved over the past decades to include the Accreditation Council for Graduate Medical Education Accreditation System of resident evaluation based on the Milestones project. Entrustable professional activities represent another means to determine learner proficiency and evaluate educational outcomes in the workplace and training environment. The objective of this project was to develop entrustable professional activities for pathology graduate medical education encompassing primary anatomic and clinical pathology residency training. The Graduate Medical Education Committee of the College of American Pathologists met over the course of 2 years to identify and define entrustable professional activities for pathology graduate medical education. Nineteen entrustable professional activities were developed, including 7 for anatomic pathology, 4 for clinical pathology, and 8 that apply to both disciplines with 5 of these concerning laboratory management. The content defined for each entrustable professional activity includes the entrustable professional activity title, a description of the knowledge and skills required for competent performance, mapping to relevant Accreditation Council for Graduate Medical Education Milestone subcompetencies, and general assessment methods. Many critical activities that define the practice of pathology fit well within the entrustable professional activity model. The entrustable professional activities outlined by the Graduate Medical Education Committee are meant to provide an initial framework for the development of entrustable professional activity–related assessment and curricular tools for pathology residency training. PMID:28725792

Molecular bases of circadian rhythmicity in renal physiology and pathology

PubMed Central

Bonny, Olivier; Vinciguerra, Manlio; Gumz, Michelle L.; Mazzoccoli, Gianluigi

2013-01-01

The physiological processes that maintain body homeostasis oscillate during the day. Diurnal changes characterize kidney functions, comprising regulation of hydro-electrolytic and acid-base balance, reabsorption of small solutes and hormone production. Renal physiology is characterized by 24-h periodicity and contributes to circadian variability of blood pressure levels, related as well to nychthemeral changes of sodium sensitivity, physical activity, vascular tone, autonomic function and neurotransmitter release from sympathetic innervations. The circadian rhythmicity of body physiology is driven by central and peripheral biological clockworks and entrained by the geophysical light/dark cycle. Chronodisruption, defined as the mismatch between environmental–social cues and physiological–behavioral patterns, causes internal desynchronization of periodic functions, leading to pathophysiological mechanisms underlying degenerative, immune related, metabolic and neoplastic diseases. In this review we will address the genetic, molecular and anatomical elements that hardwire circadian rhythmicity in renal physiology and subtend disarray of time–dependent changes in renal pathology. PMID:23901050

Pathological bolus exposure may define gastro-esophageal reflux better than pathological acid exposure in patients with globus.

PubMed

Sinn, Dong Hyun; Kim, Beom Jin; Son, Hee Jung; Kim, Jae J; Rhee, Jong Chul; Rhee, Poong-Lyul

2012-01-01

Conventionally, pathological acid exposure (PAE), defined by acid reflux only, is used to identify gastro-esophageal reflux disease (GERD). However, weak acid reflux or non-acid reflux also induces reflux symptoms. Defining abnormal reflux based on all reflux episodes may better identify GERD and would be more useful among patients with atypical GERD symptoms, such as globus. Impedance-pHmetry results of 31 globus patients, off acid suppressants, were analysed. A median of 24 episodes of reflux were observed. Of the reflux episodes, 54% were non-acid reflux and 50% reached the proximal extent. PAE was observed in 6 patients (19%). For 5 patients (16%) without PAE, there was evidence of increased bolus exposure compared to normal controls (an intraesophageal bolus exposure for more than 1.4% of the recording time, defined as pathological bolus exposure, PBE). When GERD was defined by PAE or esophagitis, the prevalence of GERD was 29%. When GERD was defined by PBE, PAE or esophagitis, the prevalence was 42%. PBE identified 13% of the patients who otherwise would have been missed. A significant proportion of patients without PAE had evidence of PBE. PBE may be a more useful definition for identifying patients with abnormal increase in reflux in patients with globus. Further studies are warranted.

Entrustable Professional Activities for Pathology: Recommendations From the College of American Pathologists Graduate Medical Education Committee.

PubMed

McCloskey, Cindy B; Domen, Ronald E; Conran, Richard M; Hoffman, Robert D; Post, Miriam D; Brissette, Mark D; Gratzinger, Dita A; Raciti, Patricia M; Cohen, David A; Roberts, Cory A; Rojiani, Amyn M; Kong, Christina S; Peterson, Jo Elle G; Johnson, Kristen; Plath, Sue; Powell, Suzanne Zein-Eldin

2017-01-01

Competency-based medical education has evolved over the past decades to include the Accreditation Council for Graduate Medical Education Accreditation System of resident evaluation based on the Milestones project. Entrustable professional activities represent another means to determine learner proficiency and evaluate educational outcomes in the workplace and training environment. The objective of this project was to develop entrustable professional activities for pathology graduate medical education encompassing primary anatomic and clinical pathology residency training. The Graduate Medical Education Committee of the College of American Pathologists met over the course of 2 years to identify and define entrustable professional activities for pathology graduate medical education. Nineteen entrustable professional activities were developed, including 7 for anatomic pathology, 4 for clinical pathology, and 8 that apply to both disciplines with 5 of these concerning laboratory management. The content defined for each entrustable professional activity includes the entrustable professional activity title, a description of the knowledge and skills required for competent performance, mapping to relevant Accreditation Council for Graduate Medical Education Milestone subcompetencies, and general assessment methods. Many critical activities that define the practice of pathology fit well within the entrustable professional activity model. The entrustable professional activities outlined by the Graduate Medical Education Committee are meant to provide an initial framework for the development of entrustable professional activity-related assessment and curricular tools for pathology residency training.

Adult Lifespan Cognitive Variability in the Cross-Sectional Cam-CAN Cohort

PubMed Central

Green, Emma; Shafto, Meredith A.; Matthews, Fiona E.; White, Simon R.

2015-01-01

This study examines variability across the age span in cognitive performance in a cross-sectional, population-based, adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study (n = 2680). A key question we highlight is whether using measures that are designed to detect age-related cognitive pathology may not be sensitive to, or reflective of, individual variability among younger adults. We present three issues that contribute to the debate for and against age-related increases in variability. Firstly, the need to formally define measures of central tendency and measures of variability. Secondly, in addition to the commonly addressed location-confounding (adjusting for covariates) there may exist changes in measures of variability due to confounder sub-groups. Finally, that increases in spread may be a result of floor or ceiling effects; where the measure is not sensitive enough at all ages. From the Cam-CAN study, a large population-based dataset, we demonstrate the existence of variability-confounding for the immediate episodic memory task; and show that increasing variance with age in our general cognitive measures is driven by a ceiling effect in younger age groups. PMID:26690191

Adult Lifespan Cognitive Variability in the Cross-Sectional Cam-CAN Cohort.

PubMed

Green, Emma; Shafto, Meredith A; Matthews, Fiona E; White, Simon R

2015-12-07

This study examines variability across the age span in cognitive performance in a cross-sectional, population-based, adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study (n = 2680). A key question we highlight is whether using measures that are designed to detect age-related cognitive pathology may not be sensitive to, or reflective of, individual variability among younger adults. We present three issues that contribute to the debate for and against age-related increases in variability. Firstly, the need to formally define measures of central tendency and measures of variability. Secondly, in addition to the commonly addressed location-confounding (adjusting for covariates) there may exist changes in measures of variability due to confounder sub-groups. Finally, that increases in spread may be a result of floor or ceiling effects; where the measure is not sensitive enough at all ages. From the Cam-CAN study, a large population-based dataset, we demonstrate the existence of variability-confounding for the immediate episodic memory task; and show that increasing variance with age in our general cognitive measures is driven by a ceiling effect in younger age groups.

Recent advances in standards for collaborative Digital Anatomic Pathology

PubMed Central

2011-01-01

Context Collaborative Digital Anatomic Pathology refers to the use of information technology that supports the creation and sharing or exchange of information, including data and images, during the complex workflow performed in an Anatomic Pathology department from specimen reception to report transmission and exploitation. Collaborative Digital Anatomic Pathology can only be fully achieved using medical informatics standards. The goal of the international integrating the Healthcare Enterprise (IHE) initiative is precisely specifying how medical informatics standards should be implemented to meet specific health care needs and making systems integration more efficient and less expensive. Objective To define the best use of medical informatics standards in order to share and exchange machine-readable structured reports and their evidences (including whole slide images) within hospitals and across healthcare facilities. Methods Specific working groups dedicated to Anatomy Pathology within multiple standards organizations defined standard-based data structures for Anatomic Pathology reports and images as well as informatic transactions in order to integrate Anatomic Pathology information into the electronic healthcare enterprise. Results The DICOM supplements 122 and 145 provide flexible object information definitions dedicated respectively to specimen description and Whole Slide Image acquisition, storage and display. The content profile “Anatomic Pathology Structured Report” (APSR) provides standard templates for structured reports in which textual observations may be bound to digital images or regions of interest. Anatomic Pathology observations are encoded using an international controlled vocabulary defined by the IHE Anatomic Pathology domain that is currently being mapped to SNOMED CT concepts. Conclusion Recent advances in standards for Collaborative Digital Anatomic Pathology are a unique opportunity to share or exchange Anatomic Pathology structured reports that are interoperable at an international level. The use of machine-readable format of APSR supports the development of decision support as well as secondary use of Anatomic Pathology information for epidemiology or clinical research. PMID:21489187

Stem Cell Pathology.

PubMed

Fu, Dah-Jiun; Miller, Andrew D; Southard, Teresa L; Flesken-Nikitin, Andrea; Ellenson, Lora H; Nikitin, Alexander Yu

2018-01-24

Rapid advances in stem cell biology and regenerative medicine have opened new opportunities for better understanding disease pathogenesis and the development of new diagnostic, prognostic, and treatment approaches. Many stem cell niches are well defined anatomically, thereby allowing their routine pathological evaluation during disease initiation and progression. Evaluation of the consequences of genetic manipulations in stem cells and investigation of the roles of stem cells in regenerative medicine and pathogenesis of various diseases such as cancer require significant expertise in pathology for accurate interpretation of novel findings. Therefore, there is an urgent need for developing stem cell pathology as a discipline to facilitate stem cell research and regenerative medicine. This review provides examples of anatomically defined niches suitable for evaluation by diagnostic pathologists, describes neoplastic lesions associated with them, and discusses further directions of stem cell pathology.

Disease-associated mutations identify a novel region in human STING necessary for the control of type I interferon signaling.

PubMed

Melki, Isabelle; Rose, Yoann; Uggenti, Carolina; Van Eyck, Lien; Frémond, Marie-Louise; Kitabayashi, Naoki; Rice, Gillian I; Jenkinson, Emma M; Boulai, Anaïs; Jeremiah, Nadia; Gattorno, Marco; Volpi, Sefano; Sacco, Olivero; Terheggen-Lagro, Suzanne W J; Tiddens, Harm A W M; Meyts, Isabelle; Morren, Marie-Anne; De Haes, Petra; Wouters, Carine; Legius, Eric; Corveleyn, Anniek; Rieux-Laucat, Frederic; Bodemer, Christine; Callebaut, Isabelle; Rodero, Mathieu P; Crow, Yanick J

2017-08-01

Gain-of-function mutations in transmembrane protein 173 (TMEM173) encoding stimulator of interferon genes (STING) underlie a recently described type I interferonopathy called STING-associated vasculopathy with onset in infancy (SAVI). We sought to define the molecular and cellular pathology relating to 3 individuals variably exhibiting the core features of the SAVI phenotype including systemic inflammation, destructive skin lesions, and interstitial lung disease. Genetic analysis, conformational studies, in vitro assays and ex vivo flow-cytometry were performed. Molecular and in vitro data demonstrate that the pathology in these patients is due to amino acid substitutions at positions 206, 281, and 284 of the human STING protein. These mutations confer cGAMP-independent constitutive activation of type I interferon signaling through TBK1 (TANK-binding kinase), independent from the alternative STING pathway triggered by membrane fusion of enveloped RNA viruses. This constitutive activation was abrogated by ex vivo treatment with the janus kinase 1/2 inhibitor ruxolitinib. Structural analysis indicates that the 3 disease-associated mutations at positions 206, 281, and 284 of the STING protein define a novel cluster of amino acids with functional importance in the regulation of type I interferon signaling. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Ultrasonography of uterine leiomyomas.

PubMed

Woźniak, Andrzej; Woźniak, Sławomir

2017-12-01

Uterine leiomyomas or uterine fibroids are the most common gynaecological tumours and occur in about 20-50% of women around the world. Ultrasonography (USG) is the first-line imaging examination in suspected fibroids and shows high sensitivity and specificity in diagnosing this condition. Ultrasound scans can be performed transvaginally (transvaginal scan - TVS) or transabdominally (transabdominal scan - TAS); both scans have advantages and limitations, but, in general, transvaginal sonography is superior to transabdominal sonography in most cases of pelvic pathology. Whether a leiomyoma is symptomatic or not depends primarily on its size and location. During ultrasound examination, leiomyomas usually appear as well-defined, solid, concentric, hypoechoic masses that cause a variable amount of acoustic shadowing. During the examination of leiomyomas differential diagnosis is important. Some of the most common misdiagnosed pathologies are adenomyosis, solid tumours of adnexa, and endometrial polyps. Misdiagnosis of a leiomyosarcoma has the most negative consequences, presenting symptoms are very similar to benign leiomyoma, and there is no pelvic imaging technique that can reliably differentiate between those pathologies. Magnetic resonance and computer tomography might be helpful in the diagnostics of uterine leiomyoma; however, ultrasound examination is the basic imaging test confirming the existence of leiomyomas, allowing the differentiation of myomas with adenomyosis, endometrial polyps, ovarian tumours, and pregnant uterus.

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration

PubMed Central

Bossuyt, V.; Provenzano, E.; Symmans, W. F.; Boughey, J. C.; Coles, C.; Curigliano, G.; Dixon, J. M.; Esserman, L. J.; Fastner, G.; Kuehn, T.; Peintinger, F.; von Minckwitz, G.; White, J.; Yang, W.; Badve, S.; Denkert, C.; MacGrogan, G.; Penault-Llorca, F.; Viale, G.; Cameron, D.; Earl, Helena; Alba, Emilio; Lluch, Ana; Albanell, Joan; Amos, Keith; Biernat, Wojciech; Bonnefoi, Hervé; Buzdar, Aman; Cane, Paul; Pinder, Sarah; Carson, Lesley; Dickson-Witmer, Diana; Gong, Gyungyub; Green, Jimmy; Hsu, Chih-Yi; Tseng, Ling-Ming; Kroep, Judith; Leitch, A. Marilyn; Sarode, Venetia; Mamounas, Eleftherios; Marcom, Paul Kelly; Nuciforo, Paolo; Paik, Soonmyung; Peg, Vicente; Peston, David; Pierga, Jean-Yves; Quintela-Fandino, Miguel; Salgado, Roberto; Sikov, William; Thomas, Jeremy; Unzeitig, Gary; Wesseling, Jelle

2015-01-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. PMID:26019189

Does short-term fasting promote pathological eating patterns?

PubMed

Schaumberg, Katherine; Anderson, Drew A; Reilly, Erin E; Anderson, Lisa M

2015-12-01

Fasting, or going a significant amount of time without eating, has been identified as a risk factor for the development of pathological eating patterns. Findings from several studies examining the impact of fasting on subsequent eating behaviors have been mixed. The current study recruited college students to record food intake, episodes of binge eating, and use of compensatory behaviors before, throughout, and following a 24-hour fast. Participants attended an initial appointment in which they completed measures of dietary restraint and disinhibition and received instructions on self-monitoring and fasting. Participants (N=122) self-monitored their eating behaviors for 96 h, including a 24-hour fasting period. Participants did not demonstrate significant increases in disordered eating behaviors following the fast (e.g., objective binge episodes, self-defined excessive eating or compensatory behavior use). Baseline disinhibition predicted excessive eating as well as objective binge episodes both before and after fasting. Altogether, findings have implications for research seeking to further understand how fasting may contribute to the development of pathological eating patterns; specifically, it seems that the ED risk associated with fasting is derived from the behavior's interaction with other individual difference variables. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Somatotype of the patients with obesity and associated cardio-vascular patholodgy. Clinical and anthropological bonds].

PubMed

Bukavneva, N S; Pozdniakov, A L; Nikitiuk, D B

2008-01-01

In the article there are presented major anthropometric parameters of patients (male and female) with obesity, combined with cardiovascular pathology, before and after treatment. Constitutional predisposition to obesity is defined. Efficacy of dietary therapy is estimated and with obesity are defined on the basil of associated cardio-vascular pathology.

Shame, Dissociation, and Complex PTSD Symptoms in Traumatized Psychiatric and Control Groups: Direct and Indirect Associations With Relationship Distress.

PubMed

Dorahy, Martin J; Corry, Mary; Black, Rebecca; Matheson, Laura; Coles, Holly; Curran, David; Seager, Lenaire; Middleton, Warwick; Dyer, Kevin F W

2017-04-01

Elevated shame and dissociation are common in dissociative identity disorder (DID) and chronic posttraumatic stress disorder (PTSD) and are part of the constellation of symptoms defined as complex PTSD. Previous work examined the relationship between shame, dissociation, and complex PTSD and whether they are associated with intimate relationship anxiety, relationship depression, and fear of relationships. This study investigated these variables in traumatized clinical samples and a nonclinical community group. Participants were drawn from the DID (n = 20), conflict-related chronic PTSD (n = 65), and nonclinical (n = 125) populations and completed questionnaires assessing the variables of interest. A model examining the direct impact of shame and dissociation on relationship functioning, and their indirect effect via complex PTSD symptoms, was tested through path analysis. The DID sample reported significantly higher dissociation, shame, complex PTSD symptom severity, relationship anxiety, relationship depression, and fear of relationships than the other two samples. Support was found for the proposed model, with shame directly affecting relationship anxiety and fear of relationships, and pathological dissociation directly affecting relationship anxiety and relationship depression. The indirect effect of shame and dissociation via complex PTSD symptom severity was evident on all relationship variables. Shame and pathological dissociation are important for not only the effect they have on the development of other complex PTSD symptoms, but also their direct and indirect effects on distress associated with relationships. © 2016 Wiley Periodicals, Inc.

Resilient Brain Aging: Characterization of Discordance between Alzheimer’s Disease Pathology and Cognition

PubMed Central

Negash, Selam; Wilson, Robert S.; Leurgans, Sue E.; Wolk, David A.; Schneider, Julie A.; Buchman, Aron S.; Bennett, David A.; Arnold, Steven. E.

2014-01-01

Background Although it is now evident that normal cognition can occur despite significant AD pathology, few studies have attempted to characterize this discordance, or examine factors that may contribute to resilient brain aging in the setting of AD pathology. Methods More than 2,000 older persons underwent annual evaluation as part of participation in the Religious Orders Study or Rush Memory Aging Project. A total of 966 subjects who had brain autopsy and comprehensive cognitive testing proximate to death were analyzed. Resilience was quantified as a continuous measure using linear regression modeling, where global cognition was entered as a dependent variable and global pathology was an independent variable. Studentized residuals generated from the model represented the discordance between cognition and pathology, and served as measure of resilience. The relation of resilience index to known risk factors for AD and related variables was examined. Results Multivariate regression models that adjusted for demographic variables revealed significant associations for early life socioeconomic status, reading ability, APOE-ε4 status, and past cognitive activity. A stepwise regression model retained reading level (estimate = 0.10, SE = 0.02; p < 0.0001) and past cognitive activity (estimate = 0.27, SE = 0.09; p = 0.002), suggesting the potential mediating role of these variables for resilience. Conclusions The construct of resilient brain aging can provide a framework for quantifying the discordance between cognition and pathology, and help identify factors that may mediate this relationship. PMID:23919768

PRospective Imaging of CErvical cancer and neoadjuvant treatment (PRICE) study: role of ultrasound to predict partial response in locally advanced cervical cancer patients undergoing chemoradiation and radical surgery.

PubMed

Testa, A C; Ferrandina, G; Moro, F; Pasciuto, T; Moruzzi, M C; De Blasis, I; Mascilini, F; Foti, E; Autorino, R; Collarino, A; Gui, B; Zannoni, G F; Gambacorta, M A; Valentini, A L; Rufini, V; Scambia, G

2018-05-01

Chemoradiation-based neoadjuvant treatment followed by radical surgery is an alternative therapeutic strategy for locally advanced cervical cancer (LACC), but ultrasound variables used to predict partial response to neoadjuvant treatment are not well defined. Our goal was to analyze prospectively the potential role of transvaginal ultrasound in early prediction of partial pathological response, assessed in terms of residual disease at histology, in a large, single-institution series of LACC patients triaged to neoadjuvant treatment followed by radical surgery. Between October 2010 and June 2014, we screened 108 women with histologically documented LACC Stage IB2-IVA, of whom 88 were included in the final analysis. Tumor volume, three-dimensional (3D) power Doppler indices and contrast parameters were obtained before (baseline examination) and after 2 weeks of treatment. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (microscopic and/or macroscopic residual tumor at pathological examination). Complete-response and partial-response groups were compared and receiver-operating characteristics (ROC) curves were generated for ultrasound variables that were statistically significant on univariate analysis to evaluate their diagnostic ability to predict partial pathological response. There was a complete pathological response to neoadjuvant therapy in 40 (45.5%) patients and a partial response in 48 (54.5%). At baseline examination, tumor volume did not differ between the two groups. However, after 2 weeks of neoadjuvant treatment, the tumor volume was significantly greater in patients with partial response than it was in those with complete response (P = 0.019). Among the 3D vascular indices, the vascularization index (VI) was significantly lower in the partial-response compared with the complete-response group, both before and after 2 weeks of treatment (P = 0.037 and P = 0.024, respectively). At baseline examination in the contrast analysis, women with partial response had lower tumor peak enhancement (PE) as well as lower tumor wash-in rate (WiR) and longer tumor rise time (RT) compared with complete responders (P = 0.006, P = 0.003, P = 0.038, respectively). There was no difference in terms of contrast parameters after 2 weeks of treatment. ROC-curve analysis of baseline parameters showed that the best cut-offs for predicting partial pathological response were 41.5% for VI (sensitivity, 63.6%; specificity, 66.7%); 16123.5 auxiliary units for tumor PE (sensitivity, 47.9%; specificity, 84.2%); 7.8 s for tumor RT (sensitivity, 68.8%; specificity, 57.9%); and 4902 for tumor WiR (sensitivity, 77.1%; specificity, 60.5%). ROC curves of parameters after 2 weeks of treatment showed that the best cut-off for predicting partial pathological response was 18.1 cm 3 for tumor volume (sensitivity, 70.8%; specificity 60.0%) and 39.5% for VI (sensitivity; 62.5%; specificity, 73.5%). Ultrasound and contrast parameters differ between LACC patients with complete response and those with partial response before and after 2 weeks of neoadjuvant treatment. However, neither ultrasound parameters before treatment nor those after 2 weeks of treatment had cut-off values with acceptable sensitivity and specificity for predicting partial pathological response to neoadjuvant therapy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Initial Construction and Validation of the Pathological Narcissism Inventory

ERIC Educational Resources Information Center

Pincus, Aaron L.; Ansell, Emily B.; Pimentel, Claudia A.; Cain, Nicole M.; Wright, Aidan G. C.; Levy, Kenneth N.

2009-01-01

The construct of narcissism is inconsistently defined across clinical theory, social-personality psychology, and psychiatric diagnosis. Two problems were identified that impede integration of research and clinical findings regarding narcissistic personality pathology: (a) ambiguity regarding the assessment of pathological narcissism vs. normal…

The Use of Central Pathology Review With Digital Slide Scanning in Advanced-stage Mycosis Fungoides and Sézary Syndrome: A Multi-institutional and International Pathology Study.

PubMed

Gru, Alejandro A; Kim, Jinah; Pulitzer, Melissa; Guitart, Joan; Battistella, Maxime; Wood, Gary S; Cerroni, Lorenzo; Kempf, Werner; Willemze, Rein; Pawade, Joya; Querfeld, Christiane; Schaffer, Andras; Pincus, Laura; Tetzlaff, Michael; Duvic, Madeleine; Scarisbrick, Julia; Porcu, Pierluigi; Mangold, Aaron R; DiCaudo, David J; Shinohara, Michi; Hong, Eric K; Horton, Bethany; Kim, Youn H

2018-06-01

This pathology PILOT study aims to define the role and feasibility of centralized pathology review in a cohort of 75 patients from different centers in the United States and Europe using digital slide scanning. The pathologic material from 75 patients who had been diagnosed with mycosis fungoides/Sézary syndrome and were clinically staged as IIb or above was retrieved from 11 participating centers. Each pathology reviewer was provided with the pathologic diagnosis (by the referring pathologist), and the following list of histopathologic criteria (presence or absence) from the initial report: epidermotropism, folliculotropism (FT), large cell transformation, syringotropism, and granulomas. Patients with advance stage were selected for this study as this is a population where there is significant variability in the diagnosis of pathologic prognostic and predictive biomarkers. The slides were digitally scanned with an Aperio scanner and consensus review of cases occurred when major or minor discrepancies between the referral diagnosis and central pathology review occurred. Among the 75 cases, 70 (93.3%) had a final consensus diagnosis between the 3 central review pathologists. The overall agreement between the consensus review and the referring pathologist was 60%. The overall agreement was also higher between the reviewers and consensus review, compared with the referring pathologist and consensus. 65.3% of cases had some type of discrepancy (major or minor) between the outside and consensus review. Major discrepancies were seen in 34 of 73 cases (46.6%; 73 cases indicated a yes or no response). Minor discrepancies were seen in 32 of 75 (42.7%) of cases. Most of the major discrepancies were accounted by a difference in interpretation in the presence or absence of large cell transformation or FT. Most minor discrepancies were explained by a different interpretation in the expression of CD30. We found digital slide scanning to be a beneficial, reliable, and practical for a methodical approach to perform central pathology review in the context of a large clinical prospective study.

Subjective and Objective Binge Eating in Relation to Eating Disorder Symptomatology, Depressive Symptoms, and Self-Esteem Among Treatment-Seeking Adolescents with Bulimia Nervosa

PubMed Central

Fitzsimmons-Craft, Ellen E.; Ciao, Anna C.; Accurso, Erin C.; Pisetsky, Emily M.; Peterson, Carol B.; Byrne, Catherine E.; Le Grange, Daniel

2014-01-01

This study investigated the importance of the distinction between objective (OBE) and subjective binge eating (SBE) among 80 treatment-seeking adolescents with bulimia nervosa (BN). We explored relationships among OBEs, SBEs, eating disorder (ED) symptomatology, depression, and self-esteem using two approaches. Group comparisons showed that OBE and SBE groups did not differ on ED symptoms or self-esteem; however, the SBE group had significantly greater depression. Examining continuous variables, OBEs (not SBEs) accounted for significant unique variance in global ED pathology, vomiting, and self-esteem. SBEs (not OBEs) accounted for significant unique variance in restraint and depression. Both OBEs and SBEs accounted for significant unique variance in eating concern; neither accounted for unique variance in weight/shape concern, laxative use, diuretic use, or driven exercise. Loss of control, rather than amount of food, may be most important in defining binge eating. Additionally, OBEs may indicate broader ED pathology while SBEs may indicate restrictive/depressive symptomatology. PMID:24852114

Pathological and 3 Tesla Volumetric Magnetic Resonance Imaging Predictors of Biochemical Recurrence after Robotic Assisted Radical Prostatectomy: Correlation with Whole Mount Histopathology.

PubMed

Tan, Nelly; Shen, Luyao; Khoshnoodi, Pooria; Alcalá, Héctor E; Yu, Weixia; Hsu, William; Reiter, Robert E; Lu, David Y; Raman, Steven S

2018-05-01

We sought to identify the clinical and magnetic resonance imaging variables predictive of biochemical recurrence after robotic assisted radical prostatectomy in patients who underwent multiparametric 3 Tesla prostate magnetic resonance imaging. We performed an institutional review board approved, HIPAA (Health Insurance Portability and Accountability Act) compliant, single arm observational study of 3 Tesla multiparametric magnetic resonance imaging prior to robotic assisted radical prostatectomy from December 2009 to March 2016. Clinical, magnetic resonance imaging and pathological information, and clinical outcomes were compiled. Biochemical recurrence was defined as prostate specific antigen 0.2 ng/cc or greater. Univariate and multivariate regression analysis was performed. Biochemical recurrence had developed in 62 of the 255 men (24.3%) included in the study at a median followup of 23.5 months. Compared to the subcohort without biochemical recurrence the subcohort with biochemical recurrence had a greater proportion of patients with a high grade biopsy Gleason score, higher preoperative prostate specific antigen (7.4 vs 5.6 ng/ml), intermediate and high D'Amico classifications, larger tumor volume on magnetic resonance imaging (0.66 vs 0.30 ml), higher PI-RADS® (Prostate Imaging-Reporting and Data System) version 2 category lesions, a greater proportion of intermediate and high grade radical prostatectomy Gleason score lesions, higher pathological T3 stage (all p <0.01) and a higher positive surgical margin rate (19.3% vs 7.8%, p = 0.016). On multivariable analysis only tumor volume on magnetic resonance imaging (adjusted OR 1.57, p = 0.016), pathological T stage (adjusted OR 2.26, p = 0.02), positive surgical margin (adjusted OR 5.0, p = 0.004) and radical prostatectomy Gleason score (adjusted OR 2.29, p = 0.004) predicted biochemical recurrence. In this cohort tumor volume on magnetic resonance imaging and pathological variables, including Gleason score, staging and positive surgical margins, significantly predicted biochemical recurrence. This suggests an important new imaging biomarker. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

North American Multicenter Volumetric CT Study for Clinical Staging of Malignant Pleural Mesothelioma: Feasibility and Logistics of Setting Up a Quantitative Imaging Study.

PubMed

Gill, Ritu R; Naidich, David P; Mitchell, Alan; Ginsberg, Michelle; Erasmus, Jeremy; Armato, Samuel G; Straus, Christopher; Katz, Sharyn; Patios, Demetrois; Richards, William G; Rusch, Valerie W

2016-08-01

Clinical tumor (T), node, and metastasis staging is based on a qualitative assessment of features defining T descriptors and has been found to be suboptimal for predicting the prognosis of patients with malignant pleural mesothelioma (MPM). Previous work suggests that volumetric computed tomography (VolCT) is prognostic and, if found practical and reproducible, could improve clinical MPM classification. Six North American institutions electronically submitted clinical, pathologic, and imaging data on patients with stages I to IV MPM to an established multicenter database and biostatistical center. Two reference radiologists blinded to clinical data independently reviewed the scans; calculated clinical T, node, and metastasis stage by standard criteria; performed semiautomated tumor volume calculations using commercially available software; and submitted the findings to the biostatistical center. Study end points included the feasibility of a multi-institutional VolCT network, concordance of independent VolCT assessments, and association of VolCT with pathological T classification. Of 164 submitted cases, 129 were evaluated by both reference radiologists. Discordant clinical staging of most cases confirmed the inadequacy of current criteria. The overall correlation between VolCT estimates was good (Spearman correlation 0.822), but some were significantly discordant. Root cause analysis of the most discordant estimates identified four common sources of variability. Despite these limitations, median tumor volume estimates were similar within subgroups of cases representing each pathological T descriptor and increased monotonically for each reference radiologist with increasing pathological T status. The good correlation between VolCT estimates obtained for most cases reviewed by two independent radiologists and qualitative association of VolCT with pathological T status combine to encourage further study. The identified sources of user error will inform design of a follow-up prospective trial to more formally assess interobserver variability of VolCT and its potential contribution to clinical MPM staging. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

An Exploration of the Associations Among Multiple Aspects of Religiousness, Body Image, Eating Pathology, and Appearance Investment.

PubMed

Goulet, Carol; Henrie, James; Szymanski, Lynda

2017-04-01

The purpose of this study was to investigate the influence of positive and negative aspects of religiousness on eating pathology, body satisfaction, and appearance investment beyond previously established variables (age, BMI, exercise frequency, weight stability, and self-esteem). Data collected from 168 adult females at a Catholic-affiliated university were analyzed using hierarchical linear regressions. As expected, some religiousness variables (spirituality and seeing one's body as having sacred qualities) were associated with eating pathology, body satisfaction, and appearance investment in potentially beneficial ways, and others (negative interaction with one's religious community) were associated in potentially harmful ways. Interestingly, greater religious meaning, or the importance of religion in one's life, was associated with greater eating pathology, and some variables (religious coping, participation in and support from one's religious community) expected to be associated with greater body satisfaction were unrelated. Results are discussed in terms of mechanisms through which the aspects of religiousness may influence body satisfaction, appearance investment, and eating pathology.

Managing demand for laboratory tests: a laboratory toolkit.

PubMed

Fryer, Anthony A; Smellie, W Stuart A

2013-01-01

Healthcare budgets worldwide are facing increasing pressure to reduce costs and improve efficiency, while maintaining quality. Laboratory testing has not escaped this pressure, particularly since pathology investigations cost the National Health Service £2.5 billion per year. Indeed, the Carter Review, a UK Department of Health-commissioned review of pathology services in England, estimated that 20% of this could be saved by improving pathology services, despite an average annual increase of 8%-10% in workload. One area of increasing importance is managing the demands for pathology tests and reducing inappropriate requesting. The Carter Review estimated that 25% of pathology tests were unnecessary, representing a huge potential waste. Certainly, the large variability in levels of requesting between general practitioners suggests that inappropriate requesting is widespread. Unlocking the key to this variation and implementing measures to reduce inappropriate requesting would have major implications for patients and healthcare resources alike. This article reviews the approaches to demand management. Specifically, it aims to (a) define demand management and inappropriate requesting, (b) assess the drivers for demand management, (c) examine the various approaches used, illustrating the potential of electronic requesting and (d) provide a wider context. It will cover issues, such as educational approaches, information technology opportunities and challenges, vetting, duplicate request identification and management, the role of key performance indicators, profile composition and assessment of downstream impact of inappropriate requesting. Currently, many laboratories are exploring demand management using a plethora of disparate approaches. Hence, this review seeks to provide a 'toolkit' with the view to allowing laboratories to develop a standardised demand management strategy.

Intraoperative assessment of laryngeal pathologies with optical coherence tomography integrated into a surgical microscope.

PubMed

Englhard, Anna S; Betz, Tom; Volgger, Veronika; Lankenau, Eva; Ledderose, Georg J; Stepp, Herbert; Homann, Christian; Betz, Christian S

2017-07-01

Endoscopic examination followed by tissue biopsy is the gold standard in the evaluation of lesions of the upper aerodigestive tract. However, it can be difficult to distinguish between healthy mucosa, dysplasia, and invasive carcinoma. Optical coherence tomography (OCT) is a non-invasive technique which acquires high-resolution, cross-sectional images of tissue in vivo. Integrated into a surgical microscope, it allows the intraoperative evaluation of lesions simultaneously with microscopic visualization. In a prospective case series, we evaluated the use of OCT integrated into a surgical microscope during microlaryngoscopy to help differentiating various laryngeal pathologies. 33 patients with laryngeal pathologies were examined with an OCT- microscope (OPMedT iOCT-camera, HS Hi-R 1000G-microscope, Haag-Streit Surgical GmbH, Wedel, Germany) during microlaryngoscopy. The suspected intraoperative diagnoses were compared to the histopathological reports of subsequent tissue biopsies. Hands-free non-contact OCT revealed high-resolution images of the larynx with a varying penetration depth of up to 1.2 mm and an average of 0.6 mm. Picture quality was variable. OCT showed disorders of horizontal tissue layering in dysplasias with a disruption of the basement membrane in carcinomas. When comparing the suspected diagnosis during OCT-supported microlaryngoscopy with histology, 79% of the laryngeal lesions could be correctly identified. Premalignant lesions were difficult to diagnose and falsely classified as carcinoma. OCT integrated into a surgical microscope seems to be a promising adjunct tool to discriminate pathologies of the upper aerodigestive tract intraoperatively. However, picture quality and penetration depth were variable. Although premalignant lesions were difficult to diagnose, the system proved overall helpful for the intraoperative discrimination of benign and malignant tumors. Further studies will be necessary to define its value in the future. Lasers Surg. Med. 49:490-497, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Entropy based quantification of Ki-67 positive cell images and its evaluation by a reader study

NASA Astrophysics Data System (ADS)

Niazi, M. Khalid Khan; Pennell, Michael; Elkins, Camille; Hemminger, Jessica; Jin, Ming; Kirby, Sean; Kurt, Habibe; Miller, Barrie; Plocharczyk, Elizabeth; Roth, Rachel; Ziegler, Rebecca; Shana'ah, Arwa; Racke, Fred; Lozanski, Gerard; Gurcan, Metin N.

2013-03-01

Presence of Ki-67, a nuclear protein, is typically used to measure cell proliferation. The quantification of the Ki-67 proliferation index is performed visually by the pathologist; however, this is subject to inter- and intra-reader variability. Automated techniques utilizing digital image analysis by computers have emerged. The large variations in specimen preparation, staining, and imaging as well as true biological heterogeneity of tumor tissue often results in variable intensities in Ki-67 stained images. These variations affect the performance of currently developed methods. To optimize the segmentation of Ki-67 stained cells, one should define a data dependent transformation that will account for these color variations instead of defining a fixed linear transformation to separate different hues. To address these issues in images of tissue stained with Ki-67, we propose a methodology that exploits the intrinsic properties of CIE L∗a∗b∗ color space to translate this complex problem into an automatic entropy based thresholding problem. The developed method was evaluated through two reader studies with pathology residents and expert hematopathologists. Agreement between the proposed method and the expert pathologists was good (CCC = 0.80).

[Study of population profiles in relation to the level of suicide risk in France: Study "Mental health in the general population"].

PubMed

Chabaud, Francis; Debarre, Julie; Serazin, Céline; Bouet, Roland; Vaïva, Guillaume; Roelandt, Jean Luc

2010-01-01

Suicidal behaviour is a very important public health issue. The French study of mental health in the general population casts a whole new insight on this issue thanks to the size of the sample used, to its representative nature and to the variety of the collected data. This study aims at defining better the relationships between the factors of suicide risk within a noninstitutionalized adult population and more specifically between the socioeconomic and the psychopathological factors. The final aim is to help define the intervention strategies which should be developed in the context of prevention programs. The method used consists in estimating the suicide risk for each person included in the study by developing a standardized indicator. Six questions taken from the MINI (Mini International Neuropsychiatric Interview) were used to define the four levels of suicide risks which compose this indicator. Next, this indicator was matched for the socioeconomic variables of the study as well as for the main psychopathological categories. A factor analysis of the numerous relations was then carried out. Its principle consisted in synthesizing the information contained in a great number of variables and individuals thanks to the mathematical projection of these features onto a graph. The variables which were retained for the analysis were those which presented the richest relationship with the main variable.(that is to say the level of suicide risk). The estimated prevalence rate of suicidal risk in the general population (with at least one positive answer) is 13.7% which can be divided into 9.7% of low risk, 2.1% of medium risk and 1.9% of high risk. The relationship between the presence of a psychopathology and a medium or high risk of suicide is quite significant. What is more, the presence of associated pathologies (comorbidities) increases the risk. The highest prevalence of risk is observed in psychotic and depressive disorders. However, suicide risk exists in some people who do not present any detected psychopathology : the statistical analysis reveals an excessive medium and high suicide risk in relation to a low family income, unemployment, separation and the 18 to 24 age group. The multidimensional analysis brings to light several specific aspects : the principal explanation shows a relationship between unfavourable socio economic status and the presence of suicide risk at a level which is not equal to zero. The second explanatory line defines the level of risk according to the principal psychopathological characteristics. These two lines define a plane which enables to differentiate low risk groups from medium risk groups and high risk groups. The latter consists mainly in isolated pathological factors or associated factors (comorbidities). The medium and high risk groups are composed mainly of the combination of the two variables. To conclude, these results - which are necessarily flimsy since they are based on epidemiological and statistical analysis - do however match up with the data of the epidemiologic literature in an interesting way and raise the question of an intervention and prevention strategy that would integrate better the medical factors and the socio economic aspects into its program. They should be completed by targeted forward clinical studies as well as by more precise epidemiological patterns. Copyright 2010 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

Recognizing and Reducing Analytical Errors and Sources of Variation in Clinical Pathology Data in Safety Assessment Studies.

PubMed

Schultze, A E; Irizarry, A R

2017-02-01

Veterinary clinical pathologists are well positioned via education and training to assist in investigations of unexpected results or increased variation in clinical pathology data. Errors in testing and unexpected variability in clinical pathology data are sometimes referred to as "laboratory errors." These alterations may occur in the preanalytical, analytical, or postanalytical phases of studies. Most of the errors or variability in clinical pathology data occur in the preanalytical or postanalytical phases. True analytical errors occur within the laboratory and are usually the result of operator or instrument error. Analytical errors are often ≤10% of all errors in diagnostic testing, and the frequency of these types of errors has decreased in the last decade. Analytical errors and increased data variability may result from instrument malfunctions, inability to follow proper procedures, undetected failures in quality control, sample misidentification, and/or test interference. This article (1) illustrates several different types of analytical errors and situations within laboratories that may result in increased variability in data, (2) provides recommendations regarding prevention of testing errors and techniques to control variation, and (3) provides a list of references that describe and advise how to deal with increased data variability.

Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries.

PubMed

Tomlinson, Lindsay; Boone, Laura I; Ramaiah, Lila; Penraat, Kelley A; von Beust, Barbara R; Ameri, Mehrdad; Poitout-Belissent, Florence M; Weingand, Kurt; Workman, Heather C; Aulbach, Adam D; Meyer, Dennis J; Brown, Diane E; MacNeill, Amy L; Bolliger, Anne Provencher; Bounous, Denise I

2013-09-01

The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology industries, and to utilize the combined experience of ASVCP RAC to provide updated recommendations. Discussion points include (1) instrumentation, validation, and sample collection, (2) routine laboratory variables, (3) cytologic laboratory variables, (4) data interpretation and reporting (including peer review, reference intervals and statistics), and (5) roles and responsibilities of clinical pathologists and laboratory personnel. Revision and improvement of current practices should be in alignment with evolving regulatory guidance documents, new technology, and expanding understanding and utility of clinical pathology. These recommendations provide a contemporary guide for the refinement of veterinary toxicologic clinical pathology best practices. © 2013 American Society for Veterinary Clinical Pathology.

[Family characteristics, organic risk factors, psychopathological picture and premorbid adjustment of hospitalized adolescent patients].

PubMed

Małkiewicz-Borkowska, M; Namysłowska, I; Siewierska, A; Puzyńska, E; Sredniawa, H; Zechowski, C; Iwanek, A; Ruszkowska, E

1996-01-01

The relation of some family characteristics such as cohesion and adaptability with organic risk factors, developmental psychopathology, clinical picture and premorbid adjustment was assessed in the group of 100 hospitalized adolescent patients and families. We found correlation between: some of organic risk factors (pathology of neonatal period, pathology of early childhood), some of indicators of developmental psychopathology (eating disorders, conduct disorders), some of clinical signs (mannerism, grandiosity, hostility, suspciousness, disturbances of content of thinking), premorbid adjustment, and variables related to families, described before. We think that biological variables characterizing child (pathology of neonatal period, pathology of early childhood) have an influence on some family characteristics as independent variable. General system theory and circular thinking support these conclusions. In order to verify them, it is necessary to undertake further investigations, based on other methodology, using this results as preliminary findings.

Chronic pancreatitis.

PubMed

Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

2017-09-07

Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

Recurrent myocardial infarction: Mechanisms of free-floating adaptation and autonomic derangement in networked cardiac neural control.

PubMed

Kember, Guy; Ardell, Jeffrey L; Shivkumar, Kalyanam; Armour, J Andrew

2017-01-01

The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as 'free-floating' in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease.

Ultrasonography of uterine leiomyomas

PubMed Central

Woźniak, Andrzej

2017-01-01

Uterine leiomyomas or uterine fibroids are the most common gynaecological tumours and occur in about 20-50% of women around the world. Ultrasonography (USG) is the first-line imaging examination in suspected fibroids and shows high sensitivity and specificity in diagnosing this condition. Ultrasound scans can be performed transvaginally (transvaginal scan – TVS) or transabdominally (transabdominal scan – TAS); both scans have advantages and limitations, but, in general, transvaginal sonography is superior to transabdominal sonography in most cases of pelvic pathology. Whether a leiomyoma is symptomatic or not depends primarily on its size and location. During ultrasound examination, leiomyomas usually appear as well-defined, solid, concentric, hypoechoic masses that cause a variable amount of acoustic shadowing. During the examination of leiomyomas differential diagnosis is important. Some of the most common misdiagnosed pathologies are adenomyosis, solid tumours of adnexa, and endometrial polyps. Misdiagnosis of a leiomyosarcoma has the most negative consequences, presenting symptoms are very similar to benign leiomyoma, and there is no pelvic imaging technique that can reliably differentiate between those pathologies. Magnetic resonance and computer tomography might be helpful in the diagnostics of uterine leiomyoma; however, ultrasound examination is the basic imaging test confirming the existence of leiomyomas, allowing the differentiation of myomas with adenomyosis, endometrial polyps, ovarian tumours, and pregnant uterus. PMID:29483851

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.

PubMed

Bossuyt, V; Provenzano, E; Symmans, W F; Boughey, J C; Coles, C; Curigliano, G; Dixon, J M; Esserman, L J; Fastner, G; Kuehn, T; Peintinger, F; von Minckwitz, G; White, J; Yang, W; Badve, S; Denkert, C; MacGrogan, G; Penault-Llorca, F; Viale, G; Cameron, D

2015-07-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A core curriculum for clinical fellowship training in pathology informatics

PubMed Central

McClintock, David S.; Levy, Bruce P.; Lane, William J.; Lee, Roy E.; Baron, Jason M.; Klepeis, Veronica E.; Onozato, Maristela L.; Kim, JiYeon; Dighe, Anand S.; Beckwith, Bruce A.; Kuo, Frank; Black-Schaffer, Stephen; Gilbertson, John R.

2012-01-01

Background: In 2007, our healthcare system established a clinical fellowship program in Pathology Informatics. In 2010 a core didactic course was implemented to supplement the fellowship research and operational rotations. In 2011, the course was enhanced by a formal, structured core curriculum and reading list. We present and discuss our rationale and development process for the Core Curriculum and the role it plays in our Pathology Informatics Fellowship Training Program. Materials and Methods: The Core Curriculum for Pathology Informatics was developed, and is maintained, through the combined efforts of our Pathology Informatics Fellows and Faculty. The curriculum was created with a three-tiered structure, consisting of divisions, topics, and subtopics. Primary (required) and suggested readings were selected for each subtopic in the curriculum and incorporated into a curated reading list, which is reviewed and maintained on a regular basis. Results: Our Core Curriculum is composed of four major divisions, 22 topics, and 92 subtopics that cover the wide breadth of Pathology Informatics. The four major divisions include: (1) Information Fundamentals, (2) Information Systems, (3) Workflow and Process, and (4) Governance and Management. A detailed, comprehensive reading list for the curriculum is presented in the Appendix to the manuscript and contains 570 total readings (current as of March 2012). Discussion: The adoption of a formal, core curriculum in a Pathology Informatics fellowship has significant impacts on both fellowship training and the general field of Pathology Informatics itself. For a fellowship, a core curriculum defines a basic, common scope of knowledge that the fellowship expects all of its graduates will know, while at the same time enhancing and broadening the traditional fellowship experience of research and operational rotations. For the field of Pathology Informatics itself, a core curriculum defines to the outside world, including departments, companies, and health systems considering hiring a pathology informatician, the core knowledge set expected of a person trained in the field and, more fundamentally, it helps to define the scope of the field within Pathology and healthcare in general. PMID:23024890

Interobserver agreement in analysis of cardiotocograms recorded during trial of labor after cesarean.

PubMed

Caning, M M; Thisted, D L A; Amer-Wählin, I; Laier, G H; Krebs, L

2018-05-17

To examine interobserver agreement in intrapartum cardiotocography (CTG) classification in women undergoing trial of labor after a cesarean section (TOLAC) at term with or without complete uterine rupture. Nineteen blinded and independent Danish obstetricians assessed CTG tracings from 47 women (174 individual pages) with a complete uterine rupture during TOLAC and 37 women (133 individual pages) with no uterine rupture during TOLAC. Individual pages with CTG tracings lasting at least 20 min were evaluated by three different assessors and counted as an individual case. The tracings were analyzed according to the modified version of the Federation of Gynaecology and Obstetrics (FIGO) guidelines elaborated for the use of STAN (ST-analysis). Occurrence of defined abnormalities was recorded and the tracings were classified as normal, suspicious, pathological, or preterminal. The interobserver agreement was evaluated using Fleiss' kappa. Agreement on classification of a preterminal CTG was almost perfect. The interobserver agreement on normal, suspicious or pathological CTG was moderate to substantial. Regarding the presence of severe variable decelerations, the agreement was moderate. No statistical difference was found in the interobserver agreement between classification of tracings from women undergoing TOLAC with and without complete uterine rupture. The interobserver agreement on classification of CTG tracings from high-risk deliveries during TOLAC is best for assessment of a preterminal CTG and the poorest for the identification of severe variable decelerations.

Perivascular epithelioid cell neoplasms: pathology and pathogenesis.

PubMed

Folpe, Andrew L; Kwiatkowski, David J

2010-01-01

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

42 CFR 485.701 - Basis and scope.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Therapy and Speech-Language Pathology Services § 485.701 Basis and scope. This subpart implements section 1861(p)(4) of the Act, which— (a) Defines outpatient physical therapy and speech pathology services; (b...

New approach to probability estimate of femoral neck fracture by fall (Slovak regression model).

PubMed

Wendlova, J

2009-01-01

3,216 Slovak women with primary or secondary osteoporosis or osteopenia, aged 20-89 years, were examined with the bone densitometer DXA (dual energy X-ray absorptiometry, GE, Prodigy - Primo), x = 58.9, 95% C.I. (58.42; 59.38). The values of the following variables for each patient were measured: FSI (femur strength index), T-score total hip left, alpha angle - left, theta angle - left, HAL (hip axis length) left, BMI (body mass index) was calculated from the height and weight of the patients. Regression model determined the following order of independent variables according to the intensity of their influence upon the occurrence of values of dependent FSI variable: 1. BMI, 2. theta angle, 3. T-score total hip, 4. alpha angle, 5. HAL. The regression model equation, calculated from the variables monitored in the study, enables a doctor in praxis to determine the probability magnitude (absolute risk) for the occurrence of pathological value of FSI (FSI < 1) in the femoral neck area, i. e., allows for probability estimate of a femoral neck fracture by fall for Slovak women. 1. The Slovak regression model differs from regression models, published until now, in chosen independent variables and a dependent variable, belonging to biomechanical variables, characterising the bone quality. 2. The Slovak regression model excludes the inaccuracies of other models, which are not able to define precisely the current and past clinical condition of tested patients (e.g., to define the length and dose of exposure to risk factors). 3. The Slovak regression model opens the way to a new method of estimating the probability (absolute risk) or the odds for a femoral neck fracture by fall, based upon the bone quality determination. 4. It is assumed that the development will proceed by improving the methods enabling to measure the bone quality, determining the probability of fracture by fall (Tab. 6, Fig. 3, Ref. 22). Full Text (Free, PDF) www.bmj.sk.

Modeling the association between HR variability and illness in elite swimmers

PubMed Central

Hellard, Philippe; Guimaraes, Fanny; Avalos, Marta; Houel, Nicolas; Hausswirth, Christophe; Toussaint, Jean François

2011-01-01

Purpose To determine whether heart rate variability, an indirect measure of autonomic control, is associated with upper respiratory tract and pulmonary infections, muscular affections and all-type pathologies in elite swimmers. Methods Seven elite international and 11 national swimmers were followed weekly for two years. The indexes of cardiac autonomic regulation in supine and orthostatic position were assessed as explanatory variables by time-domain (SD1, SD2) and spectral analyses (high frequency- HF; 0.15 Hz-0.40Hz, low frequency-LF; 0.04-0.15 Hz and HF/LF ratio) of heart rate variability. Logistic mixed models described the relationship between the explanatory variables and the risk of upper respiratory tract and pulmonary infections, muscular affections and all-type pathologies. Results The risk of all-type pathologies was higher for national swimmers and in winter (p<0.01). An increase in the parasympathetic indexes (HF, SD1) in supine position assessed one week earlier was linked to a higher risk of upper respiratory tract and pulmonary infections (p<0.05), and to a higher risk of muscular affections (increase in HF, p<0.05). Multivariate analyses showed: (1) a higher all-type pathologies risk in winter, and for an increase in the total power of heart rate variability associated with a decline SD1 in supine position; (2) a higher all-type pathologies risk in winter associated with a decline in HF assessed one week earlier in orthostatic position; and (3) a higher risk of muscular affections in winter associated with a decrease SD1 and an increase LF in orthostatic position. Conclusion Swimmers’ health maintenance requires particular attention when autonomic balance shows a sudden increase in parasympathetic indices in supine position assessed one week earlier evolving toward sympathetic predominance in supine and orthostatic positions. PMID:21085039

Universal structures of normal and pathological heart rate variability.

PubMed

Gañán-Calvo, Alfonso M; Fajardo-López, Juan

2016-02-25

The circulatory system of living organisms is an autonomous mechanical system softly tuned with the respiratory system, and both developed by evolution as a response to the complex oxygen demand patterns associated with motion. Circulatory health is rooted in adaptability, which entails an inherent variability. Here, we show that a generalized N-dimensional normalized graph representing heart rate variability reveals two universal arrhythmic patterns as specific signatures of health one reflects cardiac adaptability, and the other the cardiac-respiratory rate tuning. In addition, we identify at least three universal arrhythmic profiles whose presences raise in proportional detriment of the two healthy ones in pathological conditions (myocardial infarction; heart failure; and recovery from sudden death). The presence of the identified universal arrhythmic structures together with the position of the centre of mass of the heart rate variability graph provide a unique quantitative assessment of the health-pathology gradient.

The normalities and abnormalities associated with speech in psychometrically-defined schizotypy.

PubMed

Cohen, Alex S; Auster, Tracey L; McGovern, Jessica E; MacAulay, Rebecca K

2014-12-01

Speech deficits are thought to be an important feature of schizotypy--defined as the personality organization reflecting a putative liability for schizophrenia. There is reason to suspect that these deficits manifest as a function of limited cognitive resources. To evaluate this idea, we examined speech from individuals with psychometrically-defined schizotypy during a low cognitively-demanding task versus a relatively high cognitively-demanding task. A range of objective, computer-based measures of speech tapping speech production (silence, number and length of pauses, number and length of utterances), speech variability (global and local intonation and emphasis) and speech content (word fillers, idea density) were employed. Data for control (n=37) and schizotypy (n=39) groups were examined. Results did not confirm our hypotheses. While the cognitive-load task reduced speech expressivity for subjects as a group for most variables, the schizotypy group was not more pathological in speech characteristics compared to the control group. Interestingly, some aspects of speech in schizotypal versus control subjects were healthier under high cognitive load. Moreover, schizotypal subjects performed better, at a trend level, than controls on the cognitively demanding task. These findings hold important implications for our understanding of the neurocognitive architecture associated with the schizophrenia-spectrum. Of particular note concerns the apparent mismatch between self-reported schizotypal traits and objective performance, and the resiliency of speech under cognitive stress in persons with high levels of schizotypy. Copyright © 2014 Elsevier B.V. All rights reserved.

Restrictive allograft syndrome (RAS): a novel form of chronic lung allograft dysfunction.

PubMed

Sato, Masaaki; Waddell, Thomas K; Wagnetz, Ute; Roberts, Heidi C; Hwang, David M; Haroon, Ayesha; Wagnetz, Dirk; Chaparro, Cecilia; Singer, Lianne G; Hutcheon, Michael A; Keshavjee, Shaf

2011-07-01

Bronchiolitis obliterans syndrome (BOS) with small-airway pathology and obstructive pulmonary physiology may not be the only form of chronic lung allograft dysfunction (CLAD) after lung transplantation. Characteristics of a form of CLAD consisting of restrictive functional changes involving peripheral lung pathology were investigated. Patients who received bilateral lung transplantation from 1996 to 2009 were retrospectively analyzed. Baseline pulmonary function was taken as the time of peak forced expiratory volume in 1 second (FEV(1)). CLAD was defined as irreversible decline in FEV(1) < 80% baseline. The most accurate threshold to predict irreversible decline in total lung capacity and thus restrictive functional change was at 90% baseline. Restrictive allograft syndrome (RAS) was defined as CLAD meeting this threshold. BOS was defined as CLAD without RAS. To estimate the effect on survival, Cox proportional hazards models and Kaplan-Meier analyses were used. Among 468 patients, CLAD developed in 156; of those, 47 (30%) showed the RAS phenotype. Compared with the 109 BOS patients, RAS patients showed significant computed tomography findings of interstitial lung disease (p < 0.0001). Prevalence of RAS was approximately 25% to 35% of all CLAD over time. Patient survival of RAS was significantly worse than BOS after CLAD onset (median survival, 541 vs 1,421 days; p = 0.0003). The RAS phenotype was the most significant risk factor of death among other variables after CLAD onset (hazard ratio, 1.60; confidential interval, 1.23-2.07). RAS is a novel form of CLAD that exhibits characteristics of peripheral lung fibrosis and significantly affects survival of lung transplant patients. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

A call to standardize preanalytic data elements for biospecimens.

PubMed

Robb, James A; Gulley, Margaret L; Fitzgibbons, Patrick L; Kennedy, Mary F; Cosentino, L Mark; Washington, Kay; Dash, Rajesh C; Branton, Philip A; Jewell, Scott D; Lapham, Rosanna L

2014-04-01

Biospecimens must have appropriate clinical annotation (data) to ensure optimal quality for both patient care and research. Clinical preanalytic variables are the focus of this study. To define the essential preanalytic variables (data fields) that should be attached to every collected biospecimen and to provide a complete list of such variables, along with their relative importance, which can vary, depending on downstream use, institutional needs, and information technology capabilities. The College of American Pathologists Diagnostic Intelligence and Health Information Technology Committee sponsored a Biorepository Working Group to develop a ranked list of the preanalytic variables for annotating biospecimens. Members of the working group were experts in anatomic, clinical, and molecular pathology; biobanking; medical informatics; and accreditation. Several members had experience with federal government programs, such as the National Cancer Institute's Biospecimens and Biorepository Branch and the National Cancer Institute's Community Cancer Center Program. Potential preanalytic variables were identified and ranked along with available supporting evidence, definitions, and potential negative effects if the variable was not attached to the biospecimen. Additional national and international stakeholders reviewed the draft manuscript. The ranked listing of 170 preanalytic variables produced can be used as a guide for site-specific implementation into patient care and/or research biorepository processes. Conclusions.-In our collective experience, it is often difficult to choose which of the many preanalytic variables to attach to any specific set of biospecimens used for patient care and/or research. The provided ranked list should aid in the selection of preanalytic variables for a given biospecimen collection.

Biochemical recurrence after radical prostatectomy: what does it mean?

PubMed Central

Tourinho-Barbosa, Rafael; Srougi, Victor; Nunes-Silva, Igor; Baghdadi, Mohammed; Rembeyo, Gregory; Eiffel, Sophie S.; Barret, Eric; Rozet, Francois; Galiano, Marc; Cathelineau, Xavier; Sanchez-Salas, Rafael

2018-01-01

ABSTRACT Background Radical prostatectomy (RP) has been used as the main primary treatment for prostate cancer (PCa) for many years with excellent oncologic results. However, approximately 20-40% of those patients has failed to RP and presented biochemical recurrence (BCR). Prostatic specific antigen (PSA) has been the pivotal tool for recurrence diagnosis, but there is no consensus about the best PSA threshold to define BCR until this moment. The natural history of BCR after surgical procedure is highly variable, but it is important to distinguish biochemical and clinical recurrence and to find the correct timing to start multimodal treatment strategy. Also, it is important to understand the role of each clinical and pathological feature of prostate cancer in BCR, progression to metastatic disease and cancer specific mortality (CSM). Review design A simple review was made in Medline for articles written in English language about biochemical recurrence after radical prostatectomy. Objective To provide an updated assessment of BCR definition, its meaning, PCa natural history after BCR and the weight of each clinical/pathological feature and risk group classifications in BCR, metastatic disease and CSM. PMID:29039897

Subjective and objective binge eating in relation to eating disorder symptomatology, depressive symptoms, and self-esteem among treatment-seeking adolescents with bulimia nervosa.

PubMed

Fitzsimmons-Craft, Ellen E; Ciao, Anna C; Accurso, Erin C; Pisetsky, Emily M; Peterson, Carol B; Byrne, Catherine E; Le Grange, Daniel

2014-07-01

This study investigated the importance of the distinction between objective (OBE) and subjective binge eating (SBE) among 80 treatment-seeking adolescents with bulimia nervosa. We explored relationships among OBEs, SBEs, eating disorder (ED) symptomatology, depression, and self-esteem using two approaches. Group comparisons showed that OBE and SBE groups did not differ on ED symptoms or self-esteem; however, the SBE group had significantly greater depression. Examining continuous variables, OBEs (not SBEs) accounted for significant unique variance in global ED pathology, vomiting, and self-esteem. SBEs (not OBEs) accounted for significant unique variance in restraint and depression. Both OBEs and SBEs accounted for significant unique variance in eating concern; neither accounted for unique variance in weight/shape concern, laxative use, diuretic use, or driven exercise. Loss of control, rather than amount of food, may be most important in defining binge eating. Additionally, OBEs may indicate broader ED pathology, while SBEs may indicate restrictive/depressive symptomatology. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

Barrett’s Esophagus: A Comprehensive and Contemporary Review for Pathologists

PubMed Central

Souza, Rhonda F.; Odze, Robert D.

2015-01-01

This review provides a summary of our current understanding of, and the controversies regarding, the diagnosis, pathogenesis, histopathology, and molecular biology of Barrett's esophagus (BE) and associated neoplasia. Barrett's esophagus is defined as columnar metaplasia of the esophagus. There is worldwide controversy regarding the diagnostic criteria of BE, mainly with regard to the requirement to histologically identify goblet cells in biopsies. Patients with BE are at increased risk for adenocarcinoma which develops via a metaplasia-dysplasia-carcinoma sequence. Surveillance of patients with BE relies heavily on the presence and grade of dysplasia. However, there are significant pathologic limitations and diagnostic variability in evaluating dysplasia, particularly with regard to the more recently recognized unconventional variants. Identification of non-morphology based biomarkers may help risk stratification of BE patients and this is a subject of ongoing research. Due to recent achievements in endoscopic therapy, there has been a major shift in the treatment of BE patients with dysplasia or intramucosal cancer, away from esophagectomy and towards endoscopic mucosal resection and ablation. The pathologic issues related to treatment and its complications are also discussed in this review article. PMID:26813745

Parkinson's: a syndrome rather than a disease?

PubMed

Titova, Nataliya; Padmakumar, C; Lewis, Simon J G; Chaudhuri, K Ray

2017-08-01

Emerging concepts suggest that a multitude of pathology ranging from misfolding of alpha-synuclein to neuroinflammation, mitochondrial dysfunction, and neurotransmitter driven alteration of brain neuronal networks lead to a syndrome that is commonly known as Parkinson's disease. The complex underlying pathology which may involve degeneration of non-dopaminergic pathways leads to the expression of a range of non-motor symptoms from the prodromal stage of Parkinson's to the palliative stage. Non-motor clinical subtypes, cognitive and non-cognitive, have now been proposed paving the way for possible subtype specific and non-motor treatments, a key unmet need currently. Natural history of these subtypes remains unclear and need to be defined. In addition to in vivo biomarkers which suggest variable involvement of the cholinergic and noradrenergic patterns of the Parkinson syndrome, abnormal alpha-synuclein accumulation have now been demonstrated in the gut, pancreas, heart, salivary glands, and skin suggesting that Parkinson's is a multi-organ disorder. The Parkinson's phenotype is thus not just a dopaminergic motor syndrome, but a dysfunctional multi-neurotransmitter pathway driven central and peripheral nervous system disorder that possibly ought to be considered a syndrome and not a disease.

Barrett's Esophagus: A Comprehensive and Contemporary Review for Pathologists.

PubMed

Naini, Bita V; Souza, Rhonda F; Odze, Robert D

2016-05-01

This review provides a summary of our current understanding of, and the controversies surrounding, the diagnosis, pathogenesis, histopathology, and molecular biology of Barrett's esophagus (BE) and associated neoplasia. BE is defined as columnar metaplasia of the esophagus. There is worldwide controversy regarding the diagnostic criteria of BE, mainly with regard to the requirement to histologically identify goblet cells in biopsies. Patients with BE are at increased risk for adenocarcinoma, which develops in a metaplasia-dysplasia-carcinoma sequence. Surveillance of patients with BE relies heavily on the presence and grade of dysplasia. However, there are significant pathologic limitations and diagnostic variability in evaluating dysplasia, particularly with regard to the more recently recognized unconventional variants. Identification of non-morphology-based biomarkers may help risk stratification of BE patients, and this is a subject of ongoing research. Because of recent achievements in endoscopic therapy, there has been a major shift in the treatment of BE patients with dysplasia or intramucosal cancer away from esophagectomy and toward endoscopic mucosal resection and ablation. The pathologic issues related to treatment and its complications are also discussed in this review article.

Eating disorder pathology among overweight treatment-seeking youth: clinical correlates and cross-sectional risk modeling.

PubMed

Eddy, Kamryn T; Tanofsky-Kraff, Marian; Thompson-Brenner, Heather; Herzog, David B; Brown, Timothy A; Ludwig, David S

2007-10-01

Preliminary research suggests that pediatric overweight is associated with increased eating disorder pathology, however, little is known about which overweight youth are most vulnerable to eating disorder pathology. We therefore investigated 122 overweight treatment-seeking youth to describe eating disorder pathology and mental health correlates, and to identify psychopathological constructs that may place overweight youth at increased risk for eating disorder pathology. Youth participated in a comprehensive assessment of eating disorders, mood and anxiety disorders, general psychopathology, and risk variables involving semi-structured clinical interviews and self- and parent-report questionnaires prior to the initiation of weight-loss treatment. Ten youth met criteria for an eating disorder, and over one-third endorsed recent binge eating. Eating disorder pathology was associated with depressive and anxious symptoms (p's<0.001). Structural equation modeling indicated increased negative affect, teasing experience, and thin-ideal internalization, and decreased perfectionism were associated with increased eating disorder pathology. Findings corroborate earlier work indicating that eating disorder pathology is elevated and clinically significant in overweight treatment-seeking youth, bolstering the need for mental health assessment of such individuals. Cross-sectional modeling proposed key variables that relate to eating disorder pathology in overweight treatment-seeking youth, which following prospective replication, may inform the development of effective interventions for overweight and eating disorders.

Factors associated with vocal fold pathologies in teachers.

PubMed

Souza, Carla Lima de; Carvalho, Fernando Martins; Araújo, Tânia Maria de; Reis, Eduardo José Farias Borges Dos; Lima, Verônica Maria Cadena; Porto, Lauro Antonio

2011-10-01

To analyze factors associated with the prevalence of the medical diagnosis of vocal fold pathologies in teachers. A census-based epidemiological, cross-sectional study was conducted with 4,495 public primary and secondary school teachers in the city of Salvador, Northeastern Brazil, between March and April 2006. The dependent variable was the self-reported medical diagnosis of vocal fold pathologies and the independent variables were sociodemographic characteristics; professional activity; work organization/interpersonal relationships; physical work environment characteristics; frequency of common mental disorders, measured by the Self-Reporting Questionnaire-20 (SRQ-20 >7); and general health conditions. Descriptive statistical, bivariate and multiple logistic regression analysis techniques were used. The prevalence of self-reported medical diagnosis of vocal fold pathologies was 18.9%. In the logistic regression analysis, the variables that remained associated with this medical diagnosis were as follows: being female, having worked as a teacher for more than seven years, excessive voice use, reporting more than five unfavorable physical work environment characteristics and presence of common mental disorders. The presence of self-reported vocal fold pathologies was associated with factors that point out the need of actions that promote teachers' vocal health and changes in their work structure and organization.

The Diagnostic Dilemma of Pathological Appearance and Performance Enhancing Drug Use

PubMed Central

Hildebrandt, Tom; Lai, Justine K.; Langenbucher, James W.; Schneider, Melanie; Yehuda, Rachel; Pfaff, Donald W.

2010-01-01

Appearance and performance enhancing drug (APED) use includes the use of a range of pharmacologically distinct substances and concurrent investment in outward appearance or achievement, dietary control, and frequent exercise. A number of existing reviews and conceptual papers have defined pathological forms of APED use within the APED class of anabolic-androgenic steroids (AASs) and using the framework of AAS dependence. We review published data on APED use including human studies of AAS users and identified three defining phenomenological features associated with increased health risk and pathology. These features included (1) polypharmacy or the concurrent use of several pharmacologically distinct substances used to change outward appearance or increase likelihood of personal achievement; (2) significant body image disturbance; (3) rigid practices and preoccupations with diet and exercise. Investigations into the latent structure of APED use suggest these features cluster together in a homogenous group of APED users who have the highest health risk and most psychopathology. These features are discussed in the context of AAS dependence and problems with defining classic tolerance-withdrawal symptoms among APED users. Suggestions for a resolution and outline for future research needed to determine the best system for identifying and diagnosing pathological APED use are discussed. PMID:21115306

[Learning pathologic anatomy during medical formation: Understanding the contribution of the motivation].

PubMed

Toquet, Claire; Normand, Adeline; Guihard, Gilles

2018-05-26

The motivations of medical students for Pathologic Anatomy are little known although they can strongly influence their academic performance. Our work focused on the analysis of the relationship between performance and motivation for Pathologic Anatomy. Second-year students (n=268) from the University of Nantes were contacted to complete a motivation questionnaire and to provide indicators of performance and attendance. The responses were analyzed in order to establish the psychometric reliability and the factorial structure of the questionnaire. The relationship between motivation and performance was explored by correlation and by linear regression studies. A cluster analysis was performed to specify the distribution of the two variables in our sample. The sample corresponded to 168 respondents with a F/M ratio similar to that of our population. Our data demonstrated the reliability of the questionnaire and a structure described by 5 motivation factors (self-determination, self-efficacy, career, grade and intrinsic motivation). The academic performance was not significantly correlated with the overall motivation or with student attendance. However, it was predicted by self-determination and self-efficacy. Our work revealed gender differences as well as the existence of two distinct clusters defined by the motivation and performance of the students. This work constitutes the first study of the motivations of French medical students for cyto-pathology. It validates a quantitative assessment tool for motivation. Finally, it explores the heterogeneity of the distribution of motivation and academic performance within a population of learners. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Length of positive surgical margin after radical prostatectomy as a predictor of biochemical recurrence.

PubMed

Shikanov, Sergey; Song, Jie; Royce, Cassandra; Al-Ahmadie, Hikmat; Zorn, Kevin; Steinberg, Gary; Zagaja, Gregory; Shalhav, Arieh; Eggener, Scott

2009-07-01

Length and location of positive surgical margins are independent predictors of biochemical recurrence after open radical prostatectomy. We assessed their impact on biochemical recurrence in a large robotic prostatectomy series. Data were collected prospectively from 1,398 men undergoing robotic radical prostatectomy for clinically localized prostate cancer from 2003 to 2008 at a single institution. The associations of preoperative prostate specific antigen, pathological Gleason score, pathological stage and positive surgical margin parameters (location, length and focality) with biochemical recurrence rate were evaluated. Margin status and length were measured by a single uropathologist. Biochemical recurrence was defined as serum prostate specific antigen greater than 0.1 ng/ml on 2 consecutive tests. Cox regression models were constructed to evaluate predictors of biochemical recurrence. Of 1,398 consecutive patients who underwent robotic prostatectomy positive margins were present in 243 (17%) (11% of pathological T2 and 41% of T3). Preoperative prostate specific antigen, pathological stage, Gleason score, margin status, and margin length as a continuous and categorical variable (less than 1, 1 to 3, more than 3 mm) were independent predictors of biochemical recurrence. Patients with negative margins and those with a positive margin less than 1 mm had similar rates of biochemical recurrence (log rank test p = 0.18). Surgical margin location was not independently associated with biochemical recurrence. Margin status and length are independent predictors of biochemical recurrence following robotic radical prostatectomy. Although longer followup and validation studies are necessary for confirmation, patients with a positive margin less than 1 mm appear to have similar recurrence rates as those with negative margins.

The Pathological Buying Screener: Development and Psychometric Properties of a New Screening Instrument for the Assessment of Pathological Buying Symptoms

PubMed Central

Trotzke, Patrick; Mitchell, James E.; de Zwaan, Martina

2015-01-01

The study was designed to develop a new screening instrument for pathological buying (PB), and to examine its psychometric properties in a large-scale sample. By using a facet theoretical approach and based on literature as well as on clinical experience, a 20-item Pathological Buying Screener (PBS) was developed and administered to a representative German sample (n = 2,539). Valid data were available from 2,403 participants who were subjects for three subsequent empirical studies. The first study explored the factor structure using exploratory factor analyses in a subsample of 498 participants. Based on factor loadings, a 13-item version with the two factors loss of control / consequences and excessive buying behavior was revealed. This two-factor model was confirmed in study 2 by confirmatory factor analysis performed on another subsample (n = 1,905). Study 3 investigated age and gender effects and convergent validity of the PBS using the Compulsive Buying Scale (CBS) in the full sample (N = 2,403). The total PBS score was adequately correlated with the CBS score. Hierarchical regression analyses with the CBS score as the dependent variable and the two PBS factors as the predictors indicated an own incremental validity of the two factors in participants ≤ 65 years. The reliability of the total score as well as of the two subscales was good to excellent. Overall, the PBS represents a useful measure for PB. Future studies are needed to replicate the two-factor structure in clinical samples and to define a valid cutoff for PB. PMID:26488872

The Pathological Buying Screener: Development and Psychometric Properties of a New Screening Instrument for the Assessment of Pathological Buying Symptoms.

PubMed

Müller, Astrid; Trotzke, Patrick; Mitchell, James E; de Zwaan, Martina; Brand, Matthias

2015-01-01

The study was designed to develop a new screening instrument for pathological buying (PB), and to examine its psychometric properties in a large-scale sample. By using a facet theoretical approach and based on literature as well as on clinical experience, a 20-item Pathological Buying Screener (PBS) was developed and administered to a representative German sample (n = 2,539). Valid data were available from 2,403 participants who were subjects for three subsequent empirical studies. The first study explored the factor structure using exploratory factor analyses in a subsample of 498 participants. Based on factor loadings, a 13-item version with the two factors loss of control / consequences and excessive buying behavior was revealed. This two-factor model was confirmed in study 2 by confirmatory factor analysis performed on another subsample (n = 1,905). Study 3 investigated age and gender effects and convergent validity of the PBS using the Compulsive Buying Scale (CBS) in the full sample (N = 2,403). The total PBS score was adequately correlated with the CBS score. Hierarchical regression analyses with the CBS score as the dependent variable and the two PBS factors as the predictors indicated an own incremental validity of the two factors in participants ≤ 65 years. The reliability of the total score as well as of the two subscales was good to excellent. Overall, the PBS represents a useful measure for PB. Future studies are needed to replicate the two-factor structure in clinical samples and to define a valid cutoff for PB.

Inter- and intra-observer reliability of measurement of pedicle screw breach assessed by postoperative CT scans.

PubMed

Lavelle, William F; Ranade, Ashish; Samdani, Amer F; Gaughan, John P; D'Andrea, Linda P; Betz, Randal R

2014-01-01

Pedicle screws are used increasingly in spine surgery. Concerns of complications associated with screw breach necessitates accurate pedicle screw placement. Postoperative CT imaging helps to detect screw malposition and assess its severity. However, accuracy is dependent on the reading of the CT scans. Inter- and intra-observer variability could affect the reliability of CT scans to assess multiple screw types and sites. The purpose of this study was to assess the reliability of multi-observer analysis of CT scans for determining pedicle screw breach for various screw types and sites in patients with spinal deformity or degenerative pathologies. Axial CT scan images of 23 patients (286 screws) were read by four experienced spine surgeons. Pedicle screw placement was considered 'In' when the screw was fully contained and/or the pedicle wall breach was ≤2 mm. 'Out' was defined as a breach in the medial or lateral pedicle wall >2 mm. Intra-class coefficients (ICC) were calculated to assess the inter- and intra-observer reliability. Marked inter- and intra-observer variability was noticed. The overall inter-observer ICC was 0.45 (95% confidence limits 0.25 to 0.65). The intra-observer ICC was 0.49 (95% confidence limits 0.29 to 0.69). Underlying spinal pathology, screw type, and patient age did not seem to impact the reliability of our CT assessments. Our results indicate the evaluation of pedicle screw breach on CT by a single surgeon is highly variable, and care should be taken when using individual CT evaluations of millimeters of breach as a basis for screw removal. This was a Level III study.

The Envelope of Physiological Motion of the First Carpometacarpal Joint

PubMed Central

Crisco, Joseph J.; Patel, Tarpit; Halilaj, Eni; Moore, Douglas C.

2015-01-01

Much of the hand's functional capacity is due to the versatility of the motions at the thumb carpometacarpal (CMC) joint, which are presently incompletely defined. The aim of this study was to develop a mathematical model to completely describe the envelope of physiological motion of the thumb CMC joint and then to examine if there were differences in the kinematic envelope between women and men. In vivo kinematics of the first metacarpal with respect to the trapezium were computed from computed tomography (CT) volume images of 44 subjects (20M, 24F, 40.3 ± 17.7 yr) with no signs of CMC joint pathology. Kinematics of the first metacarpal were described with respect to the trapezium using helical axis of motion (HAM) variables and then modeled with discrete Fourier analysis. Each HAM variable was fit in a cyclic domain as a function of screw axis orientation in the trapezial articular plane; the RMSE of the fits was 14.5 deg, 1.4 mm, and 0.8 mm for the elevation, location, and translation, respectively. After normalizing for the larger bone size in men, no differences in the kinematic variables between sexes could be identified. Analysis of the kinematic data also revealed notable coupling of the primary rotations of the thumb with translation and internal and external rotations. This study advances our basic understanding of thumb CMC joint function and provides a complete description of the CMC joint for incorporation into future models of hand function. From a clinical perspective, our findings provide a basis for evaluating CMC pathology, especially the mechanically mediated aspects of osteoarthritis (OA), and should be used to inform artificial joint design, where accurate replication of kinematics is essential for long-term success. PMID:26201612

Acute myonecrosis at MRI: Etiologies in an oncologic cohort, and assessment of interobserver variability

PubMed Central

Cunningham, Jane; Sharma, Richa; Kirzner, Anna; Hwang, Sinchun; Lefkowitz, Robert; Greenspan, Daniel; Shapoval, Anton; Panicek, David M.

2016-01-01

Objective To determine etiologies of myonecrosis in oncology patients and to assess interobserver variability in interpreting its MRI features. Materials and Methods Pathology records in our tertiary cancer hospital were searched for proven myonecrosis, and MRIs of affected regions in those patients were identified. MRI reports that suggested myonecrosis also were identified. Each MRI was reviewed independently by two of six readers to assess anatomic site, size, and signal intensities of muscle changes, and presence of the previously reported stipple sign (enhancing foci within a region defined by rim enhancement). The stipple sign was assessed again, weeks after a training session. Cohen kappa and percent agreement were calculated. Medical records were reviewed for contemporaneous causes of myonecrosis. Results MRI reports in 73 patients suggested the diagnosis of myonecrosis; pathologic proof was available in another two. Myonecrosis was frequently associated with radiotherapy (n=34 (45%) patients)); less frequent causes included intraoperative immobilization, trauma, therapeutic embolization, ablation therapy, exercise, and diabetes. Myonecrosis usually involved lower extremity, pelvis, and upper extremity; mean size was 13.0 cm. Stipple sign was observed in 55–95% of patients at first assessment (k=0.09–0.42; 60–80% agreement) and 55–100% at second (k=0.0–0.58; 72–90% agreement). Enhancement surrounded myonecrosis in 55–100% patients (k=0.03 – 0.32; 58–70% agreement). Conclusion Myonecrosis in oncology patients usually occurred after radiotherapy, and less commonly after intraoperative immobilization, trauma, therapeutic embolization, ablation therapy, exercise, or diabetes. Although interobserver variability for MRI features of myonecrosis exists (even after focused training), a combination of findings facilitates diagnosis and conservative management. PMID:27105618

Recurrent myocardial infarction: Mechanisms of free-floating adaptation and autonomic derangement in networked cardiac neural control

PubMed Central

Ardell, Jeffrey L.; Shivkumar, Kalyanam; Armour, J. Andrew

2017-01-01

The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as ‘free-floating’ in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease. PMID:28692680

The ocular complications of boxing.

PubMed

Giovinazzo, V J; Yannuzzi, L A; Sorenson, J A; Delrowe, D J; Cambell, E A

1987-06-01

In cooperation with the New York State Athletic Commission, 74 boxers applying for a new or yearly renewal license were sequentially referred over a 2-year period for a complete dilated ocular examination at the Sports Vision Institute of the Manhattan Eye, Ear and Throat Hospital. At least one ocular injury was found in 66% of boxers. Vision-threatening injuries, defined as significant damage to the angle, lens, macula, or peripheral retina occurred in 58% of boxers. Nineteen percent of boxers had angle abnormalities. Nineteen percent of boxers had pathologic cataracts, over 70% of these were posterior subcapsular. Six boxers had macular lesions. A total of 24% of boxers had retinal tears. Standardized photographs were used to distinguish pathologic cataracts from congenital opacities and pathologic retinal tears from atrophic holes. Attempts were made to identify risk factors in boxing that might be predictive for ocular injury. Variables included age, weight division, left- or right-handedness, total number of losses, and total number of bouts. Significant correlations were found between the total number of bouts and the total number of losses, and the presence of retinal tears. College varsity athletes were selected as controls. Significant differences were found between boxers and controls for the total number of injuries, total vision-threatening injuries, and the number of retinal tears. A series of recommendations are proposed to aide in the early detection and prevention of serious ocular injuries.

Risk and resilience trajectories in war-exposed children across the first decade of life.

PubMed

Halevi, Galit; Djalovski, Amir; Vengrober, Adva; Feldman, Ruth

2016-10-01

Although the effects of early-onset trauma on susceptibility to psychopathology are well-acknowledged, no study to date has followed risk and resilience trajectories in war-exposed young children over lengthy periods and charted predictors of individual pathways. In this prospective longitudinal study, we followed 232 children, including 148 exposed to repeated wartime trauma and 84 controls, at three time points: early childhood (1.5-5 years), middle childhood (5-8 years), and late childhood (9-11 years). Children were diagnosed at each time point and four trajectories defined: children exhibiting no pathology at any time point, those displaying early pathology that later remitted, those showing initial resilience followed by late pathology, and children presenting chronic pathology across the entire first decade. Maternal behavioral containment during trauma evocation and child social engagement during free play were observed in early childhood and maternal emotional distress self-reported across time. War-exposed children showed significantly higher rates of psychopathology, with 81% exhibiting pathology at some point during childhood. In middle childhood, exposed children displayed more posttraumatic stress disorders (PTSD), anxiety disorders, and attention-deficit/hyperactivity disorders (ADHD), and in late childhood more PTSD, conduct/oppositional defiant disorders, and ADHD. War-exposed children had more comorbid psychopathologies and number of comorbidities increased with age. Notably, war-exposure increased prevalence of chronic pathology by 24-fold. Maternal factors, including mother's uncontained style and emotional distress, increased risk for early and chronic psychopathology, whereas reduced child social engagement augmented risk for late pathology. Early-onset chronic stress does not heal naturally, and its effects appear to exacerbate over time, with trauma-exposed children presenting a more comorbid, chronic, and externalizing profile as they grow older. Our findings demonstrate that responses to trauma are dynamic and variable and pinpoint age-specific effects of maternal and child factors on risk and resilience trajectories. Results highlight the importance of conducting long-term follow-up studies and constructing individually tailored early interventions following trauma exposure. © 2016 Association for Child and Adolescent Mental Health.

Primary central nervous system lymphoma in immunocompetent individuals: a single center experience.

PubMed

Aki, Hilal; Uzunaslan, Didem; Saygin, Caner; Batur, Sebnem; Tuzuner, Nukhet; Kafadar, Ali; Ongoren, Seniz; Oz, Buge

2013-01-01

Primary central nervous system lymphoma (PCNSL) is defined as the involvement of brain, leptomeninges, eyes or spinal cord by non-Hodgkin lymphoma. The role of various prognostic markers in predicting adverse outcome is debated. To investigate the clinical and immunohistochemical findings of immunocompetent PCNSL cases (39 cases) diagnosed at the study center, and evaluate the influence of potential prognostic factors on overall survival (OS) of patients. Data regarding patient characteristics, neuroimaging, pathological and immunohistochemical features and follow-up were obtained from patient records. The influence of potential prognostic parameters on OS was investigated by log-rank test and Cox regression analysis. Patients who received combined chemotherapy and radiotherapy had a significantly better OS when compared to chemotherapy alone. Other variables included in this study were not associated with a significant survival advantage. In this study, we failed to demonstrate a relationship between different clinicopathological variables and OS of patients. Prospective studies with large patient series are needed to investigate other potential prognostic factors.

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

[Harassment in the workplace: clinic and psychopathological factors].

PubMed

Robin, Gaëlle; Stéphan, Florian; Le Galudec, Mickaël; Hazif-Thomas, Cyril; Walter, Michel

2011-01-01

Harassment may be either moral, physical or sexual. It is defined as a phenomenon that happens repeatedly. It is underestimated in professional environments and probably even more so in private life. Without referring to a pathological personality, harassers have common pathological traits.

Monitoring for periodontal inflammatory disease in the third molar region.

PubMed

Golden, Brent A; Baldwin, Carrie; Sherwood, Colin; Abdelbaky, Omar; Phillips, Ceib; Offenbacher, Steven; White, Raymond P

2015-04-01

To assess changes at 2-year intervals in the periodontal status of the third molar region in participants enrolled with asymptomatic third molars and no clinical evidence of third molar region periodontal pathology. The included participants who presented with a healthy periodontal status (all probing depths [PDs], <4 mm) in the third molar region, defined as distal of second molars and around adjacent third molars, were from a larger longitudinal study of participants with asymptomatic third molars. Full-mouth periodontal PD data from 6 sites per tooth were obtained clinically at enrollment and at subsequent 2-year intervals. Data were aggregated to the patient level. Outcome variables were the presence or absence of periodontal pathology, defined as at least 1 PD of at least 4 mm in the third molar region. One hundred twenty-nine participants had a third molar region PD shallower than 4 mm at enrollment. Most participants were Caucasian (85%), women (60%), younger than 25 years (62%), educated beyond high school (84%), and with good oral health habits. At 6 years, excluding the 61 participants lost to follow-up, 47% participants had had third molars removed, 21% had developed at least 1 PD of at least 4 mm in the third molar region since enrollment, and 32% retained the periodontal status at enrollment (all PDs in third molar region, <4 mm). Demographic characteristics were not statistically different for participants followed for 6 years compared with those lost to follow-up. Although not all participants could be followed for 6 years after enrollment or chose to retain third molars, one third of participants maintained the third molar region periodontal status assessed at baseline for 6 years after enrollment; no clinical evidence of pathology developed over time. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

How to define pathologic pelvic floor descent in MR defecography during defecation?

PubMed

Schawkat, Khoschy; Heinrich, Henriette; Parker, Helen L; Barth, Borna K; Mathew, Rishi P; Weishaupt, Dominik; Fox, Mark; Reiner, Caecilia S

2018-06-01

To assess the extents of pelvic floor descent both during the maximal straining phase and the defecation phase in healthy volunteers and in patients with pelvic floor disorders, studied with MR defecography (MRD), and to define specific threshold values for pelvic floor descent during the defecation phase. Twenty-two patients (mean age 51 ± 19.4) with obstructed defecation and 20 healthy volunteers (mean age 33.4 ± 11.5) underwent 3.0T MRD in supine position using midsagittal T2-weighted images. Two radiologists performed measurements in reference to PCL-lines in straining and during defecation. In order to identify cutoff values of pelvic floor measurements for diagnosis of pathologic pelvic floor descent [anterior, middle, and posterior compartments (AC, MC, PC)], receiver-operating characteristic (ROC) curves were plotted. Pelvic floor descent of all three compartments was significantly larger during defecation than at straining in patients and healthy volunteers (p < 0.002). When grading pelvic floor descent in the straining phase, only two healthy volunteers showed moderate PC descent (10%), which is considered pathologic. However, when applying the grading system during defecation, PC descent was overestimated with 50% of the healthy volunteers (10 of 20) showing moderate PC descent. The AUC for PC measurements during defecation was 0.77 (p = 0.003) and suggests a cutoff value of 45 mm below the PCL to identify patients with pathologic PC descent. With the adapted cutoff, only 15% of healthy volunteers show pathologic PC descent during defecation. MRD measurements during straining and defecation can be used to differentiate patients with pelvic floor dysfunction from healthy volunteers. However, different cutoff values should be used during straining and during defecation to define normal or pathologic PC descent.

Lateral hip pain: findings from magnetic resonance imaging and clinical examination.

PubMed

Woodley, Stephanie J; Nicholson, Helen D; Livingstone, Vicki; Doyle, Terence C; Meikle, Grant R; Macintosh, Janet E; Mercer, Susan R

2008-06-01

Prospective cross-sectional study. To examine the radiological and physical therapy diagnoses of lateral hip pain (LHP), and determine the validity of selected clinical variables for predicting gluteal tendon pathology. LHP is frequently encountered by clinicians. Further investigation is required to establish the specific pathologies implicated in the cause of LHP, and which clinical tests are useful in the assessment of this problem. Forty patients with unilateral LHP underwent a physical therapy examination followed by magnetic resonance imaging (MRI) studies. Three radiologists analyzed the images of both hips for signs of pathology. Interobserver reliability of the image analyses, the agreement between the physical therapy and radiological diagnoses, and the validity of the clinical tests were examined. Gluteus medius tendon pathology, bursitis, osteoarthritis and gluteal muscle atrophy (predominantly affecting gluteus minimus) were all implicated in the imaging report of LHP. While prevalent in symptomatic hips, abnormalities were also identified in asymptomatic hips, particularly relating to the diagnosis of bursitis. The strength of agreement between radiologists was variable and little agreement existed between the physical therapy and radiological diagnoses of pathology. Nine of the 26 clinical variables examined in relation to gluteal tendon pathology had likelihood ratios above 2.0 or below 0.5, but the associated 95% confidence intervals were large. The diagnosis of LHP is challenging and our results highlight some problems associated with the use of MRI as a diagnostic reference standard. This factor, together with the imprecise point estimates of the likelihood ratios, means that no firm conclusions can be made regarding the diagnostic utility of the clinical tests used in the assessment of gluteal tendon pathology.

42 CFR 485.701 - Basis and scope.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Therapy and Speech-Language Pathology Services § 485.701 Basis and scope. This subpart implements section 1861(p)(4) of the Act, which— (a) Defines outpatient physical therapy and speech pathology services; (b... records; and (c) Authorizes the Secretary to establish by regulation other health and safety requirements...

The impulsivity and sensation-seeking mediators of the psychological consequences of pathological gambling in adolescence.

PubMed

Estevez, Ana; Herrero-Fernández, David; Sarabia, Izaskun; Jauregui, Paula

2015-03-01

Pathological gambling has severe consequences for adolescents and their families and friends. Despite its high prevalence, pathological gambling in adolescents has been insufficiently studied. Sensation seeking and impulsivity are two variables that are related to the appearance and maintenance of pathological gambling. However, few studies have determined the role these variables play in the development of the dysfunctional symptomatology of gambling behavior in adolescents and young adults. The aims of this study were to analyze the consequences of gambling in young adults and adolescents, and to evaluate the roles of sensation seeking and impulsivity in the appearance of dysfunctional symptomatology. The sample consisted of 1,241 young adults and adolescents recruited from scholar centers and free-time groups, as well as 71 subjects from associations that assist pathological gamblers. Pathological gambling, impulsive behavior, dysfunctional symptomatology and sensation seeking were assessed. The results confirmed that young adults and adolescents who gamble pathologically have more dysfunctional symptomatology related to anxiety, depression, hostility, obsessive-compulsive behavior and somatization, as well as sensation seeking, impulsivity and addictive behavior. Moreover, the results showed that sensation seeking did not mediate the appearance of dysfunctional symptomatology and that impulsivity partially mediated the appearance of anxiety, phobic anxiety, depression and psychosis and perfectly mediated somatization, obsessive-compulsive behavior, interpersonal sensitivity, paranoid ideation and hostility. These results have consequences for the development of treatment and prevention programs for adolescent pathological gambling.

Factors influencing delay in the diagnosis of colorectal cancer: a study protocol

PubMed Central

Esteva, Magdalena; Ramos, Maria; Cabeza, Elena; Llobera, Joan; Ruiz, Amador; Pita, Salvador; Segura, Josep M; Cortés, Jose M; González-Lujan, Luis

2007-01-01

Background Colorectal cancer (CRC) is the second most frequent tumor in developed countries. Since survival from CRC depends mostly on disease stage at the time of diagnosis, individuals with symptoms or signs suspicious of CRC should be examined without delay. Many factors, however, intervene between symptom onset and diagnosis. This study was designed to: 1) Describe the diagnostic process of CRC from the onset of first symptoms to diagnosis and treatment. 2) Establish the time interval from initial symptoms to diagnosis and treatment, globally and considering patient's and doctors' delay, with the latter due to family physician and/or hospital services. 3) Identify the factors related to defined types of delay. 4) Assess the concordance between information included in primary health care and hospital clinical records regarding onset of first symptoms. Methods/Design Descriptive study, coordinated, with 5 participant groups of 5 different Spanish regions (Balearic Islands, Galicia, Catalunya, Aragón and Valencia Health Districts), with a total of 8 acute public hospitals and 140 primary care centers. Incident cases of CRC during the study period, as identified from pathology services at the involved hospitals. A sample size of 896 subjects has been estimated, 150 subjects for each participant group. Information will be collected through patient interviews and primary health care and hospital clinical records. Patient variables will include sociodemographic variables, family history of cancer, symptom perception, and confidence in the family physician; tumor variables will include tumor site, histological type, grade and stage; symptom variables will include date of onset, type and number of symptoms; health system variables will include number of patient contacts with family physician, type and content of the referral, hospital services attending the patient, diagnostic modalities and results; and delay intervals, including global delays and delays attributed to the patient, family physician and hospital. Discussion To obtain a nonrestricted sample of patients with CRC we have minimized selection risk by identifying the patients from pathology services. A greater constraint may be associated with information sources based on clinical records. Due to inherent features of coordinated studies, it is important to standardize the collection of information. PMID:17697332

Social network media exposure and adolescent eating pathology in Fiji

PubMed Central

Becker, Anne E.; Fay, Kristen E.; Agnew-Blais, Jessica; Khan, A. Nisha; Striegel-Moore, Ruth H.; Gilman, Stephen E.

2011-01-01

Background Mass media exposure has been associated with an increased risk of eating pathology. It is unknown whether indirect media exposure – such as the proliferation of media exposure in an individual’s social network – is also associated with eating disorders. Aims To test hypotheses that both individual (direct) and social network (indirect) mass media exposures were associated with eating pathology in Fiji. Method We assessed several kinds of mass media exposure, media influence, cultural orientation and eating pathology by self-report among adolescent female ethnic Fijians (n = 523). We fitted a series of multiple regression models of eating pathology, assessed by the Eating Disorder Examination Questionnaire (EDE–Q), in which mass media exposures, sociodemographic characteristics and body mass index were entered as predictors. Results Both direct and indirect mass media exposures were associated with eating pathology in unadjusted analyses, whereas in adjusted analyses only social network media exposure was associated with eating pathology. This result was similar when eating pathology was operationalised as either a continuous or a categorical dependent variable (e.g. odds ratio OR = 1.60, 95% CI 1.15–2.23 relating social network media exposure to upper-quartile EDE–Q scores). Subsequent analyses pointed to individual media influence as an important explanatory variable in this association. Conclusions Social network media exposure was associated with eating pathology in this Fijian study sample, independent of direct media exposure and other cultural exposures. Findings warrant further investigation of its health impact in other populations. PMID:21200076

Social network media exposure and adolescent eating pathology in Fiji.

PubMed

Becker, Anne E; Fay, Kristen E; Agnew-Blais, Jessica; Khan, A Nisha; Striegel-Moore, Ruth H; Gilman, Stephen E

2011-01-01

Mass media exposure has been associated with an increased risk of eating pathology. It is unknown whether indirect media exposure--such as the proliferation of media exposure in an individual's social network--is also associated with eating disorders. To test hypotheses that both individual (direct) and social network (indirect) mass media exposures were associated with eating pathology in Fiji. We assessed several kinds of mass media exposure, media influence, cultural orientation and eating pathology by self-report among adolescent female ethnic Fijians (n=523). We fitted a series of multiple regression models of eating pathology, assessed by the Eating Disorder Examination Questionnaire (EDE-Q), in which mass media exposures, sociodemographic characteristics and body mass index were entered as predictors. Both direct and indirect mass media exposures were associated with eating pathology in unadjusted analyses, whereas in adjusted analyses only social network media exposure was associated with eating pathology. This result was similar when eating pathology was operationalised as either a continuous or a categorical dependent variable (e.g. odds ratio OR=1.60, 95% CI 1.15-2.23 relating social network media exposure to upper-quartile EDE-Q scores). Subsequent analyses pointed to individual media influence as an important explanatory variable in this association. Social network media exposure was associated with eating pathology in this Fijian study sample, independent of direct media exposure and other cultural exposures. Findings warrant further investigation of its health impact in other populations.

Manipulations of the features of standard video lottery terminal (VLT) games: effects in pathological and non-pathological gamblers.

PubMed

Loba, P; Stewart, S H; Klein, R M; Blackburn, J R

2001-01-01

The present study was conducted to identify game parameters that would reduce the risk of abuse of video lottery terminals (VLTs) by pathological gamblers, while exerting minimal effects on the behavior of non-pathological gamblers. Three manipulations of standard VLT game features were explored. Participants were exposed to: a counter which displayed a running total of money spent; a VLT spinning reels game where participants could no longer "stop" the reels by touching the screen; and sensory feature manipulations. In control conditions, participants were exposed to standard settings for either a spinning reels or a video poker game. Dependent variables were self-ratings of reactions to each set of parameters. A set of 2(3) x 2 x 2 (game manipulation [experimental condition(s) vs. control condition] x game [spinning reels vs. video poker] x gambler status [pathological vs. non-pathological]) repeated measures ANOVAs were conducted on all dependent variables. The findings suggest that the sensory manipulations (i.e., fast speed/sound or slow speed/no sound manipulations) produced the most robust reaction differences. Before advocating harm reduction policies such as lowering sensory features of VLT games to reduce potential harm to pathological gamblers, it is important to replicate findings in a more naturalistic setting, such as a real bar.

Relationships: empirical contribution. Understanding personality pathology in adolescents: the five factor model of personality and social information processing.

PubMed

Hessels, Christel; van den Hanenberg, Danique; de Castro, Bram Orobio; van Aken, Marcel A G

2014-02-01

This study seeks to integrate two research traditions that lie at the base of the understanding of personality pathology in adolescents. The first research tradition refers to normal personality according to the Five Factor Model (FFM). The second tradition specifies the key feature of personality disorder as the capacity to mentalize, which can be reflected in Social Information Processing (SIP). In a clinical sample of 96 adolescents, the authors investigated response generation, coping strategy, and memories of past frustrating experiences as part of SIP, as mediator in the relationship between personality and personality pathology, and a possible moderating role of personality on the relationship between SIP and personality pathology. The hypothesized mediation, by which the effects of personality dimensions on personality pathology was expected to be mediated by SIP variables, was found only for the effect of Neuroticism, most specifically on BPD, which appeared to be mediated by memories the patients had about past frustrating conflict situations with peers. Some moderating effects of personality on the relationship between SIP variables and personality pathology were found, suggesting that high Agreeableness and sometimes low Neuroticism can buffer this relationship. These results suggest that personality dimensions and social cognitions both independently and together play a role in adolescents' personality pathology.

Quantitative image variables reflect the intratumoral pathologic heterogeneity of lung adenocarcinoma.

PubMed

Choi, E-Ryung; Lee, Ho Yun; Jeong, Ji Yun; Choi, Yoon-La; Kim, Jhingook; Bae, Jungmin; Lee, Kyung Soo; Shim, Young Mog

2016-10-11

We aimed to compare quantitative radiomic parameters from dual-energy computed tomography (DECT) of lung adenocarcinoma and pathologic complexity.A total 89 tumors with clinical stage I/II lung adenocarcinoma were prospectively included. Fifty one radiomic features were assessed both from iodine images and non-contrast images of DECT datasets. Comprehensive histologic subtyping was evaluated with all surgically resected tumors. The degree of pathologic heterogeneity was assessed using pathologic index and the number of mixture histologic subtypes in a tumor. Radiomic parameters were correlated with pathologic index. Tumors were classified as three groups according to the number of mixture histologic subtypes and radiomic parameters were compared between the three groups.Tumor density and 50th through 97.5th percentile Hounsfield units (HU) of histogram on non-contrast images showed strong correlation with the pathologic heterogeneity. Radiomic parameters including 75th and 97.5th percentile HU of histogram, entropy, and inertia on 1-, 2- and 3 voxel distance on non-contrast images showed incremental changes while homogeneity showed detrimental change according to the number of mixture histologic subtypes (all Ps < 0.05).Radiomic variables from DECT of lung adenocarcinoma reflect pathologic intratumoral heterogeneity, which may help in the prediction of intratumoral heterogeneity of the whole tumor.

Pathological response to neoadjuvant chemotherapy: a new prognosis tool for the curative management of peritoneal colorectal carcinomatosis.

PubMed

Passot, Guillaume; You, Benoît; Boschetti, Gilles; Fontaine, Juliette; Isaac, Sylvie; Decullier, Evelyne; Maurice, Christele; Vaudoyer, Delphine; Gilly, François-Noël; Cotte, Eddy; Glehen, Olivier

2014-08-01

The primary objective of this study was to determine the incidence rate of pathological complete responses (pCRs) following neoadjuvant systemic chemotherapy for the treatment of peritoneal carcinomatosis (PC) of colorectal origin. The secondary objective was to evaluate whether pathological response assessments predict survival of patients treated with curative intent by complete cytoreductive surgery (CRS). A retrospective review was performed of 115 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by 124 procedures of complete CRS alone or combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The pathological response was defined as the mean percentage of cancer cells remaining within all specimens. Univariate and multivariate analyses were performed to identify predictors of survival and pathological response outcome. Twelve procedures (9.7 %) resulted in pCRs, defined as no residual cancer cells in all specimens, 25 (20.2 %) resulted in major responses (1 to 49 % residual cancer cells), and 87 (70.1 %) resulted in minor or no responses (>50 % residual cancer cells). The cumulative 5-year survival rates were 75 and 57 % for patients with pCR and major responses, respectively. Using multivariate analysis, pathological response was the only independent predictor of survival (P = 0.01; major response: hazard ratio [HR] = 4.91; minor response: HR = 13.46). No significant predictor of pathological response was identified. Pathological complete response can be achieved with preoperative systemic chemotherapy for patients with PC of colorectal origin. The degree of pathological response can be assessed and represented as a new outcome for prognosis following treatment with curative intent.

Association of α-, β-, and γ-Synuclein With Diffuse Lewy Body Disease

PubMed Central

Nishioka, Kenya; Wider, Christian; Vilariño-Güell, Carles; Soto-Ortolaza, Alexandra I.; Lincoln, Sarah J.; Kachergus, Jennifer M.; Jasinska-Myga, Barbara; Ross, Owen A.; Rajput, Alex; Robinson, Christopher A.; Ferman, Tanis J.; Wszolek, Zbigniew K.; Dickson, Dennis W.; Farrer, Matthew J.

2016-01-01

Objective To determine the association of the genes that encode α-, β-, and γ-synuclein (SNCA, SNCB, and SNCG, respectively) with diffuse Lewy body disease (DLBD). Design Case-control study. Subjects A total of 172 patients with DLBD consistent with a clinical diagnosis of Parkinson disease dementia/dementia with Lewy bodies and 350 clinically and 97 pathologically normal controls. Interventions Sequencing of SNCA, SNCB, and SNCG and genotyping of single-nucleotide polymorphisms performed on an Applied Biosystems capillary sequencer and a Sequenom MassArray pLEX platform, respectively. Associations were determined using χ2 or Fisher exact tests. Results Initial sequencing studies of the coding regions of each gene in 89 patients with DLBD did not detect any pathogenic substitutions. Nevertheless, genotyping of known polymorphic variability in sequence-conserved regions detected several single-nucleotide polymorphisms in the SNCA and SNCG genes that were significantly associated with disease (P=.05 to <.001). Significant association was also observed for 3 single-nucleotide polymorphisms located in SNCB when comparing DLBD cases and pathologically confirmed normal controls (P=.03-.01); however, this association was not significant for the clinical controls alone or the combined clinical and pathological controls (P>.05). After correction for multiple testing, only 1 single-nucleotide polymorphism in SNCG (rs3750823) remained significant in all of the analyses (P=.05-.009). Conclusion These findings suggest that variants in all 3 members of the synuclein gene family, particularly SNCA and SNCG, affect the risk of developing DLBD and warrant further investigation in larger, pathologically defined data sets as well as clinically diagnosed Parkinson disease/dementia with Lewy bodies case-control series. PMID:20697047

The immediate placement of dental implants into extraction sites with periapical lesions: a retrospective chart review.

PubMed

Bell, Christopher Lincoln; Diehl, David; Bell, Brian Michael; Bell, Robert E

2011-06-01

The purpose of this study was to evaluate the success of dental implants placed immediately into extraction sites in the presence of chronic periapical pathology. The charts of 655 patients who had implants immediately placed into fresh extraction sites were reviewed for the presence or absence of periapical radiolucencies. A total of 922 implants were included. Of the 922 implants, 285 were immediately placed into sockets that had chronic periapical infections. The remaining 637 implants, without signs of periapical pathology, were used as the control group. Success of the implants was defined as successful osseointegration, successful restoration, and absence of evidence of bone loss or peri-implantitis. Other variables such as age, gender, smoking, diabetes, bisphosphonate use, lucencies of adjacent teeth, and implant stability at the time of placement were also evaluated. Of the 922 implants, 285 were placed into sockets with periapical radiolucencies. The success rate of implants placed in the study group was 97.5%, whereas the success rate of the control group was 98.7%. The difference was not found to be statistically significant. The mean follow-up was 19.75 months, with a maximum of 93 months and a minimum of 3 months. A statistically higher failure rate was found for implants placed adjacent to retained teeth with periapical pathology. The placement of implants in sockets affected by chronic periapical pathology can be considered a safe and viable treatment option. There is a risk of implant failure when placing implants adjacent to teeth with periapical radiolucencies. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Clinical subtypes and genetic heterogeneity: of lumping and splitting in Parkinson disease.

PubMed

von Coelln, Rainer; Shulman, Lisa M

2016-12-01

Recent studies on clinical, genetic and pathological heterogeneity of Parkinson disease have renewed the old debate whether we should think of Parkinson disease as one disease with variations, or as a group of independent diseases that happen to present with similar phenotypes. Here, we provide an overview of where the debate is coming from, and how recent findings in clinical subtyping, genetics and clinico-pathological correlation have shaped this controversy over the last few years. New and innovative clinical diagnostic criteria for Parkinson disease have been proposed and await validation. Studies using functional imaging or wearable biosensors, as well as biomarker studies, provide new support for the validity of the traditional clinical subtypes of Parkinson disease (tremor-dominant versus akinetic-rigid or postural instability/gait difficulty). A recent cluster analysis (as unbiased data-driven approach to subtyping) included a wide spectrum of nonmotor variables, and showed correlation of the proposed subtypes with disease progression in a longitudinal analysis. New genetic factors contributing to Parkinson disease susceptibility continue to be identified, including rare mutations causing monogenetic disease, common variants with small effect size and risk factors (like mutations in the gene for glucocerebrosidase) that fall in between the two other categories. Recent studies show some limited correlation between genetic factors and clinical heterogeneity. Despite some variations in patterns of pathology, Lewy bodies are still the hallmark of Parkinson disease, including the vast majority of genetic subgroups. Evidence of clinical, genetic and pathological heterogeneity of Parkinson disease continues to emerge, but clearly defined subtypes that hold up in more than one of these domains remain elusive. For research to identify such subtypes, splitting is likely the way forward; until then, for clinical practice, lumping remains the more pragmatic approach.

HPV RNA CISH score identifies two prognostic groups in a p16 positive oropharyngeal squamous cell carcinoma population.

PubMed

Augustin, Jérémy; Mandavit, Marion; Outh-Gauer, Sophie; Grard, Ophélie; Gasne, Cassandre; Lépine, Charles; Mirghani, Haïtham; Hans, Stéphane; Bonfils, Pierre; Denize, Thomas; Bruneval, Patrick; Bishop, Justin A; Fontugne, Jacqueline; Péré, Hélène; Tartour, Eric; Badoual, Cécile

2018-06-20

HPV-related and HPV-unrelated oropharyngeal squamous cell carcinomas are two distinct entities according to the Union for International Cancer Control, with a better prognosis conferred to HPV-related oropharyngeal squamous cell carcinomas. However, variable clinical outcomes are observed among patients with p16 positive oropharyngeal squamous cell carcinoma, which is a surrogate marker of HPV infection. We aimed to investigate the prognostic value of RNA CISH against E6 and E7 transcripts (HPV RNA CISH) to predict such variability. We retrospectively included 50 histologically confirmed p16 positive oropharyngeal squamous cell carcinomas (p16 positive immunostaining was defined by a strong staining in 70% or more of tumor cells). HPV RNA CISH staining was assessed semi-quantitatively to define two scores: RNA CISH "low" and RNA CISH "high". Negative HPV RNA CISH cases were scored as RNA CISH "low". This series contained 29 RNA CISH low cases (58%) and 21 RNA CISH high cases (42%). Clinical and pathologic baseline characteristics were similar between the two groups. RNA CISH high staining was associated with a better overall survival in both univariate and multivariate analyses (p = 0.033 and p = 0.042, respectively). Other recorded parameters had no prognostic value. In conclusion, HPV RNA CISH might be an independent prognostic marker in p16 positive oropharyngeal squamous cell carcinomas and might help guide therapeutics.

Gender Differences in Treatment-Seeking British Pathological Gamblers

PubMed Central

Ronzitti, Silvia; Lutri, Vittorio; Smith, Neil; Clerici, Massimo; Bowden-Jones, Henrietta

2016-01-01

Background and aim Gambling is a widespread recreational activity in the UK. A significant percentage of gamblers develop subclinical or clinically relevant problem gambling issues, but only a low percentage of them seek treatment. Although characteristics of pathological gamblers from treatment-seeking population have been examined in some research, only a few studies have explored the differences between females and males. This study aimed to examine the gender-related differences in demographics, gambling measures, and clinical variables in an outpatient sample of pathological gamblers seeking treatment. Methods A total of 1,178 treatment-seeking individuals with gambling disorder were assessed at the National Problem Gambling Clinic in London. Sociodemographic characteristics, clinical variables, and gambling behavior habits were obtained during the assessment evaluation. Of the total sample, 92.5% were males and 7.5% were females. Results Males were more likely to be younger, white, and employed than females. In addition, compared to women, men showed a lower PGSI score, an earlier age of onset of gambling behavior, a higher gambling involvement, and preferred specific forms gambling. Female gamblers were more anxious and depressed, while men were more likely to use alcohol and illicit drugs. Conclusions Our findings support the importance of gender differences in a treatment-seeking population of pathological gamblers both in sociodemographic characteristics, gambling behavior variables, and clinical variables. Males and females might benefit from group-specific treatment. PMID:27348561

Superior Temporal Gyrus Volume Abnormalities and Thought Disorder in Left-Handed Schizophrenic Men

PubMed Central

Holinger, Dorothy P.; Shenton, Martha E.; Wible, Cynthia G.; Donnino, Robert; Kikinis, Ron; Jolesz, Ferenc A.; McCarley, Robert W.

2010-01-01

Objective Studies of schizophrenia have not clearly defined handedness as a differentiating variable. Moreover, the relationship between thought disorder and anatomical anomalies has not been studied extensively in left-handed schizophrenic men. The twofold purpose of this study was to investigate gray matter volumes in the superior temporal gyrus of the temporal lobe (left and right hemispheres) in left-handed schizophrenic men and left-handed comparison men, in order to determine whether thought disorder in the left-handed schizophrenic men correlated with tissue volume abnormalities. Method Left-handed male patients (N=8) with DSM-III-R diagnoses of schizophrenia were compared with left-handed comparison men (N=10) matched for age, socioeconomic status, and IQ. Magnetic resonance imaging (MRI) with a 1.5-T magnet was used to obtain scans, which consisted of contiguous 1.5-mm slices of the whole brain. MRI analyses (as previously defined by the authors) included the anterior, posterior, and total superior temporal gyrus in both the left and right hemispheres. Results There were three significant findings regarding the left-handed schizophrenic men: 1) bilaterally smaller gray matter volumes in the posterior superior temporal gyrus (16% smaller on the right, 15% smaller on the left); 2) a smaller volume on the right side of the total superior temporal gyrus; and 3) a positive correlation between thought disorder and tissue volume in the right anterior superior temporal gyrus. Conclusions These results suggest that expression of brain pathology differs between left-handed and right-handed schizophrenic men and that the pathology is related to cognitive disturbance. PMID:10553736

Human Movement Variability, Nonlinear Dynamics, and Pathology: Is There A Connection?

PubMed Central

Stergiou, Nicholas; Decker, Leslie M.

2011-01-01

Fields studying movement generation, including robotics, psychology, cognitive science and neuroscience utilize concepts and tools related to the pervasiveness of variability in biological systems. The concept of variability and the measures for nonlinear dynamics used to evaluate this concept open new vistas for research in movement dysfunction of many types. This review describes innovations in the exploration of variability and their potential importance in understanding human movement. Far from being a source of error, evidence supports the presence of an optimal state of variability for healthy and functional movement. This variability has a particular organization and is characterized by a chaotic structure. Deviations from this state can lead to biological systems that are either overly rigid and robotic or noisy and unstable. Both situations result in systems that are less adaptable to perturbations, such as those associated with unhealthy pathological states or absence of skillfulness. PMID:21802756

Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design.

PubMed

Westhall, Erik; Rosén, Ingmar; Rossetti, Andrea O; van Rootselaar, Anne-Fleur; Kjaer, Troels Wesenberg; Horn, Janneke; Ullén, Susann; Friberg, Hans; Nielsen, Niklas; Cronberg, Tobias

2014-08-16

Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest, but its value is limited by varying definitions of pathological patterns and by inter-rater variability. The American Clinical Neurophysiology Society (ACNS) has recently proposed a standardized EEG-terminology for critical care to address these limitations. In the TTM-trial, 399 post cardiac arrest patients who remained comatose after rewarming underwent a routine EEG. The presence of clinical seizures, use of sedatives and antiepileptic drugs during the EEG-registration were prospectively documented. A well-defined terminology for interpreting post cardiac arrest EEGs is critical for the use of EEG as a prognostic tool. The TTM-trial is registered at ClinicalTrials.gov (NCT01020916).

Predictive value of magnetic resonance imaging determined tumor contact length for extracapsular extension of prostate cancer.

PubMed

Baco, Eduard; Rud, Erik; Vlatkovic, Ljiljana; Svindland, Aud; Eggesbø, Heidi B; Hung, Andrew J; Matsugasumi, Toru; Bernhard, Jean-Christophe; Gill, Inderbir S; Ukimura, Osamu

2015-02-01

Tumor contact length is defined as the amount of prostate cancer in contact with the prostatic capsule. We evaluated the ability of magnetic resonance imaging determined tumor contact length to predict microscopic extracapsular extension compared to existing predictors of extracapsular extension. We retrospectively analyzed the records of 111 consecutive patients with magnetic resonance imaging/ultrasound fusion targeted, biopsy proven prostate cancer who underwent radical prostatectomy from January 2010 to July 2013. Median patient age was 64 years and median prostate specific antigen was 8.9 ng/ml. Clinical stage was cT1 in 93 cases (84%) and cT2 in 18 (16%). Postoperative pathological analysis confirmed pT2 in 71 patients (64%) and pT3 in 40 (36%). We evaluated 1) in the radical prostatectomy specimen the correlation of microscopic extracapsular extension with pathological cancer volume, pathological tumor contact length and Gleason score, 2) the correlation between microscopic extracapsular extension and magnetic resonance imaging tumor contact length, and 3) the ability of preoperative variables to predict microscopic extracapsular extension. Logistic regression analysis revealed that pathological tumor contact length correlated better with microscopic extracapsular extension than the predictive power of pathological cancer volume (0.821 vs 0.685). The Spearman correlation between pathological and magnetic resonance imaging tumor contact length was r = 0.839 (p <0.0001). ROC AUC analysis revealed that magnetic resonance imaging tumor contact length outperformed cancer core involvement on targeted biopsy and the Partin tables to predict microscopic extracapsular extension (0.88 vs 0.70 and 0.63, respectively). At a magnetic resonance imaging tumor contact length threshold of 20 mm the accuracy for diagnosing microscopic extracapsular extension was superior to that of conventional magnetic resonance imaging criteria (82% vs 67%, p = 0.015). We developed a predicted probability plot curve of extracapsular extension according to magnetic resonance imaging tumor contact length. Magnetic resonance imaging determined tumor contact length could be a promising quantitative predictor of microscopic extracapsular extension. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Assessment of mechanical properties of isolated bovine intervertebral discs from multi-parametric magnetic resonance imaging.

PubMed

Recuerda, Maximilien; Périé, Delphine; Gilbert, Guillaume; Beaudoin, Gilles

2012-10-12

The treatment planning of spine pathologies requires information on the rigidity and permeability of the intervertebral discs (IVDs). Magnetic resonance imaging (MRI) offers great potential as a sensitive and non-invasive technique for describing the mechanical properties of IVDs. However, the literature reported small correlation coefficients between mechanical properties and MRI parameters. Our hypothesis is that the compressive modulus and the permeability of the IVD can be predicted by a linear combination of MRI parameters. Sixty IVDs were harvested from bovine tails, and randomly separated in four groups (in-situ, digested-6h, digested-18h, digested-24h). Multi-parametric MRI acquisitions were used to quantify the relaxation times T1 and T2, the magnetization transfer ratio MTR, the apparent diffusion coefficient ADC and the fractional anisotropy FA. Unconfined compression, confined compression and direct permeability measurements were performed to quantify the compressive moduli and the hydraulic permeabilities. Differences between groups were evaluated from a one way ANOVA. Multi linear regressions were performed between dependent mechanical properties and independent MRI parameters to verify our hypothesis. A principal component analysis was used to convert the set of possibly correlated variables into a set of linearly uncorrelated variables. Agglomerative Hierarchical Clustering was performed on the 3 principal components. Multilinear regressions showed that 45 to 80% of the Young's modulus E, the aggregate modulus in absence of deformation HA0, the radial permeability kr and the axial permeability in absence of deformation k0 can be explained by the MRI parameters within both the nucleus pulposus and the annulus pulposus. The principal component analysis reduced our variables to two principal components with a cumulative variability of 52-65%, which increased to 70-82% when considering the third principal component. The dendograms showed a natural division into four clusters for the nucleus pulposus and into three or four clusters for the annulus fibrosus. The compressive moduli and the permeabilities of isolated IVDs can be assessed mostly by MT and diffusion sequences. However, the relationships have to be improved with the inclusion of MRI parameters more sensitive to IVD degeneration. Before the use of this technique to quantify the mechanical properties of IVDs in vivo on patients suffering from various diseases, the relationships have to be defined for each degeneration state of the tissue that mimics the pathology. Our MRI protocol associated to principal component analysis and agglomerative hierarchical clustering are promising tools to classify the degenerated intervertebral discs and further find biomarkers and predictive factors of the evolution of the pathologies.

Expanding the spectrum of neuronal pathology in multiple system atrophy

PubMed Central

Cykowski, Matthew D.; Coon, Elizabeth A.; Powell, Suzanne Z.; Jenkins, Sarah M.; Benarroch, Eduardo E.; Low, Phillip A.; Schmeichel, Ann M.

2015-01-01

Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients with multiple system atrophy, including a patient with visual hallucinations. Further, the presence of Lewy body-like inclusions in neocortex, but not hippocampal alpha-synuclein pathology, was associated with cognitive impairment (P = 0.002). However, several cases had the presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus, deep cerebellar nuclei) that are not typical for Lewy body-spectrum disease. Finally, interregional correlations (rho ≥ 0.6) in pathologic glial and neuronal lesion burden suggest shared mechanisms of disease progression between both discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types (neuronal and glial inclusions in frontal cortex and white matter, respectively). These findings suggest that in addition to glial inclusions, neuronal pathology plays an important role in the developmental and progression of multiple system atrophy. See Halliday (doi:10.1093/brain/awv151) for a scientific commentary on this article. PMID:25981961

Evaluation of Cross-Protocol Stability of a Fully Automated Brain Multi-Atlas Parcellation Tool.

PubMed

Liang, Zifei; He, Xiaohai; Ceritoglu, Can; Tang, Xiaoying; Li, Yue; Kutten, Kwame S; Oishi, Kenichi; Miller, Michael I; Mori, Susumu; Faria, Andreia V

2015-01-01

Brain parcellation tools based on multiple-atlas algorithms have recently emerged as a promising method with which to accurately define brain structures. When dealing with data from various sources, it is crucial that these tools are robust for many different imaging protocols. In this study, we tested the robustness of a multiple-atlas, likelihood fusion algorithm using Alzheimer's Disease Neuroimaging Initiative (ADNI) data with six different protocols, comprising three manufacturers and two magnetic field strengths. The entire brain was parceled into five different levels of granularity. In each level, which defines a set of brain structures, ranging from eight to 286 regions, we evaluated the variability of brain volumes related to the protocol, age, and diagnosis (healthy or Alzheimer's disease). Our results indicated that, with proper pre-processing steps, the impact of different protocols is minor compared to biological effects, such as age and pathology. A precise knowledge of the sources of data variation enables sufficient statistical power and ensures the reliability of an anatomical analysis when using this automated brain parcellation tool on datasets from various imaging protocols, such as clinical databases.

A single microfocus (5% or less) of Gleason 6 prostate cancer at biopsy--can we predict adverse pathological outcomes?

PubMed

Thong, Alan E; Shikanov, Sergey; Katz, Mark H; Gofrit, Ofer N; Eggener, Scott; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C

2008-12-01

Patients with Gleason score 6 microfocal prostate cancer, defined as 5% or less in 1 biopsy core, are often considered to have favorable disease. Few studies have addressed clinical parameters that predict pathological upgrading or up staging at radical prostatectomy. From a prospective database of 1,271 consecutive robot assisted laparoscopic prostatectomies performed from 2003 to 2008 patients with Gleason score 6 microfocal prostate cancer were identified. Adverse pathological outcome was defined as any upgrading and/or up staging on prostatectomy pathological findings. Multivariate logistic regression was used to evaluate the ability of patient age, clinical stage, the total number of biopsy cores, preoperative prostate specific antigen, prostate volume and pathological prostate specific antigen density to predict adverse pathological outcomes. A total of 192 patients with a median age of 59 years (range 42 to 73) were identified with Gleason score 6 prostate cancer involving 5% or less of 1 biopsy core, including 177 (92%) with clinical T1c disease. Mean +/- SD preoperative prostate specific antigen was 6.0 +/- 3.9 ng/ml (range 0.8 to 35). Overall 42 patients (22%) had adverse pathological outcomes, including upgrading in 35 (18%) and up staging in 16 (8%). Multivariate logistic regression revealed that age more than 65 years and pathological prostate specific antigen density greater than 0.20 ng/ml/gm were predictive of an increased risk of adverse pathological results (p = 0.0081 and 0.0169, respectively). While a microfocus of Gleason score 6 prostate cancer on biopsy is commonly considered low risk disease, there was a greater than 1/5 risk of pathological upgrading and/or up staging. Patients with Gleason score 6 microfocal prostate cancer should be counseled that they may harbor more aggressive disease, especially when pretreatment clinical risk factors are present, such as advanced age or high clinical prostate specific antigen density.

Comparison of the discontinuation rates and side-effect profiles of pilocarpine and cevimeline for xerostomia in primary Sjögren's syndrome.

PubMed

Noaiseh, Ghaith; Baker, Joshua F; Vivino, Frederick B

2014-01-01

There are currently no head-to-head comparisons of sialagogues for Primary Sjögren's syndrome (pSS). We compared the tolerability and side effect profile of pilocarpine and cevimeline in patients with pSS and determined clinical, laboratory and pathological variables associated with therapeutic failure. We retrospectively reviewed the use of pilocarpine and cevimeline in 118 patients with pSS who fulfilled the 2002 American European Consensus Group criteria in a University-based setting. Clinical, laboratory and pathological baseline variables were collected. Failure of therapy was defined as the clinician or patient's decision to stop treatment either due to lack of efficacy or side effects. Cevimeline was associated with lower failure rates compared to pilocarpine among first-time users: 27% vs. 47% (p=0.02), and all users: 32% vs. 61% (p<0.001). Severe sweating was the most frequent side effect leading to cessation of therapy and occurred more frequently in pilocarpine (25%) than cevimeline (11%) users (p=0.02). Patients who previously failed one secretagogue were less likely to discontinue treatment with the other agent, 52% of first-time users vs. 27% of second-time users (p=0.004). Only ANA positivity was associated with failure: [59% vs. 38%] (p=0.03). pSS patients were more likely to continue cevimeline than pilocarpine long-term due to fewer reported side effects with cevimeline. Therapeutic failure of one secretagogue did not predict similar results with the other since second time users were more likely to continue long-term treatment.

Health Outcomes in Individuals with Problem and Pathological Gambling: An Analysis of the 2014 North Carolina Behavioral Risk Factor Survey System (BRFSS).

PubMed

Van Patten, Ryan; Weinstock, Jeremiah; McGrath, Andrew B

2018-03-01

Problem and pathological gambling refers to subclinical and clinical levels of maladaptive gambling, respectively, and is associated with specific sociodemographic characteristics as well as a number of poor health outcomes. We examined such demographic, physical health, mental health, and health-related behaviors in a sample of 7045 low-risk gamblers and 244 problem/pathological gamblers. Participants completed the 2014 North Carolina Behavioral Risk Factor Surveillance System telephone survey. Using the National Opinion Research Center's Diagnostic Screen for Gambling Disorders-CLiP, participants were categorized as either "problem/pathological gamblers" or "low-risk gamblers." Problem/pathological gamblers were younger, more likely to be male, of ethnic minority status, unmarried, and of lower education than low-risk gamblers. No physical health variables differentiated the groups but problem/pathological gamblers reported experiencing significantly more adverse childhood experiences and engaging in significantly more tobacco and alcohol use compared to low-risk gamblers. Moreover, gender moderated relationships between gambling group and several of the alcohol use variables such that male problem/pathological gamblers exhibited greater alcohol use behavior than male low-risk gamblers but no such relationship was present in females. Overall, this study expands the current knowledgebase on disordered gambling and highlights the need to assess disordered gambling in public health samples. Clinical implications are discussed.

Standardizing the definition of adverse pathology for lower risk men undergoing radical prostatectomy.

PubMed

Kozminski, Michael A; Tomlins, Scott; Cole, Adam; Singhal, Udit; Lu, Louis; Skolarus, Ted A; Palapattu, Ganesh S; Montgomery, Jeffrey S; Weizer, Alon Z; Mehra, Rohit; Hollenbeck, Brent K; Miller, David C; He, Chang; Feng, Felix Y; Morgan, Todd M

2016-09-01

Numerous definitions of adverse pathology at radical prostatectomy (RP) have been proposed and implemented for both research and clinical care, and there is tremendous variation in the specific criteria used to define adverse pathology in these settings. Given the current landscape in which magnetic resonance imaging criteria and biomarker cutoffs are validated for disparate adverse pathology definitions, we sought to identify which of these is most closely tied to biochemical recurrence (BCR) after RP. A total of 2,837 patients who underwent RP at a single institution for localized prostate cancer (PCa) were included. We evaluated the following existing definitions of adverse pathology at RP: (1) Gleason score ≥7, (2) primary Gleason pattern ≥4, (3) Gleason score ≥7 or pathologic stage T3-4, (4) pathologic stage T3-4, (5) primary Gleason pattern ≥4 or pathologic stage T3-4. The primary outcome measure was BCR. Multiple statistical techniques were used to assess BCR prediction. Of the 5 definitions assessed, 1 (primary Gleason pattern ≥4 or pathologic stage T3-4, 540 patients [19% of cohort]) consistently outperformed the other definitions across all statistical measures. Additionally, a total of only 13 (6.6%) and 34 (10.3%) men with very-low-risk and low-risk cancer per National Comprehensive Cancer Network guideline, respectively, met this definition of adverse pathology at the time of RP. Varying definitions of adverse pathology differ in their prognostic performance. The criteria defined by either primary Gleason pattern ≥4 or pT3-4 disease appears to most accurately predict BCR in this subset of patients with lower risk PCa at the time of diagnosis. Additionally, men with very-low-risk or low-risk PCa per National Comprehensive Cancer Network guidelines are relatively unlikely to have adverse pathology at the time of surgical resection. These data may help inform the use of imaging and molecular markers as well as the intensity of surveillance in men with newly diagnosed PCa. Copyright © 2016 Elsevier Inc. All rights reserved.

Voice rest after vocal fold surgery: current practice and evidence.

PubMed

Coombs, A C; Carswell, A J; Tierney, P A

2013-08-01

Voice rest is commonly recommended after vocal fold surgery, but there is a lack of evidence base and no standard protocol. The aim of this study was to establish common practice regarding voice rest following vocal fold surgery. An online survey was circulated via e-mail invitation to members of the ENT UK Expert Panel between October and November 2011. The survey revealed that 86.5 per cent of respondents agreed that 'complete voice rest' means no sound production at all, but there was variability in how 'relative voice rest' was defined. There was no dominant type of voice rest routinely recommended after surgery for laryngeal papillomatosis or intermediate pathologies. There was considerable variability in the duration of voice rest recommended, with no statistically significant, most popular response (except for malignant lesions). Surgeons with less than 10 years of experience were more likely to recommend fewer days of voice rest. There is a lack of consistency in advice given to patients after vocal fold surgery, in terms of both type and length of voice rest. This may arise from an absence of robust evidence on which to base practice.

Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva.

PubMed

Gadducci, Angiolo; Tana, Roberta; Barsotti, Cecilia; Guerrieri, Maria Elena; Genazzani, Andrea Riccardo

2012-07-01

Several clinical-pathological parameters have been related to survival of patients with invasive squamous cell carcinoma of the vulva, whereas few studies have investigated the ability of biological variables to predict the clinical outcome of these patients. The present paper reviews the literature data on the prognostic relevance of lymph node-related parameters, primary tumor-related parameters, FIGO stage, blood variables, and tissue biological variables. Regarding these latter, the paper takes into account the analysis of DNA content, cell cycle-regulatory proteins, apoptosis-related proteins, epidermal growth factor receptor [EGFR], and proteins that are involved in tumor invasiveness, metastasis and angiogenesis. At present, the lymph node status and FIGO stage according to the new 2009 classification system are the main predictors for vulvar squamous cell carcinoma, whereas biological variables do not have yet a clinical relevance and their role is still investigational. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Plasma biochemistry RIs and age effect in European Strigiformes.

PubMed

Agusti Montolio, Susana; Cuenca Valera, Rafaela; Lavín González, Santiago; Cray, Carolyn; Molina López, Rafael; Ferron, Emmanuel Serrano; Francisco, Olga Nicolás; Marco Sánchez, Ignasi; Casas-Díaz, Encarna

2018-03-01

Blood biochemistry and hematology are essential in the laboratory diagnosis of disease. In Strigiformes, little information regarding reference values and influence of different preanalytic factors is available, while age is known to have an effect on some biochemistry analytes, especially in early life characterized by a rapid growth rate and increase in body mass. The objective of this study was to determine baseline data for 29 blood biochemistry variables in 5 species of Iberian Strigiformes assigned to different age classes. Healthy nocturnal birds living in wildlife health centers of Catalonia, Northeastern Spain were assigned to different age classes (chicks, juveniles, adults where possible and available) and their blood was collected and analyzed for different standard biochemistry variables. Species included Tawny owls, Little owls, Long-eared owls, Scop owls, and Barn owls. A total of 276 clinically healthy animals were sampled, including between 179 chicks, 52 juveniles, and 45 adults. The RIs of cholesterol, albumin, and osmolality were the only variables that did not show interspecific variability. Common trends between age class groups were observed in 4 species. Phosphorus and calcium concentrations and ALP activities decreased with increasing age, while concentrations of sodium and γ-globulins tended to increase in the Strigidae family. Differences were concentrated in chicks and no differences were observed between juveniles and adults in any variable. Our results demonstrate the importance of defining biochemical RIs specific for certain age classes. © 2018 American Society for Veterinary Clinical Pathology.

Comparing and Contrasting Siblings: Defining the Self.

ERIC Educational Resources Information Center

Schachter, Frances Fuchs; Stone, Richard K.

1987-01-01

Deidentification is the phenomenon whereby siblings are defined as different or contrasting. In pathological deidentification, the natural flow of sibling conflict and reconciliation seems obstructed as one sibling is assigned the fixed identity of "devil," who constantly harasses the other, "angel," sibling. A clinical…

Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control

NASA Astrophysics Data System (ADS)

Valenza, Gaetano; Citi, Luca; Garcia, Ronald G.; Taylor, Jessica Noggle; Toschi, Nicola; Barbieri, Riccardo

2017-02-01

The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson’s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity.

Robotic laparoscopic radical prostatectomy for biopsy Gleason 8 to 10: prediction of favorable pathologic outcome with preoperative parameters.

PubMed

Shikanov, Sergey A; Thong, Alan; Gofrit, Ofer N; Zagaja, Gregory P; Steinberg, Gary D; Shalhav, Arieh L; Zorn, Kevin C

2008-07-01

We sought to evaluate the pathologic results and postoperative outcomes for men undergoing robot-assisted laparoscopic radical prostatectomy (RLRP) for biopsy Gleason score (GS) 8 to 10 disease. Stratification of these patients according to preoperative variables was also performed in an attempt to predict organ-confined cancer. A prospective RLRP database identified all patients with preoperative biopsy GS 8 to 10. Variables, including prostate-specific antigen (PSA), percent positive biopsy cores (%PBC), maximal percentage of cancer in biopsy core (%MCB), clinical stage, pathologic stage, pathologic GS, surgical margins status, lymph node status, time to biochemical recurrence, and recurrence rate, were evaluated. Preoperative variables were treated as continuous and categorical using PSA, %PBC and %MCB cutoffs of 10 ng/mL, 50%, and 30%, respectively. Between February 2003 and September 2007, a total of 1225 RLRPs were performed at the University of Chicago Medical Center. Seventy-two (5.9%) patients had preoperative biopsy GS 8 to 10. Two patients received neoadjuvant hormonal therapy and were excluded. Among 70 patients evaluated, 33 (47%) had organconfined (pT(2)N0) disease. Forty (60.6%) patients had pathologic downgrading to GS

Prostatic cancers: understanding their molecular pathology and the 2016 WHO classification

PubMed Central

Inamura, Kentaro

2018-01-01

Accumulating evidence suggests that prostatic cancers represent a group of histologically and molecularly heterogeneous diseases with variable clinical courses. In accordance with the increased knowledge of their clinicopathologies and genetics, the World Health Organization (WHO) classification of prostatic cancers has been revised. Additionally, recent data on their comprehensive molecular characterization have increased our understanding of the genomic basis of prostatic cancers and enabled us to classify them into subtypes with distinct molecular pathologies and clinical features. Our increased understanding of the molecular pathologies of prostatic cancers has permitted their evolution from a poorly understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes that allow the implementation of personalized therapies and better patient management. This review provides perspectives on the new 2016 WHO classification of prostatic cancers as well as recent knowledge of their molecular pathologies. The WHO classification of prostatic cancers will require additional revisions to allow for reliable and clinically meaningful cancer diagnoses as a better understanding of their molecular characteristics is obtained. PMID:29581876

Attention problems and pathological gaming: resolving the 'chicken and egg' in a prospective analysis.

PubMed

Ferguson, Christopher J; Ceranoglu, T Atilla

2014-03-01

Pathological gaming (PG) behaviors are behaviors which interfere with other life responsibilities. Continued debate exists regarding whether symptoms of PG behaviors are a unique phenomenon or arise from other mental health problems, including attention problems. Development of attention problems and occurrence of pathological gaming in 144 adolescents were followed during a 1-year prospective analysis. Teens and their parents reported on pathological gaming behaviors, attention problems, and current grade point average, as well as several social variables. Results were analyzed using regression and path analysis. Attention problems tended to precede pathological gaming behaviors, but the inverse was not true. Attention problems but not pathological gaming predicted lower GPA 1 year later. Current results suggest that pathological gaming arises from attention problems, but not the inverse. These results suggest that pathological gaming behaviors are symptomatic of underlying attention related mental health issues, rather than a unique phenomenon.

Adaptive elements of aging: Self-image discrepancy, perfectionism, and eating problems.

PubMed

Landa, Carrie E; Bybee, Jane A

2007-01-01

Age-related changes in personality variables that may contribute to the reduction of symptoms of eating disorders with adult development were examined. Undergraduate sorority women (n = 52; mean age = 19.85 years) were compared with alumnae of the same sorority (n = 34; mean age = 33.74 years). Eating pathology was correlated with greater discrepancy between the real (current) and the ideal (desired) self-image and with perfectionism. Both self-image discrepancy and perfectionism were markedly lower among the alumnae. Variance in these variables together accounted for the lowered level of eating pathology among the older participants. Specific content domains of the real and ideal self-image and different facets of perfectionism showed distinctive age-related changes and differential relationships with eating pathology. Copyright 2006 APA, all rights reserved.

An optimized color transformation for the analysis of digital images of hematoxylin & eosin stained slides.

PubMed

Zarella, Mark D; Breen, David E; Plagov, Andrei; Garcia, Fernando U

2015-01-01

Hematoxylin and eosin (H&E) staining is ubiquitous in pathology practice and research. As digital pathology has evolved, the reliance of quantitative methods that make use of H&E images has similarly expanded. For example, cell counting and nuclear morphometry rely on the accurate demarcation of nuclei from other structures and each other. One of the major obstacles to quantitative analysis of H&E images is the high degree of variability observed between different samples and different laboratories. In an effort to characterize this variability, as well as to provide a substrate that can potentially mitigate this factor in quantitative image analysis, we developed a technique to project H&E images into an optimized space more appropriate for many image analysis procedures. We used a decision tree-based support vector machine learning algorithm to classify 44 H&E stained whole slide images of resected breast tumors according to the histological structures that are present. This procedure takes an H&E image as an input and produces a classification map of the image that predicts the likelihood of a pixel belonging to any one of a set of user-defined structures (e.g., cytoplasm, stroma). By reducing these maps into their constituent pixels in color space, an optimal reference vector is obtained for each structure, which identifies the color attributes that maximally distinguish one structure from other elements in the image. We show that tissue structures can be identified using this semi-automated technique. By comparing structure centroids across different images, we obtained a quantitative depiction of H&E variability for each structure. This measurement can potentially be utilized in the laboratory to help calibrate daily staining or identify troublesome slides. Moreover, by aligning reference vectors derived from this technique, images can be transformed in a way that standardizes their color properties and makes them more amenable to image processing.

Long-term follow-up of cognitive functions in patients with continuous spike-waves during sleep (CSWS).

PubMed

Maltoni, Lucia; Posar, Annio; Parmeggiani, Antonia

2016-07-01

Continuous spike-waves during sleep (CSWS) are associated with several cognitive, neurological, and psychiatric disorders, which sometimes persist after CSWS disappearance. The purpose of this retrospective study was to investigate the correlation between general (clinical and instrumental) and neuropsychological findings in CSWS, to identify variables that predispose patients to a poorer long-term neuropsychological outcome. Patients with spikes and waves during sleep with a frequency ≥25/min (spikes and waves frequency index - SWFI) were enrolled. There were patients presenting abnormal EEG activity corresponding to the classic CSWS and patients with paroxysmal abnormalities during sleep <85% with SWFI ≥25/min that was defined as excessive spike-waves during sleep (ESWS). Clinical and instrumental features and neuropsychological findings during and after the spike and wave active phase period were considered. A statistical analysis was performed utilizing the Spearman correlation test and multivariate analysis. The study included 61 patients; the mean follow-up (i.e., the period between SWFI ≥25 first recording and last observation) was 7years and 4months. The SWFI correlated inversely with full and performance IQ during CSWS/ESWS. Longer-lasting SWFI ≥25 was related to worse results in verbal IQ and performance IQ after CSWS/ESWS disappearance. Other variables may influence the neuropsychological outcome, like age at SWFI ≥25 first recording, perinatal distress, pathologic neurologic examination, and antiepileptic drug resistance. This confirms that CSWS/ESWS are a complex pathology and that many variables contribute to its outcome. The SWFI value above all during CSWS/ESWS and long-lasting SWFI ≥25 after CSWS/ESWS disappearance are the most significant indexes that appear mostly to determine cognitive evolution. This finding underscores the importance of EEG recordings during sleep in children with a developmental disorder, even if seizures are not reported, as well as the importance of using therapy with an early efficacy. Copyright © 2016 Elsevier Inc. All rights reserved.

Skeletal pathology and variable anatomy in elephant feet assessed using computed tomography

PubMed Central

Dixon, Jonathon J.I.; Warren-Smith, Chris; Hutchinson, John R.; Weller, Renate

2017-01-01

Foot problems are a major cause of morbidity and mortality in elephants, but are underreported due to difficulties in diagnosis, particularly of conditions affecting the bones and internal structures. Here we evaluate post-mortem computer tomographic (CT) scans of 52 feet from 21 elephants (seven African Loxodonta africana and 14 Asian Elephas maximus), describing both pathology and variant anatomy (including the appearance of phalangeal and sesamoid bones) that could be mistaken for disease. We found all the elephants in our study to have pathology of some type in at least one foot. The most common pathological changes observed were bone remodelling, enthesopathy, osseous cyst-like lesions, and osteoarthritis, with soft tissue mineralisation, osteitis, infectious osteoarthriti, subluxation, fracture and enostoses observed less frequently. Most feet had multiple categories of pathological change (81% with two or more diagnoses, versus 10% with a single diagnosis, and 9% without significant pathology). Much of the pathological change was focused over the middle/lateral digits, which bear most weight and experience high peak pressures during walking. We found remodelling and osteoarthritis to be correlated with increasing age, more enthesopathy in Asian elephants, and more cyst-like lesions in females. We also observed multipartite, missing and misshapen phalanges as common and apparently incidental findings. The proximal (paired) sesamoids can appear fused or absent, and the predigits (radial/tibial sesamoids) can be variably ossified, though are significantly more ossified in Asian elephants. Our study reinforces the need for regular examination and radiography of elephant feet to monitor for pathology and as a tool for improving welfare. PMID:28123909

Development of a Natural Language Processing Engine to Generate Bladder Cancer Pathology Data for Health Services Research.

PubMed

Schroeck, Florian R; Patterson, Olga V; Alba, Patrick R; Pattison, Erik A; Seigne, John D; DuVall, Scott L; Robertson, Douglas J; Sirovich, Brenda; Goodney, Philip P

2017-12-01

To take the first step toward assembling population-based cohorts of patients with bladder cancer with longitudinal pathology data, we developed and validated a natural language processing (NLP) engine that abstracts pathology data from full-text pathology reports. Using 600 bladder pathology reports randomly selected from the Department of Veterans Affairs, we developed and validated an NLP engine to abstract data on histology, invasion (presence vs absence and depth), grade, the presence of muscularis propria, and the presence of carcinoma in situ. Our gold standard was based on an independent review of reports by 2 urologists, followed by adjudication. We assessed the NLP performance by calculating the accuracy, the positive predictive value, and the sensitivity. We subsequently applied the NLP engine to pathology reports from 10,725 patients with bladder cancer. When comparing the NLP output to the gold standard, NLP achieved the highest accuracy (0.98) for the presence vs the absence of carcinoma in situ. Accuracy for histology, invasion (presence vs absence), grade, and the presence of muscularis propria ranged from 0.83 to 0.96. The most challenging variable was depth of invasion (accuracy 0.68), with an acceptable positive predictive value for lamina propria (0.82) and for muscularis propria (0.87) invasion. The validated engine was capable of abstracting pathologic characteristics for 99% of the patients with bladder cancer. NLP had high accuracy for 5 of 6 variables and abstracted data for the vast majority of the patients. This now allows for the assembly of population-based cohorts with longitudinal pathology data. Published by Elsevier Inc.

Blood platelet kinetics and platelet transfusion.

PubMed

Aster, Richard H

2013-11-01

The discovery of citrate anticoagulant in the 1920s and the development of plastic packs for blood collection in the 1960s laid the groundwork for platelet transfusion therapy on a scale not previously possible. A major limitation, however, was the finding that platelet concentrates prepared from blood anticoagulated with citrate were unsuitable for transfusion because of platelet clumping. We found that this could be prevented by simply reducing the pH of platelet-rich plasma to about 6.5 prior to centrifugation. We used this approach to characterize platelet kinetics and sites of platelet sequestration in normal and pathologic states and to define the influence of variables such as anticoagulant and ABO incompatibility on post-transfusion platelet recovery. The "acidification" approach enabled much wider use of platelet transfusion therapy until alternative means of producing concentrates suitable for transfusion became available.

Multiple expression patterns of biopathological markers in primary invasive breast carcinoma: a useful tool for elucidating its biological behaviour.

PubMed

Ceccarelli, C; Santini, D; Chieco, P; Taffurelli, M; Marrano, D; Mancini, A M

1995-03-01

Commonly used clinical and morphologic criteria have been reported to be of limited value in predicting the outcome of malignant tumours of the breast. Integrated information from the quantitative analysis in tumour tissue of biological parameters such as oestrogen and progesterone receptors (ER and PGR), proliferative activity, and proto-oncogene p53, c-erB2, and bcl-2 expression, may be useful for defining the biology of growth of breast carcinoma and to plan effective therapeutic strategies. Immunohistochemistry with antibodies recognizing ER, PGR, Ki-67, and the p53, c-erbB2, and bcl-2 encoded proteins was performed on 291 primary breast carcinomas. Results were integrated with clinico-pathological indicators and examined with multivariate statistical procedures and modeling. P53, c-erbB2, and bcl-2 gene products were detected, respectively, in 30.6%, 31.6%, and 85.9% of the examined invasive breast carcinomas, revealing variable associations with cellular differentiation and proliferation as defined by ER/PGR status, Ki-67, tumour mass and histologic and nuclear grading. A multivariate graphical display on a subset of the most informative cases revealed that bcl-2 expression parallels ER/PGR status and is of importance in separating tumour clusters with different degrees of aggressiveness. The results of this study indicate that multivariate explorative analyses conducted on biological and clinico-pathological parameters might constitute an integrated approach to data analysis useful for distinguishing different biological behaviours and therapeutic groups in breast carcinoma. Our findings also suggest that bcl-2 expression may play a pivotal role in tumours lacking ER-mediated growth regulation.

Expanding the spectrum of neuronal pathology in multiple system atrophy.

PubMed

Cykowski, Matthew D; Coon, Elizabeth A; Powell, Suzanne Z; Jenkins, Sarah M; Benarroch, Eduardo E; Low, Phillip A; Schmeichel, Ann M; Parisi, Joseph E

2015-08-01

Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients with multiple system atrophy, including a patient with visual hallucinations. Further, the presence of Lewy body-like inclusions in neocortex, but not hippocampal alpha-synuclein pathology, was associated with cognitive impairment (P = 0.002). However, several cases had the presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus, deep cerebellar nuclei) that are not typical for Lewy body-spectrum disease. Finally, interregional correlations (rho ≥ 0.6) in pathologic glial and neuronal lesion burden suggest shared mechanisms of disease progression between both discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types (neuronal and glial inclusions in frontal cortex and white matter, respectively). These findings suggest that in addition to glial inclusions, neuronal pathology plays an important role in the developmental and progression of multiple system atrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ordo ab Chao: framework for an integrated disease report.

PubMed

de Baca, Monica E; Arnaout, Ramy; Brodsky, Victor; Birdsong, George G

2015-02-01

The volume of information that must be assimilated to appropriately manage patients with complex or chronic disease can make this task difficult because of the number of data points, their variable temporal availability, and the fact that they may reside in different systems or even institutions. OBJECTIVE .- To outline a framework for building an integrated disease report (IDR) that takes advantage of the capabilities of electronic reporting to create a single, succinct, interpretative report comprising all disease pertinent data. Disease pertinent data of an IDR include pathology results, laboratory and radiology data, pathologic correlations, risk profiles, and therapeutic implications. We used cancer herein as a representative process for proposing what is, to our knowledge, the first example of standardized guidelines for such a report. The IDR was defined as a modular, dynamic, electronic summary of the most current state of a patient in regard to a particular illness such as lung cancer or diabetes, which includes all information relevant for patient management. We propose the following 11 core data concepts that an IDR should include: patient identification; patient demographics; disease, diagnosis, and prognosis; tumor board dispositions and decisions; graphic timeline; preresection workup and therapy; resection workup; interpretative comment summarizing pertinent findings; biobanking data; postresection workup; and disease and patient status at follow-up. A well-executed IDR should improve patient care and efficiency for health care team members. It would demonstrate the added value of pathology interpretation and likely contribute to a reduction in errors and improved patient safety by decreasing the risk that important data will be overlooked.

Opportunities for Improvement in Pathology Reporting of Childhood Nonrhabdomyosarcoma Soft Tissue Sarcomas:  A Report From Children's Oncology Group (COG) Study ARST0332.

PubMed

Black, Jennifer O; Coffin, Cheryl M; Parham, David M; Hawkins, Douglas S; Speights, Rose A; Spunt, Sheri L

2016-09-01

Treatment of soft tissue tumors in young patients relies on the diagnostic information conveyed in the pathology report. We examined pathology reports from Children's Oncology Group ARST0332 for inclusion of data elements required in published guidelines. Pathology reports for 551 eligible patients were examined for required data elements defined by the College of American Pathologists, including tissue type, procedure, tumor site, tumor maximum diameter, macroscopic extent of tumor, histologic type, mitotic rate, extent of necrosis, tumor grade, margin status, use of ancillary studies, and pathologic stage. Only 65 (12%) of 551 reports included all required data elements. Of reports containing synoptic templates, 57% were complete. This study reveals significant opportunity to improve the quality of pathology reports in young patients with soft tissue tumors. Use of templates or checklists improves completeness of reports. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The pathology of shin splints.

PubMed

Kues, J M

1990-01-01

The purpose of this review is to critically evaluate experimental evidence describing the pathology associated with shin splints. Shin splints are defined as medial or posteromedial leg pain which is brought about by walking, running, or related activities and which decreases with rest. The evidence indicates that shin splints may be due to pathology of the posteromedial tibial cortex, the periosteum of the posteromedial tibia, or the crural fascia of the deep posterior compartment of the leg. Research is needed to determine if increased pressure in the deep posterior compartment of the leg or pathology of the muscles, tendons, or interosseous membrane of the leg are associated with shin splints. J Orthop Sports Phys Ther 1990;12(3):115-121.

Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome.

PubMed

Sproule, Douglas M; Kaufmann, Petra

2008-10-01

Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome, is typified by characteristic neurological manifestations including seizures, encephalopathy, and strokelike episodes, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, depression, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. In this review, we discuss the history, pathogenesis, clinical features, and diagnostic and management strategies of mitochondrial disease in general and of MELAS in particular. We explore features of mitochondrial genetics, including the concepts of heteroplasmy, mitotic segregation, and threshold effect, as a basis for understanding the variability and complicated inheritance patterns seen with this group of diseases. We also describe systemic manifestations of MELAS-associated mutations, including cardiac, renal, endocrine, gastrointestinal, and endothelial abnormalities and pathology, as well as the hypothetical role of derangements to COX enzymatic function in driving the unique pathology and clinical manifestations of MELAS. Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities.

Hereditary inclusion-body myopathies.

PubMed

Broccolini, Aldobrando; Mirabella, Massimiliano

2015-04-01

The term hereditary inclusion-body myopathies (HIBMs) defines a group of rare muscle disorders with autosomal recessive or dominant inheritance and presence of muscle fibers with rimmed vacuoles and collection of cytoplasmic or nuclear 15-21 nm diameter tubulofilaments as revealed by muscle biopsy. The most common form of HIBM is due to mutations of the GNE gene that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. This results in abnormal sialylation of glycoproteins that possibly leads to muscle fiber degeneration. Mutations of the valosin containing protein are instead responsible for hereditary inclusion-body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD), with these three phenotypic features having a variable penetrance. IBMPFD probably represents a disorder of abnormal cellular trafficking of proteins and maturation of the autophagosome. HIBM with congenital joint contractures and external ophthalmoplegia is due to mutations of the Myosin Heavy Chain IIa gene that exerts a pathogenic effect through interference with filament assembly or functional defects in ATPase activity. This review illustrates the clinical and pathologic characteristics of HIBMs and the main clues available to date concerning the possible pathogenic mechanisms and therapeutic perspectives of these disorders. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

Factors Influencing Clinical Correlates of Chronic Traumatic Encephalopathy (CTE): A Review

PubMed Central

Asken, Breton M.; Sullan, Molly J.; Snyder, Aliyah R.; Houck, Zachary M.; Bryant, Vaughn E.; Hizel, Loren P.; McLaren, Molly E.; Dede, Duane E.; Jaffee, Michael S.; DeKosky, Steven T.; Bauer, Russell M.

2017-01-01

Chronic traumatic encephalopathy (CTE) is a neuropathologically defined disease reportedly linked to a history of repetitive brain trauma. As such, retired collision sport athletes are likely at heightened risk for developing CTE. Researchers have described distinct pathological features of CTE as well a wide range of clinical symptom presentations, recently termed traumatic encephalopathy syndrome (TES). These clinical symptoms are highly variable, non-specific to individuals described as having CTE pathology in case reports, and are often associated with many other factors. This review describes the cognitive, emotional, and behavioral changes associated with 1) developmental and demographic factors, 2) neurodevelopmental disorders, 3) normal aging, 4) adjusting to retirement, 5) drug and alcohol abuse, 6) surgeries and anesthesia, and 7) sleep difficulties, as well as the relationship between these factors and risk for developing dementia-related neurodegenerative disease. We discuss why some professional athletes may be particularly susceptible to many of these effects and the importance of choosing appropriate controls groups when designing research protocols. We conclude that these factors should be considered as modifiers predominantly of the clinical outcomes associated with repetitive brain trauma within a broader biopsychosocial framework when interpreting and attributing symptom development, though also note potential effects on neuropathological outcomes. Importantly, this could have significant treatment implications for improving quality of life. PMID:27561662

Study report on combining diagnostic and therapeutic considerations with subsystem and whole-body simulation

NASA Technical Reports Server (NTRS)

Furukawa, S.

1975-01-01

Current applications of simulation models for clinical research described included tilt model simulation of orthostatic intolerance with hemorrhage, and modeling long term circulatory circulation. Current capabilities include: (1) simulation of analogous pathological states and effects of abnormal environmental stressors by the manipulation of system variables and changing inputs in various sequences; (2) simulation of time courses of responses of controlled variables by the altered inputs and their relationships; (3) simulation of physiological responses of treatment such as isotonic saline transfusion; (4) simulation of the effectiveness of a treatment as well as the effects of complication superimposed on an existing pathological state; and (5) comparison of the effectiveness of various treatments/countermeasures for a given pathological state. The feasibility of applying simulation models to diagnostic and therapeutic research problems is assessed.

Updates of pathologic myopia.

PubMed

Ohno-Matsui, Kyoko; Lai, Timothy Y Y; Lai, Chi-Chun; Cheung, Chiu Ming Gemmy

2016-05-01

Complications from pathologic myopia are a major cause of visual impairment and blindness, especially in east Asia. The eyes with pathologic myopia may develop loss of the best-corrected vision due to various pathologies in the macula, peripheral retina and the optic nerve. Despite its importance, the definition of pathologic myopia has been inconsistent. The refractive error or axial length alone often does not adequately reflect the 'pathologic myopia'. Posterior staphyloma, which is a hallmark lesion of pathologic myopia, can occur also in non-highly myopic eyes. Recently a revised classification system for myopic maculopathy has been proposed to standardize the definition among epidemiological studies. In this META-PM (meta analyses of pathologic myopia) study classification, pathologic myopia was defined as the eyes having chorioretinal atrophy equal to or more severe than diffuse atrophy. In addition, the advent of new imaging technologies such as optical coherence tomography (OCT) and three dimensional magnetic resonance imaging (3D MRI) has enabled the detailed observation of various pathologies specific to pathologic myopia. New therapeutic approaches including intravitreal injections of anti-vascular endothelial growth factor agents and the advance of vitreoretinal surgeries have greatly improved the prognosis of patients with pathologic myopia. The purpose of this review article is to provide an update on topics related to the field of pathologic myopia, and to outline the remaining issues which need to be solved in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Revisiting the role of pathological analysis in transarterial chemoembolization-treated hepatocellular carcinoma after transplantation

PubMed Central

Vasuri, Francesco; Malvi, Deborah; Rosini, Francesca; Baldin, Pamela; Fiorentino, Michelangelo; Paccapelo, Alexandro; Ercolani, Giorgio; Pinna, Antonio Daniele; Golfieri, Rita; Morselli-Labate, Antonio Maria; Grigioni, Walter Franco; D’Errico-Grigioni, Antonia

2014-01-01

AIM: To define the histopathological features predictive of post-transplant hepatocellular carcinoma (HCC) recurrence after transarterial chemoembolization, applicable for recipient risk stratification. METHODS: We retrospectively reviewed the specimens of all suspicious nodules (total 275) from 101 consecutive liver transplant recipients which came to our Pathology Unit over a 6-year period. All nodules were sampled and analyzed, and follow-up data were collected. We finally considered 11 histological variables for each patient: total number of nodules, number of viable nodules, size of the major nodule, size of the major viable nodule, occurrence of microscopic vascular invasion, maximum Edmondson's grade, clear cell/sarcomatous changes, and the residual neoplastic volume. Survival data were computed by means of the Kaplan-Meier procedure and analyzed by means of the Cox proportional hazards model. The multivariate linear regression and a k-means cluster analysis were also used in order to compute the standardized histological score. RESULTS: The total number of nodules, the residual neoplastic volume (the total volume of all evaluated nodules minus the necrotic portion) and the microvascular invasion entered the Cox multivariate hazard model with HCC recurrence as dependent variable. The histological score was therefore computed and a cluster analysis sorted recipients into 3 risk groups, with 3.3%, 18.5% and 53.8% respectively of tumor recurrence rates and 1.6%, 11.1% and 38.5% of tumor-related mortality respectively at the end of follow-up. CONCLUSION: The histological score allows a reliable stratification of HCC recurrence risk, especially in those recipients found out to be beyond the Milan criteria after orthotopic liver transplantation (OLT). PMID:25309084

A Multicenter Study of Volumetric Computed Tomography for Staging Malignant Pleural Mesothelioma

PubMed Central

Rusch, Valerie W.; Gill, Ritu; Mitchell, Alan; Naidich, David; Rice, David C.; Pass, Harvey I.; Kindler, Hedy; De Perrot, Marc; Friedberg, Joseph

2016-01-01

Background Standard imaging modalities are inaccurate in staging malignant pleural mesothelioma (MPM). Single institution studies suggest that volumetric computed tomography (VolCT) is more accurate but labor intensive. We established a multicenter network to test interobserver variability, accuracy (relative to pathologic stage) and prognostic significance of semi-automated VolCT. Methods Six institutions electronically submitted clinical and pathologic data to an established multicenter database on patients with MPM who had surgery. Institutional radiologists reviewed preoperative CT scans for quality then submitted via electronic network (AG mednet) to biostatistical center (BC). Two reference radiologists, blinded to clinical data, performed semi-automated tumor volume calculations using commercially available software (Vitrea Enterprise 6.0), then submitted readings to BC. Study endpoints included: feasibility of network; interobserver variability for VolCT; correlation of tumor volume to pTN stages, and overall survival (OS). Results Of 164 cases, 129 were analyzable and read by reference radiologists. Most tumors were <500cm3. A small bias was observed between readers, as one provided consistently larger measurements than the other (mean difference=47.9, p=.0027), but for 80% of cases, the absolute difference was ≤ 200cm3. Spearman correlation between readers was 0.822. Volume correlated with pTN stages and OS, best defined by 3 groups with average volumes of: 91.2, 245.3, 511.3cm3, associated with median OS of 37, 18, 8 months respectively. Conclusions For the first time, a multicenter network was established and initial correlations of tumor volume to pTN stages and OS shown. A larger multicenter international study is planned to confirm results and refine correlations. PMID:27596916

[Prevalence of processes and pathologies dealt with by the pre-hospital emergency medical services in Spain].

PubMed

Pacheco, Andrés; Burusco, S; Senosiáin, M V

2010-01-01

This study was carried out by contacting 26 Medical Emergency Services (MES), through survey, with final data obtained from 22. Population covered: 42,538,730. Total number of calls: 7,656,768, with 711,228 interventions. Number of operational forces: intensive care units (mobile-ICUs): 329, rapid intervention vehicles (RIV) 20, health ambulances 39 and medical helicopters 39 (4 of them 24 hour: Canary Islands and Castile-La Mancha) and 3 airplanes. mobile-ICUs: 94.3%, medical helicopters: 1.4% and health ambulances: 4.3%. Number of A&E doctors/day: 388, nursing personnel 427. Pathologies dealt with, grouped according to ICE-9-MC: V-psychiatry group: 3.7%, VI-neurological group: 2.7%, VII-cardiovascular group: 9.3%, VIII-respiratory group: 3.2%, XVII-lesions poisonings group: 23.1%, IX-digestive group: 1.3%, X-XI-genital-urinary and gynaecology-obstetrics groups: 1.4%, XVI-group of other ill-defined pathologies: 40.1%. Specifically studied groups (from the MESs that provided them) were: thoracic pain- dyspnea: 3.7%, ictus/acute cerebrovascular accident: 0.9%, alteration in consciousness: 7.7%, syncope-blackout: 2.5%, self-inflicted lesions: 2,654 (0.4%). Total of pathological and syndrome groups: 59.9% and total of other ill-defined pathologies: 40.1%. Of the pathologies considered to be of greater relevance in A&E: acute coronary syndrome: 3.1%, arrhythmias: 3.2%, cardiac arrest: 1.7%, respiratory stoppage: 0.16%, total traumatisms: 34.9%, traumatisms: 1.16%, cranio-encephalic traumatism: 1.77%, intoxications: 5.1%, agressions: 6.9%, burns: 0.26%.

Increased prevalence of vegetarianism among women with eating pathology.

PubMed

Zuromski, Kelly L; Witte, Tracy K; Smith, April R; Goodwin, Natalie; Bodell, Lindsay P; Bartlett, Mary; Siegfried, Nicole

2015-12-01

Prior research has established a link between vegetarianism and disordered eating but has typically sampled vegetarians. This study examined prevalence of and variables related to vegetarianism in three samples with varying severity of eating pathology. Sample 1 consisted of female undergraduates who denied history of or current disordered eating (i.e., nonclinical; n=73), or engaged in disordered eating over past month (i.e., subclinical; n=136). Sample 2 included 69 female patients receiving residential treatment at an eating disorder center (i.e., clinical sample). Differences between groups were analyzed using Fisher's exact test. The prevalence of lifetime vegetarianism was lowest in the nonclinical group (6.80%) and highest in the clinical group (34.80%), with the subclinical group falling in between (17.60%). According to Fisher's exact test, all pairwise comparisons between groups were statistically significant (p's<.05). Regarding current vegetarian status, the clinical group was more likely (11.10%) than both other groups to self-identify as current vegetarians. Endorsement of vegetarianism was highest among females with severe eating pathology. Future research should use longitudinal data to examine the temporal relationship between these variables, or other underlying factors that may contribute to the co-occurrence of eating pathology and vegetarianism. Clinically, endorsement of vegetarianism may also be an important variable to consider in treatment disordered eating. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evidence-based pathology: umbilical cord coiling.

PubMed

Khong, T Y

2010-12-01

The generation of a pathology test result must be based on criteria that are proven to be acceptably reproducible and clinically relevant to be evidence-based. This review de-constructs the umbilical cord coiling index to illustrate how it can stray from being evidence-based. Publications related to umbilical cord coiling were retrieved and analysed with regard to how the umbilical coiling index was calculated, abnormal coiling was defined and reference ranges were constructed. Errors and other influences that can occur with the measurement of the length of the umbilical cord or of the number of coils can compromise the generation of the coiling index. Definitions of abnormal coiling are not consistent in the literature. Reference ranges defining hypocoiling or hypercoiling have not taken those potential errors or the possible effect of gestational age into account. Even the way numerical test results in anatomical pathology are generated, as illustrated by the umbilical coiling index, warrants a critical analysis into its evidence base to ensure that they are reproducible or free from errors.

The pathology and pathophysiology of vascular dementia.

PubMed

Kalaria, Raj N

2017-12-19

Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event. Atherosclerotic and cardioembolic diseases combined appear the most common subtypes of vascular brain injury. In recent years, cerebral small vessel disease (SVD) has gained prominence worldwide as an important substrate of cognitive impairment. SVD is characterised by arteriolosclerosis, lacunar infarcts and cortical and subcortical microinfarcts and diffuse white matter changes, which involve myelin loss and axonal abnormalities. Global brain atrophy and focal degeneration of the cerebrum including medial temporal lobe atrophy are also features of VaD similar to Alzheimer's disease. Hereditary arteriopathies have provided insights into the mechanisms of dementia particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment. Recently developed and validated neuropathology guidelines indicated that the best predictors of vascular cognitive impairment were small or lacunar infarcts, microinfarcts, perivascular space dilation, myelin loss, arteriolosclerosis and leptomeningeal cerebral amyloid angiopathy. While these substrates do not suggest high specificity, VaD is likely defined by key neuronal and dendro-synaptic changes resulting in executive dysfunction and related cognitive deficits. Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Defining occult injuries of the distal forearm and wrist in children.

PubMed

Elvey, Michael; Patel, S; Avisar, Erez; White, W J; Sorene, E

2016-06-01

The nonspecific terms "wrist sprain" and "suspected occult bony injury" are frequently documented as diagnoses in occult paediatric wrist injuries. To date, however, no one has accurately defined their true underlying pathology. The primary objective of this study was to identify the true pathoanatomy of occult acute paediatric wrist injuries. Our secondary objective was to compare our findings with existing adult data in order to determine any population differences that might be clinically relevant. We performed a single-centre retrospective case series evaluating MRI findings in acute paediatric wrist injuries presenting to the hand injury unit between 2011 and 2014. All patients underwent standardised radiographs of the wrist and, where clinically indicated, of the scaphoid. Where no bony anomaly was identified, MRI scanning was offered. Cohen's kappa coefficient was used to calculate the agreement between clinical and MRI diagnosis. 57 patients met the final inclusion criteria. Occult fractures and bony contusions comprised the majority of the pathologies, at 36.5 and 35.0 %, respectively. There were no cases of isolated soft-tissue injury. MRI effected management change in 35.1 % of cases. Paediatric wrists demonstrated differences in injury pattern and distribution when compared to an adult population. This study defines for the first time the true pathology of occult paediatric wrist injuries. The current definition of a wrist sprain was not applicable to a single case and therefore appears to be inappropriate for use in the paediatric population. A precise knowledge of the likely pathology facilitates accurate information delivery whilst reducing parental uncertainty and treatment variation.

[Meta-analysis of pathological gambling 1997-2007].

PubMed

Muñoz-Molina, Yaromir

2008-01-01

Determining the prevalence of pathological gambling related to variables such as age and sex; furthermore, identifying the most current tools used for measuring it and the kind of gaming associated with this type of obsessive behavior. A meta-analysis of studies concerning pathological gambling published between 1997 and 2007 was carried out. Inclusion criteria for papers consisted of having a probabilistic sample, indicating the tool used for measuring it and presenting the prevalence rate. It was observed that pathological gambling affects men more than women; furthermore, there are differences amongst adults and adolescents related to this type of behaviour, the latter group having the higher prevalence rate. Video lottery terminals are the most frequently occurring type of game associated with pathological gambling. Pathological gambling deserves more attention by public health managers. Prevalence studies help to understand it better.

Site-Specific Expression of Polycomb-Group Genes Encoding the HPC-HPH/PRC1 Complex in Clinically Defined Primary Nodal and Cutaneous Large B-Cell Lymphomas

PubMed Central

Raaphorst, Frank M.; Vermeer, Maarten; Fieret, Elly; Blokzijl, Tjasso; Dukers, Danny; Sewalt, Richard G.A.B.; Otte, Arie P.; Willemze, Rein; Meijer, Chris J.L.M.

2004-01-01

Polycomb-group (PcG) genes preserve cell identity by gene silencing, and contribute to regulation of lymphopoiesis and malignant transformation. We show that primary nodal large B-cell lymphomas (LBCLs), and secondary cutaneous deposits from such lymphomas, abnormally express the BMI-1, RING1, and HPH1 PcG genes in cycling neoplastic cells. By contrast, tumor cells in primary cutaneous LBCLs lacked BMI-1 expression, whereas RING1 was variably detected. Lack of BMI-1 expression was characteristic for primary cutaneous LBCLs, because other primary extranodal LBCLs originating from brain, testes, and stomach were BMI-1-positive. Expression of HPH1 was rarely detected in primary cutaneous LBCLs of the head or trunk and abundant in primary cutaneous LBCLs of the legs, which fits well with its earlier recognition as a distinct clinical pathological entity with different clinical behavior. We conclude that clinically defined subclasses of primary LBCLs display site-specific abnormal expression patterns of PcG genes of the HPC-HPH/PRC1 PcG complex. Some of these patterns (such as the expression profile of BMI-1) may be diagnostically relevant. We propose that distinct expression profiles of PcG genes results in abnormal formation of HPC-HPH/PRC1 PcG complexes, and that this contributes to lymphomagenesis and different clinical behavior of clinically defined LBCLs. PMID:14742259

Relationships of personality traits and stress to gingival status or soft-tissue oral pathology: an exploratory study.

PubMed

Minneman, M A; Cobb, C; Soriano, F; Burns, S; Schuchman, L

1995-01-01

The purpose of this study was to examine the relationships of personality traits and stress with gingival inflammation and with soft-tissue oral pathology. Personality traits of psychoticism (P), extroversion and introversion (E), and neuroticism (N) were measured with Eysenck's personality questionnaire (EPQ). Stress was measured with a modified organizational and individual assessment survey (OIAS) developed by Hendrix. Military recruits from Ft. Leonard Wood, Missouri, were examined for soft-tissue oral pathology and gingival status at weeks one (n = 241) and six (n = 61) of basic combat training (BCT). The EPQ and OIAS were administered to 217 recruits during week six of BCT. A discriminant analysis was used to determine correlations among study variables. Significant correlations (P < .05) were found between personality traits and various measures of tolerance of stress. Little variance was found between groups originally presenting with or without disease. Only physical stress (P < .005) was shown to affect soft-tissue pathology, while gingival inflammation correlated significantly to E scores (P < .02), tolerance to change (P < .02), and anxiety (P < .05). Data support a possible relationship among certain personality traits, stress variables, and gingival inflammation or soft-tissue pathology in recruits with extreme personality characteristics or perception of high physical stress levels in basic combat training.

Bar Coding and Tracking in Pathology.

PubMed

Hanna, Matthew G; Pantanowitz, Liron

2016-03-01

Bar coding and specimen tracking are intricately linked to pathology workflow and efficiency. In the pathology laboratory, bar coding facilitates many laboratory practices, including specimen tracking, automation, and quality management. Data obtained from bar coding can be used to identify, locate, standardize, and audit specimens to achieve maximal laboratory efficiency and patient safety. Variables that need to be considered when implementing and maintaining a bar coding and tracking system include assets to be labeled, bar code symbologies, hardware, software, workflow, and laboratory and information technology infrastructure as well as interoperability with the laboratory information system. This article addresses these issues, primarily focusing on surgical pathology. Copyright © 2016 Elsevier Inc. All rights reserved.

Bar Coding and Tracking in Pathology.

PubMed

Hanna, Matthew G; Pantanowitz, Liron

2015-06-01

Bar coding and specimen tracking are intricately linked to pathology workflow and efficiency. In the pathology laboratory, bar coding facilitates many laboratory practices, including specimen tracking, automation, and quality management. Data obtained from bar coding can be used to identify, locate, standardize, and audit specimens to achieve maximal laboratory efficiency and patient safety. Variables that need to be considered when implementing and maintaining a bar coding and tracking system include assets to be labeled, bar code symbologies, hardware, software, workflow, and laboratory and information technology infrastructure as well as interoperability with the laboratory information system. This article addresses these issues, primarily focusing on surgical pathology. Copyright © 2015 Elsevier Inc. All rights reserved.

Quality of pathology reporting is crucial for cancer care and registration: a baseline assessment for breast cancers diagnosed in Belgium in 2008.

PubMed

De Schutter, H; Van Damme, N; Colpaert, C; Galant, C; Lambein, K; Cornelis, A; Neven, P; Van Eycken, E

2015-04-01

Given the crucial role of pathology reporting in the management of breast cancers, we aimed to investigate the quality and variability of breast cancer pathology reporting in Belgium. Detailed information on non-molecular and molecular parameters was retrieved from the pathology protocols available at the Belgian Cancer Registry for 10,007 breast cancers diagnosed in Belgium in 2008. Substantial underreporting was shown for several clinically relevant non-molecular parameters, such as lymphovascular invasion. High-volume laboratories performed only slightly better than others, and analyses at the individual laboratory level showed clear inter-laboratory variability in reporting for all volume categories. Information on ER/PR and HER2 IHC was mentioned in respectively 91.7% and 90.8% of evaluative cases. HER2 ISH data were available for 78.5% of the cases judged to be 2+ for HER2 IHC. For cases with different specimens analysed, discordance between these specimens was highest for HER2, followed by PR. For HER2, results obtained from different laboratories were even less concordant. In addition, inter-laboratory differences were noted in the used ER/PR scoring systems, the proportion of ER-/PR+ cases, and the relation between histological grade and ER/PR positivity. Data on Ki67 were only available for 43.8% of the investigated cases, and showed inconsistent use of cut-off values. Breast pathology reporting in Belgium in 2008 was suboptimal and showed considerable inter-laboratory variability. Synoptic reporting has been proposed as a facilitator towards increased reporting quality and harmonization, but the lack of aligned informatics remains a major hurdle in its concrete implementation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bronchiectasis: Current Concepts in Pathogenesis, Immunology, and Microbiology.

PubMed

Boyton, Rosemary J; Altmann, Daniel M

2016-05-23

Bronchiectasis is a disorder of persistent lung inflammation and recurrent infection, defined by a common pathological end point: irreversible bronchial dilatation arrived at through diverse etiologies. This suggests an interplay between immunogenetic susceptibility, immune dysregulation, bacterial infection, and lung damage. The damaged epithelium impairs mucus removal and facilitates bacterial infection with increased cough, sputum production, and airflow obstruction. Lung infection is caused by respiratory bacterial and fungal pathogens, including Pseudomonas aeruginosa, Haemophilus, Aspergillus fumigatus, and nontuberculous mycobacteria. Recent studies have highlighted the relationship between the lung microbiota and microbial-pathogen niches. Disease may result from environments favoring interleukin-17-driven neutrophilia. Bronchiectasis may present in autoimmune disease, as well as conditions of immune dysregulation, such as combined variable immune deficiency, transporter associated with antigen processing-deficiency syndrome, and hyperimmunoglobulin E syndrome. Differences in prevalence across geography and ethnicity implicate an etiological mix of genetics and environment underpinning susceptibility.

The mycobiome of the human urinary tract: potential roles for fungi in urology

PubMed Central

Underhill, David M.

2017-01-01

The mycobiome, defined as the fungal microbiota within a host environment, is an important but understudied component of the human microbial ecosystem. New culture-independent approaches to determine microbial diversity, such as next-generation sequencing methods, have discovered specific, characteristic, commensal fungal populations present in different body sites. These studies have also identified diverse patterns in fungal communities associated with various diseases. While alterations in urinary bacterial communities have been noted in disease states, a comprehensive description of the urinary mycobiome has been lacking. Early evidence suggests the urinary mycobiome is a diverse community with high intraindividual variability. In other disease systems, the mycobiome is thought to interact with other biomes and the host to play a role in organ homeostasis and pathology; further study will be needed to elucidate the role fungi play in bladder health and disease. PMID:28217696

Recent biologic and genetic advances in neuroblastoma: Implications for diagnostic, risk stratification, and treatment strategies.

PubMed

Newman, Erika A; Nuchtern, Jed G

2016-10-01

Neuroblastoma is an embryonic cancer of neural crest cell lineage, accounting for up to 10% of all pediatric cancer. The clinical course is heterogeneous ranging from spontaneous regression in neonates to life-threatening metastatic disease in older children. Much of this clinical variance is thought to result from distinct pathologic characteristics that predict patient outcomes. Consequently, many research efforts have been focused on identifying the underlying biologic and genetic features of neuroblastoma tumors in order to more clearly define prognostic subgroups for treatment stratification. Recent technological advances have placed emphasis on the integration of genetic alterations and predictive biologic variables into targeted treatment approaches to improve patient survival outcomes. This review will focus on these recent advances and the implications they have on the diagnostic, staging, and treatment approaches in modern neuroblastoma clinical management. Copyright © 2016 Elsevier Inc. All rights reserved.

[Blood pressure variability: clinical interest or simple curiosity?].

PubMed

Ciaroni, Stefano

2007-03-14

Blood pressure variability is a physiological phenomenon influenced by many internal and external factors. This variability could be also influenced by pathological conditions such as arterial hypertension. Two forms must be mainly distinguished: the blood pressure variability at long and short-term. The latter could only be studied by continuous recordings. In this article will be analysed the interest of measuring blood pressure variability, its cardiovascular prognosis and the therapeutic tools when it is increased.

Defining a Family of Cognitive Diagnosis Models Using Log-Linear Models with Latent Variables

ERIC Educational Resources Information Center

Henson, Robert A.; Templin, Jonathan L.; Willse, John T.

2009-01-01

This paper uses log-linear models with latent variables (Hagenaars, in "Loglinear Models with Latent Variables," 1993) to define a family of cognitive diagnosis models. In doing so, the relationship between many common models is explicitly defined and discussed. In addition, because the log-linear model with latent variables is a general model for…

Pathological anxiety in animals.

PubMed

Ohl, Frauke; Arndt, Saskia S; van der Staay, F Josef

2008-01-01

Selective breeding programmes in domestic and laboratory animals generally focus on physiological and/or anatomical characteristics. However, selection may have an (unintended) impact on other characteristics and may lead to dysfunctional behaviour that can affect biological functioning and, as a consequence, compromise welfare and quality of life. In this review it is proposed that various behavioural dysfunctions in animals are due to pathological anxiety. Although several approaches have been undertaken to specify the diagnostic criteria of pathological anxiety as a behavioural disorder in animals, the causal aetiology largely remains unknown. This is mainly due to the fact that integrated concepts, combining the behavioural syndrome and (neuro-) physiological processes, are widely lacking. Moreover, even the term anxiety itself represents a poorly defined concept or category. A definition is suggested and the potential causes of pathological anxiety are explored with a plea for developing adequate diagnostic tools and therapies to fight pathological anxiety in animals based on insight from scientific research.

Retrospective and Prospective Reports of Precipitants to Relapse in Pathological Gambling

ERIC Educational Resources Information Center

Hodgins, David C.; el-Guebaly, Nady

2004-01-01

A prospective design was used to explore the precipitants of relapse in a naturalistic sample of pathological gamblers (N = 101) who had recently quit gambling. Relapse rates were high; only 8% were entirely free of gambling during the 12-month follow-up. Relapses were highly variable but occurred most frequently in the evening, when the person…

Culturally and linguistically diverse students in speech-language pathology courses: A platform for culturally responsive services.

PubMed

Attrill, Stacie; Lincoln, Michelle; McAllister, Sue

2017-06-01

Increasing the proportion of culturally and linguistically diverse (CALD) students and providing intercultural learning opportunities for all students are two strategies identified to facilitate greater access to culturally responsive speech-language pathology services. To enact these strategies, more information is needed about student diversity. This study collected descriptive information about CALD speech-language pathology students in Australia. Cultural and linguistic background information was collected through surveying 854 domestic and international speech-language pathology students from three Australian universities. Students were categorised according to defined or perceived CALD status, international student status, speaking English as an Additional Language (EAL), or speaking a Language Other than English at Home (LOTEH). Overall, 32.1% of students were either defined or perceived CALD. A total of 14.9% spoke EAL and 25.7% identified speaking a LOTEH. CALD students were more likely to speak EAL or a LOTEH than non-CALD students, were prominently from Southern and South-Eastern Asian backgrounds and spoke related languages. Many students reported direct or indirect connections with their cultural heritage and/or contributed linguistic diversity. These students may represent broader acculturative experiences in communities. The sociocultural knowledge and experience of these students may provide intercultural learning opportunities for all students and promote culturally responsive practices.

7 CFR 51.2 - Terms defined.

Code of Federal Regulations, 2013 CFR

2013-01-01

...; mechanical injuries resulting from improper handling after packing; progressive pathological, physiological, and virus diseases, including fungal and bacterial roots; and freezing damage which may occur in...

Techniques and Methods for Testing the Postural Function in Healthy and Pathological Subjects

PubMed Central

Paillard, Thierry; Noé, Frédéric

2015-01-01

The different techniques and methods employed as well as the different quantitative and qualitative variables measured in order to objectify postural control are often chosen without taking into account the population studied, the objective of the postural test, and the environmental conditions. For these reasons, the aim of this review was to present and justify the different testing techniques and methods with their different quantitative and qualitative variables to make it possible to precisely evaluate each sensory, central, and motor component of the postural function according to the experiment protocol under consideration. The main practical and technological methods and techniques used in evaluating postural control were explained and justified according to the experimental protocol defined. The main postural conditions (postural stance, visual condition, balance condition, and test duration) were also analyzed. Moreover, the mechanistic exploration of the postural function often requires implementing disturbing postural conditions by using motor disturbance (mechanical disturbance), sensory stimulation (sensory manipulation), and/or cognitive disturbance (cognitive task associated with maintaining postural balance) protocols. Each type of disturbance was tackled in order to facilitate understanding of subtle postural control mechanisms and the means to explore them. PMID:26640800

Techniques and Methods for Testing the Postural Function in Healthy and Pathological Subjects.

PubMed

Paillard, Thierry; Noé, Frédéric

2015-01-01

The different techniques and methods employed as well as the different quantitative and qualitative variables measured in order to objectify postural control are often chosen without taking into account the population studied, the objective of the postural test, and the environmental conditions. For these reasons, the aim of this review was to present and justify the different testing techniques and methods with their different quantitative and qualitative variables to make it possible to precisely evaluate each sensory, central, and motor component of the postural function according to the experiment protocol under consideration. The main practical and technological methods and techniques used in evaluating postural control were explained and justified according to the experimental protocol defined. The main postural conditions (postural stance, visual condition, balance condition, and test duration) were also analyzed. Moreover, the mechanistic exploration of the postural function often requires implementing disturbing postural conditions by using motor disturbance (mechanical disturbance), sensory stimulation (sensory manipulation), and/or cognitive disturbance (cognitive task associated with maintaining postural balance) protocols. Each type of disturbance was tackled in order to facilitate understanding of subtle postural control mechanisms and the means to explore them.

Cognitive Activities During Adulthood Are More Important than Education in Building Reserve

PubMed Central

Reed, Bruce R.; Dowling, Maritza; Farias, Sarah Tomaszewski; Sonnen, Joshua; Strauss, Milton; Schneider, Julie A.; Bennett, David A.; Mungas, Dan

2012-01-01

Cognitive reserve is thought to reflect life experiences. Which experiences contribute to reserve and their relative importance is not understood. Subjects were 652 autopsied cases from the Rush Memory and Aging Project and the Religious Orders Study. Reserve was defined as the residual variance of the regressions of cognitive factors on brain pathology and was captured in a latent variable that was regressed on potential determinants of reserve. Neuropathology variables included Alzheimer’s disease markers, Lewy bodies, infarcts, microinfarcts, and brain weight. Cognition was measured with six cognitive domain scores. Determinants of reserve were socioeconomic status (SES), education, leisure cognitive activities at age 40 (CA40) and at study enrollment (CAbaseline) in late life. The four exogenous predictors of reserve were weakly to moderately inter-correlated. In a multivariate model, all except SES had statistically significant effects on Reserve, the strongest of which were CA40 (β= .31) and CAbaseline (β= .28). The Education effect was negative in the full model (β= −.25). Results suggest that leisure cognitive activities throughout adulthood are more important than education in determining reserve. Discrepancies between cognitive activity and education may be informative in estimating late life reserve. PMID:23131600

Cognitive activities during adulthood are more important than education in building reserve.

PubMed

Reed, Bruce R; Dowling, Maritza; Tomaszewski Farias, Sarah; Sonnen, Joshua; Strauss, Milton; Schneider, Julie A; Bennett, David A; Mungas, Dan

2011-07-01

Cognitive reserve is thought to reflect life experiences. Which experiences contribute to reserve and their relative importance is not understood. Subjects were 652 autopsied cases from the Rush Memory and Aging Project and the Religious Orders Study. Reserve was defined as the residual variance of the regressions of cognitive factors on brain pathology and was captured in a latent variable that was regressed on potential determinants of reserve. Neuropathology variables included Alzheimer's disease markers, Lewy bodies, infarcts, microinfarcts, and brain weight. Cognition was measured with six cognitive domain scores. Determinants of reserve were socioeconomic status (SES), education, leisure cognitive activities at age 40 (CA40) and at study enrollment (CAbaseline) in late life. The four exogenous predictors of reserve were weakly to moderately inter-correlated. In a multivariate model, all except SES had statistically significant effects on Reserve, the strongest of which were CA40 (β = .31) and CAbaseline (β = .28). The Education effect was negative in the full model (β = -.25). Results suggest that leisure cognitive activities throughout adulthood are more important than education in determining reserve. Discrepancies between cognitive activity and education may be informative in estimating late life reserve.

[Penile dimensions in type 2 diabetes].

PubMed

Belousov, I I; Kogan, M I; Ibishev, H S; Vorobyev, S V; Khripun, I A; Gusova, Z R

2015-12-01

The current literature provides a wide range of publications on the anthropometry of the penis specifying the relationship between penile dimensions and sex hormones, weight, height and erectile function. But most of the studies involved healthy volunteers or young patients with erectile dysfunction. Our study was conducted in patients with type 2 diabetes. Penile measurements obtained in the present study were compared those of the average Russian man. The patients were divided into groups with preserved and impaired erectile function. Erectile function was also studied relative to the variability of penile dimensions. The effect of DM duration on erectile function was defined. Comparative analysis revealed the relationship between penile anatomical dimensions and erectile function. We studied the effect of type 2 diabetes on the anatomical dimensions and elasticity of the penis, established the relationship between penile dimensions and elasticity of the penis. The correlation between the severity of erectile dysfunction and serum testosterone levels on one side, and penile dimensions on the other was found. The effect of penile dimensions on erectile function in DM patients was also examined. Determining penile dimensions and their variability due to various pathological conditions or processes, may eventually lead to better result of ED management.

Low-rank Atlas Image Analyses in the Presence of Pathologies

PubMed Central

Liu, Xiaoxiao; Niethammer, Marc; Kwitt, Roland; Singh, Nikhil; McCormick, Matt; Aylward, Stephen

2015-01-01

We present a common framework, for registering images to an atlas and for forming an unbiased atlas, that tolerates the presence of pathologies such as tumors and traumatic brain injury lesions. This common framework is particularly useful when a sufficient number of protocol-matched scans from healthy subjects cannot be easily acquired for atlas formation and when the pathologies in a patient cause large appearance changes. Our framework combines a low-rank-plus-sparse image decomposition technique with an iterative, diffeomorphic, group-wise image registration method. At each iteration of image registration, the decomposition technique estimates a “healthy” version of each image as its low-rank component and estimates the pathologies in each image as its sparse component. The healthy version of each image is used for the next iteration of image registration. The low-rank and sparse estimates are refined as the image registrations iteratively improve. When that framework is applied to image-to-atlas registration, the low-rank image is registered to a pre-defined atlas, to establish correspondence that is independent of the pathologies in the sparse component of each image. Ultimately, image-to-atlas registrations can be used to define spatial priors for tissue segmentation and to map information across subjects. When that framework is applied to unbiased atlas formation, at each iteration, the average of the low-rank images from the patients is used as the atlas image for the next iteration, until convergence. Since each iteration’s atlas is comprised of low-rank components, it provides a population-consistent, pathology-free appearance. Evaluations of the proposed methodology are presented using synthetic data as well as simulated and clinical tumor MRI images from the brain tumor segmentation (BRATS) challenge from MICCAI 2012. PMID:26111390

Confounders in interpreting pathology for safety and risk assessment

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

Wolf, Douglas C.; Mann, Peter C.

2005-02-01

The contribution of pathology to toxicity assessment is invaluable but often not clearly understood. Pathology endpoints are the central response around which human health risk assessment is frequently determined; therefore, it is important that the general toxicology community understand current concepts and nomenclature of toxicologic pathology. Toxicologic pathology encompasses the study of changes in tissue morphology that help define the risk of exposure to xenobiotics. Toxicologic pathology is a discipline that has changed and adapted over time including methods of analysis and nomenclature of lesions. As risk assessments are updated for chemicals in commerce, frequently the older literature must bemore » reviewed and reevaluated. When interpreting pathology data from animal studies, it is important to consider the biological significance of a lesion as well as its relationship to the ultimate adverse health effect. Assessing the potential for a chemical to cause harm to humans must include the examination of the entire pathology database in context of the study design, the mode of action of the chemical of concern, and using the most current interpretation of a lesion to determine the significance for human health effects of a particular tissue response.« less

Assessing pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review.

PubMed

Ryan, J E; Warrier, S K; Lynch, A C; Heriot, A G

2015-10-01

Pathological complete response to neoadjuvant chemoradiotherapy is found in 20% of patients with rectal cancer undergoing long-course chemoradiotherapy. Some authors have suggested that these patients do not need to undergo surgery and can be managed with careful follow-up, with surgery only used in the event of clinical failure. Widespread adoption of this regimen is limited by the accuracy of methods to confirm a pathological complete response (pCR). A systematic search of PubMed, Medline and Cochrane databases was conducted to identify clinical, histological and radiological features in those patients with rectal cancer who achieved a pCR following chemoradiotherapy. Searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation' and 'tumour response'. After review of title and abstracts, 89 articles addressing the assessment of pCR were identified. Histology and clinical assessment are the most effective methods of assessment of pCR, with histology considered the gold standard. Clinical assessment is limited to low rectal tumours and is open to significant inter-rater variability, while histological examination requires a surgical specimen. Diffusion-weighted MRI and (18) F-fluorodeoxyglucose positron emission tomography/CT demonstrate the greatest potential for the assessment of pCR, but both modalities have limited accuracy. Determination of a pCR is crucial if a nonoperative approach is to be undertaken proactively. Various methods are available, but currently they lack sufficient sensitivity and specificity to define management. This is likely to be an area of further research in the future. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Impact of different variables on the outcome of patients with clinically confined prostate carcinoma: prediction of pathologic stage and biochemical failure using an artificial neural network.

PubMed

Ziada, A M; Lisle, T C; Snow, P B; Levine, R F; Miller, G; Crawford, E D

2001-04-15

The advent of advanced computing techniques has provided the opportunity to analyze clinical data using artificial intelligence techniques. This study was designed to determine whether a neural network could be developed using preoperative prognostic indicators to predict the pathologic stage and time of biochemical failure for patients who undergo radical prostatectomy. The preoperative information included TNM stage, prostate size, prostate specific antigen (PSA) level, biopsy results (Gleason score and percentage of positive biopsy), as well as patient age. All 309 patients underwent radical prostatectomy at the University of Colorado Health Sciences Center. The data from all patients were used to train a multilayer perceptron artificial neural network. The failure rate was defined as a rise in the PSA level > 0.2 ng/mL. The biochemical failure rate in the data base used was 14.2%. Univariate and multivariate analyses were performed to validate the results. The neural network statistics for the validation set showed a sensitivity and specificity of 79% and 81%, respectively, for the prediction of pathologic stage with an overall accuracy of 80% compared with an overall accuracy of 67% using the multivariate regression analysis. The sensitivity and specificity for the prediction of failure were 67% and 85%, respectively, demonstrating a high confidence in predicting failure. The overall accuracy rates for the artificial neural network and the multivariate analysis were similar. Neural networks can offer a convenient vehicle for clinicians to assess the preoperative risk of disease progression for patients who are about to undergo radical prostatectomy. Continued investigation of this approach with larger data sets seems warranted. Copyright 2001 American Cancer Society.

Surgical Management of Carney Complex-Associated Pituitary Pathology.

PubMed

Lonser, Russell R; Mehta, Gautam U; Kindzelski, Bogdan A; Ray-Chaudhury, Abhik; Vortmeyer, Alexander O; Dickerman, Robert; Oldfield, Edward H

2017-05-01

Carney complex (CNC) is a familial neoplasia syndrome that is associated with pituitary-associated hypersecretion of growth hormone (GH) (acromegaly). The underlying cause of pituitary GH hypersecretion and its management have been incompletely defined. To provide biological insight into CNC-associated pituitary pathology and improve management, we analyzed findings in CNC patients who underwent transsphenoidal surgery. Consecutive CNC patients at the National Institutes of Health with acromegaly and imaging evidence of a pituitary adenoma(s) who underwent transsphenoidal resection of tumor(s) were included. Prospectively acquired magnetic resonance imaging and biochemical, surgical, and histological data were analyzed. Seven acromegalic CNC patients (2 male, 5 female) were included. The mean age at surgery was 29.7 years (range, 18-44 years). The mean follow-up was 4.7 years (range, 0.2-129 months). Magnetic resonance imaging revealed a single pituitary adenoma in 4 patients and multiple pituitary adenomas in 3 patients. Whereas patients with single discrete pituitary adenomas underwent selective adenomectomy, patients with multiple adenomas underwent selective adenomectomy of multiple tumors, as well as partial or total hypophysectomy. All adenomas were either GH and prolactin positive or exclusively prolactin positive. Pituitary tissue surrounding the adenomas in patients with multiple adenomas revealed hyperplastic GH- and prolactin-positive tissue. CNC-associated acromegaly results from variable pituitary pathology, including a single GH-secreting adenoma or multiple GH-secreting adenomas and/or GH hypersecretion of the pituitary gland surrounding multiple adenomas. Although selective adenomectomy is the preferred treatment for cases of GH-secreting adenomas, multiple adenomas with associated pituitary gland GH hypersecretion may require partial or complete hypophysectomy to achieve biochemical remission. Copyright © 2017 by the Congress of Neurological Surgeons

Fractal Dimension of Tc-99m DTPA GSA Estimates Pathologic Liver Injury due to Chemotherapy in Liver Cancer Patients.

PubMed

Hiroshima, Yukihiko; Shuto, Kiyohiko; Yamazaki, Kazuto; Kawaguchi, Daisuke; Yamada, Masatoshi; Kikuchi, Yutaro; Kasahara, Kohei; Murakami, Takashi; Hirano, Atsushi; Mori, Mikito; Kosugi, Chihiro; Matsuo, Kenichi; Ishida, Yasuo; Koda, Keiji; Tanaka, Kuniya

2016-12-01

Chemotherapy-induced liver injury after potent chemotherapy is a considerable problem in patients undergoing liver resection. The aim of this study was to assess the relationship between the fractal dimension (FD) of Tc-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) and pathologic change of liver parenchyma in liver cancer patients who have undergone chemotherapy. We examined 34 patients (10 female and 24 male; mean age, 68.5 years) who underwent hepatectomy. Hepatic injury was defined as steatosis more than 30 %, grade 2-3 sinusoidal dilation, and/or steatohepatitis Kleiner score ≥4. Fractal analysis was applied to all images of Tc-99m DTPA GSA using a plug-in tool on ImageJ software (NIH, Bethesda, MD). A differential box-counting method was applied, and FD was calculated as a heterogeneity parameter. Correlations between FD and clinicopathological variables were examined. FD values of patients with steatosis and steatohepatitis were significantly higher than those without (P > .001 and P > .001, respectively). There was no difference between the FD values of patients with and without sinusoidal dilatation (P = .357). Multivariate logistic regression showed FD as the only significant predictor for steatosis (P = .005; OR 36.5; 95 % CI 3.0-446.3) and steatohepatitis (P = .012; OR, 29.1; 95 % CI 2.1-400.1). FD of Tc-99m DTPA GSA was the significant predictor for fatty liver disease in patients who underwent chemotherapy. This new modality is able to differentiate steatohepatitis from steatosis; therefore, it may be useful for predicting chemotherapy-induced pathologic liver injury.

Surgical Management of Carney Complex–Associated Pituitary Pathology

PubMed Central

Mehta, Gautam U.; Kindzelski, Bogdan A.; Ray-Chaudhury, Abhik; Vortmeyer, Alexander O.; Dickerman, Robert; Oldfield, Edward H.

2017-01-01

Abstract BACKGROUND: Carney complex (CNC) is a familial neoplasia syndrome that is associated with pituitary-associated hypersecretion of growth hormone (GH) (acromegaly). The underlying cause of pituitary GH hypersecretion and its management have been incompletely defined. OBJECTIVE: To provide biological insight into CNC-associated pituitary pathology and improve management, we analyzed findings in CNC patients who underwent transsphenoidal surgery. METHODS: Consecutive CNC patients at the National Institutes of Health with acromegaly and imaging evidence of a pituitary adenoma(s) who underwent transsphenoidal resection of tumor(s) were included. Prospectively acquired magnetic resonance imaging and biochemical, surgical, and histological data were analyzed. RESULTS: Seven acromegalic CNC patients (2 male, 5 female) were included. The mean age at surgery was 29.7 years (range, 18-44 years). The mean follow-up was 4.7 years (range, 0.2-129 months). Magnetic resonance imaging revealed a single pituitary adenoma in 4 patients and multiple pituitary adenomas in 3 patients. Whereas patients with single discrete pituitary adenomas underwent selective adenomectomy, patients with multiple adenomas underwent selective adenomectomy of multiple tumors, as well as partial or total hypophysectomy. All adenomas were either GH and prolactin positive or exclusively prolactin positive. Pituitary tissue surrounding the adenomas in patients with multiple adenomas revealed hyperplastic GH- and prolactin-positive tissue. CONCLUSION: CNC-associated acromegaly results from variable pituitary pathology, including a single GH-secreting adenoma or multiple GH-secreting adenomas and/or GH hypersecretion of the pituitary gland surrounding multiple adenomas. Although selective adenomectomy is the preferred treatment for cases of GH-secreting adenomas, multiple adenomas with associated pituitary gland GH hypersecretion may require partial or complete hypophysectomy to achieve biochemical remission. PMID:27509071

Physiological and pathological clinical conditions and light scattering in brain

NASA Astrophysics Data System (ADS)

Kurata, Tsuyoshi; Iwata, Sachiko; Tsuda, Kennosuke; Kinoshita, Masahiro; Saikusa, Mamoru; Hara, Naoko; Oda, Motoki; Ohmae, Etsuko; Araki, Yuko; Sugioka, Takashi; Takashima, Sachio; Iwata, Osuke

2016-08-01

MRI of preterm infants at term commonly reveals subtle brain lesions such as diffuse white matter injury, which are linked with later cognitive impairments. The timing and mechanism of such injury remains unclear. The reduced scattering coefficient of near-infrared light (μs’) has been shown to correlate linearly with gestational age in neonates. To identify clinical variables associated with brain μs’, 60 preterm and full-term infants were studied within 7 days of birth. Dependence of μs’ obtained from the frontal head on clinical variables was assessed. In the univariate analysis, smaller μs’ was associated with antenatal glucocorticoid, emergency Caesarean section, requirement for mechanical ventilation, smaller gestational age, smaller body sizes, low 1- and 5-minute Apgar scores, higher cord blood pH and PO2, and higher blood HCO3- at the time of study. Multivariate analysis revealed that smaller gestational age, requirement for mechanical ventilation, and higher HCO3- at the time of study were correlated with smaller μs’. Brain μs’ depended on variables associated with physiological maturation and pathological conditions of the brain. Further longitudinal studies may help identify pathological events and clinical conditions responsible for subtle brain injury and subsequent cognitive impairments following preterm birth.

Enhancement of hepatitis virus immunoassay outcome predictions in imbalanced routine pathology data by data balancing and feature selection before the application of support vector machines.

PubMed

Richardson, Alice M; Lidbury, Brett A

2017-08-14

Data mining techniques such as support vector machines (SVMs) have been successfully used to predict outcomes for complex problems, including for human health. Much health data is imbalanced, with many more controls than positive cases. The impact of three balancing methods and one feature selection method is explored, to assess the ability of SVMs to classify imbalanced diagnostic pathology data associated with the laboratory diagnosis of hepatitis B (HBV) and hepatitis C (HCV) infections. Random forests (RFs) for predictor variable selection, and data reshaping to overcome a large imbalance of negative to positive test results in relation to HBV and HCV immunoassay results, are examined. The methodology is illustrated using data from ACT Pathology (Canberra, Australia), consisting of laboratory test records from 18,625 individuals who underwent hepatitis virus testing over the decade from 1997 to 2007. Overall, the prediction of HCV test results by immunoassay was more accurate than for HBV immunoassay results associated with identical routine pathology predictor variable data. HBV and HCV negative results were vastly in excess of positive results, so three approaches to handling the negative/positive data imbalance were compared. Generating datasets by the Synthetic Minority Oversampling Technique (SMOTE) resulted in significantly more accurate prediction than single downsizing or multiple downsizing (MDS) of the dataset. For downsized data sets, applying a RF for predictor variable selection had a small effect on the performance, which varied depending on the virus. For SMOTE, a RF had a negative effect on performance. An analysis of variance of the performance across settings supports these findings. Finally, age and assay results for alanine aminotransferase (ALT), sodium for HBV and urea for HCV were found to have a significant impact upon laboratory diagnosis of HBV or HCV infection using an optimised SVM model. Laboratories looking to include machine learning via SVM as part of their decision support need to be aware that the balancing method, predictor variable selection and the virus type interact to affect the laboratory diagnosis of hepatitis virus infection with routine pathology laboratory variables in different ways depending on which combination is being studied. This awareness should lead to careful use of existing machine learning methods, thus improving the quality of laboratory diagnosis.

[Nutritional support and risk factors of appearance of enterocutaneous fistulas].

PubMed

Llop, J M; Cobo, S; Padullés, A; Farran, L; Jódar, R; Badia, M B

2012-01-01

Among the different factors described, nutritional support has been associated to prevention and management of enterocutaneous fistulae (ECF). To assess the influence that the parameters related to nutritional, clinical status, and surgical variables have on the occurrence of ECF. An observational case/control retrospective study was performed on patients admitted to the General and Digestive Surgery Department. The parameters analyzed were: diagnosis, body mass index (BMI), pathologic personal history, number of surgical interventions (SI) and complications (previous infection, bleeding, and ischemia). In patients with SI, we analyzed: number and type of SI, time until onset of nutritional support, and type of nutritional support. We performed a multiple logistic uni- and multivariate regression analysis by using the SPSSv.19.0 software. The primary diagnoses related to the occurrence of ECF were pancreatic pathology (OR = 5.346) and inflammatory bowel disease (IBD) (OR = 9.329). The surgical variables associated to higher prevalence of ECF emergency SI (OR = 5.79) and multiple SI (OR = 4.52). Regarding the nutritional variables, the late onset of nutrition (more than three days after SI) was associated to the occurrence of ECF (OR = 3.82). In surgical patients, early nutritional support , independently of the route of administration, decreases the occurrence of fistulae. Pancreatic pathology, IBD, emergency SI, and multiple SI were associated to higher prevalence of ECF. The variable hyponutrition appears as a risk factor that should be confirmed in further studies.

Data Set for Pathology Reporting of Cutaneous Invasive Melanoma

PubMed Central

Judge, Meagan J.; Evans, Alan; Frishberg, David P.; Prieto, Victor G.; Thompson, John F.; Trotter, Martin J.; Walsh, Maureen Y.; Walsh, Noreen M.G.; Ellis, David W.

2013-01-01

An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing “required” (mandatory/core) and “recommended” (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may facilitate the development of protocols for other tumor types. Widespread utilization of an internationally agreed upon, structured pathology data set for melanoma will lead not only to improved patient management but is a prerequisite for research and for international benchmarking in health care. PMID:24061524

Color deconvolution. Optimizing handling of 3D unitary optical density vectors with polar coordinates.

PubMed

Bigras, Gilbert

2012-06-01

Color deconvolution relies on determination of unitary optical density vectors (OD(3D)) derived from pure constituent stains initially defined as intensity vectors in RGB space. OD(3D) can be defined in polar coordinates (phi, theta, radius); always being equal to one, radius can be ignored. Easier handling of unitary optical density 2D vectors (OD(2D)) is shown. OD(2D) pure stains used in anatomical pathology were assessed as centroid values (phi, theta) with a measure of variance: inertia based on arc lengths between centroid value and sampled points. These variables were plotted on a stereographic projection plane. In order to assess pure stains OD(2D), different methods of sampling RGB pixels were tested and compared: (2) direct sampling of nuclei from preparations using (a) composite H&E and (b) hematoxylin only and (2) for any pure stain RGB image, different associated 8-bit masks (saturation, brightness and RGB average) were used for sampling and compared. Behaviors of phi, theta and inertia were obtained by moving threshold in 8-bit mask histograms. Phi and theta stability were tested against variable light intensity during image acquisition and by using 2 different image acquisition systems. The more saturated RGB pixels are, the more stable phi, theta and inertia values are obtained. Different commercial hematoxylins have distinct OD(2D) characteristics. UltraView DAB stain shows high inertia and is angularly closer to usual counterstains than ultraView Red stain, which also has a lower inertia. Superior accuracy is expected from the latter stain. Phi and theta OD(2D) values are sensitive to light intensity variation, to the used imaging system and to the used objectives. An ImageJ plugin was designed to plot and interactively modify OD(2D) values with instant update of color deconvolution allowing heuristic segmentation. Utilization of polar OD(2D) eases statistical characterization of OD(3D) vectors: conditions of optimal sampling were demonstrated and various factors influencing OD(2D) stability were explored. Stereographic projection plane allows intuitive visualization of OD(3D) vectors as well as heuristic vectorial modification. All findings are not restricted to anatomical pathology but can be applied to bright field microscopy and subtractive color applications in general.

Modern Pathologic Diagnosis of Renal Oncocytoma.

PubMed

Wobker, Sara E; Williamson, Sean R

2017-01-01

Oncocytoma is a well-defined benign renal tumor, with classic gross and histologic features, including a tan or mahogany-colored mass with central scar, microscopic nested architecture, bland cytology, and round, regular nuclei with prominent central nucleoli. As a result of variations in this classic appearance, difficulty in standardizing diagnostic criteria, and entities that mimic oncocytoma, such as eosinophilic variant chromophobe renal cell carcinoma and succinate dehydrogenase-deficient renal cell carcinoma, pathologic diagnosis remains a challenge. This review addresses the current state of pathologic diagnosis of oncocytoma, with emphasis on modern diagnostic markers, areas of controversy, and emerging techniques for less invasive diagnosis, including renal mass biopsy and advanced imaging.

Otosclerosis: Temporal Bone Pathology.

PubMed

Quesnel, Alicia M; Ishai, Reuven; McKenna, Michael J

2018-04-01

Otosclerosis is pathologically characterized by abnormal bony remodeling, which includes bone resorption, new bone deposition, and vascular proliferation in the temporal bone. Sensorineural hearing loss in otosclerosis is associated with extension of otosclerosis to the cochlear endosteum and deposition of collagen throughout the spiral ligament. Persistent or recurrent conductive hearing loss after stapedectomy has been associated with incomplete footplate fenestration, poor incus-prosthesis connection, and incus resorption in temporal bone specimens. Human temporal bone pathology has helped to define the role of computed tomography imaging for otosclerosis, confirming that computed tomography is highly sensitive for diagnosis, yet limited in assessing cochlear endosteal involvement. Copyright © 2017 Elsevier Inc. All rights reserved.

Elucidation of salvage laryngectomy pathologic and clinical variables to guide further treatment intensification investigation.

PubMed

Scharpf, Joseph; Ward, Matthew; Adelstein, David; Koyfman, Shlomo; Li, Mingsi

2018-04-01

There are limited treatment options beyond surgical salvage for patients who fail nonoperative treatment for laryngeal squamous cell carcinoma. In this study, we examine the failure patterns after surgical salvage and the potential pathologic and clinical prognostic variables that might guide further postoperative intensification investigation. Retrospective analysis at a tertiary academic referral center. From an institutional review board-approved institutional head and neck cancer registry, a consecutive series of 147 patients who underwent salvage laryngectomy for squamous cell cancer recurrence or persistence after radiotherapy with or without chemotherapy between May 1995 and May 2016 were identified. Variables potentially associated with oncologic outcome after surgical salvage were then collected and retrospectively evaluated. The projected 2-year locoregional failure rate was 21.8% (95% confidence interval [CI], 14.6%-29.0%]), and the overall survival 65% (95% CI, 57.5%-74.3%) for the entire cohort after salvage laryngectomy. On multivariable analysis, sarcomatoid/spindle cell pathology (hazard ratio [HR], 3.147; 95% CI, 1.181-8.386; P = 0.022), lymphovascular space invasion (LVSI) (positive vs. negative; HR, 2.31; 95% CI, 1.21-4.42; P = 0.011), and advanced initial American Joint Committee on Cancer 7th Edition grouped stage (stages III-IVB vs. stages I-II; HR, 1.64; 95% CI, 1.04-2.6; P = 0.035) were found to be independently associated with inferior disease-free survival. No other clinical or pathologic variables predicted failure. Salvage laryngectomy after nonoperative treatment failure results in successful locoregional control rates and survival in the majority of patients failing initial therapy. This should temper enthusiasm for routine treatment intensification with postoperative re-irradiation and/or other systemic treatments for the vast majority of patients. Sarcomatoid pathology, LVSI, and an advanced initial stage are associated with inferior disease-free survival. The presence of these factors may warrant further investigational study of treatment intensification after salvage laryngectomy. 4. Laryngoscope, 128:823-830, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

InterLymph hierarchical classification of lymphoid neoplasms for epidemiologic research based on the WHO classification (2008): update and future directions

PubMed Central

Morton, Lindsay M.; Linet, Martha S.; Clarke, Christina A.; Kadin, Marshall E.; Vajdic, Claire M.; Monnereau, Alain; Maynadié, Marc; Chiu, Brian C.-H.; Marcos-Gragera, Rafael; Costantini, Adele Seniori; Cerhan, James R.; Weisenburger, Dennis D.

2010-01-01

After publication of the updated World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues in 2008, the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph) now presents an update of the hierarchical classification of lymphoid neoplasms for epidemiologic research based on the 2001 WHO classification, which we published in 2007. The updated hierarchical classification incorporates all of the major and provisional entities in the 2008 WHO classification, including newly defined entities based on age, site, certain infections, and molecular characteristics, as well as borderline categories, early and “in situ” lesions, disorders with limited capacity for clinical progression, lesions without current International Classification of Diseases for Oncology, 3rd Edition codes, and immunodeficiency-associated lymphoproliferative disorders. WHO subtypes are defined in hierarchical groupings, with newly defined groups for small B-cell lymphomas with plasmacytic differentiation and for primary cutaneous T-cell lymphomas. We suggest approaches for applying the hierarchical classification in various epidemiologic settings, including strategies for dealing with multiple coexisting lymphoma subtypes in one patient, and cases with incomplete pathologic information. The pathology materials useful for state-of-the-art epidemiology studies are also discussed. We encourage epidemiologists to adopt the updated InterLymph hierarchical classification, which incorporates the most recent WHO entities while demonstrating their relationship to older classifications. PMID:20699439

InterLymph hierarchical classification of lymphoid neoplasms for epidemiologic research based on the WHO classification (2008): update and future directions.

PubMed

Turner, Jennifer J; Morton, Lindsay M; Linet, Martha S; Clarke, Christina A; Kadin, Marshall E; Vajdic, Claire M; Monnereau, Alain; Maynadié, Marc; Chiu, Brian C-H; Marcos-Gragera, Rafael; Costantini, Adele Seniori; Cerhan, James R; Weisenburger, Dennis D

2010-11-18

After publication of the updated World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues in 2008, the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph) now presents an update of the hierarchical classification of lymphoid neoplasms for epidemiologic research based on the 2001 WHO classification, which we published in 2007. The updated hierarchical classification incorporates all of the major and provisional entities in the 2008 WHO classification, including newly defined entities based on age, site, certain infections, and molecular characteristics, as well as borderline categories, early and "in situ" lesions, disorders with limited capacity for clinical progression, lesions without current International Classification of Diseases for Oncology, 3rd Edition codes, and immunodeficiency-associated lymphoproliferative disorders. WHO subtypes are defined in hierarchical groupings, with newly defined groups for small B-cell lymphomas with plasmacytic differentiation and for primary cutaneous T-cell lymphomas. We suggest approaches for applying the hierarchical classification in various epidemiologic settings, including strategies for dealing with multiple coexisting lymphoma subtypes in one patient, and cases with incomplete pathologic information. The pathology materials useful for state-of-the-art epidemiology studies are also discussed. We encourage epidemiologists to adopt the updated InterLymph hierarchical classification, which incorporates the most recent WHO entities while demonstrating their relationship to older classifications.

Mesopancreas: myth or reality?

PubMed

Agrawal, Manish K; Thakur, Dilip Singh; Somashekar, Uday; Chandrakar, Shiv Kumar; Sharma, Dhananjaya

2010-05-05

A recently published study hypothesized the concept of 'mesopancreas', defining it as a firm, well-vascularized structure extending from the posterior surface of the pancreatic head to behind the mesenteric vessels. To verify and define mesopancreas from resection specimens obtained from fresh cadavers. Postmortem anatomical-pathological study. Department of Surgery in conjunction with the Departments of Forensic Medicine and Pathology, Government Medical College and Hospital, Jabalpur, MP, India. Twenty fresh adult cadavers without any intra-abdominal injury or gross intra-abdominal pathology. Specimens containing the entire duodenum, pancreatic head and neck, gallbladder, cystic duct, common bile duct, superior mesenteric vessels, inferior vena cava and aorta were removed en-bloc. Gross and histopathological examinations of the specimens were carried out. To look for a fibrous sheath or fascia around the retropancreatic structure purported to be a mesopancreas. Loose areolar tissue, adipose tissue, peripheral nerve, nerve plexus, lymphatic and capillaries were found in the retropancreatic tissue, extending from the head, neck and uncinate process of pancreas to the aorto-caval groove but no fibrous sheath or fascia was found around these structures. The concept of 'mesopancreas' is anatomically unfounded.

Glenohumeral internal rotation deficit in throwing athletes: current perspectives

PubMed Central

Rose, Michael B; Noonan, Thomas

2018-01-01

Glenohumeral internal rotation deficit (GIRD) is an adaptive process in which the throwing shoulder experiences a loss of internal rotation (IR). GIRD has most commonly been defined by a loss of >20° of IR compared to the contralateral shoulder. Total rotational motion of the shoulder is the sum of internal and external rotation and may be more important than the absolute value of IR loss. Pathologic GIRD has been defined as a loss of IR combined with a loss of total rotational motion. The leading pathologic process in GIRD is posterior capsular and rotator-cuff tightness, due to the repetitive cocking that occurs with the overhead throwing motion. GIRD has been associated with numerous pathologic conditions, including posterior superior labral tears, partial articular-sided rotator-cuff tears, and superior labral anterior-to-posterior tears. The mainstay of treatment for patients with GIRD is posterior capsular stretching and strengthening to improve scapular mechanics. In patients who fail nonoperative therapy, shoulder arthroscopy can be performed. Arthroscopic surgery in the high-level throwing athlete should be to restore them to their functional baseline with the minimum amount of intervention possible. PMID:29593438

7 CFR 51.2 - Terms defined.

Code of Federal Regulations, 2011 CFR

2011-01-01

... resulting from improper handling after packing; progressive pathological, physiological, and virus diseases, including fungal and bacterial roots; and freezing damage which may occur in transit or storage; or any...

Imaging of acute mesenteric ischemia using multidetector CT and CT angiography in a porcine model.

PubMed

Rosow, David E; Sahani, Dushyant; Strobel, Oliver; Kalva, Sanjeeva; Mino-Kenudson, Mari; Holalkere, Nagaraj S; Alsfasser, Guido; Saini, Sanjay; Lee, Susanna I; Mueller, Peter R; Fernández-del Castillo, Carlos; Warshaw, Andrew L; Thayer, Sarah P

2005-12-01

Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols. After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findings--compared with pathologic diagnoses-- predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia.

Different tracks for pathology informatics fellowship training: Experiences of and input from trainees in a large multisite fellowship program

PubMed Central

Levy, Bruce P.; McClintock, David S.; Lee, Roy E.; Lane, William J.; Klepeis, Veronica E.; Baron, Jason M.; Onozato, Maristela L.; Kim, JiYeon; Brodsky, Victor; Beckwith, Bruce; Kuo, Frank; Gilbertson, John R.

2012-01-01

Background: Pathology Informatics is a new field; a field that is still defining itself even as it begins the formalization, accreditation, and board certification process. At the same time, Pathology itself is changing in a variety of ways that impact informatics, including subspecialization and an increased use of data analysis. In this paper, we examine how these changes impact both the structure of Pathology Informatics fellowship programs and the fellows’ goals within those programs. Materials and Methods: As part of our regular program review process, the fellows evaluated the value and effectiveness of our existing fellowship tracks (Research Informatics, Clinical Two-year Focused Informatics, Clinical One-year Focused Informatics, and Clinical 1 + 1 Subspecialty Pathology and Informatics). They compared their education, informatics background, and anticipated career paths and analyzed them for correlations between those parameters and the fellowship track chosen. All current and past fellows of the program were actively involved with the project. Results: Fellows’ anticipated career paths correlated very well with the specific tracks in the program. A small set of fellows (Clinical – one or two year – Focused Informatics tracks) anticipated clinical careers primarily focused in informatics (Director of Informatics). The majority of the fellows, however, anticipated a career practicing in a Pathology subspecialty, using their informatics training to enhance that practice (Clinical 1 + 1 Subspecialty Pathology and Informatics Track). Significantly, all fellows on this track reported they would not have considered a Clinical Two-year Focused Informatics track if it was the only track offered. The Research and the Clinical One-year Focused Informatics tracks each displayed unique value for different situations. Conclusions: It seems a “one size fits all” fellowship structure does not fit the needs of the majority of potential Pathology Informatics candidates. Increasingly, these fellowships must be able to accommodate the needs of candidates anticipating a wide range of Pathology Informatics career paths, be able to accommodate Pathology's increasingly subspecialized structure, and do this in a way that respects the multiple fellowships needed to become a subspecialty pathologist and informatician. This is further complicated as Pathology Informatics begins to look outward and takes its place in the growing, and still ill-defined, field of Clinical Informatics, a field that is not confined to just one medical specialty, to one way of practicing medicine, or to one way of providing patient care. PMID:23024889

Exit competencies in pathology and laboratory medicine for graduating medical students: the Canadian approach.

PubMed

Ford, Jason; Pambrun, Chantale

2015-05-01

Physicians in every medical and surgical field must be able to use pathology concepts and skills in their practice: for example, they must order and interpret the correct laboratory tests, they must use their understanding of pathogenesis to diagnose and treat, and they must work with the laboratory to care for their patients. These important concepts and skills may be ignored by medical schools and even national/international organizations setting graduation expectations for medical students. There is an evolving international consensus about the importance of exit competencies for medical school graduates, which define the measurable or observable behaviors each graduate must be able to demonstrate. The Canadian Association of Pathologists (CAP) Education Group set out to establish the basic competencies in pathology and laboratory medicine which should be expected of every medical graduate: not competencies for pathologists, but for medical graduates who intend to enter any residency program. We defined 4 targets for pathology and laboratory medicine exit competencies: that they represent only measurable behaviors, that they be clinically focused, that they be generalizable to every medical graduate, and that the final competency document be user-friendly. A set of competencies was developed iteratively and underwent final revision at the 2012 CAP annual meeting. These competencies were subsequently endorsed by the CAP executive and the Canadian Leadership Council on Laboratory Medicine. This clinically focused consensus document provides the first comprehensive list of exit competencies in pathology and laboratory medicine for undergraduate medical education. Copyright © 2015 Elsevier Inc. All rights reserved.

SU-E-J-136: Multimodality-Image-Based Target Delineation for Dose Painting of Pancreatic Cancer

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

Dalah, E; Paulson, E; Erickson, B

Purpose: Dose escalated RT may provide improved disease local-control for selected unresectable pancreatic cancer. Accurate delineation of the gross tumor volume (GTV) inside pancreatic head or body would allow safe dose escalation considering the tolerances of adjacent organs at risk (OAR). Here we explore the potential of multi-modality imaging (DCE-MRI, ADC-MRI, and FDG-PET) to define the GTV for dose painting of pancreatic cancer. Volumetric variations of DCE-MRI, ADC-MRI and FDG-PET defined GTVs were assessed in comparison to the findings on CT, and to pathology specimens for resectable and borderline reseactable cases of pancreatic cancer. Methods: A total of 19 representativemore » patients with DCE-MRI, ADC-MRI and FDG-PET data were analyzed. Of these, 8 patients had pathological specimens. GTV, inside pancreatic head/neck, or body, were delineated on MRI (denoted GTVDCE, and GTVADC), on FDG-PET using SUV of 2.5, 40% SUVmax, and 50% SUVmax (denoted GTV2.5, GTV40%, and GTV50%). A Kruskal-Wallis test was used to determine whether significant differences existed between GTV volumes. Results: Significant statistical differences were found between the GTVs defined by DCE-MRI, ADC-MRI, and FDG-PET, with a mean and range of 4.73 (1.00–9.79), 14.52 (3.21–25.49), 22.04 (1.00–45.69), 19.10 (4.84–45.59), and 9.80 (0.32–35.21) cm3 (p<0.0001) for GTVDCE, GTVADC, GTV2.5, GTV40%, and GTV50%, respectively. The mean difference and range in the measurements of maximum dimension of GTVs based on DCE-MRI, ADC-MRI, SUV2.5, 40% SUVmax, and 50% SUVmax compared with pathologic specimens were −0.84 (−2.24 to 0.9), 0.41 (−0.15 to 2.3), 0.58 (−1.41 to 3.69), 0.66 (−0.67 to 1.32), and 0.15 (−1.53 to 2.38) cm, respectively. Conclusion: Differences exists between DCE, ADC, and PET defined target volumes for RT of pancreatic cancer. Further studies combined with pathological specimens are required to identify the optimal imaging modality and/or acquisition method to define the GTV.« less

Digital pathology: DICOM-conform draft, testbed, and first results.

PubMed

Zwönitzer, Ralf; Kalinski, Thomas; Hofmann, Harald; Roessner, Albert; Bernarding, Johannes

2007-09-01

Hospital information systems are state of the art nowadays. Therefore, Digital Pathology, also labelled as Virtual Microscopy, has gained increased attention. Triggered by radiology, standardized information models and workflows were world-wide defined based on DICOM. However, DICOM-conform integration of Digital Pathology into existing clinical information systems imposes new problems requiring specific solutions concerning the huge amount of data as well as the special structure of the data to be managed, transferred, and stored. We implemented a testbed to realize and evaluate the workflow of digitized slides from acquisition to archiving. The experiences led to the draft of a DICOM-conform information model that accounted for extensions, definitions, and technical requirements necessary to integrate digital pathology in a hospital-wide DICOM environment. Slides were digitized, compressed, and could be viewed remotely. Real-time transfer of the huge amount of data was optimized using streaming techniques. Compared to a recent discussion in the DICOM Working Group for Digital Pathology (WG26) our experiences led to a preference of a JPEG2000/JPIP-based streaming of the whole slide image. The results showed that digital pathology is feasible but strong efforts by users and vendors are still necessary to integrate Digital Pathology into existing information systems.

Value of subjective visual reduction in patients with acute-onset floaters and/or flashes.

PubMed

Hurst, Jonathan; Johnson, Davin; Law, Christine; Schweitzer, Kelly; Sharma, Sanjay

2015-08-01

To quantify the association between subjective visual reduction (SVR) and retinal pathology in patients with acute-onset monocular floaters or flashes, or both. Prospective cohorts study involving all new patients referred for acute-onset floaters or flashes, or both, to a tertiary care emergency eye clinic in Kingston, Ontario, between July 1, 2011, and June 29, 2012 (n = 333). All patients were evaluated for the presence of SVR in a standardized fashion, as well as other known risk factors for retina pathology including a family history of retinal tear or retinal detachment, a personal history of retinal tear or detachment, high myopia, and ocular trauma. Our major outcome was urgent retinal pathology, defined as retina pathology requiring a same-day referral to a retina specialist for evaluation, management, or both. SVR was strongly associated with retinal pathology (likelihood ratio 7.9, 95% CI 5.2-12.1). Patients with SVR are at increased risk for urgent retinal pathology and should be triaged for urgent ophthalmologic examination. Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Communication skills in diagnostic pathology.

PubMed

Lehr, Hans-Anton; Bosman, Fred T

2016-01-01

Communication is an essential element of good medical practice also in pathology. In contrast to technical or diagnostic skills, communication skills are not easy to define, teach, or assess. Rules almost do not exist. In this paper, which has a rather personal character and cannot be taken as a set of guidelines, important aspects of communication in pathology are explored. This includes what should be communicated to the pathologist on the pathology request form, communication between pathologists during internal (interpathologist) consultation, communication around frozen section diagnoses, modalities of communication of a final diagnosis, with whom and how critical and unexpected findings should be communicated, (in-)adequate routes of communication for pathology diagnoses, who will (or might) receive pathology reports, and what should be communicated and how in case of an error or a technical problem. An earlier more formal description of what the responsibilities are of a pathologist as communicator and as collaborator in a medical team is added in separate tables. The intention of the paper is to stimulate reflection and discussion rather than to formulate strict rules.

Evidence that Meningeal Mast Cells Can Worsen Stroke Pathology in Mice

PubMed Central

Arac, Ahmet; Grimbaldeston, Michele A.; Nepomuceno, Andrew R.B.; Olayiwola, Oluwatobi; Pereira, Marta P.; Nishiyama, Yasuhiro; Tsykin, Anna; Goodall, Gregory J.; Schlecht, Ulrich; Vogel, Hannes; Tsai, Mindy; Galli, Stephen J.; Bliss, Tonya M.; Steinberg, Gary K.

2015-01-01

Stroke is the leading cause of adult disability and the fourth most common cause of death in the United States. Inflammation is thought to play an important role in stroke pathology, but the factors that promote inflammation in this setting remain to be fully defined. An understudied but important factor is the role of meningeal-located immune cells in modulating brain pathology. Although different immune cells traffic through meningeal vessels en route to the brain, mature mast cells do not circulate but are resident in the meninges. With the use of genetic and cell transfer approaches in mice, we identified evidence that meningeal mast cells can importantly contribute to the key features of stroke pathology, including infiltration of granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two mast cell-derived products, interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can contribute to stroke pathology. These findings indicate a novel role for mast cells in the meninges, the membranes that envelop the brain, as potential gatekeepers for modulating brain inflammation and pathology after stroke. PMID:25134760

Sense and nonsense in the process of accreditation of a pathology laboratory.

PubMed

Long-Mira, Elodie; Washetine, Kevin; Hofman, Paul

2016-01-01

The aim of accreditation of a pathology laboratory is to control and optimize, in a permanent manner, good professional practice in clinical and molecular pathology, as defined by internationally established standards. Accreditation of a pathology laboratory is a key element in fine in increasing recognition of the quality of the analyses performed by a laboratory and in improving the care it provides to patients. One of the accreditation standards applied to clinical chemistry and pathology laboratories in the European Union is the ISO 15189 norm. Continued functioning of a pathology laboratory might in time be determined by whether or not it has succeeded the accreditation process. Necessary requirements for accreditation, according to the ISO 15189 norm, include an operational quality management system and continuous control of the methods used for diagnostic purposes. Given these goals, one would expect that all pathologists would agree on the positive effects of accreditation. Yet, some of the requirements stipulated in the accreditation standards, coming from the bodies that accredit pathology laboratories, and certain normative issues are perceived as arduous and sometimes not adapted to or even useless in daily pathology practice. The aim of this review is to elaborate why it is necessary to obtain accreditation but also why certain requirements for accreditation might be experienced as inappropriate.

Differential Modulation of Retinal Degeneration by Ccl2 and Cx3cr1 Chemokine Signalling

PubMed Central

Luhmann, Ulrich F. O.; Lange, Clemens A.; Robbie, Scott; Munro, Peter M. G.; Cowing, Jill A.; Armer, Hannah E. J.; Luong, Vy; Carvalho, Livia S.; MacLaren, Robert E.; Fitzke, Frederick W.; Bainbridge, James W. B.; Ali, Robin R.

2012-01-01

Microglia and macrophages are recruited to sites of retinal degeneration where local cytokines and chemokines determine protective or neurotoxic microglia responses. Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2−/−/Crb1Rd8/RD8, Cx3cr1−/−/Crb1Rd8/RD8 and CCl2−/−/Cx3cr1−/−/Crb1Rd8/RD8 mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings indicate that CCDKO mice are not a model of AMD, but a model for an inherited retinal degeneration that is differentially modulated by Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling. PMID:22545116

Disturbed self concept mediates the relationship between childhood maltreatment and adult personality pathology.

PubMed

Cohen, Lisa; Leibu, Olga; Tanis, Thachell; Ardalan, Firouz; Galynker, Igor

2016-07-01

Despite a robust literature documenting the relationship between childhood maltreatment and personality pathology in adulthood, there is far less clarity about the mechanism underlying this relationship. One promising candidate for such a linking mechanism is disturbance in the sense of self. This paper tests the hypothesis that disturbances in the sense of self mediate the relationship between childhood maltreatment and adult personality pathology. Specifically, we assess the self-related traits of stable self-image, self-reflective functioning, self-respect and feeling recognized. The sample included 113 non-psychotic psychiatric inpatients. Participants completed the Child Trauma Questionnaire (CTQ), the Personality Diagnostic Questionnaire-4 (PDQ-4+), and the self-reflexive functioning, stable self image, self-respect, and feeling recognized scales from the Severity Indices of Personality Problems (SIPP-118). A series of linear regressions was then performed to assess the direct and indirect effects of childhood trauma on personality disorder traits (PDQ-4+ total score), as mediated by self concept (SIPP-118 scales). Aroian tests assessed the statistical significance of each mediating effect. There was a significant mediating effect for all SIPP self concept variables, with a full mediating effect for the SIPP composite score and for SIPP feeling recognized and self-reflexive functioning, such that the direct effect of childhood trauma on personality did not retain significance after accounting for the effect of these variables. There was a partial mediating effect for SIPP stable self image and self-respect, such that the direct effect of the CTQ retained significance after accounting for these variables. SIPP feeling recognized had the strongest mediating effect. Multiple facets of self concept, particularly the degree to which an individual feels understood by other people, may mediate the relationship between childhood maltreatment and adult personality pathology. This underscores the importance of attending to disturbances in the sense of self in patients with personality pathology and a history of childhood maltreatment. These findings also support the centrality of disturbed self concept to the general construct of personality pathology. Copyright © 2016. Published by Elsevier Inc.

Acculturative Stress, Self-Esteem, and Eating Pathology in Latina and Asian American Female College Students.

PubMed

Claudat, Kimberly; White, Emily K; Warren, Cortney S

2016-01-01

The overarching purpose of this study was to explore the relationships among acculturative stress, self-esteem, and eating pathology in Asian American and Latina female college students. Participants (N = 638, mean age = 19.88) completed self-report measures of the variables of interest online. Bivariate correlations indicated that for women of both ethnic groups, acculturative stress was negatively correlated with self-esteem and positively correlated with eating pathology. Multigroup structural equation modeling indicated that for Asian American and Latina women, self-esteem partially mediated the relationship between acculturative stress and eating pathology. However, self-esteem did not serve as a significant moderator of this relationship for either ethnic group. Overall, data suggest that acculturative stress is associated with increased eating pathology and self-esteem may mediate this relationship. These relationships suggest that assessment of eating pathology and self-esteem may be indicated for women presenting clinically with acculturative stress concerns. © 2015 Wiley Periodicals, Inc.

Early axonal damage and progressive myelin pathology define the kinetics of CNS histopathology in a mouse model of multiple sclerosis.

PubMed

Recks, Mascha S; Stormanns, Eva R; Bader, Jonas; Arnhold, Stefan; Addicks, Klaus; Kuerten, Stefanie

2013-10-01

Studies of MS histopathology are largely dependent on suitable animal models. While light microscopic analysis gives an overview of tissue pathology, it falls short in evaluating detailed changes in nerve fiber morphology. The ultrastructural data presented here and obtained from studies of myelin oligodendrocyte glycoprotein (MOG):35-55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice delineate that axonal damage and myelin pathology follow different kinetics in the disease course. While myelin pathology accumulated with disease progression, axonal damage coincided with the initial clinical disease symptoms and remained stable over time. This pattern applied both to irreversible axolysis and early axonal pathology. Notably, these histopathological patterns were reflected by the normal-appearing white matter (NAWM), suggesting that the NAWM is also in an active neurodegenerative state. The data underline the need for neuroprotection in MS and suggest the MOG model as a highly valuable tool for the assessment of different therapeutic strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

A Controlled Study of Variables Related to Counseling Center Use.

ERIC Educational Resources Information Center

Bosmajian, C. Perry, Jr.; Mattson, Robert E.

1980-01-01

Investigated the utility of several variables in discriminating between students who seek counseling and those who do not. Interaction between personal adjustment and help-seeking status was also examined. Alternate sources of help, counseling usefulness, and perceived severity of help-seeker pathology descriminated seekers from nonseekers.…

Variability of Target and Normal Structure Delineation Using Multimodality Imaging for Radiation Therapy of Pancreatic Cancer

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

Dalah, Entesar; Moraru, Ion; Paulson, Eric

Purpose: To explore the potential of multimodality imaging (dynamic contrast–enhanced magnetic resonance imaging [DCE-MRI], apparent diffusion-coefficient diffusion-weighted imaging [ADC-DWI], fluorodeoxyglucose positron emission tomography [FDG-PET], and computed tomography) to define the gross tumor volume (GTV) and organs at risk in radiation therapy planning for pancreatic cancer. Delineated volumetric changes of DCE-MRI, ADC-DWI, and FDG-PET were assessed in comparison with the finding on 3-dimensional/4-dimensional CT with and without intravenous contrast, and with pathology specimens for resectable and borderline resectable cases of pancreatic cancer. Methods and Materials: We studied a total of 19 representative patients, whose DCE-MRI, ADC-DWI, and FDG-PET data were reviewed.more » Gross tumor volume and tumor burden/active region inside pancreatic head/neck or body were delineated on MRI (denoted GTV{sub DCE}, and GTV{sub ADC}), a standardized uptake value (SUV) of 2.5, 40%SUVmax, and 50%SUVmax on FDG-PET (GTV2.5, GTV{sub 40%}, and GTV{sub 50%}). Volumes of the pancreas, duodenum, stomach, liver, and kidneys were contoured according to CT (V{sub CT}), T1-weighted MRI (V{sub T1}), and T2-weighted MRI (V{sub T2}) for 7 patients. Results: Significant statistical differences were found between the GTVs from DCE-MRI, ADC-DW, and FDG-PET, with a mean and range of 4.73 (1.00-9.79), 14.52 (3.21-25.49), 22.04 (1.00-45.69), 19.10 (4.84-45.59), and 9.80 (0.32-35.21) cm{sup 3} for GTV{sub DCE}, GTV{sub ADC}, GTV2.5, GTV{sub 40%}, and GTV{sub 50%}, respectively. The mean difference and range in the measurements of maximum dimension of tumor on DCE-MRI, ADC-DW, SUV2.5, 40%SUVmax, and 50%SUVmax compared with pathologic specimens were −0.84 (−2.24 to 0.9), 0.41 (−0.15 to 2.3), 0.58 (−1.41 to 3.69), 0.66 (−0.67 to 1.32), and 0.15 (−1.53 to 2.38) cm, respectively. The T1- and T2-based volumes for pancreas, duodenum, stomach, and liver were generally smaller compared with those from CT, except for the kidneys. Conclusions: Differences exists between DCE-, ADC-, and FDG-PET–defined target volumes for RT of pancreatic cancer. Organ at risk volumes based on MRI are generally smaller than those based on CT. Further studies combined with pathologic specimens are required to identify the optimal imaging modality or sequence to define GTV.« less

Neuropathological and transcriptomic characteristics of the aged brain

PubMed Central

Miller, Jeremy A; Guillozet-Bongaarts, Angela; Gibbons, Laura E; Postupna, Nadia; Renz, Anne; Beller, Allison E; Sunkin, Susan M; Ng, Lydia; Rose, Shannon E; Smith, Kimberly A; Szafer, Aaron; Barber, Chris; Bertagnolli, Darren; Bickley, Kristopher; Brouner, Krissy; Caldejon, Shiella; Chapin, Mike; Chua, Mindy L; Coleman, Natalie M; Cudaback, Eiron; Cuhaciyan, Christine; Dalley, Rachel A; Dee, Nick; Desta, Tsega; Dolbeare, Tim A; Dotson, Nadezhda I; Fisher, Michael; Gaudreault, Nathalie; Gee, Garrett; Gilbert, Terri L; Goldy, Jeff; Griffin, Fiona; Habel, Caroline; Haradon, Zeb; Hejazinia, Nika; Hellstern, Leanne L; Horvath, Steve; Howard, Kim; Howard, Robert; Johal, Justin; Jorstad, Nikolas L; Josephsen, Samuel R; Kuan, Chihchau L; Lai, Florence; Lee, Eric; Lee, Felix; Lemon, Tracy; Li, Xianwu; Marshall, Desiree A; Melchor, Jose; Mukherjee, Shubhabrata; Nyhus, Julie; Pendergraft, Julie; Potekhina, Lydia; Rha, Elizabeth Y; Rice, Samantha; Rosen, David; Sapru, Abharika; Schantz, Aimee; Shen, Elaine; Sherfield, Emily; Shi, Shu; Sodt, Andy J; Thatra, Nivretta; Tieu, Michael; Wilson, Angela M; Montine, Thomas J; Larson, Eric B; Bernard, Amy; Crane, Paul K; Ellenbogen, Richard G

2017-01-01

As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer’s disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology and cognitive abilities with advancing age, indicative of individual variation in resilience to pathology. Here, we generated a comprehensive neuropathological, molecular, and transcriptomic characterization of hippocampus and two regions cortex in 107 aged donors (median = 90) from the Adult Changes in Thought (ACT) study as a freely-available resource (http://aging.brain-map.org/). We confirm established associations between AD pathology and dementia, albeit with increased, presumably aging-related variability, and identify sets of co-expressed genes correlated with pathological tau and inflammation markers. Finally, we demonstrate a relationship between dementia and RNA quality, and find common gene signatures, highlighting the importance of properly controlling for RNA quality when studying dementia. PMID:29120328

Types of Psychotherapy for Pathological Gamblers

PubMed Central

2005-01-01

Several types of psychotherapy are currently used to treat pathological gamblers. These include Gambler's Anonymous, cognitive behavioral therapy, behavioral therapy, psychodynamic therapy, and family therapy. Research into which types of psychotherapy are the most effective for pathological gambling is limited but is a growing area of study. Group therapy, namely Gambler's Anonymous, provides peer support and structure. Cognitive behavior therapy aims to identify and correct cognitive distortions about gambling. Psychodynamic psychotherapy can help recovering gamblers address core conflicts and hidden psychological meanings of gambling. Family therapy is helpful by providing support and education and eliminating enabling behaviors. To date, no single type of psychotherapy has emerged as the most effective form of treatment. As in other addictive disorders, treatment retention of pathological gamblers is highly variable. Understanding the types of psychotherapy that are available for pathological gamblers, as well their underlying principles, will assist clinicians in managing this complex behavioral disorder. PMID:21152147

Metacognition in Pathological Gambling and Its Relationship with Anxious and Depressive Symptomatology.

PubMed

Jauregui, Paula; Urbiola, Irache; Estevez, Ana

2016-06-01

Gambling disorder is associated with elevated comorbidity with depressive and anxious disorders, and one variable that might help in the understanding of this association is metacognition. In the present study, the relationship between gambling and metacognition and the mediating role of metacognition in the relationship between gambling and depressive and anxious symptomatology were assessed. The sample comprised 124 pathological gamblers from centers that assist pathological gamblers and 204 participants from the general population. The results showed that pathological gamblers had higher levels of depressive and anxious symptomatology. Additionally, pathological gamblers had higher scores for positive beliefs about worry, negative beliefs of uncontrollability and danger, and beliefs about the need to control thoughts; these factors were also positively correlated with depressive and anxious symptomatology. Metacognition also fully mediated the association between gambling and depressive and anxious symptomatology. These results suggest that metacognition could contribute to explaining gambling disorder and the symptomatology associated with it.

[Dual pathology].

PubMed

Rougier, A

2008-05-01

Dual pathology is defined as the association of two potentially epileptogenic lesions, hippocampal (sclerosis, neuronal loss) and extrahippocampal (temporal or extratemporal). Epileptic activity may be generated by either lesion and the relative importance of every lesion's epileptogenicity conditions the surgical strategy adopted. Most frequently associated with hippocampal sclerosis are cortical dysplasias. The common physiopathology of the two lesions is not clearly established. Extrahippocampal lesions may be undetectable on MRI (microdysgenesis, for example) and ictal discharge patterns may vary among dual pathology patients. The surgical strategy depends on the location of the extrahippocampal lesion and its relative role in seizure generation; however, reported surgical results suggest that simultaneous resection of mesial temporal structures along with the extrahippocampal lesion should be performed.

Pathology of melanocytic lesions: new, controversial, and clinically important issues.

PubMed

Scolyer, Richard A; Thompson, John F; Stretch, Jonathan R; Sharma, Raghwa; McCarthy, Stanley W

2004-07-01

Patients with primary cutaneous melanocytic lesions rely not only on the knowledge, skills, and experience of their treating clinician but also on the fundamentally important input of their pathologist for accurate diagnosis and appropriate management. Free and precise communication between pathologists and surgeons is important and undoubtedly improves patient care, particularly when managing difficult or complicated cases. To provide both patient and surgeon with the necessary information they require to make the most appropriate decisions, the pathology report should include all pathologic factors that are important in determining the patient's prognosis and management. Use of a synoptic format for pathology reporting of melanomas can facilitate this. Recent studies have established that the dermal mitotic rate of a primary cutaneous melanoma is a major prognostic determinant, and have shown that its assessment and that of other important histopathologic prognostic variables are reproducible between pathologists. Sentinel node (SN) biopsy has provided a minimally invasive procedure that can accurately predict the regional node status of melanoma patients. It is well demonstrated that the use of immunohistochemical stains assists in the detection of melanoma micrometastases in SNs, although it remains unclear which is the optimal pathologic protocol for SN evaluation and whether there is a role for reverse transcriptase polymerase chain reaction (RT-PCR) in SN assessment. False negative SN biopsies may occur as a result of errors in lymphatic mapping or sentinel lymphadenectomy, or because of a deficiency in the process of histopathologic evaluation. Recent studies have shown that the likelihood of non-SN involvement when the SN is positive correlates mostly with the extent of SN involvement, in particular the tumor penetrative depth (defined as the maximum distance of melanoma cells from the inner margin of the SN capsule). It appears that assessment of the micromorphometric features of positive SNs may be useful in predicting which patients have a low probability of having metastatic tumor in non-SNs, and therefore in selecting patients who potentially may be spared a completion lymph node dissection. It is likely that future advances in our understanding of the molecular biology of melanoma will provide new insights into tumor classification, improve diagnostic accuracy and prognostic ability, and lead to the development of more precisely targeted therapies. Copyright 2004 Wiley-Liss, Inc.

Pathological video-gaming among Singaporean youth.

PubMed

Choo, Hyekyung; Gentile, Douglas A; Sim, Timothy; Li, Dongdong; Khoo, Angeline; Liau, Albert K

2010-11-01

Increase in internet use and video-gaming contributes to public concern on pathological or obsessive play of video games among children and adolescents worldwide. Nevertheless, little is known about the prevalence of pathological symptoms in video-gaming among Singaporean youth and the psychometric properties of instruments measuring pathological symptoms in video-gaming. A total of 2998 children and adolescents from 6 primary and 6 secondary schools in Singapore responded to a comprehensive survey questionnaire on sociodemographic characteristics, video-gaming habits, school performance, somatic symptoms, various psychological traits, social functioning and pathological symptoms of video-gaming. After weighting, the survey data were analysed to determine the prevalence of pathological video-gaming among Singaporean youth and gender differences in the prevalence. The construct validity of instrument used to measure pathological symptoms of video-gaming was tested. Of all the study participants, 8.7% were classified as pathological players with more boys reporting more pathological symptoms than girls. All variables, including impulse control problem, social competence, hostility, academic performance, and damages to social functioning, tested for construct validity, were significantly associated with pathological status, providing good evidence for the construct validity of the instrument used. The prevalence rate of pathological video-gaming among Singaporean youth is comparable with that from other countries studied thus far, and gender differences are also consistent with the findings of prior research. The positive evidence of construct validity supports the potential use of the instrument for future research and clinical screening on Singapore children and adolescents' pathological video-gaming.

Ectodermal dysplasias: a new clinical-genetic classification

PubMed Central

Priolo, M.; Lagana, C.

2001-01-01

The ectodermal dysplasias (EDs) are a large and complex nosological group of diseases, first described by Thurnam in 1848. In the last 10 years more than 170 different pathological clinical conditions have been recognised and defined as EDs, all sharing in common anomalies of the hair, teeth, nails, and sweat glands. Many are associated with anomalies in other organs and systems and, in some conditions, with mental retardation.
The anomalies affecting the epidermis and epidermal appendages are extremely variable and clinical overlap is present among the majority of EDs. Most EDs are defined by particular clinical signs (for example, eyelid adhesion in AEC syndrome, ectrodactyly in EEC). To date, few causative genes have been identified for these diseases.
We recently reviewed genes known to be responsible for EDs in light of their molecular and biological function and proposed a new approach to EDs, integrating both molecular-genetic data and corresponding clinical findings. Based on our previous report, we now propose a clinical-genetic classification of EDs, expand it to other entities in which no causative genes have been identified based on the phenotype, and speculate on possible candidate genes suggested by associated "non-ectodermal" features.


Keywords: ectodermal dysplasia; clinical-functional correlation; epithelial-mesenchymal interaction; ectodermal structural proteins PMID:11546825

Prevalence and risk factors of vision impairment among children of employees of Telecom, Italy.

PubMed

Nucci, Carlo; Cofini, Vincenza; Mancino, Raffaele; Ricci, Federico; Martucci, Alessio; Cecilia, Maria Rosita; Ciciarelli, Vincenzo; Zazzara, Francesca; Cedrone, Claudio; di Orio, Ferdinando

2016-06-10

To define the prevalence, causes, and risk factors of vision impairment (VI) in children. In this study, relatives of Association for Supplemental Health Insurance to the Employees of Telecom members aged 5-16 years were examined in all Italian regions. A standardized record card was used to collect data on medical history; keratometry; objective refraction; uncorrected, presenting, and best-corrected visual acuity (VA); examination of the pupils, adnexa, and anterior segment; direct ophthalmoscopy; posterior segment and fundus examination; and assessment for ocular pathology. Binocular and monocular VI were defined by a VA <5/10 (or <20/40). The campaign included 17,508 children, 12,798 of whom (73.1%) were examined (and 12,740 on whom all VA data were gathered). The prevalence of uncorrected, presenting, and best-corrected VI in the better eye was 9.0%, 2.51%, and 0.10%, respectively. The following variables were associated with presenting VI: age 10-16 years, family history of myopia, female sex, family history of keratoconus, and hypertension. Myopia is the main cause of VI (82.6%). A total of 96% of children with presenting VI had correctable VI. Correctable VI because of myopia is an important public health problem in school-age children in Italy.

Smoking topography and outcome expectancies among individuals with schizotypy

PubMed Central

Stewart, Diana W.; Vinci, Christine; Adams, Claire E.; Cohen, Alex S.; Copeland, Amy L.

2013-01-01

Compared to smokers in the general population, smokers with schizophrenia smoke more cigarettes per day and have higher nicotine dependence and biochemical indicators of nicotine intake. They also have more intense smoking topography and greater positive smoking expectancies. Little is known about the relationship between smoking and schizotypy, defined as the personality organization reflecting a vulnerability to schizophrenia-spectrum pathology. This study assessed schizotypy symptoms, smoking characteristics and behaviors, and smoking expectancies in young adults with psychometrically defined schizotypy and demographically matched controls without schizotypy. Smokers with schizotypy had higher nicotine dependence and smoked more cigarettes per week compared to control smokers. They were also more likely to endorse greater positive consequences (i.e., improved state enhancement, stimulation, social facilitation, taste/sensorimotor manipulation, reduced negative affect and boredom) and fewer negative consequences of smoking. Smokers with schizotypy and control smokers did not differ on smoking topography or carbon monoxide levels. This is the first known study to investigate relationships between these smoking-related variables in smokers with schizotypy. Individuals with schizotypy possessed certain smoking-related characteristics and smoking expectancies similar to those with schizophrenia. This offers preliminary insight into unique smoking-related factors among individuals with schizotypy and highlights the importance of continued research in this area. PMID:23261186

Prognostic value of seminal vesicle involvement due to prostate cancer in radical prostatectomy specimens.

PubMed

Algarra, R; Barba, J; Merino, I; Tienza, A; Tolosa, E; Robles, J E; Zudaire, J

2015-04-01

To study the influence, in terms of prognosis, of the finding of seminal vesicle involvement in patients with prostate adenocarcinoma treated with radical prostatectomy. We reviewed a series of patients with seminal vesicle involvement with clinically localized prostate adenocarcinoma who underwent radical prostatectomy between 1989 and 2009, focusing on their clinical-pathological characteristics, biochemical progression-free survival (BPFS) and specific survival (SS). We assessed the variables that influenced BPFS and designed a risk model. A total of 127 out of 1,132 patients who underwent surgery (11%) presented seminal vesicle invasion (i.e., pT3b). In the multivariate study of the entire series (Cox model), pT3b affects the BPFS (HR: 2; 95% CI: 1.4-3.3; P=.001). Other influential factors were the affected borders, initial prostate-specific antigen levels, pathological Gleason score and the presence of palpated tumor. The pT3b tumors have poorer clinical-pathological variables when compared with pT2 and pT3a tumors. Sixty-five percent of the patients evidenced biochemical progression. The BPFS was significantly poorer for pT3b (40 ± 4% and 28 ± 4% at 5 and 10 years, respectively) than for pT2 and pT3a (P<.0001). The SS was also poorer in patients with pT3b tumors (91 ± 2% and 76 ± 4% at 5 and 10 years, respectively) (P<.0001). The predictors within the pT3b patient group were: PSA levels >10 ng/mL (HR: 1.9; 95% CI: 1.04-3.6; P=.04) and pathological Gleason score 8-10 (HR: 2.1; 95% CI: 1.2-3.5; P=.03). We designed a risk model that accounts for the variables involved, which entails 2 groups with different BPFS (P=.004): Group 1 (0-1 variable), with a BPFS of 46 ± 7% and 27 ± 8% at 5 and 10 years, respectively; and Group 2 (2 variables), with a BPFS of 14 ± 7% and 5 ± 5% at 5 and 10 years, respectively. Seminal vesicle involvement severely and negatively affects the BPFS and SS. We designed a risk model with the independent influential variables in BPFS (pathological Gleason score 8-10 and PSA levels >10 ng/mL). This model confirms that pT3b tumors are a heterogeneous group, which includes an important group with better prognosis when surgical treatment is performed. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Why Synchrony Matters during Mother-Child Interactions: A Systematic Review

PubMed Central

Leclère, Chloë; Viaux, Sylvie; Avril, Marie; Achard, Catherine; Chetouani, Mohamed; Missonnier, Sylvain; Cohen, David

2014-01-01

Background Assessment of mother-child interactions is a core issue of early child development and psychopathology. This paper focuses on the concept of “synchrony” and examines (1) how synchrony in mother-child interaction is defined and operationalized; (2) the contribution that the concept of synchrony has brought to understanding the nature of mother-child interactions. Method Between 1977 and 2013, we searched several databases using the following key-words: « synchrony » « interaction » and « mother-child ». We focused on studies examining parent-child interactions among children aged 2 months to 5 years. From the 63 relevant studies, we extracted study description variables (authors, year, design, number of subjects, age); assessment conditions and modalities; and main findings. Results The most common terms referring to synchrony were mutuality, reciprocity, rhythmicity, harmonious interaction, turn-taking and shared affect; all terms were used to characterize the mother-child dyad. As a consequence, we propose defining synchrony as a dynamic and reciprocal adaptation of the temporal structure of behaviors and shared affect between interactive partners. Three main types of assessment methods for studying synchrony emerged: (1) global interaction scales with dyadic items; (2) specific synchrony scales; and (3) micro-coded time-series analyses. It appears that synchrony should be regarded as a social signal per se as it has been shown to be valid in both normal and pathological populations. Better mother-child synchrony is associated with familiarity (vs. unknown partner), a healthy mother (vs. pathological mother), typical development (vs. psychopathological development), and a more positive child outcomes. Discussion Synchrony is a key feature of mother-infant interactions. Adopting an objective approach in studying synchrony is not a simple task given available assessment tools and due to its temporality and multimodal expression. We propose an integrative approach combining clinical observation and engineering techniques to improve the quality of synchrony analysis. PMID:25469637

Mastoid foramen, mastoid emissary vein and clinical implications in neurosurgery.

PubMed

Hampl, Martin; Kachlik, David; Kikalova, Katerina; Riemer, Roxane; Halaj, Matej; Novak, Vlastimil; Stejskal, Premysl; Vaverka, Miroslav; Hrabalek, Lumir; Krahulik, David; Nanka, Ondrej

2018-05-20

Mastoid emissary vein is especially important from the neurosurgical point of view, because it is located in variable number in the area of the occipitomastoid suture and it can become a source of significant bleeding in surgical approaches through the mastoid process, especially in retrosigmoid craniotomy, which is used for approaches to pathologies localized in the cerebellopontine angle. Ideal imaging method for diagnosis of these neglected structures when planning a surgical approach is high-resolution computed tomography. The aim of this work was to provide detailed information about this issue. We studied a group of 295 skulls obtained from collections of five anatomy departments and the National Museum. Both quantitative and qualitative parameters of the mastoid foramen were evaluated depending on side of appearance and gender. Individual distances of the mastoid foramen from clearly defined surface landmarks (asterion, apex of mastoid process, foramen magnum) and other anatomical structures closely related to this issue (width of groove for sigmoid sinus, diameters of internal and external openings of mastoid foramen) were statistically processed. The most frequently represented type of the mastoid foramen is type II by Louis (41.2%). The differences between right and left sides were not statistically significant. In men there was a higher number of openings on the right side and in qualitative parameters the type III and IV predominated, whereas in women the types I and II were more frequent. In men, greater distances from the mastoid foramen were observed when evaluating qualitative parameters for defined surface landmarks. Mean size of the external opening diameter was 1.3 mm; however, several openings measured up to 7 mm. Despite excellent knowledge of anatomy, however, good pre-operative examination using imaging methods and mastering of microsurgical techniques create the base for successful treatment of pathological structures in these anatomically complex areas.

Predicting Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer with Textural Features Derived from Pretreatment 18F-FDG PET/CT Imaging.

PubMed

Beukinga, Roelof J; Hulshoff, Jan B; van Dijk, Lisanne V; Muijs, Christina T; Burgerhof, Johannes G M; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Slump, Cornelis H; Mul, Véronique E M; Plukker, John Th M

2017-05-01

Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUV max in 18 F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18 F-FDG PET/CT-derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18 F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18 F-FDG PET and CT. The current most accurate prediction model with SUV max as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model's performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2-5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18 F-FDG PET-derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUV max model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion: The predictive values of the constructed models were superior to the standard method (SUV max ). These results can be considered as an initial step in predicting tumor response to nCRT in locally advanced EC. Further research in refining the predictive value of these models is needed to justify omission of surgery. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Brain Vulnerability to Repeated Blast Overpressure and Polytrauma

DTIC Science & Technology

2014-11-01

define underlying neurobiological mechanisms and rationally establish effective guidelines (e.g. return-to-duty) and 8 countermeasures to lessen...show a positive correlation with the accumulation of APP in different brain regions suggesting a distinct pathological mechanism leading to Alzheimer’s...date, the etiologies of these injuries are largely undefined. A high fidelity animal model is critical to define the mechanism (s) of injury and develop

High Intratumoral Stromal Content Defines Reactive Breast Cancer as a Low-risk Breast Cancer Subtype | Office of Cancer Genomics

Cancer.gov

Improved biomarker tests are required to minimize overdiagnosis and overtreatment of breast cancers. A number of pathologic criteria have been established to differentiate indolent or aggressive behavior, such as Nottingham grade of cancer cells. However, the effects of the tumor microenvironment on patient outcomes have not been integrated into pathologic criteria. In the current study, the Reactive subtype of breast cancer, identified by reverse-phase protein arrays, was demonstrated to indicate a favorable outcome.

Analysis of spatial heterogeneity in normal epithelium and preneoplastic alterations in mouse prostate tumor models

PubMed Central

Valkonen, Mira; Ruusuvuori, Pekka; Kartasalo, Kimmo; Nykter, Matti; Visakorpi, Tapio; Latonen, Leena

2017-01-01

Cancer involves histological changes in tissue, which is of primary importance in pathological diagnosis and research. Automated histological analysis requires ability to computationally separate pathological alterations from normal tissue with all its variables. On the other hand, understanding connections between genetic alterations and histological attributes requires development of enhanced analysis methods suitable also for small sample sizes. Here, we set out to develop computational methods for early detection and distinction of prostate cancer-related pathological alterations. We use analysis of features from HE stained histological images of normal mouse prostate epithelium, distinguishing the descriptors for variability between ventral, lateral, and dorsal lobes. In addition, we use two common prostate cancer models, Hi-Myc and Pten+/− mice, to build a feature-based machine learning model separating the early pathological lesions provoked by these genetic alterations. This work offers a set of computational methods for separation of early neoplastic lesions in the prostates of model mice, and provides proof-of-principle for linking specific tumor genotypes to quantitative histological characteristics. The results obtained show that separation between different spatial locations within the organ, as well as classification between histologies linked to different genetic backgrounds, can be performed with very high specificity and sensitivity. PMID:28317907

Pathological motivations for exercise and eating disorder specific health-related quality of life.

PubMed

Cook, Brian; Engel, Scott; Crosby, Ross; Hausenblas, Heather; Wonderlich, Stephen; Mitchell, James

2014-04-01

To examine associations among pathological motivations for exercise with eating disorder (ED) specific health-related quality of life (HRQOL). Survey data assessing ED severity (i.e., Eating Disorder Diagnostic Survey), ED specific HRQOL (i.e., Eating Disorders Quality of Life Instrument), and pathological motivations for exercise (i.e., Exercise Dependence Scale) were collected from female students (N = 387) at seven universities throughout the United States. Regression analyses were conducted to examine the associations among exercise dependence, ED-specific HRQOL and ED severity, and the interaction of exercise dependence and ED severity on HRQOL scores. The overall model examining the impact of ED severity and exercise dependence (independent variables) on HRQOL (dependent variable) was significant and explained 16.1% of the variance in HRQOL scores. Additionally, the main effects for ED severity and exercise dependence and the interaction among ED severity and exercise dependence were significant, suggesting that the combined effects of ED severity and exercise dependence significantly impacts HRQOL. Our results suggest that pathological motivations for exercise may exacerbate ED's detrimental impact on HRQOL. Our results offer one possible insight into why exercise may be associated with deleterious effects on ED HRQOL. Future research is needed to elucidate the relationship among psychological aspects of exercise, ED, and HRQOL. Copyright © 2013 Wiley Periodicals, Inc.

Preoperative Assessment of Craniopharyngioma Adherence: Magnetic Resonance Imaging Findings Correlated with the Severity of Tumor Attachment to the Hypothalamus.

PubMed

Prieto, Ruth; Pascual, José M; Rosdolsky, Maria; Barrios, Laura

2018-02-01

Craniopharyngioma (CP) adherence represents a heterogeneous pathologic feature that critically influences the potentially safe and radical resection. The aim of this study was to define the magnetic resonance imaging (MRI) predictors of CP adherence severity. This study retrospectively investigated a cohort of 200 surgically treated CPs with their corresponding preoperative conventional MRI scans. MRI findings related to the distortions of anatomic structures along the sella turcica-third ventricle axis caused by CPs, in addition to the tumor's shape and calcifications, were analyzed and correlated with the definitive type of CP adherence observed during the surgical procedures. CP adherence is defined by 3 components, as follows: 1) the specific structures attached to the tumor, 2) the adhesion's extent, and 3) its strength. Combination of these 3 components determines 5 hierarchical levels of adherence severity with gradually increasing surgical risk of hypothalamic injury. Multivariate analysis identified 4 radiologic variables that allowed a correct overall prediction of the levels of CP adherence severity in 81.5% of cases: 1) the position of the hypothalamus in relation to the tumor-the most discriminant factor; 2) the type of pituitary stalk distortion; 3) the tumor shape; and 4) the presence of calcifications. A binary logistic regression model including the first 3 radiologic variables correctly identified the CPs showing the highest level of adherence severity (severe/critical) in almost 90% of cases. A position of the hypothalamus around the middle portion of the tumor, an amputated or infiltrated appearance of the pituitary stalk, and the elliptical shape of the tumor are reliable predictors of strong and extensive CP adhesions to the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of Transcutaneous Electrical Nerve Stimulation and Cryotherapy for Increasing Quadriceps Activation in Patients With Knee Pathologies.

PubMed

Gabler, Conrad M; Lepley, Adam S; Uhl, Tim L; Mattacola, Carl G

2016-08-01

Proper neuromuscular activation of the quadriceps muscle is essential for maintaining quadriceps (quad) strength and lower-extremity function. Quad activation (QA) failure is a common characteristic observed in patients with knee pathologies, defined as an inability to voluntarily activate the entire alpha-motor-neuron pool innervating the quad. One of the more popular techniques used to assess QA is the superimposed burst (SIB) technique, a force-based technique that uses a supramaximal, percutaneous electrical stimulation to activate all of the motor units in the quad during a maximal, voluntary isometric contraction. Central activation ratio (CAR) is the formula used to calculate QA level (CAR = voluntary force/SIB force) with the SIB technique. People who can voluntarily activate 95% or more (CAR = 0.95-1.0) of their motor units are defined as being fully activated. Therapeutic exercises aimed at improving quad strength in patients with knee pathologies are limited in their effectiveness due to a failure to fully activate the muscle. Within the past decade, several disinhibitory interventions have been introduced to treat QA failure in patients with knee pathologies. Transcutaneous electrical nerve stimulation (TENS) and cryotherapy are sensory-targeted modalities traditionally used to treat pain, but they have been shown to be 2 of the most successful treatments for increasing QA levels in patients with QA failure. Both modalities are hypothesized to positively affect voluntary QA by disinhibiting the motor-neuron pool of the quad. In essence, these modalities provide excitatory afferent stimuli to the spinal cord, which thereby overrides the inhibitory afferent signaling that arises from the involved joint. However, it remains unknown whether 1 is more effective than the other for restoring QA levels in patients with knee pathologies. By knowing the capabilities of each disinhibitory modality, clinicians can tailor treatments based on the rehabilitation goals of their patients. Focused Clinical Question: Is TENS or cryotherapy the more effective disinhibitory modality for treating QA failure (quantified via CAR) in patients with knee pathologies?

Trouble shooting in toxicopathology

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

Rousseaux, C.G.

2005-09-01

Toxicopathology, also referred to as toxicologic pathology, can be defined as the study of structural and functional changes in cells, tissues, and organs that are induced by toxicants (such as drugs, industrial and agricultural chemicals), toxins (chemicals of biological origin such as mycotoxins and phycotoxins), and physical agents (such as heat and radiation); the investigation of the mechanisms by which these changes are induced; and the development of risk assessment and risk management policies based on such information. Toxicologic pathology primarily deals with the morphologic or structural effects of the toxicant and the mechanism by which this structural effect ismore » induced. This article highlights some of the problems that toxicologic pathologists may encounter in obtaining and interpreting pathology lesions. By alerting toxicologists to some of these issues, it is hoped that a better understanding of the use and limitations of toxicologic pathology data will occur.« less

The α‐synuclein gene in multiple system atrophy

PubMed Central

Ozawa, T; Healy, D G; Abou‐Sleiman, P M; Ahmadi, K R; Quinn, N; Lees, A J; Shaw, K; Wullner, U; Berciano, J; Moller, J C; Kamm, C; Burk, K; Josephs, K A; Barone, P; Tolosa, E; Goldstein, D B; Wenning, G; Geser, F; Holton, J L; Gasser, T; Revesz, T; Wood, N W

2006-01-01

Background The formation of α‐synuclein aggregates may be a critical event in the pathogenesis of multiple system atrophy (MSA). However, the role of this gene in the aetiology of MSA is unknown and untested. Method The linkage disequilibrium (LD) structure of the α‐synuclein gene was established and LD patterns were used to identify a set of tagging single nucleotide polymorphisms (SNPs) that represent 95% of the haplotype diversity across the entire gene. The effect of polymorphisms on the pathological expression of MSA in pathologically confirmed cases was also evaluated. Results and conclusion In 253 Gilman probable or definite MSA patients, 457 possible, probable, and definite MSA cases and 1472 controls, a frequency difference for the individual tagging SNPs or tag‐defined haplotypes was not detected. No effect was observed of polymorphisms on the pathological expression of MSA in pathologically confirmed cases. PMID:16543523

Relationship between thoracic auscultation and lung pathology detected by ultrasonography in sheep.

PubMed

Scott, Phil; Collie, Dave; McGorum, Bruce; Sargison, Neil

2010-10-01

The utility of routine auscultation to detect and characterise the nature of a range of superficial lung and pleural pathologies in domestic sheep was assessed using ultrasonographic examination to indicate and localise pathologies pre-mortem. Necropsy examination was then used to fully characterise the nature and extent of the lesions. Auscultation recordings were made from 10 normal sheep with no clinical evidence of respiratory disease and with absence of significant superficial lung pathology, which was confirmed initially by ultrasound examination and subsequently at necropsy examination. A further two sheep with endotoxaemia and 30 sheep with well-defined lung lesions were also examined. Increased audibility of normal lung sounds in 4/10 normal sheep was associated with tachypnoea as a consequence of handling and transport during hot weather and was also observed in the two sheep with endotoxaemia. Moderate to severe coarse crackles detected in all advanced cases of ovine pulmonary adenocarcinoma (n=16) were audible over an area larger than the lesion distribution identified during ultrasound examination, and confirmed later at necropsy. Auscultation did not detect abnormal sounds in any of the five sheep with focal pleural abscesses (up to 10 cm diameter). Unilateral pyothorax caused attenuation of sounds relative to the contra-lateral normal lung in all three sheep with this condition. Marked fibrinous pleurisy caused attenuation of sounds relative to normal areas of lung in six sheep. No sounds resembling the description of pleural frictions rubs were heard in the sheep with marked fibrinous pleurisy (n=6) or associated with focal pleural abscesses (n=5). Routine interpretation of auscultated sound did not allow the presence of superficial lung pathology or its distribution to be accurately defined in the respiratory diseases represented in this study. Copyright © 2009 Elsevier Ltd. All rights reserved.

A historical perspective on crush syndrome: the clinical application of its pathogenesis, established by the study of wartime crush injuries.

PubMed

Peiris, Dilini

2017-04-01

Crush syndrome is a fine example of how pathology can play a direct role in revealing the best treatment and management for diseases. It can occur when crush injuries are sustained. Skeletal muscle becomes damaged under the weight of a heavy object, and victims experience severe shock and renal failure. The discovery of the pathology of crush syndrome belongs to two individuals: Seigo Minami and Eric Bywaters. They separately helped to define the pathogenesis of crush syndrome during World Wars I and II. Seigo Minami is believed to have been the first to record the pathogenesis of crush syndrome. In 1923, he described the cases of three soldiers who died of renal failure caused by crush injury during World War I. Using microscopic studies to investigate the pathology of their kidneys, he found the soldiers had died due to 'autointoxication' caused by rhabdomyolysis. This discovery was not known to Eric Bywaters, who described crush syndrome in 1941, having studied victims of the London Blitz during World War II. He defined the 'autointoxication' as the release of rhabdomyolysis products via reperfusion. He therefore established the need for emergency fluid replacement to treat crush syndrome. The findings made by Minami and Bywaters highlight a remarkable achievement in clinical pathology, despite the adversity of war. It is these findings on which current guidelines are based. By reviewing their work, it is hoped that the role of pathology can be better appreciated as a valuable resource for delineating the treatment and management of diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A novel method for morphological pleomorphism and heterogeneity quantitative measurement: Named cell feature level co-occurrence matrix.

PubMed

Saito, Akira; Numata, Yasushi; Hamada, Takuya; Horisawa, Tomoyoshi; Cosatto, Eric; Graf, Hans-Peter; Kuroda, Masahiko; Yamamoto, Yoichiro

2016-01-01

Recent developments in molecular pathology and genetic/epigenetic analysis of cancer tissue have resulted in a marked increase in objective and measurable data. In comparison, the traditional morphological analysis approach to pathology diagnosis, which can connect these molecular data and clinical diagnosis, is still mostly subjective. Even though the advent and popularization of digital pathology has provided a boost to computer-aided diagnosis, some important pathological concepts still remain largely non-quantitative and their associated data measurements depend on the pathologist's sense and experience. Such features include pleomorphism and heterogeneity. In this paper, we propose a method for the objective measurement of pleomorphism and heterogeneity, using the cell-level co-occurrence matrix. Our method is based on the widely used Gray-level co-occurrence matrix (GLCM), where relations between neighboring pixel intensity levels are captured into a co-occurrence matrix, followed by the application of analysis functions such as Haralick features. In the pathological tissue image, through image processing techniques, each nucleus can be measured and each nucleus has its own measureable features like nucleus size, roundness, contour length, intra-nucleus texture data (GLCM is one of the methods). In GLCM each nucleus in the tissue image corresponds to one pixel. In this approach the most important point is how to define the neighborhood of each nucleus. We define three types of neighborhoods of a nucleus, then create the co-occurrence matrix and apply Haralick feature functions. In each image pleomorphism and heterogeneity are then determined quantitatively. For our method, one pixel corresponds to one nucleus feature, and we therefore named our method Cell Feature Level Co-occurrence Matrix (CFLCM). We tested this method for several nucleus features. CFLCM is showed as a useful quantitative method for pleomorphism and heterogeneity on histopathological image analysis.

A level-set method for pathology segmentation in fluorescein angiograms and en face retinal images of patients with age-related macular degeneration

NASA Astrophysics Data System (ADS)

Mohammad, Fatimah; Ansari, Rashid; Shahidi, Mahnaz

2013-03-01

The visibility and continuity of the inner segment outer segment (ISOS) junction layer of the photoreceptors on spectral domain optical coherence tomography images is known to be related to visual acuity in patients with age-related macular degeneration (AMD). Automatic detection and segmentation of lesions and pathologies in retinal images is crucial for the screening, diagnosis, and follow-up of patients with retinal diseases. One of the challenges of using the classical level-set algorithms for segmentation involves the placement of the initial contour. Manually defining the contour or randomly placing it in the image may lead to segmentation of erroneous structures. It is important to be able to automatically define the contour by using information provided by image features. We explored a level-set method which is based on the classical Chan-Vese model and which utilizes image feature information for automatic contour placement for the segmentation of pathologies in fluorescein angiograms and en face retinal images of the ISOS layer. This was accomplished by exploiting a priori knowledge of the shape and intensity distribution allowing the use of projection profiles to detect the presence of pathologies that are characterized by intensity differences with surrounding areas in retinal images. We first tested our method by applying it to fluorescein angiograms. We then applied our method to en face retinal images of patients with AMD. The experimental results included demonstrate that the proposed method provided a quick and improved outcome as compared to the classical Chan-Vese method in which the initial contour is randomly placed, thus indicating the potential to provide a more accurate and detailed view of changes in pathologies due to disease progression and treatment.

Hematologic reference intervals and age effect in European Strigiformes.

PubMed

Agusti Montolio, Susana; Molina López, Rafael; Cray, Carolyn; Lavín González, Santiago; Nicolás Francisco, Olga; Marco Sánchez, Ignasi; Casas-Díaz, Encarna; Cuenca Valera, Rafaela

2017-09-01

The clinical importance of hematologic testing in avian veterinary medicine is reflected in the increasing number of studies for the establishment of hematologic RIs of Strigiformes and other species. Age is an important physiologic factor in birds and the effect on hematology variable should be understood. The objective of this study was to determine baseline data of hematologic variables in 5 species of Iberian Strigiformes in different age classes. Nocturnal birds of prey were sampled at Wildlife Health Centers. Packed cell volume was determined by the microhematocrit centrifugation method, and RBC and WBC counts were determined using the direct hemocytometer count method with Natt and Herrick solution. Hemoglobin concentration was measured spectrophotometrically. The MCV, MCHC, and MHC were calculated using the standard formulas. The differential WBC count was performed by the routine microscopic evaluation of 200 cells on a blood smear manually stained with Wright stain. Thrombocyte blood count estimate was obtained from the blood film. No differences were observed between juveniles and adults for any variable evaluated in Tawny owl, Little owl, Scops owl, Long-eared owl, and Barn owl. In addition, PCV, RBC, and HGB of chicks were statistically significantly lower than in juveniles and adults, and total WBC was significantly higher in Tawny owl, Little owl, Scops owl, and Long-eared owl. Our findings provide evidence that laboratory data from chicks of Strigiformes are different compared to juveniles and adults; therefore, separate RIs were defined. © 2017 American Society for Veterinary Clinical Pathology.

Study of Heart Rate Variability in Bipolar Disorder: Linear and Non-Linear Parameters during Sleep

PubMed Central

Migliorini, Matteo; Mendez, Martin O.; Bianchi, Anna M.

2012-01-01

The aim of the study is to define physiological parameters and vital signs that may be related to the mood and mental status in patients affected by bipolar disorder. In particular we explored the autonomic nervous system through the analysis of the heart rate variability. Many different parameters, in the time and in the frequency domain, linear and non-linear were evaluated during the sleep in a group of normal subject and in one patient in four different conditions. The recording of the signals was performed through a wearable sensorized T-shirt. Heart rate variability (HRV) signal and movement analysis allowed also obtaining sleep staging and the estimation of REM sleep percentage over the total sleep time. A group of eight normal females constituted the control group, on which normality ranges were estimated. The pathologic subject was recorded during four different nights, at time intervals of at least 1 week, and during different phases of the disturbance. Some of the examined parameters (MEANNN, SDNN, RMSSD) confirmed reduced HRV in depression and bipolar disorder. REM sleep percentage was found to be increased. Lempel–Ziv complexity and sample entropy, on the other hand, seem to correlate with the depression level. Even if the number of examined subjects is still small, and the results need further validation, the proposed methodology and the calculated parameters seem promising tools for the monitoring of mood changes in psychiatric disorders. PMID:22291638

Radiological Study of the Carotid-Clival Window and Its Application in Endoscopic Endonasal Expanded Approaches.

PubMed

Pérez de San Román-Mena, Laila; Simal-Julián, Juan Antonio; Miranda-Lloret, Pablo; Sanromán-Álvarez, Pablo; Botella-Asunción, Carlos

2017-08-01

The surgical approach to the petrous apex (PA) and petroclival junction (PCJ) remains a challenge. The carotid-clival window (CCW) represents the widest window available to approach the PCJ from a mediolateral endoscopic route. Here we define the CCW radiologically in nonpathological conditions, to establish the anatomic variability of the PCJ, relate this variability to pneumatization patterns, and evaluate some technical concerns conditioned by the CCW. This was an analytical study of 10 multislice computed tomography scans from patients without SB pathology. Bilateral measures were taken at the roof and floor levels of the lacerum canal (LC) and its posterior projection over the PCJ (segments DE and QR). All measures were compared across different pneumatization patterns. The DE and QR lengths were found to be the most important measures affecting the width of the CCW. Wide variability was observed, with a mean DE length of 8.52 mm (range, 2.4-12.8 mm) at the LC floor level and a mean QR length of 9.11 mm (range, 4.3-13.1 mm) at the LC roof level. The presence of retrocarotid pneumatization was statistically significantly associated with longer DE and QR segments. No differences were found among other pneumatization patterns. The CCW varies widely among individuals. The presence of pneumatization behind the paraclival carotid represents an advantageous characteristic when planning an endoscopic approach to the PCJ. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparing Two Methods for Reducing Variability in Voice Quality Measurements

ERIC Educational Resources Information Center

Kreiman, Jody; Gerratt, Bruce R.

2011-01-01

Purpose: Interrater disagreements in ratings of quality plague the study of voice. This study compared 2 methods for handling this variability. Method: Listeners provided multiple breathiness ratings for 2 sets of pathological voices, one including 20 male and 20 female voices unselected for quality and one including 20 breathy female voices.…

A Novel Feature Level Fusion for Heart Rate Variability Classification Using Correntropy and Cauchy-Schwarz Divergence.

PubMed

Goshvarpour, Ateke; Goshvarpour, Atefeh

2018-04-30

Heart rate variability (HRV) analysis has become a widely used tool for monitoring pathological and psychological states in medical applications. In a typical classification problem, information fusion is a process whereby the effective combination of the data can achieve a more accurate system. The purpose of this article was to provide an accurate algorithm for classifying HRV signals in various psychological states. Therefore, a novel feature level fusion approach was proposed. First, using the theory of information, two similarity indicators of the signal were extracted, including correntropy and Cauchy-Schwarz divergence. Applying probabilistic neural network (PNN) and k-nearest neighbor (kNN), the performance of each index in the classification of meditators and non-meditators HRV signals was appraised. Then, three fusion rules, including division, product, and weighted sum rules were used to combine the information of both similarity measures. For the first time, we propose an algorithm to define the weights of each feature based on the statistical p-values. The performance of HRV classification using combined features was compared with the non-combined features. Totally, the accuracy of 100% was obtained for discriminating all states. The results showed the strong ability and proficiency of division and weighted sum rules in the improvement of the classifier accuracies.

Aggregates, Crystals, Gels, and Amyloids: Intracellular and Extracellular Phenotypes at the Crossroads of Immunoglobulin Physicochemical Property and Cell Physiology

PubMed Central

2013-01-01

Recombinant immunoglobulins comprise an important class of human therapeutics. Although specific immunoglobulins can be purposefully raised against desired antigen targets by various methods, identifying an immunoglobulin clone that simultaneously possesses potent therapeutic activities and desirable manufacturing-related attributes often turns out to be challenging. The variable domains of individual immunoglobulins primarily define the unique antigen specificities and binding affinities inherent to each clone. The primary sequence of the variable domains also specifies the unique physicochemical properties that modulate various aspects of individual immunoglobulin life cycle, starting from the biosynthetic steps in the endoplasmic reticulum, secretory pathway trafficking, secretion, and the fate in the extracellular space and in the endosome-lysosome system. Because of the diverse repertoire of immunoglobulin physicochemical properties, some immunoglobulin clones' intrinsic properties may manifest as intriguing cellular phenotypes, unusual solution behaviors, and serious pathologic outcomes that are of scientific and clinical importance. To gain renewed insights into identifying manufacturable therapeutic antibodies, this paper catalogs important intracellular and extracellular phenotypes induced by various subsets of immunoglobulin clones occupying different niches of diverse physicochemical repertoire space. Both intrinsic and extrinsic factors that make certain immunoglobulin clones desirable or undesirable for large-scale manufacturing and therapeutic use are summarized. PMID:23533417

Impaired Decisional Impulsivity in Pathological Videogamers

PubMed Central

Irvine, Michael A.; Worbe, Yulia; Bolton, Sorcha; Harrison, Neil A.; Bullmore, Edward T.; Voon, Valerie

2013-01-01

Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management. PMID:24146789

Evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy.

PubMed

Sebagh, Mylène; Allard, Marc-Antoine; Bosselut, Nelly; Dao, Myriam; Vibert, Eric; Lewin, Maïté; Lemoine, Antoinette; Cherqui, Daniel; Adam, René; Sa Cunha, Antonio

2016-04-19

In patients receiving preoperative chemotherapy, colorectal liver metastases (CLM) are expected to demonstrate a similar behaviour because of similar organ microenvironment and tumour cell chemosensitivity. We focused on the occurrence of pathological and genetic heterogeneity within CLM. Patients resected for multiple CLM between 2004 and 2011 after > three cycles of chemotherapy were included. Pathological heterogeneity was arbitrarily defined as a > 50% difference in the percentage of remaining tumour cells between individual CLM. In patients with pathological heterogeneity, the mutational genotyping (KRAS, NRAS, BRAF and PIK3CA) was determined from the most heterogeneous CLM. Pathological heterogeneity was observed in 31 of 157 patients with multiple CLM (median = 4, range, 2-32) (19.7%). In 72.4% of them, we found a concordance of the mutation status between the paired CLM: both wild-type in 55%, and both mutated in 17.2%. We observed a discordance of the mutation status of 27.6% between CLM: one mutated and the other wild-type. The mutated CLM was the less florid one in 75% of patients with genetic heterogeneity. Pathological heterogeneity is present in 19.7% of patients with multiple CLM. Genetic heterogeneity is present in 27.6% of patients with pathological heterogeneity. Heterogeneity could refine guide management for tissue sampling.

Analyses related to the development of DSM-5 criteria for substance use related disorders: 3. An assessment of Pathological Gambling criteria.

PubMed

Denis, Cécile; Fatséas, Mélina; Auriacombe, Marc

2012-04-01

The DSM-5 Substance-Related Disorders Work Group proposed to include Pathological Gambling within the current Substance-Related Disorders section. The objective of the current report was to assess four possible sets of diagnostic criteria for Pathological Gambling. Gamblers (N=161) were defined as either Pathological or Non-Pathological according to four classification methods. (a) Option 1: the current DSM-IV criteria for Pathological Gambling; (b) Option 2: dropping the "Illegal Acts" criterion, while keeping the threshold at 5 required criteria endorsed; (c) Option 3: the proposed DSM-5 approach, i.e., deleting "Illegal Acts" and lowering the threshold of required criteria from 5 to 4; (d) Option 4: to use a set of Pathological Gambling criteria modeled on the DSM-IV Substance Dependence criteria. Cronbach's alpha and eigenvalues were calculated for reliability, Phi, discriminant function analyses, correlations and multivariate regression models were performed for validity and kappa coefficients were calculated for diagnostic consistency of each option. All criteria sets were reliable and valid. Some criteria had higher discriminant properties than others. The proposed DSM-5 criteria in Options 2 and 3 performed well and did not appear to alter the meanings of the diagnoses of Pathological Gambling from DSM-IV. Future work should further explore if Pathological Gambling might be assessed using the same criteria as those used for Substance Use Disorders. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Automated extraction of Biomarker information from pathology reports.

PubMed

Lee, Jeongeun; Song, Hyun-Je; Yoon, Eunsil; Park, Seong-Bae; Park, Sung-Hye; Seo, Jeong-Wook; Park, Peom; Choi, Jinwook

2018-05-21

Pathology reports are written in free-text form, which precludes efficient data gathering. We aimed to overcome this limitation and design an automated system for extracting biomarker profiles from accumulated pathology reports. We designed a new data model for representing biomarker knowledge. The automated system parses immunohistochemistry reports based on a "slide paragraph" unit defined as a set of immunohistochemistry findings obtained for the same tissue slide. Pathology reports are parsed using context-free grammar for immunohistochemistry, and using a tree-like structure for surgical pathology. The performance of the approach was validated on manually annotated pathology reports of 100 randomly selected patients managed at Seoul National University Hospital. High F-scores were obtained for parsing biomarker name and corresponding test results (0.999 and 0.998, respectively) from the immunohistochemistry reports, compared to relatively poor performance for parsing surgical pathology findings. However, applying the proposed approach to our single-center dataset revealed information on 221 unique biomarkers, which represents a richer result than biomarker profiles obtained based on the published literature. Owing to the data representation model, the proposed approach can associate biomarker profiles extracted from an immunohistochemistry report with corresponding pathology findings listed in one or more surgical pathology reports. Term variations are resolved by normalization to corresponding preferred terms determined by expanded dictionary look-up and text similarity-based search. Our proposed approach for biomarker data extraction addresses key limitations regarding data representation and can handle reports prepared in the clinical setting, which often contain incomplete sentences, typographical errors, and inconsistent formatting.

Bone marrow failure in childhood: central pathology review of a nationwide registry.

PubMed

Ito, Masafumi

2017-01-01

Refractory cytopenia of childhood (RCC) was proposed as a provisional entity in the 2008 WHO classification of myelodysplastic syndromes (MDS). It is defined as a childhood MDS featuring persistent cytopenia without increase blasts in bone marrow (BM) or peripheral blood (PB). Because the majority of RCC cases feature hypocellularity and pancytopenia, it is quite challenging to differentiate RCC from acquired aplastic anemia (AA) and many kinds of inherited bone marrow failure syndromes (IBMFS). Diagnosis of RCC requires BM histology of characteristic features such as isolated erythroid islet with left shift, abnormal localization and micromegakaryocytes. The Japanese Society of Pediatric Hematology/Oncology has opened the central registry review system since 2009 to evaluate childhood cases of bone marrow failure (BMF). It has reviewed cytology and BM pathology of all registered BMF cases, which number more than 1,700. In the evaluation of BMF, BM pathology is important to assess the mechanism of hematopoiesis. Pathological dysplasia should be differentiated from cytological dysplasia. A central review system is important for rare diseases, such as pediatric BMF. Standardization of pathological diagnosis should be established upon consensus findings, descriptions, and diagnostic approaches. In this review, the pathology of pediatric BMF syndromes is summarized.

Methylene blue does not reverse existing neurofibrillary tangle pathology in the rTg4510 mouse model of tauopathy.

PubMed

Spires-Jones, Tara L; Friedman, Taylor; Pitstick, Rose; Polydoro, Manuela; Roe, Allyson; Carlson, George A; Hyman, Bradley T

2014-03-06

Alzheimer's disease is characterized pathologically by aggregation of amyloid beta into senile plaques and aggregation of pathologically modified tau into neurofibrillary tangles. While changes in amyloid processing are strongly implicated in disease initiation, the recent failure of amyloid-based therapies has highlighted the importance of tau as a therapeutic target. "Tangle busting" compounds including methylene blue and analogous molecules are currently being evaluated as therapeutics in Alzheimer's disease. Previous studies indicated that methylene blue can reverse tau aggregation in vitro after 10 min, and subsequent studies suggested that high levels of drug reduce tau protein levels (assessed biochemically) in vivo. Here, we tested whether methylene blue could remove established neurofibrillary tangles in the rTg4510 model of tauopathy, which develops robust tangle pathology. We find that 6 weeks of methylene blue dosing in the water from 16 months to 17.5 months of age decreases soluble tau but does not remove sarkosyl insoluble tau, or histologically defined PHF1 or Gallyas positive tangle pathology. These data indicate that methylene blue treatment will likely not rapidly reverse existing tangle pathology. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Methylene blue does not reverse existing neurofibrillary tangle pathology in the rTg4510 mouse model of tauopathy

PubMed Central

Spires-Jones, Tara L; Friedman, Taylor; Pitstick, Rose; Polydoro, Manuela; Roe, Allyson; Carlson, George A; Hyman, Bradley T

2014-01-01

Alzheimer's disease is characterized pathologically by aggregation of amyloid beta into senile plaques and aggregation of pathologically modified tau into neurofibrillary tangles. While changes in amyloid processing are strongly implicated in disease initiation, the recent failure of amyloid-based therapies has highlighted the importance of tau as a therapeutic target. “Tangle busting” compounds including methylene blue and analogous molecules are currently being evaluated as therapeutics in Alzheimer's disease. Previous studies indicated that methylene blue can reverse tau aggregation in vitro after 10 minutes, and subsequent studies suggested that high levels of drug reduce tau protein levels (assessed biochemically) in vivo. Here, we tested whether methylene blue could remove established neurofibrillary tangles in the rTg4510 model of tauopathy, which develops robust tangle pathology. We find that 6 weeks of methylene blue dosing in the water from 16 months to 17.5 months of age decreases soluble tau but does not remove sarkosyl insoluble tau, or histologically defined PHF1 or Gallyas positive tangle pathology. These data indicate that methylene blue treatment will likely not rapidly reverse existing tangle pathology. PMID:24462887

[Pathological features of myositis with myositis -specific autoantibodies].

PubMed

Shimizu, Jun; Mimori, Tsuneyo

2014-01-01

Myositis is a heterogeneous group of systemic autoimmune disorders characterized by inflammation of skeletal muscle. Historically, myositis has been defined using clinical features including muscle weakness, skin disease, internal organ involvement, and an association with cancer in adults. From a clinicopathologic approach, myositis has been classified into pathologically distinct subsets, polymyositis, dermatomyositis(DM), necrotizing autoimmune myositis, amyopathic DM, and non-specific myositis. Although the characteristic pathological changes are believed to be important in pathological mechanisms of each subset of myositis, in clinical practices, the percentages of the patients with typical pathological findings are usually not high. On the other hand, with the recent discovery of new myositis-specific autoantibodies (MSAs), it has been revealed that around 60% of patients with IIMs have been shown to have a anti-myositis-specific autoantibody, including anti-synthetase, anti-Mi-2, anti-MDA5, anti-TIF1 and anti-SRP antibodies. Because of striking association between unique MSAs and distinct clinical phenotypes, these antibodies are thought to be important not only for classifications of IIMs, but also as factors involved in the mechanism underlying their pathogenesis. This review reports recent progress in understanding of pathological features of myositis with MSAs.

The validity of the Personality Diagnostic Questionnaire-4 Narcissistic Personality Disorder scale for assessing pathological grandiosity.

PubMed

Hopwood, Christopher J; Donnellan, M Brent; Ackerman, Robert A; Thomas, Katherine M; Morey, Leslie C; Skodol, Andrew E

2013-01-01

Although controversy surrounds the definition and measurement of narcissism, the claim that pathological grandiosity is central to the construct generates little disagreement. Yet representations of pathological grandiosity vary across measures of narcissism, leading to conceptual confusion in the literature. The validity of a DSM-based measure of pathological narcissism, the Personality Diagnostic Questionnaire-4 Narcissistic Personality Disorder scale (PDQ-4 NPD), was evaluated in 1 clinical and 3 nonclinical samples (total N=2,391) for its ability to measure pathological grandiosity. Findings were generally supportive: average scores were higher in the clinical than nonclinical samples and the PDQ-4 NPD scale correlated most strongly with (a) other measures of NPD; (b) other DSM Cluster B personality disorders; (c) traits involving antagonism, hostility, and assertiveness; and (d) interpersonal distress and disaffiliative dominance. However, the low internal consistency of the PDQ-4 NPD scale and unexpected associations with Cluster A and obsessive-compulsive features point to potential psychometric weaknesses with this instrument. These findings are useful for evaluating the PDQ-4 NPD scale and for informing ongoing debates regarding how to define and assess pathological narcissism.

Detailed Analysis of the African Green Monkey Model of Nipah Virus Disease

PubMed Central

Johnston, Sara C.; Briese, Thomas; Bell, Todd M.; Pratt, William D.; Shamblin, Joshua D.; Esham, Heather L.; Donnelly, Ginger C.; Johnson, Joshua C.; Hensley, Lisa E.; Lipkin, W. Ian; Honko, Anna N.

2015-01-01

Henipaviruses are implicated in severe and frequently fatal pneumonia and encephalitis in humans. There are no approved vaccines or treatments available for human use, and testing of candidates requires the use of well-characterized animal models that mimic human disease. We performed a comprehensive and statistically-powered evaluation of the African green monkey model to define parameters critical to disease progression and the extent to which they correlate with human disease. African green monkeys were inoculated by the intratracheal route with 2.5×104 plaque forming units of the Malaysia strain of Nipah virus. Physiological data captured using telemetry implants and assessed in conjunction with clinical pathology were consistent with shock, and histopathology confirmed widespread tissue involvement associated with systemic vasculitis in animals that succumbed to acute disease. In addition, relapse encephalitis was identified in 100% of animals that survived beyond the acute disease phase. Our data suggest that disease progression in the African green monkey is comparable to the variable outcome of Nipah virus infection in humans. PMID:25706617

Attitudes and Beliefs of Pathology Residents Regarding the Subspecialty of Clinical Chemistry: Results of a Survey.

PubMed

Haidari, Mehran; Yared, Marwan; Olano, Juan P; Alexander, C Bruce; Powell, Suzanne Z

2017-02-01

-Previous studies suggest that training in pathology residency programs does not adequately prepare pathology residents to become competent in clinical chemistry. -To define the beliefs of pathology residents in the United States regarding their preparation for practicing clinical chemistry in their career, their attitude toward the discipline, and the attractiveness of clinical chemistry as a career. -The residents of all pathology residency programs in the United States were given the opportunity to participate in an online survey. -Three hundred thirty-six pathology residents responded to the survey. Analysis of the survey results indicates that pathology residents are more likely to believe that their income may be lower if they select a career that has a clinical chemistry focus and that their faculty do not value clinical chemistry as much as the anatomic pathology part of the residency. Residents also report that clinical chemistry is not as enjoyable as anatomic pathology rotations during residency or preferable as a sole career path. A large proportion of residents also believe that they will be slightly prepared or not prepared to practice clinical chemistry by the end of their residency and that they do not have enough background and/or time to learn clinical chemistry during their residency programs to be able to practice this specialty effectively post graduation. -Our survey results suggest that many pathology residents do not have a positive attitude toward clinical chemistry and do not experience a supportive learning environment with an expectation that they will become competent in clinical chemistry with a residency alone.

Systemic Inflammation: Methodological Approaches to Identification of the Common Pathological Process.

PubMed

Zotova, N V; Chereshnev, V A; Gusev, E Yu

2016-01-01

We defined Systemic inflammation (SI) as a "typical, multi-syndrome, phase-specific pathological process, developing from systemic damage and characterized by the total inflammatory reactivity of endotheliocytes, plasma and blood cell factors, connective tissue and, at the final stage, by microcirculatory disorders in vital organs and tissues." The goal of the work: to determine methodological approaches and particular methodical solutions for the problem of identification of SI as a common pathological process. SI can be defined by the presence in plasma of systemic proinflammatory cell stress products-cytokines and other inflammatory mediators, and also by the complexity of other processes signs. We have developed 2 scales: 1) The Reactivity Level scale (RL)-from 0 to 5 points: 0-normal level; RL-5 confirms systemic nature of inflammatory mediator release, and RL- 2-4 defines different degrees of event probability. 2) The SI scale, considering additional criteria along with RL, addresses more integral criteria of SI: the presence of ≥ 5 points according to the SI scale proves the high probability of SI developing. To calculate the RL scale, concentrations of 4 cytokines (IL-6, IL-8, IL-10, TNF-α) and C-reactive protein in plasma were examined. Additional criteria of the SI scale were the following: D-dimers>500ng/ml, cortisol>1380 or <100nmol/l, troponin I≥0.2ng/ml and/or myoglobin≥800ng/ml. 422 patients were included in the study with different septic (n-207) and aseptic (n-215) pathologies. In 190 cases (of 422) there were signs of SI (lethality 38.4%, n-73). In only 5 of 78 cases, lethality was not confirmed by the presence of SI. SI was registered in 100% of cases with septic shock (n-31). There were not significant differences between AU-ROC of CR, SI scale and SOFA to predict death in patients with sepsis and trauma.

Self-Other Knowledge Asymmetries in Personality Pathology

PubMed Central

Carlson, Erika N.; Vazire, Simine; Oltmanns, Thomas F.

2012-01-01

Objective Self-reports of personality provide valid information about personality disorders (PDs). However, informant-reports provide information about PDs that self-reports alone do not provide. The current paper examines if and when one perspective is more valid than the other in identifying PDs. Method Using a representative sample of adults 55 to 65 year of age (N = 991; 45% males), we compared the validity of self- and informant- (e.g., spouse, family, or friend) reports of the FFM traits in predicting PD scores (i.e., composite of interviewer, self-, and informant-reports of PDs). Results Self-reports (particularly of neuroticism) were more valid than informant-reports for most internalizing PDs (i.e., PDs defined by high neuroticism). Informant-reports (particularly of agreeableness and conscientiousness) were more valid than self-reports for externalizing and/or antagonistic PDs (i.e., PDs defined by low agreeableness, conscientiousness). Neither report was consistently more valid for thought disorder PDs (i.e., PDs defined by low extraversion). However, informant-reports (particularly of agreeableness) were more valid than self-reports for PDs that were both internalizing and externalizing (i.e., PDs defined by high neuroticism and low agreeableness). Conclusions The intrapersonal and interpersonal manifestations of PDs differ, and these differences influence who knows more about pathology. PMID:22583054

Assessing the Optimal Timing for Early Salvage Radiation Therapy in Patients with Prostate-specific Antigen Rise After Radical Prostatectomy.

PubMed

Fossati, Nicola; Karnes, R Jeffrey; Cozzarini, Cesare; Fiorino, Claudio; Gandaglia, Giorgio; Joniau, Steven; Boorjian, Stephen A; Goldner, Gregor; Hinkelbein, Wolfgang; Haustermans, Karin; Tombal, Bertrand; Shariat, Shahrokh; Karakiewicz, Pierre I; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas; Briganti, Alberto

2016-04-01

Early salvage radiation therapy (eSRT) represents a treatment option for patients who experience a prostate-specific antigen (PSA) rise after radical prostatectomy (RP); however, the optimal PSA level for eSRT administration is still unclear. To test the impact of PSA level on cancer control after eSRT according to pathologic tumour characteristics. The study included 716 node-negative patients with undetectable postoperative PSA who experienced a PSA rise after RP. All patients received eSRT, defined as local radiation to the prostate and seminal vesicle bed, delivered at PSA ≤ 0.5 ng/ml. Biochemical recurrence (BCR) after eSRT was defined as two consecutive PSA values ≥ 0.2 ng/ml. Multivariable Cox regression analysis tested the association between pre-eSRT PSA level and BCR after eSRT. Covariates consisted of pathologic stage (pT2 vs pT3a vs pT3b or higher), pathologic Gleason score (≤ 6, 7, or ≥ 8), and surgical margin status (negative vs positive). We tested an interaction with PSA level and baseline pathologic risk for the hypothesis that BCR-free survival differed by pre-eSRT PSA level. Three pathologic risk factors were identified: pathologic stage pT3b or higher, pathologic Gleason score ≥ 8, and negative surgical margins. Median follow-up among patients who did not experience BCR after eSRT was 57 mo (interquartile range: 27-105). At 5 yr after eSRT, BCR-free survival rate was 82% (95% confidence interval [CI], 78-85). At multivariable Cox regression analysis, pre-eSRT PSA level was significantly associated with BCR after eSRT (hazard ratio: 4.89; 95% CI, 1.40-22.9; p < 0.0001). When patients were stratified according to the number of risk factors at final pathology, patients with at least two pathologic risk factors showed an increased risk of 5-yr BCR as high as 10% per 0.1 ng/ml of PSA level compared with only 1.5% in patients with one or no pathologic risk factors. In this retrospective study, cancer control after eSRT greatly depended on pretreatment PSA. The absolute PSA level had a different prognostic value depending on the pathologic characteristics of the tumour. In patients with more adverse pathologic features, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Conversely, the benefit of eSRT was less evident in men with favourable disease at RP. In this retrospective study, cancer control after early salvage radiation therapy (eSRT) was influenced by pretreatment prostate-specific antigen (PSA) level. This effect was highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥ 8, and negative surgical margins. In these patients, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Cognitive distortions, anxiety, and depression among regular and pathological gambling online poker players.

PubMed

Barrault, Servane; Varescon, Isabelle

2013-03-01

The aims were to assess cognitive distortions and psychological distress (anxiety and depression) among online poker players of different levels of gambling intensity (non-pathological gamblers [NPG], problem gamblers [PbG], and pathological gamblers [PG]), and to examine the relationship between these variables and gambling pathology. Overall, 245 regular online poker players recruited on an Internet forum completed online self-report scales assessing pathological gambling (South Oaks Gambling Screen [SOGS]), psychological distress (Hospital Anxiety and Depression Scale [HADS]) and cognitive distortions (Gambling-Related Cognition Scale). Based on their SOGS scores, poker players were ranked into three groups: NPG (n=146), PbG (n=55), and PG (n=44). All poker players appeared to be more anxious than depressive. PG exhibited higher levels of depression and anxiety than did PbG and NPG. Cognitive distortions also significantly discriminated PG from PbG and NPG. A regression model showed that the perceived inability to stop gambling, the illusion of control, depression (HADS D), and anxiety were good predictors for pathological gambling among poker players. Our results suggest that cognitive distortions play an important role in the development and maintenance of gambling pathology. This study also underlines the role of anxiety and depression in pathological gambling among poker players. It seems relevant to take these elements into account in the research, prevention, and treatment of pathological gambling poker players.

Wives of pathological gamblers: personality traits, depressive symptoms and social adjustment.

PubMed

Mazzoleni, Maria Helena B; Gorenstein, Clarice; Fuentes, Daniel; Tavares, Hermano

2009-12-01

Wives of pathological gamblers tend to endure long marriages despite financial and emotional burden. Difficulties in social adjustment, personality psychopathology, and comorbidity with psychiatric disorders are pointed as reasons for remaining on such overwhelming relationships. The goal was to examine the social adjustment, personality and negative emotionality of wives of pathological gamblers. The sample consisted of 25 wives of pathological gamblers, mean age 40.6, SD = 9.1 from a Gambling Outpatient Unit and at GAM-ANON, and 25 wives of non-gamblers, mean age 40.8, SD = 9.1, who answered advertisements placed at the Universidade de São Paulo hospital and medical school complex. They were selected in order to approximately match demographic characteristics of the wives of pathological gamblers. Subjects were assessed by the Social Adjustment Scale, Temperament and Character Inventory, Beck Depression Inventory and State-Trait Anxiety Inventory. Three variables remained in the final Multiple Logistic Regression model, wives of pathological gamblers presented greater dissatisfaction with their marital bond, and higher scores on Reward Dependence and Persistence temperament factors. Both, Wives of pathological gamblers and wives of non-gamblers presented well-structured character factors excluding personality disorders. This personality profile may explain wives of pathological gamblers emotional resilience and their marriage longevity. Co-dependence and other labels previously used to describe them may work as a double edged sword, legitimating wives of pathological gamblers problems, while stigmatizing them as inapt and needy.

Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach

PubMed Central

Blanco-Calvo, Moisés; Concha, Ángel; Figueroa, Angélica; Garrido, Federico; Valladares-Ayerbes, Manuel

2015-01-01

Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity. Thus, with the increasing available information of inter-tumor and intra-tumor heterogeneity, the classical pathological approach is being displaced in favor of novel molecular classifications. In the present article, we summarize the most relevant proposals of molecular classifications obtained from the analysis of colorectal tumors using powerful high throughput techniques and devices. We also discuss the role that cancer systems biology may play in the integration and interpretation of the high amount of data generated and the challenges to be addressed in the future development of precision oncology. In addition, we review the current state of implementation of these novel tools in the pathological laboratory and in clinical practice. PMID:26084042

Pro: 'The usefulness of biomarkers in glomerular diseases'. The problem: moving from syndrome to mechanism--individual patient variability in disease presentation, course and response to therapy.

PubMed

Mariani, Laura H; Kretzler, Matthias

2015-06-01

The diagnosis and treatment decisions in glomerular disease are principally based on renal pathology and nonspecific clinical laboratory measurements such as serum creatinine and urine protein. Using these classification approaches, patients have marked variability in rate of progression and response to therapy, exposing a significant number of patients to toxicity without benefit. Additionally, clinical trials are at risk of not being able to detect an efficacious therapy in relevant subgroups as patients with shared clinical-pathologic diagnoses have heterogeneous underlying pathobiology. To change this treatment paradigm, biomarkers that reflect the molecular mechanisms underlying the clinical-pathologic diagnoses are needed. Recent progress to identify such biomarkers has been aided by advances in molecular profiling, large-scale data generation and multi-scalar data integration, including prospectively collected clinical data. This article reviews the evolving success stories in glomerular disease biomarkers across the genotype-phenotype continuum and highlights opportunities to transition to precision medicine in glomerular disease. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Military sexual trauma as a determinant in the development of mental and physical illness in male and female veterans.

PubMed

O'Brien, Betsy S; Sher, Leo

2013-01-01

Military Sexual Trauma (MST) is defined as sexual harassment and or sexual assault experienced by a military service member. It is much more widespread and common than reported. It is associated with pre-combat traumatic experiences and pathologic sequelae including mental and medical illness. An electronic search of the major behavioral science databases was conducted to retrieve studies detailing the social, epidemiological and clinical characteristics of MST and its relationship to psychiatric and medical illness. Studies indicate that military sexual trauma is related to an increase in psychiatric pathology, including posttraumatic stress disorder (PTSD), substance abuse and dependence, depression, anxiety, eating disorders and suicidal behavior. MST is also related to an increase in medical illness, primarily pain-related symptoms involving multiple organ systems, including gastrointestinal, neurological, genitourinary and musculoskeletal. MST is associated with an increased prevalence of mental and physical illness. Although there are some gender differences in the reported rates of MST and there may be some variables, such as prior traumatic experiences, that may make an individual more vulnerable to the psychiatric and medical sequela of MST, it is clear that MST is a major healthcare issue that affects both sexes and warrants further attention and an increase in clinical resources devoted to it. Some preventive measures for decreasing the prevalence of MST may include increasing education and legal prosecution of perpetrators in the military, and increasing access to mental health services for individuals who have suffered from MST.

Linking Essential Tremor to the Cerebellum-Neuroimaging Evidence.

PubMed

Cerasa, Antonio; Quattrone, Aldo

2016-06-01

Essential tremor (ET) is the most common pathological tremor disorder in the world, and post-mortem evidence has shown that the cerebellum is the most consistent area of pathology in ET. In the last few years, advanced neuroimaging has tried to confirm this evidence. The aim of the present review is to discuss to what extent the evidence provided by this field of study may be generalised. We performed a systematic literature search combining the terms ET with the following keywords: MRI, VBM, MRS, DTI, fMRI, PET and SPECT. We summarised and discussed each study and placed the results in the context of existing knowledge regarding the cerebellar involvement in ET. A total of 51 neuroimaging studies met our search criteria, roughly divided into 19 structural and 32 functional studies. Despite clinical and methodological differences, both functional and structural imaging studies showed similar findings but without defining a clear topography of neurodegeneration. Indeed, the vast majority of studies found functional and structural abnormalities in several parts of the anterior and posterior cerebellar lobules, but it remains to be established to what degree these neural changes contribute to clinical symptoms of ET. Currently, advanced neuroimaging has confirmed the involvement of the cerebellum in pathophysiological processes of ET, although a high variability in results persists. For this reason, the translation of this knowledge into daily clinical practice is again partially limited, although new advanced multivariate neuroimaging approaches (machine-learning) are proving interesting changes of perspective.

[Relationship between the ankle-arm index determined by Doppler ultrasonography and cardiovascular outcomes and amputations, in a group of patients with type 2 diabetes mellitus from the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán].

PubMed

Miranda Garduño, Luis Miguel; Bermúdez Rocha, Rocío; Gómez Pérez, Francisco J; Aguilar Salinas, Carlos A

2011-01-01

An ankle/arm index < 0.90 and ≥ 1.41 is considered as abnormal. This study was aimed to investigate the prevalence of peripheral arterial disease through the identification of the ankle/arm index using Doppler ultrasound, and the possible association between pathological ankle/arm index and the micro- and macrovascular complications of diabetes and amputation. The ankle/arm index was determined in outpatient type 2 diabetic subjects. There were the following variables: age and cardiovascular outcomes. To find if the ankle/arm index is related to the cardiovascular outcomes or with the presence of micro- or macrovascular complications we determined the index of correlation of Pearson and also used logistic regression methods to analyze the association between ankle/arm index with the categorical variables. We calculated the ankle/arm index in 242 patients. The prevalence of ischemic ankle/arm index (< 0.90) was 13.6%. The Pearson correlation coefficient for ankle/arm index pathological and cardiovascular outcomes was 0.180 (p = 0.005), amputation 0.130 (p < 0.05), retinopathy 0.132 (p < 0.05), and nephropathy 0.158 (p = 0.01). In logistic regression analysis, the factors associated with pathological ankle/arm index were age > 51 years, cardiovascular outcomes, and amputation. With the Mann Whitney U test we found that a relationship exists between pathological and amputation iliotibial band (p < 0.05). Diabetic patients have a high prevalence of pathological ankle/arm index.

Two-phase computed tomography study of warthin tumor of parotid gland: differentiation from other parotid gland tumors and its pathologic explanation.

PubMed

Woo, Seung Hoon; Choi, Dae-Seob; Kim, Jin-pyeong; Park, Jung Je; Joo, Yeon Hee; Chung, Phil-Sang; Kim, Bo-Young; Ko, Young-Hyeh; Jeong, Han-Sin; Kim, Hyung-Jin

2013-01-01

The objective of this study was to define the radiological characteristics of 2-phase computed tomography (CT) of parotid gland Warthin tumors (WTs) with a pathologic basis for these findings. We prospectively enrolled 116 patients with parotid gland tumor who underwent preoperative 2-phase CT scans(scanning delays of 30 and 120 seconds). The attenuation changes and enhancement patterns were analyzed according to pathology. We also evaluated size-matched samples of WTs and pleomorphic adenoma by staining CD31, vascular endothelial growth factor-receptor 2, collagen IV, and smooth muscle actin. Computed tomography numbers in WTs were significantly higher than those in other tumors in early-phase scans and lower in delayed scans. Pathologically, CD31(+) blood vessel area was significantly higher in WTs than in pleomorphic adenomas. In addition, WTs had an extensive capillary network and many leaky blood vessels. The enhancement pattern of early fill-in and early washout is the typical finding of WTs on 2-phase CT scans, which may be attributed pathologically to abundant blood vessel and extensive capillary network.

The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics.

PubMed

Pritchard, Susanne M; Dolan, Philip J; Vitkus, Alisa; Johnson, Gail V W

2011-08-01

It has been almost 25 years since the initial discovery that tau was the primary component of the neurofibrillary tangles (NFTs) in Alzheimer disease (AD) brain. Although AD is defined by both β-amyloid (Aβ) pathology (Aβ plaques) and tau pathology (NFTs), whether or not tau played a critical role in disease pathogenesis was a subject of discussion for many years. However, given the increasing evidence that pathological forms of tau can compromise neuronal function and that tau is likely an important mediator of Aβ toxicity, there is a growing awareness that tau is a central player in AD pathogenesis. In this review we begin with a brief history of tau, then provide an overview of pathological forms of tau, followed by a discussion of the differential degradation of tau by either the proteasome or autophagy and possible mechanisms by which pathological forms of tau may exert their toxicity. We conclude by discussing possible avenues for therapeutic intervention based on these emerging themes of tau's role in AD. © 2011 The Authors Journal compilation © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Gambling

PubMed Central

Potenza, Marc N; Fiellin, David A; Heninger, George R; Rounsaville, Bruce J; Mazure, Carolyn M

2002-01-01

Over the past several decades, and particularly during the last 10 to 15 years, there has been a rapid increase in the accessibility of legalized gambling in the United States and other parts of the world. Few studies have systematically explored the relationships between patterns of gambling and health status. Existing data support the notion that some gambling behaviors, particularly problem and pathological gambling, are associated with nongambling health problems. The purpose of this article is to provide a perspective on the relationship between gambling behaviors and substance use disorders, review the data regarding health associations and screening and treatment options for problem and pathological gambling, and suggest a role for generalist physicians in assessing problem and pathological gambling. A rationale for conceptualization of pathological gambling as an addictive disorder and a model proposing stress as a possible mediating factor in the relationship between gambling and health status are presented. More research is needed to investigate directly the biological and health correlates associated with specific types of gambling behaviors and to define the role for generalist physicians in the prevention and treatment of problem and pathological gambling. PMID:12220370

How the shapes of seeds can influence pathology.

PubMed

Melki, Ronald

2018-01-01

It is widely accepted that the loss of function of different cellular proteins following their aggregation into highly stable aggregates or the gain of pathologic function of the resulting macromolecular assemblies or both processes are tightly associated to distinct debilitating neurodegenerative diseases such as Alzheimer's, Parkinson's, Creutzfeldt-Jacob, Amyotrophic Lateral Sclerosis and Huntington's diseases. How the aggregation of one given protein leads to distinct diseases is unclear. Here, a structural-molecular explanation based on the ability of proteins such as α-synuclein or tau to form assemblies that differ by their intrinsic architecture, stability, seeding capacity, and surfaces is proposed to account for distinct synucleinopathies and tauopathies. The shape and surfaces of the seeds is proposed to define at the same time their seeding capacity, interactome and tropism for defined neuronal cells within the central nervous system. Copyright © 2017 Elsevier Inc. All rights reserved.

Inherited and acquired disorders of myelin: the underling myelin pathology

PubMed Central

Duncan, Ian D.; Radcliff, Abigail B.

2016-01-01

Remyelination is a major therapeutic goal in human myelin disorders, serving to restore function to demyelinated axons and providing neuroprotection. The target disorders that might be amenable to the promotion of this repair process are diverse and increasing in number. They range primarily from those of genetic, inflammatory to toxic origin. In order to apply remyelinating strategies to these disorders, it is essential to know whether the myelin damage results from a primary attack on myelin or the oligodendrocyte or both, and whether indeed these lead to myelin breakdown and demyelination. In some disorders, myelin sheath abnormalities are prominent but demyelination does not occur. This review explores the range of human and animal disorders where myelin pathology exists and focusses on defining the myelin changes in each and their cause, to help define whether they are targets for myelin repair therapy. PMID:27068622

Deaf: A Concept Analysis From a Cultural Perspective Using the Wilson Method of Concept Analysis Development.

PubMed

Pendergrass, Kathy M; Newman, Susan D; Jones, Elaine; Jenkins, Carolyn H

2017-07-01

The purpose of this article is to provide an analysis of the concept Deaf to increase health care provider (HCP) understanding from a cultural perspective. Deaf signers, people with hearing loss who communicate primarily in American Sign Language (ASL), generally define the term Deaf as a cultural heritage. In the health care setting, the term deaf is most often defined as a pathological condition requiring medical intervention. When HCPs are unaware that there are both cultural and pathological views of hearing loss, significant barriers may exist between the HCP and the Deaf individual. The concept of Deaf is analyzed using the Wilsonian method. Essential elements of the concept "Deaf" from a cultural perspective include a personal choice to communicate primarily in ASL and identify with the Deaf community. Resources for HCPs are needed to quickly identify Deaf signers and provide appropriate communication.

[Medical indications for acupuncture: Systematic review].

PubMed

Muñoz-Ortego, Juan; Solans-Domènech, Maite; Carrion, Carme

2016-09-16

Acupuncture is a medical procedure with a very wide range of indications according to the WHO. However the indications require robust scientific evidence to support them. We have conducted a systematic review (2010-2015) in order to define in which pathologies acupuncture can be an effective strategy, STRICTA criteria that aim to set up acupuncture clinical trials standard criteria were defined in 2010. Only systematic reviews and meta-analyses of good or very good methodological quality according to SIGN criteria were selected. Its main objective was to evaluate the effectiveness of acupuncture in the management of any disease. Most of the final 31 selected reviews focus on chronic pain-related diseases, mainly in the disciplines of Neurology, Orthopaedics and Rheumatology. Current evidence supports the use of acupuncture in the treatment of headaches, migraines, back pain, cervical pain and osteoarthritis. The remaining pathologies still require further good quality studies. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Examination of changes in pathology tests ordered by Diagnosis-Related Group (DRGs) following CPOE introduction.

PubMed

Vecellio, Elia; Georgiou, Andrew; Toouli, George; Eigenstetter, Alex; Li, Ling; Wilson, Roger; Westbrook, Johanna I

2013-01-01

Electronic test ordering, via the Electronic Medical Record (EMR), which incorporates computerised provider order entry (CPOE), is widely considered as a useful tool to support appropriate pathology test ordering. Diagnosis-related groups (DRGs) are clinically meaningful categories that allow comparisons in pathology utilisation by patient groups by controlling for many potentially confounding variables. This study used DRG data linked to pathology test data to examine changes in rates of test ordering across four years coinciding with the introduction of an EMR in six hospitals in New South Wales, Australia. This method generated a list of high pathology utilisation DRGs. We investigated patients with a Chest pain DRG to examine whether tests rates changed for specific test groups by hospital emergency department (ED) pre- and post-EMR. There was little change in testing rates between EDs or between time periods pre- and post-EMR. This is a valuable method for monitoring the impact of EMR and clinical decision support on test order rates.

Spatiotemporal movement variability in ALS: Speaking rate effects on tongue, lower lip, and jaw motor control

PubMed Central

Kuruvilla-Dugdale, Mili; Mefferd, Antje

2017-01-01

Purpose Although it is frequently presumed that bulbar muscle degeneration in Amyotrophic Lateral Sclerosis (ALS) is associated with progressive loss of speech motor control, empirical evidence is limited. Furthermore, because speaking rate slows with disease progression and rate manipulations are used to improve intelligibility in ALS, this study sought to (i) determine between and within-group differences in articulatory motor control as a result of speaking rate changes and (ii) identify the strength of association between articulatory motor control and speech impairment severity. Method Ten talkers with ALS and 11 healthy controls repeated the target sentence at habitual, fast, and slow rates. The spatiotemporal variability index (STI) was calculated to determine tongue, lower lip, and jaw movement variability. Results During habitual speech, talkers with mild-moderate dysarthria displayed significantly lower tongue and lip movement variability whereas those with severe dysarthria showed greater variability compared to controls. Within-group rate effects were significant only for talkers with ALS. Specifically, lip and tongue movement variability significantly increased during slow speech relative to habitual and fast speech. Finally, preliminary associations between speech impairment severity and movement variability were moderate to strong in talkers with ALS. Conclusion Between-group differences for habitual speech and within-group effects for slow speech replicated previous findings for lower lip and jaw movements. Preliminary findings of moderate to strong associations between speech impairment severity and STI suggest that articulatory variability may vary from pathologically low (possibly indicating articulatory compensation) to pathologically high variability (possibly indicating loss of control) with dysarthria progression in ALS. PMID:28528293

Classification and regression tree (CART) analysis of endometrial carcinoma: Seeing the forest for the trees.

PubMed

Barlin, Joyce N; Zhou, Qin; St Clair, Caryn M; Iasonos, Alexia; Soslow, Robert A; Alektiar, Kaled M; Hensley, Martee L; Leitao, Mario M; Barakat, Richard R; Abu-Rustum, Nadeem R

2013-09-01

The objectives of the study are to evaluate which clinicopathologic factors influenced overall survival (OS) in endometrial carcinoma and to determine if the surgical effort to assess para-aortic (PA) lymph nodes (LNs) at initial staging surgery impacts OS. All patients diagnosed with endometrial cancer from 1/1993-12/2011 who had LNs excised were included. PALN assessment was defined by the identification of one or more PALNs on final pathology. A multivariate analysis was performed to assess the effect of PALNs on OS. A form of recursive partitioning called classification and regression tree (CART) analysis was implemented. Variables included: age, stage, tumor subtype, grade, myometrial invasion, total LNs removed, evaluation of PALNs, and adjuvant chemotherapy. The cohort included 1920 patients, with a median age of 62 years. The median number of LNs removed was 16 (range, 1-99). The removal of PALNs was not associated with OS (P=0.450). Using the CART hierarchically, stage I vs. stages II-IV and grades 1-2 vs. grade 3 emerged as predictors of OS. If the tree was allowed to grow, further branching was based on age and myometrial invasion. Total number of LNs removed and assessment of PALNs as defined in this study were not predictive of OS. This innovative CART analysis emphasized the importance of proper stage assignment and a binary grading system in impacting OS. Notably, the total number of LNs removed and specific evaluation of PALNs as defined in this study were not important predictors of OS. Copyright © 2013 Elsevier Inc. All rights reserved.

Dynamic Responses of Intact Post Mortem Human Surrogates from Inferior-to-Superior Loading at the Pelvis.

PubMed

Yoganandan, Narayan; Moore, Jason; Arun, Mike W J; Pintar, Frank A

2014-11-01

During certain events such as underbody blasts due to improvised explosive devices, occupants in military vehicles are exposed to inferior-to-superior loading from the pelvis. Injuries to the pelvis-sacrum-lumbar spine complex have been reported from these events. The mechanism of load transmission and potential variables defining the migration of injuries between pelvis and or spinal structures are not defined. This study applied inferior-to-superior impacts to the tuberosities of the ischium of supine-positioned five post mortem human subjects (PMHS) using different acceleration profiles, defined using shape, magnitude and duration parameters. Seventeen tests were conducted. Overlay temporal plots were presented for normalized (impulse momentum approach) forces and accelerations of the sacrum and spine. Scatter plots showing injury and non-injury data as a function of peak normalized forces, pulse characteristics, impulse and power, loading rate and sacrum and spine accelerations were evaluated as potential metrics related to pathological outcomes with the focus of examining the role of the pulse characteristics from inferior-to-superior loading of the pelvis-sacrum-lumbar spine complex. Interrelationships were explored between non-fracture and fracture outcomes, and fracture patterns with a focus on migration of injuries from the hip-only to hip and spine to spine-only regions. Observations indicate that injury to the pelvis and or spine from inferior-to-superior loading is associated with pulse and not just peak velocity. The role of the effect of mass recruitment and injury migration parallel knee-thigh-hip complex studies, suggest a wider application of the recruitment concept and the role of the pulse characteristics.

Marketing the pathology practice.

PubMed

Berkowitz, E N

1995-07-01

Effective marketing of the pathology practice is essential in the face of an increasingly competitive market. Successful marketing begins with a market-driven planning process. As opposed to the traditional planning process used in health care organizations, a market-driven approach is externally driven. Implementing a market-driven plan also requires recognition of the definition of the service. Each market to which pathologists direct their service defines the service differently. Recognition of these different service definitions and creation of a product to meet these needs could lead to competitive advantages in the marketplace.

[The significance of electronic CTG for intrauterine volvulus in the 32nd week of gestation].

PubMed

Schiermeier, S; Reinhard, J; Westhof, G; Hatzmann, W

2008-02-01

Intrauterine intestinal volvulus is a difficult diagnosis to make, but has life-threatening implications for the fetus. We present a case of vulvulus without malrotation in a single fetus revealed in the 32nd gestation week in a 44-year-old woman. The presenting complaint of this patient was reduced fetal movements. Ultrasound examination showed a normal result except for a dilated stomach. Doppler ultrasound results were within the normal range. Computed cardiotocography (CTG) showed pathological results for acceleration and suspect values for variability. Short-term variability (STV) was at 2.80 ms. Due to the pathological computed CTG results a Caesarian section was carried out. The newborn received prompt postnatal surgical treatment and continues to be in good overall condition.

[Orthorexia nervosa and adaptation of ORTO-11 into Turkish].

PubMed

Arusoğlu, Gülcan; Kabakçi, Elif; Köksal, Gülden; Merdol, Türkan Kutluay

2008-01-01

Orthorexia is a pathological fixation about the consumption of healthy food. The present study aimed to reveal the psychometric properties of the Turkish version of ORTO-15, which was developed to evaluate orthorexia, and to investigate the relationship betweenorthorexia, and eating attitude, obsessive-compulsive symptoms, and some demographic variables. The study included 994 participants aged between 19 and 66 years. ORTO-15, the Maudsley Obsessive-Compulsive Inventory, and the Eating Attitude Test-40 were administered to the participants. A 3-factor solution with varimax rotation explained 40.62% of the variance. When 4 items with factor loadings below+/- 0.50 were eliminated from ORTO-15, the Cronbach's alpha coefficient was 0.62. The remaining 11 items were thought to have statistically satisfactory properties for the Turkish version of ORTO and were collectively referred to as ORTO-11. This version was used to investigate the relationship between orthorexia, and eating attitude and obsessive-compulsive symptoms. Pathological eating attitude and obsessive-compulsive symptoms were related to orthorexia. Women exhibited more orthorexic symptoms then men. In the present study high a body mass index was an important variable for orthorexia, but only together with gender (female), pathological eating attitude, and increased obsessive-compulsive symptoms. The results, implications, and limitations of the study are discussed. ORTO-11 demonstrated statistically satisfactory properties. Orthorexia was related to pathological eating attitude and obsessive-compulsive symptoms; however, caution should be used when generalizing the reported results.

Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group.

PubMed

Roman, S; Gyawali, C P; Savarino, E; Yadlapati, R; Zerbib, F; Wu, J; Vela, M; Tutuian, R; Tatum, R; Sifrim, D; Keller, J; Fox, M; Pandolfino, J E; Bredenoord, A J

2017-10-01

An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD). Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings. Reflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter-based or wireless pH-monitoring or pH-impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH-impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom-reflux association in the absence of pathological AET defines hypersensitivity to reflux. The consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled. © 2017 John Wiley & Sons Ltd.

Analysis of perceived similarity between pairs of microcalcification clusters in mammograms

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

Wang, Juan; Jing, Hao; Wernick, Miles N.

2014-05-15

Purpose: Content-based image retrieval aims to assist radiologists by presenting example images with known pathology that are visually similar to the case being evaluated. In this work, the authors investigate several fundamental issues underlying the similarity ratings between pairs of microcalcification (MC) lesions on mammograms as judged by radiologists: the degree of variability in the similarity ratings, the impact of this variability on agreement between readers in retrieval of similar lesions, and the factors contributing to the readers’ similarity ratings. Methods: The authors conduct a reader study on a set of 1000 image pairs of MC lesions, in which amore » group of experienced breast radiologists rated the degree of similarity between each image pair. The image pairs are selected, from among possible pairings of 222 cases (110 malignant, 112 benign), based on quantitative image attributes (features) and the results of a preliminary reader study. Next, the authors apply analysis of variance (ANOVA) to quantify the level of variability in the readers’ similarity ratings, and study how the variability in individual reader ratings affects consistency between readers. The authors also measure the extent to which readers agree on images which are most similar to a given query, for which the Dice coefficient is used. To investigate how the similarity ratings potentially relate to the attributes underlying the cases, the authors study the fraction of perceptually similar images that also share the same benign or malignant pathology as the query image; moreover, the authors apply multidimensional scaling (MDS) to embed the cases according to their mutual perceptual similarity in a two-dimensional plot, which allows the authors to examine the manner in which similar lesions relate to one another in terms of benign or malignant pathology and clustered MCs. Results: The ANOVA results show that the coefficient of determination in the reader similarity ratings is 0.59. The variability level in the similarity ratings is proved to be a limiting factor, leading to only moderate correlation between the readers in their readings. The Dice coefficient, measuring agreement between readers in retrieval of similar images, can vary from 0.45 to 0.64 with different levels of similarity for individual readers, but is higher for average ratings from a group of readers (from 0.59 to 0.78). More importantly, the fraction of retrieved cases that match the benign or malignant pathology of the query image was found to increase with the degree of similarity among the retrieved images, reaching average value as high as 0.69 for the radiologists (p-value <10{sup −4} compared to random guessing). Moreover, MDS embedding of all the cases shows that cases having the same pathology tend to cluster together, and that neighboring cases in the plot tend to be similar in their clustered MCs. Conclusions: While individual readers exhibit substantial variability in their similarity ratings, similarity ratings averaged from a group of readers can achieve a high level of intergroup consistency and agreement in retrieval of similar images. More importantly, perceptually similar cases are also likely to be similar in their underlying benign or malignant pathology and image features of clustered MCs, which could be of diagnostic value in computer-aided diagnosis for lesions with clustered MCs.« less

Cost-benefit value of microscopic examination of intervertebral discs.

PubMed

Grzybicki, D M; Callaghan, E J; Raab, S S

1998-09-01

Given the virtual absence of histologically detected, clinically unsuspected disease in intervertebral disc specimens, some authors have advocated that histological examination be discontinued. However, the examination of intervertebral disc specimens remains common practice in most pathology laboratories. No cost-benefit analysis of this practice has been made; therefore, the authors' goal in this study was perform such an analysis. Using the University of Iowa surgical pathology database, 1109 patients who had undergone a laminectomy were identified retrospectively. These cases were classified into four categories based on the patients' preoperative clinical diagnosis and final histopathological diagnosis: insignificant clinical diagnosis/insignificant pathological diagnosis (ICIP), significant clinical diagnosis/insignificant pathological diagnosis (SCIP), significant clinical diagnosis/significant pathological diagnosis (SCSP), and insignificant clinical diagnosis/significant pathological diagnosis (ICSP). A significant clinical diagnosis was defined as one other than a benign, noninfectious indication for laminectomy. A significant pathological diagnosis was a diagnosis other than degenerative changes. The cost-benefit value of performing a histological examination in cases with significant or insignificant clinical diagnoses was examined. The cases were classified as: 1068 ICIP, 17 SCIP, 21 SCSP, and three ICSP. On chart review, in all three cases of ICSP an epidural abscess was identified perioperatively and the subsequent histological diagnosis did not affect patient care. The costs per case of identifying a significant pathological diagnosis with a significant and an insignificant clinical diagnosis were $44.79 and $8811, respectively. Histological examination of intervertebral disc specimens is cost beneficial only if there is a significant preoperative clinical diagnosis.

Pathological narcissism and somatic symptoms among men and women attending an outpatient mental health clinic.

PubMed

Kealy, David; Tsai, Michelle; Ogrodniczuk, John S

2016-09-01

To explore the relationship between types of pathological narcissism and somatic symptoms among psychiatric outpatients. Patients (N = 95) completed measures of somatic symptoms, narcissistic grandiosity and vulnerability, and psychiatric symptoms. Relationships among variables were analysed using t-tests and correlations, controlling for psychiatric distress. Somatic symptoms were positively associated with two types of narcissistic dysfunction. Among women there was a positive association between somatic symptoms and narcissistic vulnerability, but not grandiosity. Among men, somatic symptoms were positively associated with narcissistic grandiosity, but not vulnerability. The connection between narcissistic pathology and somatic symptom severity appears to differ based on gender. Further research is needed to confirm and extend this preliminary finding.

Challenges of multimorbidity of the aging brain: a critical update.

PubMed

Jellinger, Kurt A; Attems, Johannes

2015-04-01

A major problem in elderly patients is the high incidence of multiple pathologies, referred to as multimorbidity, in the aging brain. It has been increasingly recognized that co-occurrence of neurodegenerative proteinopathies and other pathologies including cerebrovascular disorders is a frequent event in the brains of both cognitively intact and impaired aged subjects. Although clinical and neuropathological diagnostic criteria of the major neurodegenerative diseases have been improved, major challenges arise from cerebral multimorbidity, and the thresholds to cause clinical overt dementia are ill defined. More than 80% of aged human brains show neurodegenerative non-Alzheimer type proteinopathies and other pathologies which, however, frequently have been missed clinically and are even difficult to identify at neuropathological examination. Autopsy studies differ in selection criteria and the applied evaluation methods. Therefore, irrespective of the clinical symptoms, the frequency of cerebral pathologies vary considerably: Alzheimer-related pathology is seen in 19-100%, with "pure" Alzheimer's disease (AD) in 17-72%, Lewy pathology in 6-39% (AD + Lewy disease 9-28%), vascular pathologies in 28-93% (10.7-78% "pure" vascular dementia), TDP-43 proteinopathy in 6-39%, hippocampal sclerosis in 8-1%, and mixed pathologies in 10-93%. These data clearly suggest that pathologically deposited proteins in neurodegenerating diseases mutually interact and are influenced by other factors, in particular cardiovascular and cerebrovascular ones, to promote cognitive decline and other clinical symptoms. It is obvious that cognitive and other neuropsychiatric impairment in the aged result from a multimorbid condition in the CNS rather than from a single disease and that the number of complex pathologies progresses with increasing age. These facts have implications for improvement of the clinical diagnosis and prognosis, the development of specific biomarkers, preventive strategies and better treatment of cerebral multimorbidity.

C-Arm Cone-Beam CT-Guided Transthoracic Lung Core Needle Biopsy as a Standard Diagnostic Tool

PubMed Central

Jaconi, Marta; Pagni, Fabio; Vacirca, Francesco; Leni, Davide; Corso, Rocco; Cortinovis, Diego; Bidoli, Paolo; Bono, Francesca; Cuttin, Maria S.; Valente, Maria G.; Pesci, Alberto; Bedini, Vittorio A.; Leone, Biagio E.

2015-01-01

Abstract C-arm cone-beam computed tomography (CT)-guided transthoracic lung core needle biopsy (CNB) is a safe and accurate procedure for the evaluation of patients with pulmonary nodules. This article will focus on the clinical features related to CNB in terms of diagnostic performance and complication rate. Moreover, the concept of categorizing pathological diagnosis into 4 categories, which could be used for clinical management, follow-up, and quality assurance is also introduced. We retrospectively collected data regarding 375 C-arm cone-beam CT-guided CNBs from January 2010 and June 2014. Clinical and radiological variables were evaluated in terms of success or failure rate. Pathological reports were inserted in 4 homogenous groups (nondiagnostic-L1, benign-L2, malignant not otherwise specified-L3, and malignant with specific histotype-L4), defining for each category a hierarchy of suggested actions. The sensitivity, specificity, and positive and negative predictive value and accuracy for patients subjected to CNBs were of 96.8%, 100%, 100%, 100%, and 97.2%, respectively. Roughly 75% of our samples were diagnosed as malignant, with 60% lung adenocarcinoma diagnoses. Molecular analyses were performed on 85 malignant samples to verify applicability of targeted therapy. The rate of “nondiagnostic” samples was 12%. C-arm cone-beam CT-guided transthoracic lung CNB can represent the gold standard for the diagnostic evaluation of pulmonary nodules. A clinical and pathological multidisciplinary evaluation of CNBs was needed in terms of integration of radiological, histological, and oncological data. This approach provided exceptional performances in terms of specificity, positive and negative predictive values; sensitivity in our series was lower compared with other large studies, probably due to the application of strong criteria of adequacy for CNBs (L1 class rate). The satisfactory rate of collected material was evaluated not only in terms of merely diagnostic performances but also for predictive results by molecular analysis. PMID:25816042

European Veterinary Renal Pathology Service: A Survey Over a 7-Year Period (2008-2015).

PubMed

Aresu, L; Martini, V; Benali, S L; Brovida, C; Cianciolo, R E; Dalla Riva, R; Trez, D; Van Der Lugt, J J; Van Dongen, A; Zini, E

2017-09-01

The European Veterinary Renal Pathology Service (EVRPS) is the first Web-based registry for canine renal biopsy specimens in Europe. The aim was to verify whether differences exist between the clinical and laboratory presentation of dogs with nephropathy according to renal pathological findings, as defined by light and electron microscopy of renal biopsy specimens submitted to EVRPS. Renal biopsy specimens of dogs were collected from the archive of the service (n = 254). Cases were included if both light and electron microscopy were available (n = 162). Renal biopsy specimens were classified based on the morphological diagnoses. Thereafter, they were grouped into 3 disease categories, including immune-complex-mediated glomerulonephritis (ICGN), non-immune-complex-mediated GN (non-ICGN), and renal lesions not otherwise specified (RL-NOS). Differences among morphological diagnoses and among disease categories were investigated for clinical and laboratory variables. Serum albumin concentration was lower in dogs with ICGN than in those with non-ICGN (P = 0.006) or RL-NOS (P = 0.000), and the urine protein-to-creatinine ratio (UPC) was significantly higher in ICGN than in the other 2 disease categories. Regarding morphological diagnoses, albumin was significantly lower in amyloidosis (AMY) and membranous (MGN), membranoproliferative (MPGN) or mixed glomerulonephritis (MixGN) than in minimal change disease, primary (FSGS I) or secondary (FSGS II) focal and segmental glomerulosclerosis and juvenile nephropathies (JN). The UPC was higher in MPGN than in FSGS I and FSGS II. Dogs with ICGN, in particular MPGN, had higher protein loss than those with non-ICGN or RL-NOS, leading to more severe hypoalbuminemia. Clinical and laboratory differentiation among dogs with the different morphological diagnoses and among dogs with different disease categories was difficult due to overlapping results. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

C-arm cone-beam CT-guided transthoracic lung core needle biopsy as a standard diagnostic tool: an observational study.

PubMed

Jaconi, Marta; Pagni, Fabio; Vacirca, Francesco; Leni, Davide; Corso, Rocco; Cortinovis, Diego; Bidoli, Paolo; Bono, Francesca; Cuttin, Maria S; Valente, Maria G; Pesci, Alberto; Bedini, Vittorio A; Leone, Biagio E

2015-03-01

C-arm cone-beam computed tomography (CT)-guided transthoracic lung core needle biopsy (CNB) is a safe and accurate procedure for the evaluation of patients with pulmonary nodules. This article will focus on the clinical features related to CNB in terms of diagnostic performance and complication rate. Moreover, the concept of categorizing pathological diagnosis into 4 categories, which could be used for clinical management, follow-up, and quality assurance is also introduced. We retrospectively collected data regarding 375 C-arm cone-beam CT-guided CNBs from January 2010 and June 2014. Clinical and radiological variables were evaluated in terms of success or failure rate. Pathological reports were inserted in 4 homogenous groups (nondiagnostic--L1, benign--L2, malignant not otherwise specified--L3, and malignant with specific histotype--L4), defining for each category a hierarchy of suggested actions. The sensitivity, specificity, and positive and negative predictive value and accuracy for patients subjected to CNBs were of 96.8%, 100%, 100%, 100%, and 97.2%, respectively. Roughly 75% of our samples were diagnosed as malignant, with 60% lung adenocarcinoma diagnoses. Molecular analyses were performed on 85 malignant samples to verify applicability of targeted therapy. The rate of "nondiagnostic" samples was 12%. C-arm cone-beam CT-guided transthoracic lung CNB can represent the gold standard for the diagnostic evaluation of pulmonary nodules. A clinical and pathological multidisciplinary evaluation of CNBs was needed in terms of integration of radiological, histological, and oncological data. This approach provided exceptional performances in terms of specificity, positive and negative predictive values; sensitivity in our series was lower compared with other large studies, probably due to the application of strong criteria of adequacy for CNBs (L1 class rate). The satisfactory rate of collected material was evaluated not only in terms of merely diagnostic performances but also for predictive results by molecular analysis.

Dual-sugar tests of small intestinal permeability are poor predictors of bacterial infections and mortality in cirrhosis: A prospective study.

PubMed

Vogt, Anika; Reuken, Philipp A; Stengel, Sven; Stallmach, Andreas; Bruns, Tony

2016-03-21

To prospectively analyze the impact of increased intestinal permeability (IP) on mortality and the occurrence of infections in patients with cirrhosis. IP was quantified using the lactulose/mannitol (L/M) test in 46 hospitalized patients with cirrhosis (25 Child-Pugh A/B, 21 Child-Pugh C) and in 16 healthy controls. Markers of inflammation [LPS-binding protein, Interleukin-6 (IL-6)] and enterocyte death [intestinal fatty-acid binding protein (I-FABP)] were determined in serum using enzyme-linked immunosorbent assays. Patients were followed for one year and assessed for survival, liver transplantation, the necessity of hospitalization and the occurrence of bacterial infections. The primary endpoint of the study was defined as differences in survival between patients with pathological and without pathological lactulose/mannitol test. Thirty-nine (85%) patients with cirrhosis had a pathologically increased IP index (L/M ratio > 0.07) compared to 4 (25%) healthy controls (P < 0.0001). The IP index correlated with the Child-Pugh score (r = 0.484, P = 0.001) and with serum IL-6 (r = 0.342, P = 0.02). Within one year, nineteen (41%) patients developed a total of 33 episodes of hospitalization with bacterial or fungal infections. Although patients who developed spontaneous bacterial peritonitis (SBP) (n = 7) had a higher IP index than patients who did not (0.27 vs 0.14, P = 0.018), the baseline IP index did not predict time to infection, infection-free survival or overall survival, neither when assessed as linear variable, as tertiles, nor dichotomized using an established cut-off. In contrast, model for end-stage liver disease score, Child-Pugh score, the presence of ascites, serum IL-6 and I-FABP were univariate predictors of infection-free survival. Although increased IP is a frequent phenomenon in advanced cirrhosis and may predispose to SBP, it failed to predict infection-free and overall survival in this prospective cohort study.

Twenty-four-hour ambulatory electrocardiography characterization of heart rhythm in Vipera berus-envenomed dogs.

PubMed

Vestberg, Anna Rave; Tidholm, Anna; Ljungvall, Ingrid

2017-05-03

Vipera berus has a worldwide distribution and causes high morbidity in dogs annually. A complication to envenomation may be cardiac arrhythmias. The purpose of this study was to investigate the prevalence, types, and timing of arrhythmias, using 24-h ambulatory electrocardiography (24-AECG), in dogs bitten by V. berus in the first 24-32 h after envenomation. In addition, this study aimed to investigate if there were differences in selected clinical and hematological- and biochemical variables (including cardiac troponin I) at admission between V. berus-envenomed dogs with and without detected pathologic arrhythmias. Seventeen prospectively recruited client-owned dogs acutely envenomed by V. berus, were therefore examined clinically and echocardiographically, sampled for blood, hospitalized, and monitored by 24-AECG. Clinically significant pathologic arrhythmias in this study were of ventricular origin, such as frequent single ventricular premature contractions (VPCs) and couplets of VPCs, episodes of ventricular tachycardia and idioventricular rhythm, and "R-on-T phenomenon". Variations of these arrhythmias were detected by 24-AECG in eight (47%) of included dogs. No arrhythmias were detected by cardiac auscultation. Twenty-four hours following envenomation, four out of eight dogs experienced decreases (all P < 0.039), and three out of eight dogs experienced increases (all P < 0.034), in arrhythmic episodes. All four dogs bitten on a limb developed pathologic arrhythmias. Otherwise, no significant differences in clinical, hematological or biochemical variables were seen between dogs with pathologic arrhythmias and those without. Forty-seven percent of dogs bitten by V. berus included in this study experienced pathologic arrhythmias of abnormal ventricular depolarization. During the first 24-32 h from the snakebite, some dogs experienced a decrease in arrhythmic episodes and others an increase in arrhythmic episodes. These findings indicate a potential value of repeated or prolonged electrocardiography monitoring of envenomed dogs for identification of which dogs that might benefit the most from prolonged hospitalization for optimal monitoring and treatment of cardiac abnormalities. In the present study, dogs that developed arrhythmias could not be differentiated from dogs that did not based on clinical findings or hematological or biochemical variables obtained at admission.

Simultaneous analysis of cerebrospinal fluid biomarkers using microsphere-based xMAP multiplex technology for early detection of Alzheimer's disease.

PubMed

Kang, Ju-Hee; Vanderstichele, Hugo; Trojanowski, John Q; Shaw, Leslie M

2012-04-01

The xMAP-Luminex multiplex platform for measurement of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers using Innogenetics AlzBio3 immunoassay reagents that are for research use only has been shown to be an effective tool for early detection of an AD-like biomarker signature based on concentrations of CSF Aβ(1-42), t-tau and p-tau(181). Among the several advantages of the xMAP-Luminex platform for AD CSF biomarkers are: a wide dynamic range of ready-to-use calibrators, time savings for the simultaneous analyses of three biomarkers in one analytical run, reduction of human error, potential of reduced cost of reagents, and a modest reduction of sample volume as compared to conventional enzyme-linked immunosorbant assay (ELISA) methodology. Recent clinical studies support the use of CSF Aβ(1-42), t-tau and p-tau(181) measurement using the xMAP-Luminex platform for the early detection of AD pathology in cognitively normal individuals, and for prediction of progression to AD dementia in subjects with mild cognitive impairment (MCI). Studies that have shown the prediction of risk for progression to AD dementia by MCI patients provide the basis for the use of CSF Aβ(1-42), t-tau and p-tau(181) testing to assign risk for progression in patients enrolled in therapeutic trials. Furthermore emerging study data suggest that these pathologic changes occur in cognitively normal subjects 20 or more years before the onset of clinically detectable memory changes thus providing an objective measurement for use in the assessment of treatment effects in primary treatment trials. However, numerous previous ELISA and Luminex-based multiplex studies reported a wide range of absolute values of CSF Aβ(1-42), t-tau and p-tau(181) indicative of substantial inter-laboratory variability as well as varying degrees of intra-laboratory imprecision. In order to address these issues a recent inter-laboratory investigation that included a common set of CSF pool aliquots from controls as well as AD patients over a range of normal and pathological Aβ(1-42), t-tau and p-tau(181) values as well as agreed-on standard operating procedures (SOPs) assessed the reproducibility of the multiplex methodology and Innogenetics AlzBio3 immunoassay reagents. This study showed within-center precision values of 5% to a little more than 10% and good inter-laboratory %CV values (10-20%). There are several likely factors influencing the variability of CSF Aβ(1-42), t-tau and p-tau(181) measurements. In this review, we describe the pre-analytical, analytical and post-analytical sources of variability including sources inherent to kits, and describe procedures to decrease the variability. A CSF AD biomarker Quality Control program has been established and funded by the Alzheimer Association, and global efforts are underway to further define optimal pre-analytical SOPs and best practices for the methodologies available or in development including plans for production of a standard reference material that could provide for a common standard against which manufacturers of immunoassay kits would assign calibration standard values. Copyright © 2012 Elsevier Inc. All rights reserved.

SU-E-I-88: Realistic Pathological Simulations of the NCAT and Zubal Anthropomorphic Models, Based on Clinical PET/CT Data.

PubMed

Papadimitroulas, P; Loudos, G; Le Maitre, A; Efthimiou, N; Visvikis, D; Nikiforidis, G; Kagadis, G C

2012-06-01

In the present study a patient-specific dataset of realistic PET simulations was created, taking into account the variability of clinical oncology data. Tumor variability was tested in the simulated results. A comparison of the produced simulated data was performed to clinical PET/CT data, for the validation and the evaluation of the procedure. Clinical PET/CT data of oncology patients were used as the basis of the simulated variability inserting patient-specific characteristics in the NCAT and the Zubal anthropomorphic phantoms. GATE Monte Carlo toolkit was used for simulating a commercial PET scanner. The standard computational anthropomorphic phantoms were adapted to the CT data (organ shapes), using a fitting algorithm. The activity map was derived from PET images. Patient tumors were segmented and inserted in the phantom, using different activity distributions. The produced simulated data were reconstructed using the STIR opensource software and compared to the original clinical ones. The accuracy of the procedure was tested in four different oncology cases. Each pathological situation was illustrated simulating a) a healthy body, b) insertion of the clinical tumor with homogenous activity, and c) insertion of the clinical tumor with variable activity (voxel-by-voxel) based on the clinical PET data. The accuracy of the presented dataset was compared to the original PET/CT data. Partial Volume Correction (PVC) was also applied in the simulated data. In this study patient-specific characteristics were used in computational anthropomorphic models for simulating realistic pathological patients. Voxel-by-voxel activity distribution with PVC within the tumor gives the most accurate results. Radiotherapy applications can utilize the benefits of the accurate realistic imaging simulations, using the anatomicaland biological information of each patient. Further work will incorporate the development of analytical anthropomorphic models with motion and cardiac correction, combined with pathological patients to achieve high accuracy in tumor imaging. This research was supported by the Joint Research and Technology Program between Greece and France; 2009-2011 (protocol ID: 09FR103). © 2012 American Association of Physicists in Medicine.

Personality Disorder Models and their Coverage of Interpersonal Problems

PubMed Central

Williams, Trevor F.; Simms, Leonard J.

2015-01-01

Interpersonal dysfunction is a defining feature of personality disorders (PDs) and can serve as a criterion for comparing PD models. In this study, the interpersonal coverage of four competing PD models was examined using a sample of 628 current or recent psychiatric patients who completed the NEO Personality Inventory-3 First Half (NEO-PI-3FH; McCrae & Costa, 2007), Personality Inventory for the DSM-5 (PID-5; Krueger et al., 2012), Computerized Adaptive Test of Personality Disorder-Static Form (CAT-PD-SF; Simms et al., 2011), and Structured Clinical Interview for DSM-IV Personality Questionnaire (SCID-II PQ; First, Spitzer, Gibbon, & Williams, 1995). Participants also completed the Inventory of Interpersonal Problems-Short Circumplex (IIP-SC; Soldz, Budman, Demby, & Merry, 1995) to assess interpersonal dysfunction. Analyses compared the severity and style of interpersonal problems that characterize PD models. Previous research with DSM-5 Section II and III models was generally replicated. Extraversion and Agreeableness facets related to the most well defined interpersonal problems across normal-range and pathological traits. Pathological trait models provided more coverage of dominance problems, whereas normal-range traits covered nonassertiveness better. These results suggest that more work may be needed to reconcile descriptions of personality pathology at the level of specific constructs. PMID:26168406

Industry-contract research organization pathology interactions: a perspective of contract research organizations in producing the best quality pathology report.

PubMed

Gosselin, Sylvie J; Palate, Bernard; Parker, George A; Engelhardt, Jeffery A; Hardisty, Jerry F; McDorman, Kevin S; Tellier, Pierre A; Silverman, Lee R

2011-02-01

This article provides observations on the features of sponsor-contract research organization communication that will achieve the best quality pathology report based on our collective experience. Information on the test article and any anticipated findings should be provided, and initial slide examination should be done with knowledge of treatment group (but may be followed by blinded review of target tissues to determine no-effect levels). Only a pathologist should write or revise the pathology report or the pathology section of the overall study report. To address concerns related to undue sponsor influence, comments by sponsors should be presented as suggestions rather than directives. Adversity should be defined for each finding by the study pathologist, but the no-observed adverse effect level should not be discussed in the pathology report. Board-certified pathologists are recommended, but are not essential. Sponsors that have a particular format or report preferences should make them known well in advance. Histologic processing "to glass" of protocol-specified tissues from all dosage groups is recommended for rapid evaluation of target tissues. Telepathology is beneficial in certain situations, but it is usually more efficient for the study pathologist and reviewing pathologist to be in the same physical location to review differences of opinion and reach a consensus.

The Nun Study: risk factors for pathology and clinical-pathologic correlations.

PubMed

Mortimer, James A

2012-07-01

The Nun Study was the first cohort study to enroll and follow a large, well-defined population that included demented and non-demented participants, all of whom agreed to donate their brains for research. The inclusion of systematic neuropathologic analysis in this study has resulted in a greater understanding of the role of Alzheimer and vascular pathology in the expression of memory deficits and dementia and has provided data showing that biomarkers for the pathology may be evident many decades earlier in adult life. Findings related to neuropathology in this study have included the following: (1) Although clinical outcomes were strongly correlated with Alzheimer neuropathology, about one-third of the participants fulfilling criteria for neuropathologic Alzheimer's disease (AD) were not demented at the time of death. (2) Brain infarcts by themselves had little effect on cognitive status, but played an important role in increasing the risk of dementia associated with Alzheimer pathology. (3) Hippocampal volume was strongly correlated with Braak neurofibrillary stage even in participants with normal cognitive function. (4) A linguistic characteristic of essays written in early adult life, idea density, had a strong association with not only clinical outcomes in late life, but the severity of Alzheimer neuropathology as well. (5) The effect of apolipoprotein E-e4 on dementia was mediated through Alzheimer, but not vascular pathology.

Alzheimer Disease Pathology in Subjects Without Dementia in Two Studies of Aging: The Nun Study and the Adult Changes in Thought Study

PubMed Central

SantaCruz, Karen S.; Sonnen, Joshua A.; Pezhouh, Maryam Kherad; Desrosiers, Mark F.; Nelson, Peter T.; Tyas, Suzanne L.

2012-01-01

Individuals with antemortem preservation of cognition who show autopsy evidence of at least moderate Alzheimer disease (AD) pathology suggest the possibility of brain reserve, that is, functional resistance to structural brain damage. This reserve would, however, only be relevant if the pathologic markers correlate well with dementia. Using data from the Nun Study (n = 498) and the Adult Changes in Thought (ACT) Study (n = 323), we show that Braak staging correlates strongly with dementia status. Moreover, participants with severe (Braak stage V–VI) AD pathology who remained not demented represent only 12% (Nun Study) and 8% (ACT study) of nondemented subjects. Comparison of these subjects to those who were demented revealed that the former group was often significantly memory impaired despite not being classified as demented. Most of these nondemented participants showed only stage V neurofibrillary pathology and frontal tangle counts that were slightly lower than a comparable (Braak stage V) dementia group. In summary, these data indicate that, in individuals with AD-type pathology who do not meet criteria for dementia, neocortical neurofibrillary tangles are somewhat reduced and incipient cognitive decline is present. Our data provide a foundation for helping to define additional factors that may impair, or be protective of, cognition in older adults. PMID:21937909

Alzheimer disease pathology in subjects without dementia in 2 studies of aging: the Nun Study and the Adult Changes in Thought Study.

PubMed

SantaCruz, Karen S; Sonnen, Joshua A; Pezhouh, Maryam Kherad; Desrosiers, Mark F; Nelson, Peter T; Tyas, Suzanne L

2011-10-01

Individuals with antemortem preservation of cognition who show autopsy evidence of at least moderate Alzheimer disease (AD) pathology suggest the possibility of brain reserve, that is, functional resistance to structural brain damage. This reserve would, however, only be relevant if the pathologic markers correlate well with dementia. Using data from the Nun Study (n = 498) and the Adult Changes in Thought (ACT) Study (n = 323), we show that Braak staging correlates strongly with dementia status. Moreover, participants with severe(Braak stage V-VI) AD pathology who remained not demented represent only 12% (Nun Study) and 8% (ACT study) of nondemented subjects. Comparison of these subjects to those who were demented revealed that the former group was often significantly memory-impaired despite not being classified as demented. Most of these nondemented participants showed only stage V neurofibrillary pathology and frontal tangle counts that were slightly lower than a comparable (Braak stage V) dementia group. In summary, these data indicate that, in individuals with AD-type pathology who do not meet criteria for dementia, neocortical neurofibrillary tangles are somewhat reduced and incipient cognitive decline is present. Our data provide a foundation for helping to define additional factors that may impair, or be protective of, cognition in older adults.

Childhood Maltreatment as Predictor of Pathological Personality Traits Using PSY-5 in an Adult Psychiatric Sample.

PubMed

Choi, Ji Young; Park, Soo Hyun

2018-02-01

Extant literature indicates that childhood maltreatment is significantly associated with personality disorders. With the recent call for a more dimensional approach to understanding personality and pathological personality traits, the aim of the present study was to examine whether the experience of childhood maltreatment is associated with pathological personality traits as measured by the Personality Psychopathology Five (PSY-5). We analyzed data from 557 adult psychiatric patients with diverse psychiatric diagnoses, including mood disorders, schizophrenia spectrum disorders, and anxiety disorders. Hierarchical multiple regression analyses were conducted to determine the degree to which childhood maltreatment explained the five trait dimensions after controlling for demographic variables, presence of psychotic symptoms, and degree of depressive symptoms. Childhood maltreatment significantly predicted all of the five trait dimensions of the PSY-5. This suggests that childhood maltreatment may negatively affect the development of an adaptive adjustment system, thereby potentially contributing to the emergence of pathological personality traits.

The Rorschach Egocentricity Index in subjects with intellectual disability: a study on the incidence of different psychological pathologies.

PubMed

Colucci, G; Pellicciotta, A; Buono, S; Di Nuovo, S F

1998-10-01

The aims of the present research were to assess the level of self-concern in people with intellectual disability using the Rorschach Egocentricity Index, to correlate the Index with other Rorschach and IQ variables, and to study the effect of associated psychological pathology. The Rorschach Inkblot Test and the Wechsler Intelligence Scale were administered to a group of 75 subjects with intellectual disability, aged between 18 and 38 years, who were divided into subgroups according to their additional diagnosis (i.e. personality disorders, psychosis and depression). A fourth subgroup was composed of people with intellectual disability but without other pathologies. The Egocentricity Index was very low in the subjects with intellectual disability and differences were a result of the effects of additional psychological pathologies. The meaning of the measurement of egocentricity in people with intellectual disability is discussed.

Alzheimer’s disease is not “brain aging”: neuropathological, genetic, and epidemiological human studies

PubMed Central

Head, Elizabeth; Schmitt, Frederick A.; Davis, Paulina R.; Neltner, Janna H.; Jicha, Gregory A.; Abner, Erin L.; Smith, Charles D.; Van Eldik, Linda J.; Kryscio, Richard J.; Scheff, Stephen W.

2011-01-01

Human studies are reviewed concerning whether “aging”-related mechanisms contribute to Alzheimer’s disease (AD) pathogenesis. AD is defined by specific neuropathology: neuritic amyloid plaques and neocortical neurofibrillary tangles. AD pathology is driven by genetic factors related not to aging per se, but instead to the amyloid precursor protein (APP). In contrast to genes involved in APP-related mechanisms, there is no firm connection between genes implicated in human “accelerated aging” diseases (progerias) and AD. The epidemiology of AD in advanced age is highly relevant but deceptively challenging to address given the low autopsy rates in most countries. In extreme old age, brain diseases other than AD approximate AD prevalence while the impact of AD pathology appears to peak by age 95 and decline thereafter. Many distinct brain diseases other than AD afflict older human brains and contribute to cognitive impairment. Additional prevalent pathologies include cerebrovascular disease and hippocampal sclerosis, both high-morbidity brain diseases that appear to peak in incidence later than AD chronologically. Because of these common brain diseases of extreme old age, the epidemiology differs between clinical “dementia” and the subset of dementia cases with AD pathology. Additional aging-associated mechanisms for cognitive decline such as diabetes and synapse loss have been linked to AD and these hypotheses are discussed. Criteria are proposed to define an “aging-linked” disease, and AD fails all of these criteria. In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging. PMID:21516511

[Type 2 Diabetes Mellitus, Depression and Eating Disorders in Patients Submitted to Bariatric Surgery].

PubMed

Brandão, Isabel; Marques Pinho, Ana; Arrojado, Filipa; Pinto-Bastos, Ana; Maia da Costa, José; Coelho, Rui; Calhau, Conceição; Conceição, Eva

2016-03-01

Obesity is associated with a great number of complications, including type 2 diabetes mellitus and psychiatric pathology. Bariatric surgery is the best solution to weight loss and improvement of complications in morbid obese patients. This study aims to analyze the evolution of type 2 diabetes mellitus and psychopathologic variables before and after bariatric surgery and assess the importance of different variables in weight loss. This is a longitudinal study, which evaluates 75 patients before and after bariatric surgery (47 - LAGB - laparoscopic adjustable gastric band; 19 - RYGB - Roux-en-Y gastric bypass; 9 - sleeve) with a follow-up time between 18 and 46 months. A clinical interview and self report questionnaires were applied - Eating Disorder Examination questionnaire - EDE-Q and Beck Depression Inventory - BDI. Results show an improvement in type 2 diabetes mellitus after surgery (X2 (1) = 26.132, p < 0.001). There was not a significant improvement among psychiatric pathology when we controlled the analysis for the type of surgery. It was verified that type 2 diabetes mellitus, depression and eating disorders in post-operative period are associated with less weight loss. This model explains 27% of weight variance after surgery (R2 = 0.265) and it is significant F (3.33) = 2.981, p = 0.038. Type 2 diabetes mellitus, psychiatric pathology and eating disorders after surgery influenced weight loss. It was not clear in what way this relation was verified, neither the relation that these metabolic and psychological variables may have during the postoperative period. Type 2 diabetes mellitus improved after surgery. Type 2 diabetes mellitus, depression and eating disorders influenced weight loss in the postoperative period. These variables did not influence weight loss in the preoperative period.

Hippocampal sclerosis of aging, a prevalent and high-morbidity brain disease

PubMed Central

Smith, Charles D.; Abner, Erin L.; Wilfred, Bernard J.; Wang, Wang-Xia; Neltner, Janna H.; Baker, Michael; Fardo, David W.; Kryscio, Richard J.; Scheff, Stephen W.; Jicha, Gregory A.; Jellinger, Kurt A.; Van Eldik, Linda J.; Schmitt, Frederick A.

2013-01-01

Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5–30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available. PMID:23864344

Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility

DOE PAGES

Berry, Anne S.; Shah, Vyoma D.; Baker, Suzanne L.; ...

2016-12-14

Aging is accompanied by profound changes in the brain’s dopamine system that affect cognitive function. Evidence of powerful individual differences in cognitive aging has sharpened focus on identifying biological factors underlying relative preservation versus vulnerability to decline. Dopamine represents a key target in these efforts. Alterations of dopamine receptors and dopamine synthesis are seen in aging, with receptors generally showing reduction and synthesis demonstrating increases. Using the PET tracer 6-[ 18F]fluoro-L- m-tyrosine, we found strong support for upregulated striatal dopamine synthesis capacity in healthy older adult humans free of amyloid pathology, relative to young people. We next used fMRI tomore » define the functional impact of elevated synthesis capacity on cognitive flexibility, a core component of executive function. We found clear evidence in young adults that low levels of synthesis capacity were suboptimal, associated with diminished cognitive flexibility and altered frontoparietal activation relative to young adults with highest synthesis values. Critically, these relationships between dopamine, performance, and activation were transformed in older adults with higher synthesis capacity. Variability in synthesis capacity was related to intrinsic frontoparietal functional connectivity across groups, suggesting that striatal dopamine synthesis influences the tuning of networks underlying cognitive flexibility. Altogether, these findings define striatal dopamine’s association with cognitive flexibility and its neural underpinnings in young adults, and reveal the alteration in dopamine-related neural processes in aging.« less

Brain abnormality segmentation based on l1-norm minimization

NASA Astrophysics Data System (ADS)

Zeng, Ke; Erus, Guray; Tanwar, Manoj; Davatzikos, Christos

2014-03-01

We present a method that uses sparse representations to model the inter-individual variability of healthy anatomy from a limited number of normal medical images. Abnormalities in MR images are then defined as deviations from the normal variation. More precisely, we model an abnormal (pathological) signal y as the superposition of a normal part ~y that can be sparsely represented under an example-based dictionary, and an abnormal part r. Motivated by a dense error correction scheme recently proposed for sparse signal recovery, we use l1- norm minimization to separate ~y and r. We extend the existing framework, which was mainly used on robust face recognition in a discriminative setting, to address challenges of brain image analysis, particularly the high dimensionality and low sample size problem. The dictionary is constructed from local image patches extracted from training images aligned using smooth transformations, together with minor perturbations of those patches. A multi-scale sliding-window scheme is applied to capture anatomical variations ranging from fine and localized to coarser and more global. The statistical significance of the abnormality term r is obtained by comparison to its empirical distribution through cross-validation, and is used to assign an abnormality score to each voxel. In our validation experiments the method is applied for segmenting abnormalities on 2-D slices of FLAIR images, and we obtain segmentation results consistent with the expert-defined masks.

Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility

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

Berry, Anne S.; Shah, Vyoma D.; Baker, Suzanne L.

Aging is accompanied by profound changes in the brain’s dopamine system that affect cognitive function. Evidence of powerful individual differences in cognitive aging has sharpened focus on identifying biological factors underlying relative preservation versus vulnerability to decline. Dopamine represents a key target in these efforts. Alterations of dopamine receptors and dopamine synthesis are seen in aging, with receptors generally showing reduction and synthesis demonstrating increases. Using the PET tracer 6-[ 18F]fluoro-L- m-tyrosine, we found strong support for upregulated striatal dopamine synthesis capacity in healthy older adult humans free of amyloid pathology, relative to young people. We next used fMRI tomore » define the functional impact of elevated synthesis capacity on cognitive flexibility, a core component of executive function. We found clear evidence in young adults that low levels of synthesis capacity were suboptimal, associated with diminished cognitive flexibility and altered frontoparietal activation relative to young adults with highest synthesis values. Critically, these relationships between dopamine, performance, and activation were transformed in older adults with higher synthesis capacity. Variability in synthesis capacity was related to intrinsic frontoparietal functional connectivity across groups, suggesting that striatal dopamine synthesis influences the tuning of networks underlying cognitive flexibility. Altogether, these findings define striatal dopamine’s association with cognitive flexibility and its neural underpinnings in young adults, and reveal the alteration in dopamine-related neural processes in aging.« less

Comorbidity, family history and personality traits in pathological gamblers compared with healthy controls.

PubMed

Mann, K; Lemenager, T; Zois, E; Hoffmann, S; Nakovics, H; Beutel, M; Vogelgesang, M; Wölfling, K; Kiefer, F; Fauth-Bühler, M

2017-05-01

While DSM-5 classified pathological gambling as an addictive disorder, there is debate as to whether ICD-11 should follow suit. The debate hinges on scientific evidence such as neurobiological findings, family history of psychiatric disorders, psychiatric comorbidity, and personality variables. In the "Baden-Württemberg Study of Pathological Gambling", we compared a group of 515 male pathological gamblers receiving treatment with 269 matched healthy controls. We studied differences in sociodemographic characteristics, gambling-related variables, psychiatric comorbidity (lifetime), family history of psychiatric conditions, as well as personality traits such as impulsivity (Barratt Impulsiveness Scale), sensation seeking (Zuckerman's Sensation Seeking Scale) and the NEO-FFI big five. Personality traits were validated in an age- and ethnicity-matched subsample of "pure" gamblers without any psychiatric comorbidity (including nicotine dependence). Data were analyzed using two-sample t-tests, Chi 2 analyses, Fisher's exact test and Pearson correlation analysis, as appropriate. Bonferroni correction was applied to correct for multiple comparisons. Only 1% of the gamblers had been diagnosed with an impulse control disorder other than gambling (ICD-10). Notably, 88% of the gamblers in our sample had a comorbid diagnosis of substance dependence. The highest axis I comorbidity rate was for nicotine dependence (80%), followed by alcohol dependence (28%). Early age of first gambling experience was correlated with gambling severity. Compared to first-degree relatives of controls, first-degree relatives of pathological gamblers were more likely to suffer from alcohol dependence (27.0% vs. 7.4%), pathological gambling (8.3% vs. 0.7%) and suicide attempts (2.7% vs. 0.4%). Significant group differences were observed for the NEO-FFI factors neuroticism, agreeableness and conscientiousness. Gamblers were also more impulsive than controls, but did not differ from controls in terms of sensation seeking. Our findings support classifying pathological gambling as a behavioural addiction in the ICD-11. This decision will have a significant impact on the approaches available for prevention (e.g. age limits) and treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Social Information Processing and Cluster B Personality Pathology among Clinic-Referred Adolescents.

PubMed

Hessels, Christel; van Aken, Marcel A G; Orobio de Castro, Bram; Laceulle, Odilia M; van Voorst, Guus

2016-01-01

This study investigated relations between personality pathology and mentalizing capacities reflected in social information processing (SIP) of adolescents. 96 adolescent outpatients completed a structured interview regarding SIP. Their clinicians completed a checklist based on DSM-IV, assessing severity of personality pathology. Significant relations were found between the severity of personality pathology and SIP: the more severe the personality pathology, the higher the intensity of reported emotions, the more likely adolescents were to choose inadequate coping strategies and aggressive reactions in social situations, and the more positively they evaluated aggressive reactions. Severity of traits of antisocial (ASPD) and borderline personality disorder (BPD) had unique associations with distinctive SIP variables: ASPD being more related to inadequate coping strategies, less reflection on other's motives and aggressive responses, and BPD being more related to avoidant or prosocial responses and in particular to memories of frustrating events. This study provides evidence for difficulties in SIP among adolescents with more severe personality pathology, suggesting that the steps in the SIP model can be used to operationalize mentalizing problems. The results seem to paint a picture of ASPD and BPD having a shared background, but their own specific problems concerning SIP. © 2016 S. Karger AG, Basel.

Memory self-awareness in the preclinical and prodromal stages of Alzheimer's disease.

PubMed

Vannini, Patrizia; Amariglio, Rebecca; Hanseeuw, Bernard; Johnson, Keith A; McLaren, Donald G; Chhatwal, Jasmeer; Pascual-Leone, Alvaro; Rentz, Dorene; Sperling, Reisa A

2017-05-01

While loss of insight of cognitive deficits, anosognosia, is a common symptom in Alzheimer's disease dementia, there is a lack of consensus regarding the presence of altered awareness of memory function in the preclinical and prodromal stages of the disease. Paradoxically, very early in the Alzheimer's disease process, individuals may experience heightened awareness of memory changes before any objective cognitive deficits can be detected, here referred to as hypernosognosia. In contrast, awareness of memory dysfunction shown by individuals with mild cognitive impairment (MCI) is very variable, ranging from marked concern to severe lack of insight. This study aims at improving our mechanistic understanding of how alterations in memory self-awareness are related to pathological changes in clinically normal (CN) adults and MCI patients. 297 CN and MCI patients underwent PiB-PET (Positron Emission Tomography using Pittsburgh Compound B) in vivo amyloid imaging. Amyloid burden was estimated from Alzheimer's disease vulnerable regions, including the frontal, lateral parietal and lateral temporal, and retrosplenial cortex. Memory self-awareness was assessed using discrepancy scores between subjective and objective measures of memory function. A set of univariate analysis of variance were performed to assess the relationship between self-awareness of memory and amyloid pathology. Whereas CN individuals harboring amyloid pathology demonstrated hypernosognosia, MCI patients with increased amyloid pathology demonstrated anosognosia. In contrast, MCI patients with low amounts of amyloid were observed to have normal insight into their memory functions. Altered self-awareness of memory tracks with amyloid pathology. The findings of variability of awareness may have important implications for the reliability of self-report of dysfunction across the spectrum of preclinical and prodromal Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Memory self-awareness in the preclinical and prodromal stages of Alzheimer’s disease

PubMed Central

Vannini, Patrizia; Amariglio, Rebecca; Hanseeuw, Bernard; Johnson, Keith A.; McLaren, Donald G; Chhatwal, Jasmeer; Pascual-Leone, Alvaro; Rentz, Dorene; Sperling, Reisa A.

2017-01-01

While loss of insight of cognitive deficits, anosognosia, is a common symptom in Alzheimer’s disease dementia, there is a lack of consensus regarding the presence of altered awareness of memory function in the preclinical and prodromal stages of the disease. Paradoxically, very early in the Alzheimer’s disease process, individuals may experience heightened awareness of memory changes before any objective cognitive deficits can be detected, here referred to as hypernosognosia. In contrast, awareness of memory dysfunction shown by individuals with mild cognitive impairment (MCI) is very variable, ranging from marked concern to severe lack of insight. This study aims at improving our mechanistic understanding of how alterations in memory self-awareness are related to pathological changes in clinically normal (CN) adults and MCI patients. 297 CN and MCI patients underwent PiB-PET (Positron Emission Tomography using Pittsburgh Compound B) in vivo amyloid imaging. Amyloid burden was estimated from Alzheimer’s disease vulnerable regions, including the frontal, lateral parietal and lateral temporal, and retrosplenial cortex. Memory self-awareness was assessed using discrepancy scores between subjective and objective measures of memory function. A set of univariate analysis of variance were performed to assess the relationship between self-awareness of memory and amyloid pathology. Whereas CN individuals harboring amyloid pathology demonstrated hypernosognosia, MCI patients with increased amyloid pathology demonstrated anosognosia. In contrast, MCI patients with low amounts of amyloid were observed to have normal insight into their memory functions. Altered self-awareness of memory tracks with amyloid pathology. The findings of variability of awareness may have important implications for the reliability of self-report of dysfunction across the spectrum of preclinical and prodromal Alzheimer’s disease. PMID:28385579

MRI Predictive Factors for Tumor Response in Rectal Cancer Following Neoadjuvant Chemoradiation Therapy - Implications for Induction Chemotherapy?

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

Yu, Stanley K.T.; Tait, Diana; Chau, Ian

2013-11-01

Purpose: Clinical and magnetic resonance imaging (MRI) characteristics at baseline and following chemoradiation therapy (CRT) most strongly associated with histopathologic response were investigated and survival outcomes evaluated in accordance with imaging and pathological response. Methods and Materials: Responders were defined as mrT3c/d-4 downstaged to ypT0-2 on pathology or low at risk mrT2 downstaged to ypT1 or T0. Multivariate logistic regression of baseline and posttreatment MRI: T, N, extramural venous invasion (EMVI), circumferential resection margin, craniocaudal length <5 cm, and MRI tumor height ≤5 cm were used to identify independent predictor(s) for response. An association between induction chemotherapy and EMVI statusmore » was analyzed. Survival outcomes for pathologic and MRI responders and nonresponders were analyzed. Results: Two hundred eighty-one patients were eligible; 114 (41%) patients were pathology responders. Baseline MRI negative EMVI (odds ratio 2.94, P=.007), tumor height ≤5 cm (OR 1.96, P=.02), and mrEMVI status change (positive to negative) following CRT (OR 3.09, P<.001) were the only predictors for response. There was a strong association detected between induction chemotherapy and ymrEMVI status change after CRT (OR 9.0, P<.003). ymrT0-2 gave a positive predictive value of 80% and OR of 9.1 for ypT0-2. ymrN stage accuracy of ypN stage was 75%. Three-year disease-free survival for pathology and MRI responders were similar at 80% and 79% and significantly better than poor responders. Conclusions: Tumor height and mrEMVI status are more important than baseline size and stage of the tumor as predictors of response to CRT. Both MRI- and pathologic-defined responders have significantly improved survival. “Good response” to CRT in locally advanced rectal cancer with ypT0-2 carries significantly better 3-year overall survival and disease-free survival. Use of induction chemotherapy for improving mrEMVI status and knowledge of MRI predictive factors could be taken into account in the pursuit of individualized neoadjuvant treatments for patients with rectal cancer.« less

Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature.

PubMed

Dell'Isola, A; Allan, R; Smith, S L; Marreiros, S S P; Steultjens, M

2016-10-12

Knee Osteoarthritis (KOA) is a heterogeneous pathology characterized by a complex and multifactorial nature. It has been hypothesised that these differences are due to the existence of underlying phenotypes representing different mechanisms of the disease. The aim of this study is to identify the current evidence for the existence of groups of variables which point towards the existence of distinct clinical phenotypes in the KOA population. A systematic literature search in PubMed was conducted. Only original articles were selected if they aimed to identify phenotypes of patients aged 18 years or older with KOA. The methodological quality of the studies was independently assessed by two reviewers and qualitative synthesis of the evidence was performed. Strong evidence for existence of specific phenotypes was considered present if the phenotype was supported by at least two high-quality studies. A total of 24 studies were included. Through qualitative synthesis of evidence, six main sets of variables proposing the existence of six phenotypes were identified: 1) chronic pain in which central mechanisms (e.g. central sensitisation) are prominent; 2) inflammatory (high levels of inflammatory biomarkers); 3) metabolic syndrome (high prevalence of obesity, diabetes and other metabolic disturbances); 4) Bone and cartilage metabolism (alteration in local tissue metabolism); 5) mechanical overload characterised primarily by varus malalignment and medial compartment disease; and 6) minimal joint disease characterised as minor clinical symptoms with slow progression over time. This study identified six distinct groups of variables which should be explored in attempts to better define clinical phenotypes in the KOA population.

Deep residual networks for automatic segmentation of laparoscopic videos of the liver

NASA Astrophysics Data System (ADS)

Gibson, Eli; Robu, Maria R.; Thompson, Stephen; Edwards, P. Eddie; Schneider, Crispin; Gurusamy, Kurinchi; Davidson, Brian; Hawkes, David J.; Barratt, Dean C.; Clarkson, Matthew J.

2017-03-01

Motivation: For primary and metastatic liver cancer patients undergoing liver resection, a laparoscopic approach can reduce recovery times and morbidity while offering equivalent curative results; however, only about 10% of tumours reside in anatomical locations that are currently accessible for laparoscopic resection. Augmenting laparoscopic video with registered vascular anatomical models from pre-procedure imaging could support using laparoscopy in a wider population. Segmentation of liver tissue on laparoscopic video supports the robust registration of anatomical liver models by filtering out false anatomical correspondences between pre-procedure and intra-procedure images. In this paper, we present a convolutional neural network (CNN) approach to liver segmentation in laparoscopic liver procedure videos. Method: We defined a CNN architecture comprising fully-convolutional deep residual networks with multi-resolution loss functions. The CNN was trained in a leave-one-patient-out cross-validation on 2050 video frames from 6 liver resections and 7 laparoscopic staging procedures, and evaluated using the Dice score. Results: The CNN yielded segmentations with Dice scores >=0.95 for the majority of images; however, the inter-patient variability in median Dice score was substantial. Four failure modes were identified from low scoring segmentations: minimal visible liver tissue, inter-patient variability in liver appearance, automatic exposure correction, and pathological liver tissue that mimics non-liver tissue appearance. Conclusion: CNNs offer a feasible approach for accurately segmenting liver from other anatomy on laparoscopic video, but additional data or computational advances are necessary to address challenges due to the high inter-patient variability in liver appearance.

Clinical validity of prototype personality disorder ratings in adolescents.

PubMed

Defife, Jared A; Haggerty, Greg; Smith, Scott W; Betancourt, Luis; Ahmed, Zain; Ditkowsky, Keith

2015-01-01

A growing body of research shows that personality pathology in adolescents is clinically distinctive and frequently stable into adulthood. A reliable and useful method for rating personality pathology in adolescent patients has the potential to enhance conceptualization, dissemination, and treatment effectiveness. The aim of this study is to examine the clinical validity of a prototype matching approach (derived from the Shedler Westen Assessment Procedure-Adolescent Version) for quantifying personality pathology in an adolescent inpatient sample. Sixty-six adolescent inpatients and their parents or legal guardians completed forms of the Child Behavior Checklist (CBCL) assessing emotional and behavioral problems. Clinical criterion variables including suicide history, substance use, and fights with peers were also assessed. Patients' individual and group therapists on the inpatient unit completed personality prototype ratings. Prototype diagnoses demonstrated substantial reliability (median intraclass correlation coefficient =.75) across independent ratings from individual and group therapists. Personality prototype ratings correlated with the CBCL scales and clinical criterion variables in anticipated and meaningful ways. As seen in prior research with adult samples, prototype personality ratings show clinical validity across independent clinician raters previously unfamiliar with the approach, and they are meaningfully related to clinical symptoms, behavioral problems, and adaptive functioning.

Borderline pathology and the Personality Assessment Inventory (PAI): an evaluation of criterion and concurrent validity.

PubMed

Stein, Michelle B; Pinsker-Aspen, Janet H; Hilsenroth, Mark J

2007-02-01

In this study, we examined how patients diagnosed with borderline pathology (BP) would respond on the Personality Assessment Inventory (PAI; Morey, 1991) Borderline (BOR) scales in relation to patients without BP pathology. In addition, we examined whether the PAI BOR scales would be related to variables on the Social Cognition and Object Relations Scale (SCORS; Hilsenroth, Stein, & Pinsker, 2004; Westen, 1995) derived from early memory narratives. Results indicate that outpatients with a Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) diagnosis of BP scored significantly higher on the PAI BOR Total (BOR-Total) score, Identity Problems, and Self- Harm scales in comparison to a Non-BP clinical sample. The overall correct classification rate for the presence or absence of BP using the BOR Total scale (T >or= 70) was 73%. In addition, there were several significant relationships between dimensional PAI BOR scales and the presence versus absence of DSM-IV BP. Moreover, both the BOR-Total and Affect Instability scales were significantly related to the SCORS variable Complexity of Representations. We provide clinical examples to illustrate these research findings in an applied manner.

Measurement of psychological disorders using cognitive diagnosis models.

PubMed

Templin, Jonathan L; Henson, Robert A

2006-09-01

Cognitive diagnosis models are constrained (multiple classification) latent class models that characterize the relationship of questionnaire responses to a set of dichotomous latent variables. Having emanated from educational measurement, several aspects of such models seem well suited to use in psychological assessment and diagnosis. This article presents the development of a new cognitive diagnosis model for use in psychological assessment--the DINO (deterministic input; noisy "or" gate) model--which, as an illustrative example, is applied to evaluate and diagnose pathological gamblers. As part of this example, a demonstration of the estimates obtained by cognitive diagnosis models is provided. Such estimates include the probability an individual meets each of a set of dichotomous Diagnostic and Statistical Manual of Mental Disorders (text revision [DSM-IV-TR]; American Psychiatric Association, 2000) criteria, resulting in an estimate of the probability an individual meets the DSM-IV-TR definition for being a pathological gambler. Furthermore, a demonstration of how the hypothesized underlying factors contributing to pathological gambling can be measured with the DINO model is presented, through use of a covariance structure model for the tetrachoric correlation matrix of the dichotomous latent variables representing DSM-IV-TR criteria. Copyright 2006 APA

[Nuclear magnetic resonance tomography diagnosis of changes in the glenoid process in patients with unstable shoulder joints].

PubMed

Jerosch, J; Castro, W H; Assheuer, J

1992-09-01

In 4 fresh specimens and in 14 healthy volunteers we studied normal anatomy of the glenoid labrum by MRI. In a total of 124 patients we examined the shoulder joints by MRI. 69 patients had any kind of subacromial pathology. 55 patients showed a glenohumeral instability. All MRI findings were compared with the surgical findings during arthroscopy and during open surgery. 44 patients showed a recurrent anterior instability, 7 patients showed a multidirectional instability, 2 patients showed a posterior instability, and 2 patients presented acute anterior dislocation. We found significant variability in the labral shape as well as significant variability of anterior capsular attachment. The pathologic changes of the glenoid labrum were classified in four different types. In 78% we found a concomitant Hill-Sachs lesion of various diameter. 5 patients suffered from an additional complete rotator cuff tear. Compared to the intraoperative findings MRI had a sensitivity of 95%, a specificity of 94%, an accuracy of 94%, a positive predictive value of 91%, and a negative predictive value of 96% in detecting labral pathology. Presenting a high diagnostic value for detecting Bankart lesions, MRI may replace other diagnostic modalities like CT-arthrography.

Clinical Validity of Prototype Personality Disorder Ratings in Adolescents

PubMed Central

DeFife, Jared A.; Haggerty, Greg; Smith, Scott W.; Betancourt, Luis; Ahmed, Zain; Ditkowsky, Keith

2015-01-01

A growing body of research shows that personality pathology in adolescents is clinically distinctive and frequently stable into adulthood. A reliable and useful method for rating personality pathology in adolescent patients has the potential to enhance conceptualization, dissemination, and treatment effectiveness. The aim of this study is to examine the clinical validity of a prototype matching approach (derived from the Shedler Westen Assessment Procedure – Adolescent Version) for quantifying personality pathology in an adolescent inpatient sample. Sixty-six adolescent inpatients and their parents or legal guardians completed forms of the Child Behavior Checklist (CBCL) assessing emotional and behavioral problems. Clinical criterion variables including suicide history, substance use, and fights with peers were also assessed. Patients’ individual and group therapists on the inpatient unit completed personality prototype ratings. Prototype diagnoses demonstrated substantial reliability (median ICC = .75) across independent ratings from individual and group therapists. Personality prototype ratings correlated with the CBCL scales and clinical criterion variables in anticipated and meaningful ways. As seen in prior research with adult samples, prototype personality ratings show clinical validity across independent clinician raters previously unfamiliar with the approach, and they are meaningfully related to clinical symptoms, behavioral problems, and adaptive functioning. PMID:25457971

A comparative study on pathological features of transgenic rat lines expressing either three or four repeat misfolded tau.

PubMed

Valachova, Bernadeta; Brezovakova, Veronika; Bugos, Ondrej; Jadhav, Santosh; Smolek, Tomas; Novak, Petr; Zilka, Norbert

2018-08-01

Human tauopathies represent a heterogeneous group of neurodegenerative disorders characterized by distinct clinical features, typical histopathological structures, and defined ratio(s) of three-repeat and four-repeat tau isoforms within pathological aggregates. How the optional microtubule-binding repeat of tau influences this differentiation of pathologies is understudied. We have previously generated and characterized transgenic rodent models expressing human truncated tau aa151-391 with either three (SHR24) or four microtubule-binding repeats (SHR72). Here, we compare the behavioral and neuropathological hallmarks of these two transgenic lines using a battery of tests for sensorimotor, cognitive, and neurological functions over the age range of 3.5-15 months. Progression of sensorimotor and neurological deficits was similar in both transgenic lines; however, the lifespan of transgenic line SHR72 expressing truncated four-repeat tau was markedly shorter than SHR24. Moreover, the expression of three or four-repeat tau induced distinct neurofibrillary pathology in these lines. Transgenic lines displayed different distribution of tau pathology and different type of neurofibrillary tangles. Our results suggest that three- and four-repeat isoforms of tau may display different modes of action in the diseased brain. © 2018 Wiley Periodicals, Inc.

Use of Severity Grades to Characterize Histopathologic Changes.

PubMed

Schafer, Kenneth A; Eighmy, John; Fikes, James D; Halpern, Wendy G; Hukkanen, Renee R; Long, Gerald G; Meseck, Emily K; Patrick, Daniel J; Thibodeau, Michael S; Wood, Charles E; Francke, Sabine

2018-04-01

The severity grade is an important component of a histopathologic diagnosis in a nonclinical toxicity study that helps distinguish treatment-related effects from background findings and aids in determining adverse dose levels during hazard characterization. Severity grades should be assigned based only on the extent (i.e., amount and complexity) of the morphologic change in the examined tissue section(s) and be clearly defined in the pathology report for critical lesions impacting study interpretation. However, the level of detail provided and criteria by which severity grades are assigned can vary, which can lead to inappropriate comparisons and confusion when evaluating pathology results. To help address this issue, a Working Group of the Society of Toxicologic Pathology's Scientific and Regulatory Policy Committee was formed to provide a "points to consider" article on the assignment and application of pathology severity grades. Overall, the Working Group supports greater transparency and consistency in the reporting of grading scales and provides recommendations to improve selection of diagnoses requiring more detailed severity criteria. This information should enhance the overall understanding by toxicologic pathologists, toxicologists, and regulatory reviewers of pathology findings and thereby improve effective communication in regulatory submissions.

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

PubMed Central

Menon, S.; Timms, P.; Allan, J. A.; Alexander, K.; Rombauts, L.; Horner, P.; Keltz, M.; Hocking, J.

2015-01-01

SUMMARY Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen worldwide. Infection can result in serious reproductive pathologies, including pelvic inflammatory disease, ectopic pregnancy, and infertility, in women. However, the processes that result in these reproductive pathologies have not been well defined. Here we review the evidence for the human disease burden of these chlamydial reproductive pathologies. We then review human-based evidence that links Chlamydia with reproductive pathologies in women. We present data supporting the idea that host, immunological, epidemiological, and pathogen factors may all contribute to the development of infertility. Specifically, we review the existing evidence that host and pathogen genotypes, host hormone status, age of sexual debut, sexual behavior, coinfections, and repeat infections are all likely to be contributory factors in development of infertility. Pathogen factors such as infectious burden, treatment failure, and tissue tropisms or ascension capacity are also potential contributory factors. We present four possible processes of pathology development and how these processes are supported by the published data. We highlight the limitations of the evidence and propose future studies that could improve our understanding of how chlamydial infertility in women occurs and possible future interventions to reduce this disease burden. PMID:26310245

7 CFR 51.2 - Terms defined.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) Applicant. “Applicant” means any interested party who has applied for inspection service under the... resulting from improper handling after packing; progressive pathological, physiological, and virus diseases... this part, to any interested party the quality, quantity and/or condition of any fresh product covered...

Physical Linguistics.

ERIC Educational Resources Information Center

Tice, Bradley S.

Physical linguistics is defined as the use of treatments from the field of speech pathology to enhance first and second language production in healthy individuals, resulting in increased quality and strength of phonation and articulation. A series of exercises for treating dysarthria (weakness, paralysis, discoordination, primary and secondary…

Defining Dose across Different Experimental Designs: Fiber Equivalent Diameter and Surface Area

EPA Science Inventory

Inhaled fibers (elongated bio-durable particles) of all lengths have been shown to induce pathological responses, but different sizes are respirable in different species. To be able to accurately assess the health effects observed in toxicological or epidemiological studies,...

Clinical features of pathologic childhood aerophagia: early recognition and essential diagnostic criteria.

PubMed

Hwang, Jin-Bok; Choi, Won Joung; Kim, Jun Sik; Lee, Sang Yun; Jung, Chul-Ho; Lee, Young Hwan; Kam, Sin

2005-11-01

This study investigated the early recognition and diagnosis of pathologic childhood aerophagia to avoid unnecessary diagnostic approaches and serious complications. Between 1995 and 2003, data from 42 consecutive patients with pathologic childhood aerophagia, aged 2 to 16 years, were reviewed. An esophageal air sign was defined as an abnormal air shadow on the proximal esophagus adjacent to the trachea on a full-inflated chest radiograph. Of the 42 patients, the chief complaints were abdominal distention (52.4%), recurrent abdominal pain syndrome (21.4%), chronic diarrhea (11.9%), acute abdominal pain (7.1%) and others (7.2%). Mean symptom duration before diagnosis was 10.6 months (range, 1 to 60 months), and it exceeded 12 months for 16 (38.1%) patients. The clinical features common to all patients were abdominal distention that increased progressively during the day, increased flatus on sleep, increased bowel sound on auscultation and an air-distended stomach with increased gas in the small and large bowel by radiography. Visible or audible air swallowing (26.2%) and repetitive belching (9.5%) were also noted. Esophageal air sign was observed in 76.2% of the patients and in 9.7% of the controls (P=0.0001). The subgroups of pathologic childhood aerophagia divided by underlying associations were pathologic childhood aerophagia without severe mental retardation (76.2%), which consisted of psychological stresses and uncertain condition, and pathologic childhood aerophagia with severe mental retardation (23.8%). The common manifestations of pathologic childhood aerophagia may be its essential diagnostic criteria, and esophageal air sign may be useful for the early recognition of pathologic childhood aerophagia. Our observations show that the diagnostic clinical profiles suggested by Rome II criteria should be detailed and made clearer if they are to serve as diagnostic criteria for pathologic childhood aerophagia.

Clinical and Pathological Staging Validation in the Eighth Edition of the TNM Classification for Lung Cancer: Correlation between Solid Size on Thin-Section Computed Tomography and Invasive Size in Pathological Findings in the New T Classification.

PubMed

Aokage, Keiju; Miyoshi, Tomohiro; Ishii, Genichiro; Kusumoto, Masahiro; Nomura, Shogo; Katsumata, Shinya; Sekihara, Keigo; Hishida, Tomoyuki; Tsuboi, Masahiro

2017-09-01

The aim of this study was to validate the new eighth edition of the TNM classification and to elucidate whether radiological solid size corresponds to pathological invasive size incorporated in this T factor. We analyzed the data on 1792 patients who underwent complete resection from 2003 to 2011 at the National Cancer Center Hospital East, Japan. We reevaluated preoperative thin-section computed tomography (TSCT) to determine solid size and pathological invasive size using the fourth edition of the WHO classification and reclassified them according to the new TNM classification. The discriminative power of survival curves by the seventh edition was compared with that by the eighth edition by using concordance probability estimates and Akaike's information criteria calculated using a univariable Cox regression model. Pearson's correlation coefficient was calculated to elucidate the correlation between radiological solid size using TSCT and pathological invasive size. The overall survival curves in the eighth edition were well distinct at each clinical and pathological stage. The 5-year survival rates of patients with clinical and pathological stage 0 newly defined were both 100%. The concordance probability estimate and Akaike's information criterion values of the eighth edition were higher than those of the seventh edition in discriminatory power for overall survival. Solid size on TSCT scan and pathological invasive size showed a positive linear relationship, and Pearson's correlation coefficient was calculated as 0.83, which indicated strong correlation. This TNM classification will be feasible regarding patient survival, and radiological solid size correlates significantly with pathological invasive size as a new T factor. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Informatics for practicing anatomical pathologists: marking a new era in pathology practice.

PubMed

Gabril, Manal Y; Yousef, George M

2010-03-01

Informatics can be defined as using highly advanced technologies to improve patient diagnosis or management. Pathology informatics had evolved as a response to the overwhelming amount of information that was available, in an attempt to better use and maintain them. The most commonly used tools of informatics can be classified into digital imaging, telepathology, as well as Internet and electronic data mining. Digital imaging is the storage of anatomical pathology information, either gross pictures or microscopic slides, in an electronic format. These images can be used for education, archival, diagnosis, and consultation. Virtual microscopy is the more advanced form of digital imaging with enhanced efficiency and accessibility. Telepathology is now increasingly becoming a useful tool in anatomical pathology practice. Different types of telepathology communications are available for both diagnostic and consultation services. The spectrum of applications of informatics in the field of anatomical pathology is broad and encompasses medical education, clinical services, and pathology research. Informatics is now settling on solid ground as an important tool for pathology teaching, with digital teaching becoming the standard tool in many institutions. After a slow start, we now witness the transition of informatics from the research bench to bedside. As we are moving into a new era of extensive pathology informatics utilization, several challenges have to be addressed, including the cost of the new technology, legal issues, and resistance of pathologists. It is clear from the current evidence that pathology informatics will continue to grow and have a major role in the future of our specialty. However, it is also clear that it is not going to fully replace the human factor or the regular microscope.

Surgical pathology to describe the clinical margin of debridement of chronic wounds using a wound electronic medical record.

PubMed

Golinko, Michael S; Joffe, Renata; de Vinck, David; Chandrasekaran, Eashwar; Stojadinovic, Olivera; Barrientos, Stephan; Vukelic, Sasa; Tomic-Canic, Marjana; Brem, Harold

2009-08-01

Chronic wounds, including diabetic foot ulcers (DFU), pressure ulcers (PU), and venous ulcers (VU) result from multiple physiologic impairments. Operative debridement is a mainstay of treatment to remove nonviable tissue and to stimulate wound healing. Unlike tumor resection, however, operative wound specimens are not routinely sent for pathology. The objective of this study was to describe the pathology present in chronic wounds. Pathology reports of the skin edge and wound base from 397 initial debridements in 336 consecutive patients with chronic wounds were retrospectively reviewed. All data were entered and stored in a Wound Electronic Medical Record. Pathology data were extracted from the Wound Electronic Medical Record, coded, and quantified. Up to 15 distinct histopathologic findings across 7 tissue types were observed after review of pathology reports from chronic wounds. Specifically, the pathology of epidermis revealed hyperkeratosis: 66% in DFUs, 31% in PUs, and 29% in VUs. Dermal pathology revealed fibrosis in 49% of DFUs, 30% of PUs, and 15% of VUs. Wound bed pathology revealed necrosis in the subcutaneous tissue in 67% of DFUs, 55% of PUs, and 19% of VUs. Fibrosis was reported in between 19% and 52% of all wound types. Acute osteomyelitis was present in 39% of DFUs, 33% of PUs, and 29% of VUs. This observational study of the histopathology of initial surgical debridement of chronic wounds revealed a wide range of findings across multiple tissue levels. Although certain findings such as osteomyelitis and gangrene have been shown to directly relate to impaired wound healing and amputation, other findings require additional investigation. To rigorously define a margin of debridement, a prospective study relating histopathology and clinical outcomes such as healing rates and amputation is needed.

Institutional pathology consultation.

PubMed

Tsung, Jeffrey S H

2004-03-01

Sun Yat-Sen Cancer Center is the only cancer center in Taiwan. The hospital maintains a policy, and the division of oncology makes a concerted effort to obtain and review pertinent pathologic specimens in all patients who had pathologic diagnosis performed at other institution before rendering therapy. A 1-year retrospective study was undertaken to assess the frequency of discordant diagnosis of our second-opinion pathology slide review and determine its impact on patient care. Discrepancies were classified into four basic categories: A) no diagnostic disagreement; B) no diagnostic disagreement but pertinent information not included, such as tumor size, lymphovascular invasion, perineural invasion, histologic grading, margin status, extracapsular spread in metastatic lymph nodes; and C) major diagnostic disagreement, which was defined as follows; 1) change from benign to malignant, 2) change from malignant to benign, 3) a different type of neoplasm, and 4) change in N and M classification in TMN staging framework. Of 715 cases, a total of 673 (94%) showed no discrepancy. However, 35 of 673 (5.2%) cases failed to offer pertinent information (category B). Major disagreement was found in 42 16%) cases (category C). This study illustrated the fact that second pathology slide review prior to therapy can identify a small group of cases that result in a major change in their therapeutic plan. Admittedly, the review of pathology slides involves additional time and effort for both consulting and referring institutions. It can ensure quality medical care and limit medicolegal liability. As the Association of Directors of Anatomic and Surgical Pathology recommended, second pathology review should be standard practice. It is necessary that our major Pathology Association and Societies adopt a strong position on this matter to influence government or insurance company to pay for this service rendered by pathologists.

Practicing pathology in the era of big data and personalized medicine.

PubMed

Gu, Jiang; Taylor, Clive R

2014-01-01

The traditional task of the pathologist is to assist physicians in making the correct diagnosis of diseases at the earliest possible stage to effectuate the optimal treatment strategy for each individual patient. In this respect surgical pathology (the traditional tissue diagnosis) is but a tool. It is not, of itself, the purpose of pathology practice; and change is in the air. This January 2014 issue of Applied Immunohistochemistry and Molecular Morphology (AIMM) embraces that change by the incorporation of the agenda and content of the journal Diagnostic Molecular Morphology (DMP). Over a decade ago AIMM introduced and promoted the concept of "molecular morphology," and has sought to publish molecular studies that correlate with the morphologic features that continue to define cancer and many diseases. That intent is now reinforced and extended by the merger with DMP, as a logical and timely response to the growing impact of a wide range of genetic and molecular technologies that are beginning to reshape the way in which pathology is practiced. The use of molecular and genomic techniques already demonstrates clear value in the diagnosis of disease, with treatment tailored specifically to individual patients. Personalized medicine is the future, and personalized medicine demands personalized pathology. The need for integration of the flood of new molecular data, with surgical pathology, digital pathology, and the full range of pathology data in the electronic medical record has never been greater. This review describes the possible impact of these pressures upon the discipline of pathology, and examines possible outcomes. There is a sense of excitement and adventure. Active adaption and innovation are required. The new AIMM, incorporating DMP, seeks to position itself for a central role in this process.

Practicing Pathology in the Era of Big Data and Personalized Medicine

PubMed Central

Gu, Jiang; Taylor, Clive R.; Phil, D

2014-01-01

The traditional task of the pathologist is to assist physicians in making the correct diagnosis of diseases at the earliest possible stage to effectuate the optimal treatment strategy for each individual patient. In this respect surgical pathology (the traditional tissue diagnosis) is but a tool. It is not, of itself, the purpose of pathology practice; and change is in the air. This January 2014 issue of Applied Immunohistochemistry and Molecular Morphology (AIMM) embraces that change by the incorporation of the agenda and content of the journal Diagnostic Molecular Morphology (DMP). Over a decade ago AIMM introduced and promoted the concept of “molecular morphology,” and has sought to publish molecular studies that correlate with the morphologic features that continue to define cancer and many diseases. That intent is now reinforced and extended by the merger with DMP, as a logical and timely response to the growing impact of a wide range of genetic and molecular technologies that are beginning to reshape the way in which pathology is practiced. The use of molecular and genomic techniques already demonstrates clear value in the diagnosis of disease, with treatment tailored specifically to individual patients. Personalized medicine is the future, and personalized medicine demands personalized pathology. The need for integration of the flood of new molecular data, with surgical pathology, digital pathology, and the full range of pathology data in the electronic medical record has never been greater. This review describes the possible impact of these pressures upon the discipline of pathology, and examines possible outcomes. There is a sense of excitement and adventure. Active adaption and innovation are required. The new AIMM, incorporating DMP, seeks to position itself for a central role in this process. PMID:24326463

Multicenter Validation Study of Pathologic Response and Tumor Thickness at the Tumor–Normal Liver Interface as Independent Predictors of Disease-Free Survival after Preoperative Chemotherapy and Surgery for Colorectal Liver Metastases

PubMed Central

Brouquet, Antoine; Zimmitti, Giuseppe; Kopetz, Scott; Stift, Judith; Julié, Catherine; Lemaistre, Anne-Isabelle; Agarwal, Atin; Patel, Viren; Benoist, Stephane; Nordlinger, Bernard; Gandini, Alessandro; Rivoire, Michel; Stremitzer, Stefan; Gruenberger, Thomas; Vauthey, Jean-Nicolas; Maru, Dipen M.

2014-01-01

Purpose To validate pathologic markers of response to preoperative chemotherapy as predictors of disease-free survival (DFS) after resection of colorectal liver metastases (CLM). Patients and Methods One hundred seventy one patients who underwent resection of CLM after preoperative chemotherapy at 4 centers were studied. Pathologic response defined as proportion of tumor cells remaining (categorized complete (0%), major (<50%) or minor (≥50%)) and tumor thickness at tumor–normal liver interface (TNI) (categorized <0.5 mm, 0.5 mm-<5 mm and ≥5 mm)—were assessed by a central pathology reviewer and local pathologists. Results Pathologic response was complete in 8%, major in 49% and minor in 43%. Tumor thickness at the TNI was <0.5 mm in 21%, 0.5 mm-<5 mm in 56% and ≥5 mm in 23%.In multivariate analyses, using either pathologic response or tumor thickness at TNI, pathologic response (P=.002,.009), tumor thickness at TNI (P=0.015, <.001), duration of preoperative chemotherapy(P=.028,.043), number of CLM (P=.038,.037) and margin (P=.011,.016) were associated with DFS. In a multivariate analysis using both parameters, tumor thickness at TNI (P=.004,.015), duration of preoperative chemotherapy(P=.025), number of nodules(P=.027) and margin(P=.014) were associated with DFS. Tumor size by pathology examination was the predictor of pathologic response. Predictors of tumor thickness at the TNI were tumor size and chemotherapy regimen. There was near perfect agreement for pathologic response (κ=.82) and substantial agreement (κ=.76) for tumor thickness between central reviewer and local pathologists. Conclusion Pathologic response and tumor thickness at the TNI are valid predictors of DFS after preoperative chemotherapy and surgery for CLM. PMID:23868456

Multicenter validation study of pathologic response and tumor thickness at the tumor-normal liver interface as independent predictors of disease-free survival after preoperative chemotherapy and surgery for colorectal liver metastases.

PubMed

Brouquet, Antoine; Zimmitti, Giuseppe; Kopetz, Scott; Stift, Judith; Julié, Catherine; Lemaistre, Anne-Isabelle; Agarwal, Atin; Patel, Viren; Benoist, Stephane; Nordlinger, Bernard; Gandini, Alessandro; Rivoire, Michel; Stremitzer, Stefan; Gruenberger, Thomas; Vauthey, Jean-Nicolas; Maru, Dipen M

2013-08-01

To validate pathologic markers of response to preoperative chemotherapy as predictors of disease-free survival (DFS) after resection of colorectal liver metastases (CLM). One hundred seventy-one patients who underwent resection of CLM after preoperative chemotherapy at 4 centers were studied. Pathologic response-defined as the proportion of tumor cells remaining (complete, 0%; major, <50%; minor, ≥50%) and tumor thickness at the tumor-normal liver interface (TNI) (<0.5 mm, 0.5 to <5 mm, ≥5 mm)-was assessed by a central pathology reviewer and local pathologists. Pathologic response was complete in 8% of patients, major in 49% of patients, and minor in 43% of patients. Tumor thickness at the TNI was <0.5 mm in 21% of patients, 0.5 to <5 mm in 56% of patients, and ≥5 mm in 23% of patients. On multivariate analyses, using either pathologic response or tumor thickness at TNI, pathologic response (P = .002, .009), tumor thickness at TNI (P = 0.015, <.001), duration of preoperative chemotherapy (P = .028, .043), number of CLM (P = .038, . 037), and margin (P = .011, .016) were associated with DFS. In a multivariate analysis using both parameters, tumor thickness at TNI (P = .004, .015), duration of preoperative chemotherapy (P = .025), number of nodules (P = .027), and margin (P = .014) were associated with DFS. Tumor size by pathology examination was the predictor of pathologic response. Predictors of tumor thickness at the TNI were tumor size and chemotherapy regimen. There was near perfect agreement for pathologic response (κ = .82) and substantial agreement (κ = .76) for tumor thickness between the central reviewer and local pathologists. Pathologic response and tumor thickness at the TNI are valid predictors of DFS after preoperative chemotherapy and surgery for CLM. Copyright © 2013 American Cancer Society.

Extracapillary proliferation in IgA nephropathy; recent findings and new ideas.

PubMed

Nasri, Hamid; Mubarak, Muhammed

2015-01-01

IgA nephropathy (IgAN) is an autoimmune disorder and is the most common form of primary glomerulonephritis (GN) worldwide. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. It is a slowly progressing disorder that leads to end-stage renal disease (ESRD) in up to 50% of the patients within 25 years of the onset of the disease. IgAN is defined by predominant IgA deposition in the mesangial area on immunofluorescence (IF) microscopy. Its histology varies from mild focal segmental proliferation of mesangial cells to severe diffuse global proliferation with extracapillary proliferation (crescent formation). The Oxford classification, designed in 2009, is a new classification for the evaluation of morphologic lesions of IgAN. This classification, containing four pathology variables, was found to have prognostic implications. The variables included are mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S) and the proportion of interstitial fibrosis and tubular atrophy (T). However, crescents were not included in the Oxford classification. In this mini-review, we describe the recent publications about the significance of extracapillary proliferation in IgAN and we conclude that, there is much controversy about the role of extracapillary proliferation as a significant prognostic factor in IgAN. Hence, it is important to re-consider crescents in IgAN patients. Therefore, we suggest further investigations on this aspect of IgAN disease.

Predictive factors suggesting an underestimation of gastric lesions initially diagnosed as adenomas by forceps biopsy.

PubMed

Ko, Sung Jun; Yang, Min A; Yun, So Hee; Park, Moon Sik; Han, Shang Hoon; Cho, Jin Woong

2016-03-01

The endoscopic forceps biopsy of gastric lesion may provide inadequate specimens for a correct diagnosis of the entire lesion. Therefore, a histologic discrepancy may exist between specimens obtained by forceps biopsy and by endoscopic resection. The aim of this study was to evaluate the endoscopic characteristics of an underestimation in gastric carcinomas initially diagnosed as adenomas by forceps biopsy. We retrospectively reviewed 431 lesions diagnosed as gastric adenomas by forceps biopsy and resected by endoscopic submucosal dissection (ESD) between January 2008 and December 2011. The endoscopic findings were reviewed for location, size, gross appearance, ulceration, and surface color. We compared these variables between the adenoma group and the carcinoma group, as defined by the post-resection pathological findings. The mean patient age was 65.63±9.30 years in the adenoma group and 64.75±10.30 years in the carcinoma group. The mean size of the lesion was 21.04±8.65 mm in the adenoma group and 22.06±7.46 mm in the carcinoma group. In the multivariate analysis, high-grade dysplasia from endoscopic forceps biopsy and red discoloration were significant variables associated with carcinoma in post-resection histology. Gastric adenomatous lesions with endoscopic characteristics of surface redness and high-grade dysplasia on forceps biopsy should be resected completely by ESD because of the high possibility of an underestimation after ESD.

The Mouse Heart Attack Research Tool (mHART) 1.0 Database.

PubMed

DeLeon-Pennell, Kristine Y; Iyer, Rugmani Padmanabhan; Ma, Yonggang; Yabluchanskiy, Andriy; Zamilpa, Rogelio; Chiao, Ying Ann; Cannon, Presley; Cates, Courtney; Flynn, Elizabeth R; Halade, Ganesh V; de Castro Bras, Lisandra E; Lindsey, Merry L

2018-05-18

The generation of Big Data has enabled systems-level dissections into the mechanisms of cardiovascular pathology. Integration of genetic, proteomic, and pathophysiological variables across platforms and laboratories fosters discoveries through multidisciplinary investigations and minimizes unnecessary redundancy in research efforts. The Mouse Heart Attack Research Tool (mHART) consolidates a large dataset of over 10 years of experiments from a single laboratory for cardiovascular investigators to generate novel hypotheses and identify new predictive markers of progressive left ventricular remodeling following myocardial infarction (MI) in mice. We designed the mHART REDCap database using our own data to integrate cardiovascular community participation. We generated physiological, biochemical, cellular, and proteomic outputs from plasma and left ventricles obtained from post-MI and no MI (naïve) control groups. We included both male and female mice ranging in age from 3 to 36 months old. After variable collection, data underwent quality assessment for data curation (e.g. eliminate technical errors, check for completeness, remove duplicates, and define terms). Currently, mHART 1.0 contains >888,000 data points and includes results from >2,100 unique mice. Database performance was tested and an example provided to illustrate database utility. This report explains how the first version of the mHART database was established and provides researchers with a standard framework to aid in the integration of their data into our database or in the development of a similar database.

A-kinase anchoring proteins that regulate cardiac remodeling.

PubMed

Carnegie, Graeme K; Burmeister, Brian T

2011-11-01

In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation-contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multiprotein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function.

A-Kinase Anchoring Proteins That Regulate Cardiac Remodeling

PubMed Central

Carnegie, Graeme K.; Burmeister, Brian T.

2012-01-01

In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation–contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multi-protein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function. PMID:22075671

Lateral ankle instability: MR imaging of associated injuries and surgical treatment procedures.

PubMed

Alparslan, Leyla; Chiodo, Christopher P

2008-12-01

Chronic ankle instability has been defined as the development of recurrent ankle sprains and persistent symptoms after initial lateral ankle sprain. The diagnosis of ankle instability is usually established on the patient's history, physical examination, and radiographic assessment. Patients have signs of both functional and mechanical instability, and the repetitive, chronic nature of the injury may lead to intra-articular and periarticular pathologies. This article discusses the incidence, etiology, and magnetic resonance (MR) imaging of these pathologies, reviews the surgical treatment procedures for lateral ankle instability, and presents the postoperative MR imaging findings.

Inverse relation between Braak stage and cerebrovascular pathology in Alzheimer predominant dementia

PubMed Central

Goulding, J.; Signorini, D.; Chatterjee, S.; Nicoll, J.; Stewart, J.; Morris, R.; Lammie, G

1999-01-01

The most common neuropathological substrates of dementia are Alzheimer's disease, cerebrovascular disease, and dementia with Lewy bodies. A preliminary, retrospective postmortem analysis was performed of the relative burden of each pathology in 25 patients with predominantly Alzheimer's disease-type dementia. Log linear modelling was used to assess the relations between ApoE genotype, Alzheimer's disease, and cerebrovascular disease pathology scores. Sixteen of 18 cases (89%) with a Braak neuritic pathology score ⩽4 had, in addition, significant cerebrovascular disease, or dementia with Lewy bodies, or both. There was a significant inverse relation between cerebrovascular disease and Braak stage (p=0.015). The frequency of the ApoE-ε4 allele was 36.4%. No evidence was found for an association between possession of the ApoE-ε4 allele and any one pathological variable over another. In this series most brains from patients with dementia for which Alzheimer's disease is the predominant neuropathological substrate also harboured significant cerebrovascular disease or dementia with Lewy bodies. The data suggest that these diseases are perhaps pathogenetically distinct, yet conspire to produce the dementing phenotype.

 PMID:10519874

The Integrative Role of the Sigh in Psychology, Physiology, Pathology, and Neurobiology

PubMed Central

Ramirez, Jan-Marino

2015-01-01

“Sighs, tears, grief, distress” expresses Johann Sebastian Bach in a musical example for the relationship between sighs and deep emotions. This review explores the neurobiological basis of the sigh and its relationship with psychology, physiology, and pathology. Sighs monitor changes in brain states, induce arousal, and reset breathing variability. These behavioral roles homeostatically regulate breathing stability under physiological and pathological conditions. Sighs evoked in hypoxia evoke arousal and thereby become critical for survival. Hypoarousal and failure to sigh have been associated with sudden infant death syndrome. Increased breathing irregularity may provoke excessive sighing and hyperarousal, a behavioral sequence that may play a role in panic disorders. Essential for generating sighs and breathing is the pre-Bötzinger complex. Modulatory and synaptic interactions within this local network and between networks located in the brainstem, cerebellum, cortex, hypothalamus, amygdala, and the periaqueductal gray may govern the relationships between physiology, psychology, and pathology. Unraveling these circuits will lead to a better understanding of how we balance emotions and how emotions become pathological. PMID:24746045

The possibilities of improvement in the sensitivity of cancer fluorescence diagnostics by computer image processing

NASA Astrophysics Data System (ADS)

Ledwon, Aleksandra; Bieda, Robert; Kawczyk-Krupka, Aleksandra; Polanski, Andrzej; Wojciechowski, Konrad; Latos, Wojciech; Sieron-Stoltny, Karolina; Sieron, Aleksander

2008-02-01

Background: Fluorescence diagnostics uses the ability of tissues to fluoresce after exposition to a specific wavelength of light. The change in fluorescence between normal and progression to cancer allows to see early cancer and precancerous lesions often missed by white light. Aim: To improve by computer image processing the sensitivity of fluorescence images obtained during examination of skin, oral cavity, vulva and cervix lesions, during endoscopy, cystoscopy and bronchoscopy using Xillix ONCOLIFE. Methods: Function of image f(x,y):R2 --> R 3 was transformed from original color space RGB to space in which vector of 46 values refers to every point labeled by defined xy-coordinates- f(x,y):R2 --> R 46. By means of Fisher discriminator vector of attributes of concrete point analalyzed in the image was reduced according to two defined classes defined as pathologic areas (foreground) and healthy areas (background). As a result the highest four fisher's coefficients allowing the greatest separation between points of pathologic (foreground) and healthy (background) areas were chosen. In this way new function f(x,y):R2 --> R 4 was created in which point x,y corresponds with vector Y, H, a*, c II. In the second step using Gaussian Mixtures and Expectation-Maximisation appropriate classificator was constructed. This classificator enables determination of probability that the selected pixel of analyzed image is a pathologically changed point (foreground) or healthy one (background). Obtained map of probability distribution was presented by means of pseudocolors. Results: Image processing techniques improve the sensitivity, quality and sharpness of original fluorescence images. Conclusion: Computer image processing enables better visualization of suspected areas examined by means of fluorescence diagnostics.

Advancing the Assessment of Personality Pathology With the Cognitive-Affective Processing System.

PubMed

Huprich, Steven K; Nelson, Sharon M

2015-01-01

The Cognitive-Affective Processing System (CAPS) is a dynamic and expansive model of personality proposed by Mischel and Shoda (1995) that incorporates dispositional and processing frameworks by considering the interaction of the individual and the situation, and the patterns of variation that result. These patterns of cognition, affect, and behavior are generally defined through the use of if … then statements, and provide a rich understanding of the individual across varying levels of assessment. In this article, we describe the CAPS model and articulate ways in which it can be applied to conceptualizing and assessing personality pathology. We suggest that the CAPS model is an ideal framework that integrates a number of current theories of personality pathology, and simultaneously overcomes a number of limits that have been empirically identified in the past.

A classification of the mechanisms producing pathological tissue changes.

PubMed

Grippo, John O; Oh, Daniel S

2013-05-01

The objectives are to present a classification of mechanisms which can produce pathological changes in body tissues and fluids, as well as to clarify and define the term biocorrosion, which has had a singular use in engineering. Considering the emerging field of biomedical engineering, it is essential to use precise definitions in the lexicons of engineering, bioengineering and related sciences such as medicine, dentistry and veterinary medicine. The mechanisms of stress, friction and biocorrosion and their pathological effects on tissues are described. Biocorrosion refers to the chemical, biochemical and electrochemical changes by degradation or induced growth of living body tissues and fluids. Various agents which can affect living tissues causing biocorrosion are enumerated which support the necessity and justify the use of this encompassing and more precise definition of biocorrosion. A distinction is made between the mechanisms of corrosion and biocorrosion.

[Mourning and depression, from the attachment theory perspective].

PubMed

Wolfberg, Elsa; Ekboir, Alberto; Faiman, Graciela; Finzi, Josefina; Freedman, Margarita; Heath, Adela; Martínez de Cipolatti, María C

2011-01-01

Since depression, according to OMS, is such a worldwide condition, it is necessary to be able to distinguish a normal mourning from a pathological mourning and a depression, so as to qualify patients and health professionals to be able to support a normal mourning without medicating it nor hurrying (hasting) it, as well as being able to treat a depression adequately when it appears as a complication. Attachment theory focuses on mourning after loss with notions such as 1- acceptance of search for the lost person as a normal fact; 2- that mourning in children may have non-pathological outcomes; 3- that a non-processed mourning may be transmitted in an intergenerational way, and 4- also defines which elements may determine a pathological mourning or a depression. A clinical case is presented with an analysis of these notions.

Clinical predictors of severe cerebral amyloid angiopathy and influence of APOE genotype in persons with pathologically verified Alzheimer disease.

PubMed

Ringman, John M; Sachs, Michael C; Zhou, Yan; Monsell, Sarah E; Saver, Jeffrey L; Vinters, Harry V

2014-07-01

Although cerebral amyloid angiopathy (CAA) has important clinical implications, our understanding of it and ability to diagnose it are limited. To determine pathological correlates and clinical factors identifiable during life that predict the presence of severe CAA in persons with pathologically confirmed Alzheimer disease (AD). We compared demographic and clinical variables at the earliest visit during life at which participants were found to have cognitive impairment and compared pathological variables between persons ultimately found to have no or severe CAA at autopsy using logistic regression. Analyses were repeated separately for carriers and noncarriers of the APOE ε4 allele. Data were obtained from the Uniform Data Set, which comprises longitudinal clinical assessments performed in the Alzheimer's Disease Centers funded by the National Institute on Aging. Participants included 193 persons with AD and severe CAA and 232 persons with AD and no CAA. All participants had cognitive impairment and met National Institute on Aging-Reagan Institute neuropathological criteria for AD. Prevalence of demographic characteristics and the APOE ε4 allele and odds ratios (ORs) of clinical variables for the prediction of severe CAA. Persons with severe CAA compared with those without CAA were more likely to carry an APOE ε4 allele (64.9% vs 42.8%, respectively; P < .001), to be Hispanic (6.8% vs 1.3%, respectively; P = .003), to have had a transient ischemic attack (12.5% vs 6.1%, respectively; OR = 2.1; 95% CI, 1.0-4.4), and to have lower degrees of diffuse amyloid plaque pathology (mean [SD] Consortium to Establish a Registry for Alzheimer's Disease score, 1.2 [0.5] vs 1.4 [0.8], respectively; P = .01). Those with CAA compared with those without CAA more commonly had intracerebral hemorrhage (9.3% vs 3.5%, respectively; P = .01), cortical microinfarcts (20.7% vs 12.9%, respectively; P = .03), and subcortical leukoencephalopathy (20.5% vs 12.1%, respectively; P = .02). Noncarriers of the APOE ε4 allele with severe CAA compared with those without CAA had a higher prevalence of stroke (11.1% vs 3.9%, respectively; OR = 3.8; 95% CI, 1.0-14.6) and hypercholesterolemia (50.0% vs 32.7%, respectively; OR = 2.3; 95% CI, 1.1-4.7). Being Hispanic and having had a transient ischemic attack-like episode were predictors of CAA in persons with AD. Less diffuse parenchymal amyloid pathology in persons with severe CAA suggests a difference in β-amyloid trafficking.

Retrospective reports of attachment disruptions, parental abuse and neglect mediate the relationship between pathological narcissism and self-esteem.

PubMed

Maxwell, Kendal; Huprich, Steven

2014-10-01

Studies have shown a direct relationship between pathological narcissism and self-esteem; however, there have not been many studies that have empirically tested which theoretically relevant variables mediate this relationship. In the present study, we evaluated how self-reported, early negative childhood experiences with parental figures mediate the relationship between pathological narcissism and self-esteem. Four-hundred eight-five undergraduates from a Midwestern university retrospectively assessed their experiences of parental attachment and bonding, as well as their levels of pathological narcissism and current self-esteem. There was a significant correlation among all pathological narcissism subscales and self-esteem, except for the Exploitativeness subscale. Self-esteem was negatively correlated with all negative childhood experiences on the Childhood Trauma Questionnaire (CTQ) and was positively correlated with positive childhood experiences on the Parental Attachment Questionnaire (PAQ). The parental relationship quality was negatively associated with all but one Pathological Narcissism Inventory subscale, as was the PAQ total score. Lastly, emotional neglect on the CTQ significantly mediated the relationship between several pathological narcissism subscales and self-esteem. When investigating parental attachment and parental bonding, the quality of the relationship with the parent was a significant mediator between pathological narcissism and self-esteem. These findings demonstrate the importance of understanding the adverse effects of parental abuse and neglect on healthy development of the self and self-esteem. Clinical implications of these findings are discussed. Copyright © 2014 John Wiley & Sons, Ltd.

REVIEW - Thermal Physiology of Laboratory Mice: Defining Thermoneutrality

EPA Science Inventory

In terms of total number of publications, the laboratory mouse (Mus musculus) has emerged as the most popular test subject in biomedical research. Mice are used as models to study obesity, diabetes, eNS diseases and variety of other pathologies. Mice are classified as homeotherms...

Action-angle variables for the harmonic oscillator: Ambiguity spin × duplication spin

NASA Astrophysics Data System (ADS)

de Oliveira, César R.; Malta, Coraci P.

1984-07-01

The difficulties of obtaining for the harmonic oscillator a well-defined unitary transformation to action-angle variables were overcome by M. Moshinsky and T. H. Seligman ( Ann. Phys. (N.Y.)114 (1978), 243) through the introduction of a spinlike variable (ambiguity spin) from a classical point of view. The difficulty of defining a unitary phase operator for the harmonic oscillator was overcome by Roger G. Newton ( Ann. Phys. (N.Y.)124 (1980), 324) also through the introduction of a spinlike variable (named duplication spin by us) but within a quantum framework. Here the relation between the ambiguity spin and the duplication spin is investigated by introducing these two types of spins in the canonical transformation to action-angle variables. In this way both well-defined unitary transformation and phase operators were obtained.

Herpes Keratitis

PubMed Central

Rowe, A.; St Leger, A.; Jeon, S.; Dhaliwal, D.K.; Knickelbein, J.E.; Hendricks, R.L.

2012-01-01

Herpes Simplex Virus-1 (HSV-1) infects the majority of the world’s population. These infections are often asymptomatic, but ocular HSV-1 infections cause multiple pathologies with perhaps the most destructive being Herpes Stromal Keratitis (HSK). HSK lesions, which are immunoinflammatory in nature, can recur throughout life and often cause progressive corneal scaring resulting in visual impairment. Current treatment involves broad local immunosuppression with topical steroids along with antiviral coverage. Unfortunately, the immunopathologic mechanisms defined in animal models of HSK have not yet translated into improved therapy. Herein, we review the clinical epidemiology and pathology of the disease and summarize the large amount of basic research regarding the immunopathology of HSK. We examine the role of the innate and adaptive immune system in the clearance of virus and the destruction of the normal corneal architecture that is typical of HSK. Our goal is to define current knowledge of the pathogenic mechanisms and recurrent nature of HSK and identify areas that require further study. PMID:22944008

Comparative speaking, shouting and singing voice range profile measurement: physiological and pathological aspects.

PubMed

Hacki, T

1996-01-01

The Voice Range Profile (VRP) measurement offers a method for the investigation of voice modalities i.e. speaking voice, shouting voice and singing voice in their mutual pitch and intensity relations. The parameters FO and SPL are evaluated by means of automatic pitch and SPL measurements from (1) sustained phonation /a:/ in the speaker's natural pitch and intensity range, (2) the continuous speaking voice beginning with Pianissimo up to Fortissimo, (3) the shouting voice. Vocal intensity is plotted vertically, vocal pitch horizontally. The displays of the vocal intensity versus fundamental frequency are defined as singing voice range profile (VRP), speaking VRP and shouting VRP. The VRPs are superimposed on the same plot. Their form, their shape and their position to each other are analysed. The physiological relationships between the VRPs of the different voice modalities to each other are defined. The pathological relationships between the VRPs (i.e. reduction, shifting) give information about etiology and pathomechanism of voice disorders.

[DSM-5: important changes in the field of addictive diseases].

PubMed

Heinz, A; Friedel, E

2014-05-01

There are two major changes in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) concerning the field of addiction. Firstly, the previous distinction between abuse and dependence has been abolished and both disorders are now subsumed under the category addiction and related disorders. Secondly, pathological gambling has now been included in the section of addiction with slight changes in diagnostic criteria. Both changes have major implications for the definition and conceptualization of what we call a psychiatric "disease" or "disorder", which have also been addressed in the introductory statement of DSM-5. Concerning the category of abuse that is now part of substance use disorders, there is a concern that a well-defined disorder ("dependence") is now mixed with a less well-defined syndrome ("abuse"). The inclusion of non-substance, behavioral addictions poses the danger of pathologizing a wide range of human behavior in future revisions of the classification. Both concerns are further addressed in this article.

Workflow computing. Improving management and efficiency of pathology diagnostic services.

PubMed

Buffone, G J; Moreau, D; Beck, J R

1996-04-01

Traditionally, information technology in health care has helped practitioners to collect, store, and present information and also to add a degree of automation to simple tasks (instrument interfaces supporting result entry, for example). Thus commercially available information systems do little to support the need to model, execute, monitor, coordinate, and revise the various complex clinical processes required to support health-care delivery. Workflow computing, which is already implemented and improving the efficiency of operations in several nonmedical industries, can address the need to manage complex clinical processes. Workflow computing not only provides a means to define and manage the events, roles, and information integral to health-care delivery but also supports the explicit implementation of policy or rules appropriate to the process. This article explains how workflow computing may be applied to health-care and the inherent advantages of the technology, and it defines workflow system requirements for use in health-care delivery with special reference to diagnostic pathology.

Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype

PubMed Central

Wei, Caimiao; Gould, Rebekah; Yu, Xian; Zhang, Ya; Liu, Mei; Walls, Andrew; Bousamra, Alex; Ramineni, Maheshwari; Sinn, Bruno; Hunt, Kelly; Buchholz, Thomas A.; Valero, Vicente; Buzdar, Aman U.; Yang, Wei; Brewster, Abenaa M.; Moulder, Stacy; Pusztai, Lajos; Hatzis, Christos; Hortobagyi, Gabriel N.

2017-01-01

Purpose To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)–targeted treatment. Methods We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor–negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor–negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. Conclusion RCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated. PMID:28135148

Impact of menstruation on select hematology and clinical chemistry variables in cynomolgus macaques.

PubMed

Perigard, Christopher J; Parrula, M Cecilia M; Larkin, Matthew H; Gleason, Carol R

2016-06-01

In preclinical studies with cynomolgus macaques, it is common to have one or more females presenting with menses. Published literature indicates that the blood lost during menses causes decreases in red blood cell mass variables (RBC, HGB, and HCT), which would be a confounding factor in the interpretation of drug-related effects on clinical pathology data, but no scientific data have been published to support this claim. This investigation was conducted to determine if the amount of blood lost during menses in cynomolgus macaques has an effect on routine hematology and serum chemistry variables. Ten female cynomolgus macaques (Macaca fascicularis), 5 to 6.5 years old, were observed daily during approximately 3 months (97 days) for the presence of menses. Hematology and serum chemistry variables were evaluated twice weekly. The results indicated that menstruation affects the erythrogram including RBC, HGB, HCT, MCHC, MCV, reticulocyte count, RDW, the leukogram including neutrophil, lymphocyte, and monocyte counts, and chemistry variables, including GGT activity, and the concentrations of total proteins, albumin, globulins, and calcium. The magnitude of the effect of menstruation on susceptible variables is dependent on the duration of the menstrual phase. Macaques with menstrual phases lasting ≥ 7 days are more likely to develop changes in variables related to chronic blood loss. In preclinical toxicology studies with cynomolgus macaques, interpretation of changes in several commonly evaluated hematology and serum chemistry variables requires adequate clinical observation and documentation concerning presence and duration of menses. There is a concern that macaques with long menstrual cycles can develop iron deficiency anemia due to chronic menstrual blood loss. © 2016 American Society for Veterinary Clinical Pathology.

Routine Digital Pathology Workflow: The Catania Experience

PubMed Central

Fraggetta, Filippo; Garozzo, Salvatore; Zannoni, Gian Franco; Pantanowitz, Liron; Rossi, Esther Diana

2017-01-01

Introduction: Successful implementation of whole slide imaging (WSI) for routine clinical practice has been accomplished in only a few pathology laboratories worldwide. We report the transition to an effective and complete digital surgical pathology workflow in the pathology laboratory at Cannizzaro Hospital in Catania, Italy. Methods: All (100%) permanent histopathology glass slides were digitized at ×20 using Aperio AT2 scanners. Compatible stain and scanning slide racks were employed to streamline operations. eSlide Manager software was bidirectionally interfaced with the anatomic pathology laboratory information system. Virtual slide trays connected to the two-dimensional (2D) barcode tracking system allowed pathologists to confirm that they were correctly assigned slides and that all tissues on these glass slides were scanned. Results: Over 115,000 glass slides were digitized with a scan fail rate of around 1%. Drying glass slides before scanning minimized them sticking to scanner racks. Implementation required introduction of a 2D barcode tracking system and modification of histology workflow processes. Conclusion: Our experience indicates that effective adoption of WSI for primary diagnostic use was more dependent on optimizing preimaging variables and integration with the laboratory information system than on information technology infrastructure and ensuring pathologist buy-in. Implementation of digital pathology for routine practice not only leveraged the benefits of digital imaging but also creates an opportunity for establishing standardization of workflow processes in the pathology laboratory. PMID:29416914

Routine Digital Pathology Workflow: The Catania Experience.

PubMed

Fraggetta, Filippo; Garozzo, Salvatore; Zannoni, Gian Franco; Pantanowitz, Liron; Rossi, Esther Diana

2017-01-01

Successful implementation of whole slide imaging (WSI) for routine clinical practice has been accomplished in only a few pathology laboratories worldwide. We report the transition to an effective and complete digital surgical pathology workflow in the pathology laboratory at Cannizzaro Hospital in Catania, Italy. All (100%) permanent histopathology glass slides were digitized at ×20 using Aperio AT2 scanners. Compatible stain and scanning slide racks were employed to streamline operations. eSlide Manager software was bidirectionally interfaced with the anatomic pathology laboratory information system. Virtual slide trays connected to the two-dimensional (2D) barcode tracking system allowed pathologists to confirm that they were correctly assigned slides and that all tissues on these glass slides were scanned. Over 115,000 glass slides were digitized with a scan fail rate of around 1%. Drying glass slides before scanning minimized them sticking to scanner racks. Implementation required introduction of a 2D barcode tracking system and modification of histology workflow processes. Our experience indicates that effective adoption of WSI for primary diagnostic use was more dependent on optimizing preimaging variables and integration with the laboratory information system than on information technology infrastructure and ensuring pathologist buy-in. Implementation of digital pathology for routine practice not only leveraged the benefits of digital imaging but also creates an opportunity for establishing standardization of workflow processes in the pathology laboratory.

Integrating Ecosystem Carbon Dynamics into State-and-Transition Simulation Models of Land Use/Land Cover Change

NASA Astrophysics Data System (ADS)

Sleeter, B. M.; Daniel, C.; Frid, L.; Fortin, M. J.

2016-12-01

State-and-transition simulation models (STSMs) provide a general approach for incorporating uncertainty into forecasts of landscape change. Using a Monte Carlo approach, STSMs generate spatially-explicit projections of the state of a landscape based upon probabilistic transitions defined between states. While STSMs are based on the basic principles of Markov chains, they have additional properties that make them applicable to a wide range of questions and types of landscapes. A current limitation of STSMs is that they are only able to track the fate of discrete state variables, such as land use/land cover (LULC) classes. There are some landscape modelling questions, however, for which continuous state variables - for example carbon biomass - are also required. Here we present a new approach for integrating continuous state variables into spatially-explicit STSMs. Specifically we allow any number of continuous state variables to be defined for each spatial cell in our simulations; the value of each continuous variable is then simulated forward in discrete time as a stochastic process based upon defined rates of change between variables. These rates can be defined as a function of the realized states and transitions of each cell in the STSM, thus providing a connection between the continuous variables and the dynamics of the landscape. We demonstrate this new approach by (1) developing a simple IPCC Tier 3 compliant model of ecosystem carbon biomass, where the continuous state variables are defined as terrestrial carbon biomass pools and the rates of change as carbon fluxes between pools, and (2) integrating this carbon model with an existing LULC change model for the state of Hawaii, USA.

A SYSTEMATIC REVIEW OF PLACENTAL PATHOLOGY IN MATERNAL DIABETES MELLITUS

PubMed Central

Huynh, J.; Dawson, D.; Roberts, D.; Bentley-Lewis, R.

2014-01-01

During a pregnancy complicated by diabetes, the human placenta undergoes a number of functional and structural pathologic changes, such as increased placental weight and increased incidence of placental lesions including villous maturational defects and fibrinoid necrosis. The pathologic findings reported have differed among studies, potentially reflecting differences in type of diabetes, study methodology, or glycemic control of study participants. Alternatively, these discrepancies may represent different biologic adaptations to distinct metabolic diseases. In order to clarify these distinctions, we conducted a comprehensive review of English language citations in Pubmed and Embase using the keywords “diabetes”, “placenta”, AND “pathology”. Abstracts were reviewed for relevance then full-text articles were reviewed in order to extract a comprehensive summary of current pathological findings associated with pregestational and gestational diabetes mellitus, as well as an understanding of the impact of glycemic control on placental pathology. Placental abnormalities most consistently associated with maternal diabetes are an increased incidence of villous immaturity, increased measures of angiogenesis, and increased placental weight. The literature suggests that, despite similarities in placental abnormalities, differences in placental pathology may reflect differences in pathophysiology among different types of diabetes. Consequently, standardization of terminology used to define placental lesions is warranted. Moreover, further research is needed to investigate the impact of pathophysiology, glycemic control and clinical factors, such as infant sex, weight and race, on placental structure and function. PMID:25524060

A call for a value based approach to laboratory medicine funding.

PubMed

St John, A; Edwards, G; Fisher, S; Badrick, T; Callahan, J; Crothers, J

2015-09-01

All areas of healthcare, including pathology, are being challenged by the reality that the days of ever increasing budgets are over and the key debate is about how to provide value for money. As originally described by Porter and Tiesberg, value-based healthcare is defined as maximising outcomes over cost by moving away from fee for service models to ones that reward providers on the basis of outcomes (1). While production efficiencies will continue to evolve, the opportunities for future stepwise improvements in production costs are likely to have diminished. The focus now is on delivering improved testing outcomes in a relatively cost neutral or at least cost effective way. This brings pathology into line with other health services that focus on value for money for payers, and maximising health outcomes for consumers. This would signal a break from the existing pathology funding model, which does not directly recognise or reward the contribution of pathology towards improved health outcomes, or seek to decommission tests that offer little clinical value. Pathology has a direct impact on clinical and economic outcomes that extend from testing and it is important to garner support for a new approach to funding that incentivises improvements of the overall quality and contribution of the pathology service. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Age and Alzheimer's pathology disrupt default mode network functioning via alterations in white matter microstructure but not hyperintensities.

PubMed

Brown, Christopher A; Jiang, Yang; Smith, Charles D; Gold, Brian T

2018-04-19

The default mode network (DMN) comprises defined brain regions contributing to internally-directed thought processes. Reductions in task-induced deactivation in the DMN have been associated with increasing age and poorer executive task performance, but factors underlying these functional changes remain unclear. We investigated contributions of white matter (WM) microstructure, WM hyperintensities (WMH) and Alzheimer's pathology to age-related alterations in DMN function. Thirty-five cognitively normal older adults and 29 younger adults underwent working memory task fMRI and diffusion tensor imaging. In the older adults, we measured cerebrospinal fluid tau and Aβ 42 (markers of AD pathology), and WMH on FLAIR imaging (marker of cerebrovascular disease). We identified a set of regions showing DMN deactivation and a set of inter-connecting WM tracts (DMN-WM) common to both age groups. There were negative associations between DMN deactivation and task performance in older adults, consistent with previous studies. Decreased DMN deactivation was associated with AD pathology and WM microstructure but not with WMH volume. Mediation analyses showed that WM microstructure mediated declines in DMN deactivation associated with both aging and AD pathology. Together these results suggest that AD pathology may exert a "second-hit" on WM microstructure, over-and-above the effects of age, both contributing to diminished DMN deactivation in older adults. Copyright © 2018 Elsevier Ltd. All rights reserved.

Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer: Implications for Adjuvant Radiation Therapy

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

Reddy, Abhinav V.; Pariser, Joseph J.; Pearce, Shane M.

2016-04-01

Purpose: In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy. Methods and Materials: Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined usingmore » follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariate analysis for association with LF and overall survival. Results: A total of 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 years old, and median follow-up was 11 months. On univariate analysis, margin status, pT stage, and pN stage, were all associated with LF (P<.05), however, on multivariate analysis, only pT and pN stages were significantly associated with LF (P<.05). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence. Conclusions: Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.« less

Stereotyped high-frequency oscillations discriminate seizure onset zones and critical functional cortex in focal epilepsy.

PubMed

Liu, Su; Gurses, Candan; Sha, Zhiyi; Quach, Michael M; Sencer, Altay; Bebek, Nerses; Curry, Daniel J; Prabhu, Sujit; Tummala, Sudhakar; Henry, Thomas R; Ince, Nuri F

2018-01-30

High-frequency oscillations in local field potentials recorded with intracranial EEG are putative biomarkers of seizure onset zones in epileptic brain. However, localized 80-500 Hz oscillations can also be recorded from normal and non-epileptic cerebral structures. When defined only by rate or frequency, physiological high-frequency oscillations are indistinguishable from pathological ones, which limit their application in epilepsy presurgical planning. We hypothesized that pathological high-frequency oscillations occur in a repetitive fashion with a similar waveform morphology that specifically indicates seizure onset zones. We investigated the waveform patterns of automatically detected high-frequency oscillations in 13 epilepsy patients and five control subjects, with an average of 73 subdural and intracerebral electrodes recorded per patient. The repetitive oscillatory waveforms were identified by using a pipeline of unsupervised machine learning techniques and were then correlated with independently clinician-defined seizure onset zones. Consistently in all patients, the stereotypical high-frequency oscillations with the highest degree of waveform similarity were localized within the seizure onset zones only, whereas the channels generating high-frequency oscillations embedded in random waveforms were found in the functional regions independent from the epileptogenic locations. The repetitive waveform pattern was more evident in fast ripples compared to ripples, suggesting a potential association between waveform repetition and the underlying pathological network. Our findings provided a new tool for the interpretation of pathological high-frequency oscillations that can be efficiently applied to distinguish seizure onset zones from functionally important sites, which is a critical step towards the translation of these signature events into valid clinical biomarkers.awx374media15721572971001. © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Use of Multiple Correspondence Analysis to Explore Associations between Categories of Qualitative Variables in Healthy Ageing.

PubMed

Costa, Patrício Soares; Santos, Nadine Correia; Cunha, Pedro; Cotter, Jorge; Sousa, Nuno

2013-01-01

The main focus of this study was to illustrate the applicability of multiple correspondence analysis (MCA) in detecting and representing underlying structures in large datasets used to investigate cognitive ageing. Principal component analysis (PCA) was used to obtain main cognitive dimensions, and MCA was used to detect and explore relationships between cognitive, clinical, physical, and lifestyle variables. Two PCA dimensions were identified (general cognition/executive function and memory), and two MCA dimensions were retained. Poorer cognitive performance was associated with older age, less school years, unhealthier lifestyle indicators, and presence of pathology. The first MCA dimension indicated the clustering of general/executive function and lifestyle indicators and education, while the second association was between memory and clinical parameters and age. The clustering analysis with object scores method was used to identify groups sharing similar characteristics. The weaker cognitive clusters in terms of memory and executive function comprised individuals with characteristics contributing to a higher MCA dimensional mean score (age, less education, and presence of indicators of unhealthier lifestyle habits and/or clinical pathologies). MCA provided a powerful tool to explore complex ageing data, covering multiple and diverse variables, showing if a relationship exists and how variables are related, and offering statistical results that can be seen both analytically and visually.

Personality Constellations of Adolescents with Histories of Traumatic Parental Separations

PubMed Central

Malone, Johanna C.; Westen, Drew; Levendosky, Alytia A.

2014-01-01

Consistent with attachment theory and a developmental psychopathology framework, a growing body of research suggests that traumatic parental separations may lead to unique pathways of personality adaptation and maladaptation. The present study both examined personality characteristics and identified personality subtypes of adolescents with histories of traumatic separations. Randomly selected psychologists and psychiatrists provided data on 236 adolescents with histories of traumatic separations using a personality pathology instrument designed for use by clinically experienced observers, the Shedler-Westen Assessment Procedure (SWAP-II-A). Using a Q factor analysis, five distinct personality subtypes were identified: internalizing/avoidant, psychopathic, resilient, impulsive dysregulated, and immature dysregulated. Initial support for the validity of the subtypes was established based on Axis I and Axis II pathology, adaptive functioning, developmental history, and family history variables. The personality subtypes demonstrated substantial incremental validity in predicting adaptive functioning, above and beyond demographic variables and histories of other traumatic experiences. PMID:24647212

A tissue-engineered subcutaneous pancreatic cancer model for antitumor drug evaluation.

PubMed

He, Qingyi; Wang, Xiaohui; Zhang, Xing; Han, Huifang; Han, Baosan; Xu, Jianzhong; Tang, Kanglai; Fu, Zhiren; Yin, Hao

2013-01-01

The traditional xenograft subcutaneous pancreatic cancer model is notorious for its low incidence of tumor formation, inconsistent results for the chemotherapeutic effects of drug molecules of interest, and a poor predictive capability for the clinical efficacy of novel drugs. These drawbacks are attributed to a variety of factors, including inoculation of heterogeneous tumor cells from patients with different pathological histories, and use of poorly defined Matrigel(®). In this study, we aimed to tissue-engineer a pancreatic cancer model that could readily cultivate a pancreatic tumor derived from highly homogenous CD24(+)CD44(+) pancreatic cancer stem cells delivered by a well defined electrospun scaffold of poly(glycolide-co-trimethylene carbonate) and gelatin. The scaffold supported in vitro tumorigenesis from CD24(+)CD44(+) cancer stem cells for up to 7 days without inducing apoptosis. Moreover, CD24(+)CD44(+) cancer stem cells delivered by the scaffold grew into a native-like mature pancreatic tumor within 8 weeks in vivo and exhibited accelerated tumorigenesis as well as a higher incidence of tumor formation than the traditional model. In the scaffold model, we discovered that oxaliplatin-gemcitabine (OXA-GEM), a chemotherapeutic regimen, induced tumor regression whereas gemcitabine alone only capped tumor growth. The mechanistic study attributed the superior antitumorigenic performance of OXA-GEM to its ability to induce apoptosis of CD24(+)CD44(+) cancer stem cells. Compared with the traditional model, the scaffold model demonstrated a higher incidence of tumor formation and accelerated tumor growth. Use of a tiny population of highly homogenous CD24(+)CD44(+) cancer stem cells delivered by a well defined scaffold greatly reduces the variability associated with the traditional model, which uses a heterogeneous tumor cell population and poorly defined Matrigel. The scaffold model is a robust platform for investigating the antitumorigenesis mechanism of novel chemotherapeutic drugs with a special focus on cancer stem cells.

Automated Surgical Approach Planning for Complex Skull Base Targets: Development and Validation of a Cost Function and Semantic At-las.

PubMed

Aghdasi, Nava; Whipple, Mark; Humphreys, Ian M; Moe, Kris S; Hannaford, Blake; Bly, Randall A

2018-06-01

Successful multidisciplinary treatment of skull base pathology requires precise preoperative planning. Current surgical approach (pathway) selection for these complex procedures depends on an individual surgeon's experiences and background training. Because of anatomical variation in both normal tissue and pathology (eg, tumor), a successful surgical pathway used on one patient is not necessarily the best approach on another patient. The question is how to define and obtain optimized patient-specific surgical approach pathways? In this article, we demonstrate that the surgeon's knowledge and decision making in preoperative planning can be modeled by a multiobjective cost function in a retrospective analysis of actual complex skull base cases. Two different approaches- weighted-sum approach and Pareto optimality-were used with a defined cost function to derive optimized surgical pathways based on preoperative computed tomography (CT) scans and manually designated pathology. With the first method, surgeon's preferences were input as a set of weights for each objective before the search. In the second approach, the surgeon's preferences were used to select a surgical pathway from the computed Pareto optimal set. Using preoperative CT and magnetic resonance imaging, the patient-specific surgical pathways derived by these methods were similar (85% agreement) to the actual approaches performed on patients. In one case where the actual surgical approach was different, revision surgery was required and was performed utilizing the computationally derived approach pathway.

Longitudinal β-Amyloid Deposition and Hippocampal Volume in Preclinical Alzheimer Disease and Suspected Non-Alzheimer Disease Pathophysiology.

PubMed

Gordon, Brian A; Blazey, Tyler; Su, Yi; Fagan, Anne M; Holtzman, David M; Morris, John C; Benzinger, Tammie L S

2016-10-01

Preclinical Alzheimer disease (AD) can be staged using a 2-factor model denoting the presence or absence of β-amyloid (Aβ+/-) and neurodegeneration (ND+/-). The association of these stages with longitudinal biomarker outcomes is unknown. To examine whether longitudinal Aβ accumulation and hippocampal atrophy differ based on initial preclinical staging. This longitudinal population-based cohort study used data collected at the Knight Alzheimer Disease Research Center, Washington University, St Louis, Missouri, from December 1, 2006, to June 31, 2015. Cognitively normal older adults (n = 174) were recruited from the longitudinal Adult Children Study and Healthy Aging and Senile Dementia Study at the Knight Alzheimer Disease Research Center. At baseline, all participants had magnetic resonance imaging (MRI) scans, positron emission tomography (PET) scans with carbon 11-labeled Pittsburgh Compound B (PiB), and cerebrospinal fluid assays of tau and phosphorylated tau (ptau) acquired within 12 months. Using the baseline biomarkers, individuals were classified into preclinical stage 0 (Aβ-/ND-), 1 (Aβ+/ND-), or 2+ (Aβ+/ND+) or suspected non-AD pathophysiology (SNAP; Aβ-/ND+). Subsequent longitudinal accumulation of Aβ assessed with PiB PET and loss of hippocampal volume assessed with MRI in each group. Among the 174 participants (81 men [46.6%]; 93 women [53.4%]; mean [SD] age, 65.7 [8.9] years), a proportion (14%-17%) of individuals with neurodegeneration alone (SNAP) later demonstrated Aβ+. The rates of Aβ accumulation and loss of hippocampal volume in individuals with SNAP were indistinguishable from those without any pathologic features at baseline (for Aβ accumulation: when hippocampal volume was used to define ND, t = 0.00 [P > .99]; when tau and ptau were used to define ND, t = -0.02 [P = .98]; for loss of hippocampal volume: when hippocampal volume was used to define ND, t = -1.34 [P = .18]; when tau and ptau were used to define ND, t = 0.84 [P = .40]). Later preclinical stages (stages 1 and 2+) had elevated Aβ accumulation. Using hippocampal volume to define ND, individuals with stage 1 had accelerated Aβ accumulation relative to stage 0 (t = 11.06; P < .001), stage 2+ (t = 2.10; P = .04), and SNAP (t = 9.32; P < .001), and those with stage 2+ had accelerated Aβ accumulation relative to stage 0 (t = 4.38; P < .001) and SNAP (t = 4.08; P < .001). When ND was defined using tau and ptau, individuals with stage 2+ had accelerated Aβ accumulation relative to stage 0 (t = 4.96) and SNAP (t = 4.06), and those with stage 1 had accelerated Aβ accumulation relative to stage 0 (t = 8.44) and SNAP (t = 6.61) (P < .001 for all comparisons). When ND was defined using cerebrospinal fluid biomarkers, individuals with stage 2+ had accelerated hippocampal atrophy relative to stage 0 (t = -3.41; P < .001), stage 1 (t = -2.48; P = .03), and SNAP (t = -2.26; P = .03). More advanced preclinical stages of AD have greater longitudinal Aβ accumulation. SNAP appears most likely to capture inherent individual variability in brain structure or to represent comorbid pathologic features rather than early emerging AD. Low hippocampal volumes or elevated levels of tau or ptau in isolation may not accurately represent ongoing neurodegenerative processes.

The use of pathological grief outcomes in bereavement studies on African Americans.

PubMed

Granek, Leeat; Peleg-Sagy, Tal

2017-06-01

Pathological bereavement outcomes (i.e., complicated grief, traumatic grief, prolonged grief disorder) are a robust and growing research area in the psychological and medical sciences. Although grief is considered to be a universal phenomenon, it is well documented that grieving processes and outcomes are culturally and contextually bound. The objectives of this study were: (a) to examine representations of African Americans in the grief and mourning literature and to assess the extent to which this research utilizes pathological grief outcomes; and (b) to examine the characteristics of pathological grief constructs in the literature to assess their relevance for African American populations. We conducted comprehensive searches of three scientific databases including PsycNET, Medline, and CINAHL, which contain the majority of grief and mourning literature published between January 1998 and February 2014. We found 59 studies addressing grief and mourning in African Americans. Thirteen of these studies used pathological grief outcomes. Pathological grief outcomes that were constructed and validated on White populations were frequently used as outcome variables with African American participants. We discuss the implications for the grief and mourning field and argue that the failure to use culturally sensitive outcome measures in research studies is a form of epistemological violence that may have negative research and clinical implications for African Americans and other ethnic minorities.

Pathological Gambling among Italian Nursing Students.

PubMed

Cicolini, Giancarlo; Della Pelle, Carlo; Simonetti, Valentina; Comparcini, Dania; Sepede, Gianna; Cipollone, Francesco

2018-04-01

To investigate the role of psychiatric dimensions, behavioral or substance addictions and demographical variables as determinants of pathological gambling among nursing students. Multicenter cross-sectional study. From June to October 2015 a survey was carried out among Italian Nursing students. Data were collected using a six-section tool. Nursing students who completed the survey numbered 1083, 902 (83.3%) had some problems with gambling and 29 (2.7%) showed pathological gambling. Percentage of pathological gambling was significantly associate with illicit drug/alcohol use (65.5%; p=0.001) and with male gender (58.6%) comparing to student nurse with non-pathological gambling (20%) and those with some problem (24.2%). Significant main effect was observed for IAT score (Beta=0.119, t=3.28, p=0.001): higher IAT scores were associated with higher SOGS scores. Italian nursing students have some problems with gambling and pathological gambling problem, and males are those who have more problems. Results might be useful for faculties of health professionals to identify students at risk in an early stage, to direct prevention tailored interventions. Nursing faculties should be aware of the prevalence of Gambling among students. Prevention interventions should be planned to minimize the risk of gambling behavior in the future nurses' health care workers. Copyright © 2017 Elsevier Inc. All rights reserved.

Microbiota, cirrhosis, and the emerging oral-gut-liver axis

PubMed Central

Acharya, Chathur; Bajaj, Jasmohan S.

2017-01-01

Cirrhosis is a prevalent cause of morbidity and mortality, especially for those at an advanced decompensated stage. Cirrhosis development and progression involves several important interorgan communications, and recently, the gut microbiome has been implicated in pathophysiology of the disease. Dysbiosis, defined as a pathological change in the microbiome, has a variable effect on the compensated versus decompensated stage of cirrhosis. Adverse microbial changes, both in composition and function, can act at several levels within the gut (stool and mucosal) and have also been described in the blood and oral cavity. While dysbiosis in the oral cavity could be a source of systemic inflammation, current cirrhosis treatment modalities are targeted toward the gut-liver axis and do not address the oral microbiome. As interventions designed to modulate oral dysbiosis may delay progression of cirrhosis, a better understanding of this process is of the utmost importance. The concept of oral microbiota dysbiosis in cirrhosis is relatively new; therefore, this review will highlight the emerging role of the oral-gut-liver axis and introduce perspectives for future research. PMID:28978799

Impact of anti-inflammatory nutrients on obesity-associated metabolic-inflammation from childhood through to adulthood.

PubMed

Connaughton, Ruth M; McMorrow, Aoibheann M; McGillicuddy, Fiona C; Lithander, Fiona E; Roche, Helen M

2016-05-01

Obesity-related metabolic conditions such as insulin resistance (IR), type 2 diabetes and CVD share a number of pathological features, one of which is metabolic-inflammation. Metabolic-inflammation results from the infiltration of immune cells into the adipose tissue, driving a pro-inflammatory environment, which can induce IR. Furthermore, resolution of inflammation, an active process wherein the immune system counteracts pro-inflammatory states, may be dysregulated in obesity. Anti-inflammatory nutritional interventions have focused on attenuating this pro-inflammatory environment. Furthermore, with inherent variability among individuals, establishing at-risk populations who respond favourably to nutritional intervention strategies is important. This review will focus on chronic low-grade metabolic-inflammation, resolution of inflammation and the putative role anti-inflammatory nutrients have as a potential therapy. Finally, in the context of personalised nutrition, the approaches used in defining individuals who respond favourably to nutritional interventions will be highlighted. With increasing prevalence of obesity in younger people, age-dependent biological processes, preventative strategies and therapeutic options are important to help protect against development of obesity-associated co-morbidities.

Monitoring-Based Model for Personalizing the Clinical Process of Crohn’s Disease

PubMed Central

de Ramón-Fernández, Alberto; Ruiz-Fernández, Daniel; Vives-Boix, Víctor

2017-01-01

Crohn’s disease is a chronic pathology belonging to the group of inflammatory bowel diseases. Patients suffering from Crohn’s disease must be supervised by a medical specialist for the rest of their lives; furthermore, each patient has its own characteristics and is affected by the disease in a different way, so health recommendations and treatments cannot be generalized and should be individualized for a specific patient. To achieve this personalization in a cost-effective way using technology, we propose a model based on different information flows: control, personalization, and monitoring. As a result of the model and to perform a functional validation, an architecture based on services and a prototype of the system has been defined. In this prototype, a set of different devices and technologies to monitor variables from patients and their environment has been integrated. Artificial intelligence algorithms are also included to reduce the workload related to the review and analysis of the information gathered. Due to the continuous and automated monitoring of the Crohn’s patient, this proposal can help in the personalization of the Crohn’s disease clinical process. PMID:28678162

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

Is synaptic loss a unique hallmark of Alzheimer's disease?

PubMed Central

Scheff, Stephen W.; Neltner, Janna H.; Nelson, Peter T.

2014-01-01

Synapses may represent a key nidus for dementia including Alzheimer's disease (AD) pathogenesis. Here we review published studies and present new ideas related to the question of the specificity of synapse loss in AD. Currently, AD is defined by the regional presence of neuritic plaques and neurofibrillary tangles in the brain. The severity of involvement by those pathological hallmarks tends to correlate both with antemortem cognitive status, and also with synapse loss in multiple brain areas. Recent studies from large autopsy series have led to a new standard of excellence with regard to clinical–pathological correlation and to improved comprehension of the numerous brain diseases of the elderly. These studies have provided evidence that it is the rule rather than the exception for brains of aged individuals to demonstrate pathologies (often multiple) other than AD plaques and tangles. For many of these comorbid pathologies, the extent of synapse loss is imperfectly understood but could be substantial. These findings indicate that synapse loss is probably not a hallmark specific to AD but rather a change common to many diseases associated with dementia. PMID:24412275

Fighting flu: military pathology, vaccines, and the conflicted identity of the 1918-19 pandemic in Britain.

PubMed

Bresalier, Michael

2013-01-01

This article explores the decisive role of British military medicine in shaping official approaches to the 1918 influenza pandemic. It contends that British approaches were defined through a system of military pathology, which had been established by the War Office as part of the mobilization of medicine for the First World War. Relying on the bacteriological laboratory for the identification and control of pathogenic agents, military pathology delivered therapeutic and preventive measures against a range of battlefield diseases, and military and civilian authorities trusted that it could do the same with influenza. This article traces how it shaped efforts to establish the etiology of the pandemic and to produce a general influenza vaccine. It highlights the challenges involved in both strategies. Understanding the central role of military pathology helps make sense of the nature, direction, scale, and limitations of medical mobilization against the pandemic in Britain and the authority accorded to specific medical bodies for elaborating and coordinating strategies. Crucially, it demands that we rethink the relationship between the war and pandemic as one about the social organization of medical knowledge and institutions.

Automated scoring of regional lung perfusion in children from contrast enhanced 3D MRI

NASA Astrophysics Data System (ADS)

Heimann, Tobias; Eichinger, Monika; Bauman, Grzegorz; Bischoff, Arved; Puderbach, Michael; Meinzer, Hans-Peter

2012-03-01

MRI perfusion images give information about regional lung function and can be used to detect pulmonary pathologies in cystic fibrosis (CF) children. However, manual assessment of the percentage of pathologic tissue in defined lung subvolumes features large inter- and intra-observer variation, making it difficult to determine disease progression consistently. We present an automated method to calculate a regional score for this purpose. First, lungs are located based on thresholding and morphological operations. Second, statistical shape models of left and right children's lungs are initialized at the determined locations and used to precisely segment morphological images. Segmentation results are transferred to perfusion maps and employed as masks to calculate perfusion statistics. An automated threshold to determine pathologic tissue is calculated and used to determine accurate regional scores. We evaluated the method on 10 MRI images and achieved an average surface distance of less than 1.5 mm compared to manual reference segmentations. Pathologic tissue was detected correctly in 9 cases. The approach seems suitable for detecting early signs of CF and monitoring response to therapy.

Second Opinion Reviews for Cancer Diagnoses in Anatomic Pathology: A Comprehensive Cancer Center's Experience.

PubMed

Strosberg, Carolina; Gibbs, Julie; Braswell, Diana; Leslie, Ronni R; Messina, Jane; Centeno, Barbara A; Coppola, Domenico

2018-05-01

The objective of this study was to define the rates of discrepancy between outside pathological diagnoses and secondary reviews. We assessed the rates of discordance between outside diagnoses and secondary reviews, categorizing by organ site and minor or major (affecting patient care) discordances. A total of 9,289 consecutive surgical pathology (SP) and cytopathology (CP) cases reviewed in 2015 were identified. For 8,191 outside SP cases reviewed, the overall discordance rate (DR) was 14.2% (2.2% major, 12.0% minor). Specifically, neuropathology had the highest DR (10.9%), cutaneous and breast the lowest (1.1% each). Among 1,098 CP cases, the total DR was 13.7% (3.0% major, 10.7% minor). The majority of CP cases (1,066) were non-gynecological and had a total DR of 13.4% (2.7% major, 10.7% minor). While major DR was low, certain subspecialties had high DRs. This project can help identify areas where focused education could help improve pathological diagnostic accuracy for cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Ventromedial prefrontal cortex activity and pathological worry in generalised anxiety disorder.

PubMed

Via, E; Fullana, M A; Goldberg, X; Tinoco-González, D; Martínez-Zalacaín, I; Soriano-Mas, C; Davey, C G; Menchón, J M; Straube, B; Kircher, T; Pujol, J; Cardoner, N; Harrison, B J

2018-05-09

Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.AimsTo study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals. In total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging. Compared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety-threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC. Poor vmPFC safety-threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.Declaration of interestNone.

Relationship status predicts lower restrictive eating pathology for bisexual and gay men across 10-year follow-up.

PubMed

Brown, Tiffany A; Keel, Pamela K

2015-09-01

Cross-sectional studies support that bisexual and gay (BG) men are at increased risk for eating pathology, and romantic relationships may buffer against risk; however, no studies have examined this association longitudinally. The current study examined how romantic relationships impact the trajectory of eating pathology in BG versus heterosexual men. BG (n = 51) and heterosexual (n = 522) men completed surveys of health and eating behaviors at baseline and 10-year follow-up. For BG men, being single at baseline prospectively predicted an increase in Drive for Thinness scores over 10-year follow-up. Additionally, for BG men in relationships at baseline, lower relationship satisfaction predicted an increase in Drive for Thinness scores over time. Conversely, these relationship variables did not predict trajectory of eating pathology for heterosexual men. Implications for theoretical models of risk, including objectification theory and sexual minority stress theory, and prevention, including peer-led cognitive dissonance based interventions, are discussed. © 2015 Wiley Periodicals, Inc.

Relationship Status Predicts Lower Restrictive Eating Pathology for Bisexual and Gay Men across 10-year Follow-up

PubMed Central

Brown, Tiffany A.; Keel, Pamela K.

2015-01-01

Objective Cross-sectional studies support that bisexual and gay (BG) men are at increased risk for eating pathology, and romantic relationships may buffer against risk; however, no studies have examined this association longitudinally. The current study examined how romantic relationships impact the trajectory of eating pathology in BG versus heterosexual men. Method BG (n=51) and heterosexual (n=522) men completed surveys of health and eating behaviors at baseline and 10-year follow-up. Results For BG men, being single at baseline prospectively predicted an increase in Drive for Thinness scores over 10-year follow-up. Additionally, for BG men in relationships at baseline, lower relationship satisfaction predicted an increase in Drive for Thinness scores over time. Conversely, these relationship variables did not predict trajectory of eating pathology for heterosexual men. Discussion Implications for theoretical models of risk, including objectification theory and sexual minority stress theory, and prevention, including peer-led cognitive dissonance based interventions, are discussed. PMID:26172055

MYC Amplification as a Predictive Factor of Complete Pathologic Response to Docetaxel-based Neoadjuvant Chemotherapy for Breast Cancer.

PubMed

Pereira, Cynthia Brito Lins; Leal, Mariana Ferreira; Abdelhay, Eliana Saul Furquim Werneck; Demachki, Sâmia; Assumpção, Paulo Pimentel; de Souza, Mirian Carvalho; Moreira-Nunes, Caroline Aquino; Tanaka, Adriana Michiko da Silva; Smith, Marília Cardoso; Burbano, Rommel Rodríguez

2017-06-01

Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response. We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer. After neoadjuvant chemotherapy, 82.4% of patients showed pathologic partial response, with only 9.8% showing pathologic complete response. In multivariate analysis, MYC immunoreactivity and high MYC gain defined as MYC/nucleus ≥ 5 were significant predictor factors for pathologic partial response. Using the receiver operating characteristic curve analysis, the ratio of 2.5 MYC/CEP8 (sensitivity of 80% and specificity of 89.1%) or 7 MYC/nuclei copies (sensitivity of 80% and specificity of 73.9%) as the best cutoff in predicting a pathologic complete response was identified. Thus, MYC may have a role in chemosensitivity to AC and/or docetaxel drugs. Additionally, MYC amplification may be a predictor factor of pathologic response to the AC+T regimen in patients with breast cancer. Moreover, patients with an increased number of MYC copies showed pathologic complete response to this neoadjuvant treatment more frequently. The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation.

PubMed

Bensignor, T; Brouquet, A; Dariane, C; Thirot-Bidault, A; Lazure, T; Julié, C; Nordlinger, B; Penna, C; Benoist, S

2015-06-01

Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC). Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin < 2 mm) and synchronous metastatic disease or a contraindication to pelvic irradiation underwent rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed. All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent. Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

Nonlinear time series analysis of normal and pathological human walking

NASA Astrophysics Data System (ADS)

Dingwell, Jonathan B.; Cusumano, Joseph P.

2000-12-01

Characterizing locomotor dynamics is essential for understanding the neuromuscular control of locomotion. In particular, quantifying dynamic stability during walking is important for assessing people who have a greater risk of falling. However, traditional biomechanical methods of defining stability have not quantified the resistance of the neuromuscular system to perturbations, suggesting that more precise definitions are required. For the present study, average maximum finite-time Lyapunov exponents were estimated to quantify the local dynamic stability of human walking kinematics. Local scaling exponents, defined as the local slopes of the correlation sum curves, were also calculated to quantify the local scaling structure of each embedded time series. Comparisons were made between overground and motorized treadmill walking in young healthy subjects and between diabetic neuropathic (NP) patients and healthy controls (CO) during overground walking. A modification of the method of surrogate data was developed to examine the stochastic nature of the fluctuations overlying the nominally periodic patterns in these data sets. Results demonstrated that having subjects walk on a motorized treadmill artificially stabilized their natural locomotor kinematics by small but statistically significant amounts. Furthermore, a paradox previously present in the biomechanical literature that resulted from mistakenly equating variability with dynamic stability was resolved. By slowing their self-selected walking speeds, NP patients adopted more locally stable gait patterns, even though they simultaneously exhibited greater kinematic variability than CO subjects. Additionally, the loss of peripheral sensation in NP patients was associated with statistically significant differences in the local scaling structure of their walking kinematics at those length scales where it was anticipated that sensory feedback would play the greatest role. Lastly, stride-to-stride fluctuations in the walking patterns of all three subject groups were clearly distinguishable from linearly autocorrelated Gaussian noise. As a collateral benefit of the methodological approach taken in this study, some of the first steps at characterizing the underlying structure of human locomotor dynamics have been taken. Implications for understanding the neuromuscular control of locomotion are discussed.

Cancer Recurrence After Esophagectomy: Impact of Postoperative Infection in Propensity-Matched Cohorts.

PubMed

Tam, Vernissia; Luketich, James D; Winger, Daniel G; Sarkaria, Inderpal S; Levy, Ryan M; Christie, Neil A; Awais, Omar; Shende, Manisha R; Nason, Katie S

2016-11-01

Postoperative infection increases cancer recurrence and worsens survival in colorectal cancer, but the relationship for esophagogastric adenocarcinoma after esophagectomy is not well defined. We aimed to determine whether recurrence and survival after minimally invasive esophagectomy for esophagogastric adenocarcinoma were influenced by postoperative infection using propensity-matched analysis. We abstracted data for 810 patients (1997-2010) and defined exposure as at least 1 in-hospital or 30-day infectious complication (n = 206 [25%]). Using 29 pretreatment/intraoperative variables, patients were propensity-score matched (caliper = 0.05). Time to cancer recurrence and survival (Kaplan-Meier curves and the Breslow test), and associated factors (Cox regression with shared frailty) were assessed. After propensity matching (n = 167 pairs), median bias across propensity-score variables was reduced from 12.9% (p < 0.001) to 4.4% (p = 1.000). Postoperative infection was not associated with rate (n = 60 versus 63; McNemar p = 0.736) or time to recurrence in those in whom disease recurred (median, 10.7 versus 11.1 months; Wilcoxon signed-rank p = 0.455) but was associated with shorter overall survival (n = 124 versus 102 deaths; median, 26 versus 41 months; Breslow p = 0.002). After adjusting for age, body mass index, neoadjuvant therapy, sex, comorbidity score, positive resection margins, pathologic stage, R0 resection, and recurrence, postoperative infection was associated with a 44% greater hazard for death (hazard ratio, 1.44; 95% confidence interval, 1.10-1.89). In patients with esophagogastric adenocarcinoma, infections after esophagectomy were not associated with an increased rate or earlier time to recurrence when baseline characteristics associated with infection risk were balanced using propensity-score matching. Despite this, overall survival was shorter in patients with infectious complications. After adjusting for other important survival predictors, infections after esophagectomy continued to be independently associated with worse survival. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Between DSM and ICD: Paraphilias and the Transformation of Sexual Norms.

PubMed

Giami, Alain

2015-07-01

The simultaneous revision of the two major international classifications of disease, the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases, serves as an opportunity to observe the dynamic processes through which social norms of sexuality are constructed and are subject to change in relation to social, political, and historical context. This article argues that the classifications of sexual disorders, which define pathological aspects of "sexually arousing fantasies, sexual urges or behaviors" are representations of contemporary sexual norms, gender identifications, and gender relations. It aims to demonstrate how changes in the medical treatment of sexual perversions/paraphilias passed, over the course of the 20th century, from a model of pathologization (and sometimes criminalization) of non-reproductive sexual behaviors to a model that reflects and privileges sexual well-being and responsibility, and pathologizes the absence or the limitation of consent in sexual relations.

Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart.

PubMed

Abdul-Ghani, Mohammad; Suen, Colin; Jiang, Baohua; Deng, Yupu; Weldrick, Jonathan J; Putinski, Charis; Brunette, Steve; Fernando, Pasan; Lee, Tom T; Flynn, Peter; Leenen, Frans H H; Burgon, Patrick G; Stewart, Duncan J; Megeney, Lynn A

2017-10-01

The post-natal heart adapts to stress and overload through hypertrophic growth, a process that may be pathologic or beneficial (physiologic hypertrophy). Physiologic hypertrophy improves cardiac performance in both healthy and diseased individuals, yet the mechanisms that propagate this favorable adaptation remain poorly defined. We identify the cytokine cardiotrophin 1 (CT1) as a factor capable of recapitulating the key features of physiologic growth of the heart including transient and reversible hypertrophy of the myocardium, and stimulation of cardiomyocyte-derived angiogenic signals leading to increased vascularity. The capacity of CT1 to induce physiologic hypertrophy originates from a CK2-mediated restraining of caspase activation, preventing the transition to unrestrained pathologic growth. Exogenous CT1 protein delivery attenuated pathology and restored contractile function in a severe model of right heart failure, suggesting a novel treatment option for this intractable cardiac disease.

Microglia: new roles for the synaptic stripper.

PubMed

Kettenmann, Helmut; Kirchhoff, Frank; Verkhratsky, Alexei

2013-01-09

Any pathologic event in the brain leads to the activation of microglia, the immunocompetent cells of the central nervous system. In recent decades diverse molecular pathways have been identified by which microglial activation is controlled and by which the activated microglia affects neurons. In the normal brain microglia were considered "resting," but it has recently become evident that they constantly scan the brain environment and contact synapses. Activated microglia can remove damaged cells as well as dysfunctional synapses, a process termed "synaptic stripping." Here we summarize evidence that molecular pathways characterized in pathology are also utilized by microglia in the normal and developing brain to influence synaptic development and connectivity, and therefore should become targets of future research. Microglial dysfunction results in behavioral deficits, indicating that microglia are essential for proper brain function. This defines a new role for microglia beyond being a mere pathologic sensor. Copyright © 2013 Elsevier Inc. All rights reserved.

Core components of a comprehensive quality assurance program in anatomic pathology.

PubMed

Nakhleh, Raouf E

2009-11-01

In this article the core components of a comprehensive quality assurance and improvement plan are outlined. Quality anatomic pathology work comes with focus on accurate, timely, and complete reports. A commitment to continuous quality improvement and a systems approach with a persistent effort helps to achieve this end. Departments should have a quality assurance and improvement plan that includes a risk assessment of real and potential problems facing the laboratory. The plan should also list the individuals responsible for carrying out the program with adequate resources, a defined timetable, and annual assessment for progress and future directions. Quality assurance monitors should address regulatory requirements and be organized by laboratory division (surgical pathology, cytology, etc) as well as 5 segments (preanalytic, analytic, postanalytic phases of the test cycle, turn-around-time, and customer satisfaction). Quality assurance data can also be used to evaluate individual pathologists using multiple parameters with peer group comparison.

Pathological complete response in patients with esophageal cancer after the trimodality approach: The association with baseline variables and survival-The University of Texas MD Anderson Cancer Center experience.

PubMed

Blum Murphy, Mariela; Xiao, Lianchum; Patel, Viren R; Maru, Dipen M; Correa, Arlene M; G Amlashi, Fatemeh; Liao, Zhongxing; Komaki, Ritsuko; Lin, Steven H; Skinner, Heath D; Vaporciyan, Ara; Walsh, Garrett L; Swisher, Stephen G; Sepesi, Boris; Lee, Jeffrey H; Bhutani, Manoop S; Weston, Brian; Hofstetter, Wayne L; Ajani, Jaffer A

2017-11-01

Reports are limited regarding clinical and pretreatment features that might predict a pathological complete response (pathCR) after treatment in patients with esophageal cancer (EC). This might allow patient selection for different strategies. This study examines the association of a pathCR with pretreatment variables, overall survival (OS), recurrence-free survival (RFS), and patterns of recurrence in a large cohort from a single institution. The baseline clinical features of 911 consecutive patients with EC who were treated with trimodality therapy from January 2000 to November 2013 were analyzed. A pathCR was defined as a surgical specimen with no residual carcinoma (primary or nodes). Logistic regressions were used to identify independent baseline features associated with a pathCR. We applied log-rank testing and Cox models to determine the association between a pathCR and the time-to-event outcomes (OS and RFS). Of 911 patients, 218 (23.9%) achieved a pathCR. The pathCR rate was 23.1% for adenocarcinoma and 32.2% for squamous cell carcinoma. A lower pathCR rate was observed for 1) older patients (>60 years), 2) patients with poorly differentiated tumors, 3) patients with signet ring cells (SRCs), and 4) patients with a higher T stage. Patients with a pathCR had longer OS and RFS than those without a pathCR (P = .0021 and P = .0011, respectively). Recurrences occurred more in non-pathCR patients. Distant metastases were the most common type of recurrence. PathCR patients developed brain metastases at a marginally higher rate than non-pathCR patients (P = .051). In this large cohort study, a pathCR is confirmed to be associated with better OS and RFS. The presence of a poorly differentiated tumor or SRCs reduces the likelihood of a pathCR. Future research should focus on molecular classifiers. Cancer 2017;123:4106-4113. © 2017 American Cancer Society. © 2017 American Cancer Society.

HUMAN--A Comprehensive Physiological Model.

ERIC Educational Resources Information Center

Coleman, Thomas G.; Randall, James E.

1983-01-01

Describes computer program (HUMAN) used to simulate physiological experiments on patient pathology. Program (available from authors, including versions for microcomputers) consists of dynamic interactions of over 150 physiological variables and integrating approximations of cardiovascular, renal, lung, temperature regulation, and some hormone…

Intracranial investigation of a patient with nodular heterotopia and hippocampal sclerosis: dealing with a dual pathology.

PubMed

Ladino, Lady Diana; Dash, Chelsea; Wu, Adam; Tellez-Zenteno, Jose Francisco

2017-06-01

The pre-operative assessment and surgical management of patients with dual pathology is challenging. We describe a patient with drug-resistant focal epilepsy with hippocampal sclerosis and extensive periventricular nodular heterotopia in the same hemisphere. The semiology, scalp EEG, and imaging were divergent, but the presence of focal interictal and ictal epileptic discharges of the putative ictal onset zone resulted in successful localization of the epileptogenic zone. A less aggressive resection was performed based on intracranial EEG recording. The patient has been seizure-free for three years since resection. Electroclinical hypotheses and challenges in defining the epileptogenic network are discussed.

Histopathology of lung disease in the connective tissue diseases.

PubMed

Vivero, Marina; Padera, Robert F

2015-05-01

The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. Copyright © 2015 Elsevier Inc. All rights reserved.

Echolalia: issues and clinical applications.

PubMed

Schuler, A L

1979-11-01

Echolalic behaviors have been reported within the context of various pathologies but have remained poorly defined. Consequently, it is not easy to determine whether and to what extent normal repetition can be separated from pathological echoing. Hence, it is unclear whether the occurrence of echolalic behavior may be useful for differential diagnostic purposes. Also, much room is left for controversies about the clinical management of echolalic behavior. This article reviews the various conditions associated with echolalia and the role of repetitions in normal language behavior. Suggestions are made in terms of the various dimensions along which echolalic behavior should be assessed, as well as of the desirability of particular intervention techniques.

Pathological Buying Online as a Specific Form of Internet Addiction: A Model-Based Experimental Investigation

PubMed Central

Trotzke, Patrick; Starcke, Katrin; Müller, Astrid; Brand, Matthias

2015-01-01

The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior, cue-induced craving should also constitute an important factor for online pathological buying. The theoretical model was tested in this study by investigating 240 female participants with a cue-reactivity paradigm, which was composed of online shopping pictures, to assess excitability from shopping. Craving (before and after the cue-reactivity paradigm) and online shopping expectancies were measured. The tendency for pathological buying and online pathological buying were screened with the Compulsive Buying Scale (CBS) and the Short Internet Addiction Test modified for shopping (s-IATshopping). The results demonstrated that the relationship between individual’s excitability from shopping and online pathological buying tendency was partially mediated by specific Internet use expectancies for online shopping (model’s R² = .742, p < .001). Furthermore, craving and online pathological buying tendencies were correlated (r = .556, p < .001), and an increase in craving after the cue presentation was observed solely in individuals scoring high for online pathological buying (t(28) = 2.98, p < .01, d = 0.44). Both screening instruments were correlated (r = .517, p < .001), and diagnostic concordances as well as divergences were indicated by applying the proposed cut-off criteria. In line with the model for specific Internet addiction, the study identified potential vulnerability factors for online pathological buying and suggests potential parallels. The presence of craving in individuals with a propensity for online pathological buying emphasizes that this behavior merits potential consideration within the non-substance/behavioral addictions. PMID:26465593

Pathological Buying Online as a Specific Form of Internet Addiction: A Model-Based Experimental Investigation.

PubMed

Trotzke, Patrick; Starcke, Katrin; Müller, Astrid; Brand, Matthias

2015-01-01

The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior, cue-induced craving should also constitute an important factor for online pathological buying. The theoretical model was tested in this study by investigating 240 female participants with a cue-reactivity paradigm, which was composed of online shopping pictures, to assess excitability from shopping. Craving (before and after the cue-reactivity paradigm) and online shopping expectancies were measured. The tendency for pathological buying and online pathological buying were screened with the Compulsive Buying Scale (CBS) and the Short Internet Addiction Test modified for shopping (s-IATshopping). The results demonstrated that the relationship between individual's excitability from shopping and online pathological buying tendency was partially mediated by specific Internet use expectancies for online shopping (model's R² = .742, p < .001). Furthermore, craving and online pathological buying tendencies were correlated (r = .556, p < .001), and an increase in craving after the cue presentation was observed solely in individuals scoring high for online pathological buying (t(28) = 2.98, p < .01, d = 0.44). Both screening instruments were correlated (r = .517, p < .001), and diagnostic concordances as well as divergences were indicated by applying the proposed cut-off criteria. In line with the model for specific Internet addiction, the study identified potential vulnerability factors for online pathological buying and suggests potential parallels. The presence of craving in individuals with a propensity for online pathological buying emphasizes that this behavior merits potential consideration within the non-substance/behavioral addictions.

Whole-slide imaging: routine pathologic diagnosis.

PubMed

Cornish, Toby C; Swapp, Ryan E; Kaplan, Keith J

2012-05-01

Digital pathology systems offer pathologists an alternate, emerging mechanism to manage and interpret information. They offer increasingly fast and scalable hardware platforms for slide scanning and software that facilitates remote viewing, slide conferencing, archiving, and image analysis. Deployed initially and validated largely within the research and biopharmaceutical industries, WSI is increasingly being implemented for direct patient care. Improvements in image quality, scan times, and imageviewing browsers will hopefully allow pathologists to more seamlessly convert to digital pathology, much like our radiology colleagues have done before us. However, WSI creates both opportunities and challenges. Although niche applications of WSI technology for clinical, educational, and research purposes are clearly successful, it is evident that several areas still require attention and careful consideration before more widespread clinical adoption of WSI takes place. These include regulatory issues, development of standards of practice and validation guidelines, workflow modifications, as well as defining situations where WSI technology will really improve practice in a cost-effective way. Current progress on these and other issues, along with improving technology, will no doubt pave the way for increased adoption over the next decade, allowing the pathology community as a whole to harness the true potential of WSI for patient care. The digital decade will likely redefine how pathology is practiced and the role of the pathologist.

Speech and Hearing Science, Anatomy and Physiology.

ERIC Educational Resources Information Center

Zemlin, Willard R.

Written for those interested in speech pathology and audiology, the text presents the anatomical, physiological, and neurological bases for speech and hearing. Anatomical nomenclature used in the speech and hearing sciences is introduced and the breathing mechanism is defined and discussed in terms of the respiratory passage, the framework and…

Toward a definition of 'childhood mourning'.

PubMed

Sekaer, C

1987-04-01

Though a young child cannot mourn like an adult, optimal responses may be distinguished from pathological ones and used to define "childhood mourning." Aspects of mourning such as identification and decathexis must be related to the child's developmental level. Creative use of an "imaginary parent" may help master a parent loss.

Defining the genus Fusarium in a scientifically robust way that best preserves longstanding use

USDA-ARS?s Scientific Manuscript database

In this talk I will present the argument of a diverse group of scientists advocating a phylogenetic circumscription of the genus Fusarium, that includes virtually all Fusarium species of importance in plant pathology, mycotoxicology, medicine, and basic research. This will free scientists from any o...

40 CFR 60.32e - Designated facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... modification was commenced on or before March 16, 1998. (2) For which construction was commenced after June 20, 1996 but no later than December 1, 2008, or for which modification is commenced after March 16, 1998... only pathological waste, low-level radioactive waste, and/or chemotherapeutic waste (all defined in...

Impression Management in the Psychiatric Interview: Quality, Style, and Individual Differences

ERIC Educational Resources Information Center

Sherman, Mark; And Others

1975-01-01

The ability of 24 Veterans Administration Day Treatment Center psychiatric outpatients to vary intentionally their degree of apparent psychopathology during structured interviews was studied. Patients defined as sick presenters behaved in a significantly more pathological manner during an interview preceded by "fake sick" instructions than they…

42 CFR 493.1405 - Standard; Laboratory director qualifications.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Osteopathic Board of Pathology or possess qualifications that are equivalent to those required for such... supervising non-waived laboratory testing; or (B) Beginning September 1, 1993, have at least 20 continuing... defined in § 493.1407; or (C) Laboratory training equivalent to paragraph (b)(2)(ii)(B) of this section...

42 CFR 493.1405 - Standard; Laboratory director qualifications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Osteopathic Board of Pathology or possess qualifications that are equivalent to those required for such... supervising non-waived laboratory testing; or (B) Beginning September 1, 1993, have at least 20 continuing... defined in § 493.1407; or (C) Laboratory training equivalent to paragraph (b)(2)(ii)(B) of this section...

42 CFR 493.1405 - Standard; Laboratory director qualifications.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Osteopathic Board of Pathology or possess qualifications that are equivalent to those required for such... supervising non-waived laboratory testing; or (B) Beginning September 1, 1993, have at least 20 continuing... defined in § 493.1407; or (C) Laboratory training equivalent to paragraph (b)(2)(ii)(B) of this section...

Visualising Disability in the Past

ERIC Educational Resources Information Center

Devlieger, Patrick; Grosvenor, Ian; Simon, Frank; Van Hove, Geert; Vanobbergen, Bruno

2008-01-01

In recent years there has been a growth in interdisciplinary work which has argued that disability is not an isolated, individual medical pathology but instead a key defining social category like "race", class and gender. Seen in this way disability provides researchers with another analytic tool for exploring the nature of power. Running almost…

Evidence for cardiovascular autonomic dysfunction in neonates with coarctation of the aorta.

PubMed

Polson, Jaimie W; McCallion, Naomi; Waki, Hidefumi; Thorne, Gareth; Tooley, Mark A; Paton, Julian F R; Wolf, Andrew R

2006-06-20

Coarctation of the aorta (CoA) is associated with hypertension and abnormalities of blood pressure control, which persist after late repair. Assumptions that neonatal repair would prevent development of blood pressure abnormalities have not been supported by recent data. We hypothesized that early pathological adjustment of autonomic cardiovascular function may already be established in the neonate with coarctation. We studied 8 otherwise well neonates with simple CoA and compared measures of spontaneous baroreflex sensitivity, heart rate variability, and blood pressure variability with 13 healthy newborn babies. Spontaneous baroreflex sensitivity was calculated with sequence methodology from an ECG, and noninvasive blood pressure was recorded with a Portapres. Heart rate variability was determined with time- and frequency-domain measures. Blood pressure variability was measured in the frequency domain. In comparison with normal controls, neonates with CoA had raised blood pressure (78.9+/-3.8 versus 67.1+/-2.1 mm Hg), depressed baroreflex sensitivity (8.7+/-1.5 versus 13.8+/-1.1 ms/mm Hg), reduced heart rate variability (total power 16.5+/-3.1 versus 31.5+/-2.2 ms2), and an increase in the high-frequency component of blood pressure variability (3.1+/-0.3 versus 2.2+/-0. 2 mm Hg2). This is not the pattern expected if neonates with CoA simply had subclinical cardiac failure. These data suggest that infants with CoA already show signs of pathological adjustment of autonomic cardiovascular homeostasis. Further longitudinal studies are required to determine whether these alterations play a role in the increased risk of late hypertension in these patients.

Why do pathological stage IA lung adenocarcinomas vary from prognosis?: a clinicopathologic study of 176 patients with pathological stage IA lung adenocarcinoma based on the IASLC/ATS/ERS classification.

PubMed

Zhang, Jie; Wu, Jie; Tan, Qiang; Zhu, Lei; Gao, Wen

2013-09-01

Patients with pathological stage IA adenocarcinoma (AC) have a variable prognosis, even if treated in the same way. The postoperative treatment of pathological stage IA patients is also controversial. We identified 176 patients with pathological stage IA AC who had undergone a lobectomy and mediastinal lymph node dissection at the Shanghai Chest Hospital, Shanghai, China, between 2000 and 2006. No patient had preoperative treatment. The histologic subtypes of all patients were classified according to the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary lung AC classification. Patients' 5-year overall survival (OS) and 5-year disease-free survival (DFS) were calculated using Kaplan-Meier and Cox regression analyses. One hundred seventy-six patients with pathological stage IA AC had an 86.6% 5-year OS and 74.6% 5-year DFS. The 10 patients with micropapillary predominant subtype had the lowest 5-year DFS (40.0%).The 12 patients with solid predominant with mucin production subtype had the lowest 5-year OS (66.7%). Univariate and multivariate analysis showed that sex and prognositic groups of the IASLC/ATS/ERS histologic classification were significantly associated with 5-year DFS of pathological stage IA AC. Our study revealed that sex was an independent prognostic factor of pathological stage IA AC. The IASLC/ATS/ERS classification of lung AC identifies histologic categories with prognostic differences that could be helpful in clinical therapy.

The risk factors of laryngeal pathology in Korean adults using a decision tree model.

PubMed

Byeon, Haewon

2015-01-01

The purpose of this study was to identify risk factors affecting laryngeal pathology in the Korean population and to evaluate the derived prediction model. Cross-sectional study. Data were drawn from the 2008 Korea National Health and Nutritional Examination Survey. The subjects were 3135 persons (1508 male and 2114 female) aged 19 years and older living in the community. The independent variables were age, sex, occupation, smoking, alcohol drinking, and self-reported voice problems. A decision tree analysis was done to identify risk factors for predicting a model of laryngeal pathology. The significant risk factors of laryngeal pathology were age, gender, occupation, smoking, and self-reported voice problem in decision tree model. Four significant paths were identified in the decision tree model for the prediction of laryngeal pathology. Those identified as high risk groups for laryngeal pathology included those who self-reported a voice problem, those who were males in their 50s who did not recognize a voice problem, those who were not economically active males in their 40s, and male workers aged 19 and over and under 50 or 60 and over who currently smoked. The results of this study suggest that individual risk factors, such as age, sex, occupation, health behavior, and self-reported voice problem, affect the onset of laryngeal pathology in a complex manner. Based on the results of this study, early management of the high-risk groups is needed for the prevention of laryngeal pathology. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Assessment of orofacial characteristics and oral pathology associated with cri-du-chat syndrome.

PubMed

Rodríguez-Caballero, A; Torres-Lagares, D; Yáñez-Vico, R-M; Gutiérrez-Pérez, J-L; Machuca-Portillo, G

2012-03-01

To obtain a deeper insight into the difficulties individuals with cri-du-chat syndrome experience by means of the analysis of the most common features and oral pathology observed in the subjects enrolled in the study. Intra-oral and extra-oral features of a total of 33 patients with cri-du-chat syndrome (the larger sample so far analyzed) through their clinical and photographic examination. Models, orthopantomographies, and teleradiographies have been collected to establish a pattern as accurate as possible of the oral pathology associated with these patients. The present descriptive study shows that patients with cri-du-chat syndrome present with a series of orofacial features such as mandibular retrognathism, high palate, and variable malocclusion, more commonly anterior open-bite. Most patients also present with perioral muscle relaxation with labial incompetence and short philtrum. As regards oral pathology, these patients suffer dental erosions provoked by gastroesophageal reflux and attritions because of intense day-and-night bruxism. The odontologists' familiarity with the orofacial pathology associated with cri-du-chat syndrome and with the specific needs such disorder conveys should improve the quality of the buccodental treatment these professionals may offer to these patients. © 2011 John Wiley & Sons A/S.

A system of three-dimensional complex variables

NASA Technical Reports Server (NTRS)

Martin, E. Dale

1986-01-01

Some results of a new theory of multidimensional complex variables are reported, including analytic functions of a three-dimensional (3-D) complex variable. Three-dimensional complex numbers are defined, including vector properties and rules of multiplication. The necessary conditions for a function of a 3-D variable to be analytic are given and shown to be analogous to the 2-D Cauchy-Riemann equations. A simple example also demonstrates the analogy between the newly defined 3-D complex velocity and 3-D complex potential and the corresponding ordinary complex velocity and complex potential in two dimensions.

Improved prediction of biochemical recurrence after radical prostatectomy by genetic polymorphisms.

PubMed

Morote, Juan; Del Amo, Jokin; Borque, Angel; Ars, Elisabet; Hernández, Carlos; Herranz, Felipe; Arruza, Antonio; Llarena, Roberto; Planas, Jacques; Viso, María J; Palou, Joan; Raventós, Carles X; Tejedor, Diego; Artieda, Marta; Simón, Laureano; Martínez, Antonio; Rioja, Luis A

2010-08-01

Single nucleotide polymorphisms are inherited genetic variations that can predispose or protect individuals against clinical events. We hypothesized that single nucleotide polymorphism profiling may improve the prediction of biochemical recurrence after radical prostatectomy. We performed a retrospective, multi-institutional study of 703 patients treated with radical prostatectomy for clinically localized prostate cancer who had at least 5 years of followup after surgery. All patients were genotyped for 83 prostate cancer related single nucleotide polymorphisms using a low density oligonucleotide microarray. Baseline clinicopathological variables and single nucleotide polymorphisms were analyzed to predict biochemical recurrence within 5 years using stepwise logistic regression. Discrimination was measured by ROC curve AUC, specificity, sensitivity, predictive values, net reclassification improvement and integrated discrimination index. The overall biochemical recurrence rate was 35%. The model with the best fit combined 8 covariates, including the 5 clinicopathological variables prostate specific antigen, Gleason score, pathological stage, lymph node involvement and margin status, and 3 single nucleotide polymorphisms at the KLK2, SULT1A1 and TLR4 genes. Model predictive power was defined by 80% positive predictive value, 74% negative predictive value and an AUC of 0.78. The model based on clinicopathological variables plus single nucleotide polymorphisms showed significant improvement over the model without single nucleotide polymorphisms, as indicated by 23.3% net reclassification improvement (p = 0.003), integrated discrimination index (p <0.001) and likelihood ratio test (p <0.001). Internal validation proved model robustness (bootstrap corrected AUC 0.78, range 0.74 to 0.82). The calibration plot showed close agreement between biochemical recurrence observed and predicted probabilities. Predicting biochemical recurrence after radical prostatectomy based on clinicopathological data can be significantly improved by including patient genetic information. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Changes in the etiology, incidence and prognosis of acute lower respiratory track infections in human immunodeficiency virus patients.

PubMed

Perelló, Rafael; Escoda, Ona; Camón, Silvia; Miró, Òscar; Castañeda, Marta; Moreno, Asunción; Marcos, Maria Ángeles; Perea, Verónica; Alcolea, Natalia; Sánchez, Miquel; Gatell, Josep Maria; Martínez, Esteban

2015-04-01

To describe the incidence, the changes in the etiology and the prognosis of lower respiratory tract infection (LRTI) in HIV infected patients, presenting by the first time to the Emergency Department (ED), during years 2000-2010. Prospective collection of data. Data were collected on the first visit of HIV-infected patients at our ED due to a LRTI, (defined according to the criteria of the European Respiratory Society), between 1/1/2000 and 31/12/2010. A series of epidemiological and laboratory variables as well as the need for admission to the intensive care unit (ICU). LRTI etiology were also collected. The influence ofthe mentioned variables on 30-day mortality were analyzed. One hundred thirty one patients were included. LRTI represented 27% of visits to the ED by HIV-infected patients. Mean age was 39±9 years. 72% of patients were males. 18% required admission to the ICU. The most frequent LRTI was pneumonia by P. jiroveci in 35 cases, bacterial penumonia in 27 and pulmonary tuberculosis in 20. LRTI incidence gradually reduced significantly over time from 6.13 × 1000 patients/year in year 2000 to 0.23 × 1000 patients/year in 2010 (p<0.05). Overall mortality was 14%. Logistic regression analysis showed that admission to ICU (p<0.004) and viral load (p<0.029) were independent variables predicting mortality. LRTI is a pathology with a decreasing incidence, probably related to the widespread utilization increased of HAART regimens. lts etiology has also been changing, but with a non negligible mortality, mostly when ICU admission was required. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders.

PubMed

Hurst, John R; Verma, Nisha; Lowe, David; Baxendale, Helen E; Jolles, Stephen; Kelleher, Peter; Longhurst, Hilary J; Patel, Smita Y; Renzoni, Elisabetta A; Sander, Clare R; Avery, Gerard R; Babar, Judith L; Buckland, Matthew S; Burns, Siobhan; Egner, William; Gompels, Mark M; Gordins, Pavels; Haddock, Jamanda A; Hart, Simon P; Hayman, Grant R; Herriot, Richard; Hoyles, Rachel K; Huissoon, Aarnoud P; Jacob, Joseph; Nicholson, Andrew G; Rassl, Doris M; Sargur, Ravishankar B; Savic, Sinisa; Seneviratne, Suranjith L; Sheaff, Michael; Vaitla, Prashantha M; Walters, Gareth I; Whitehouse, Joanna L; Wright, Penny A; Condliffe, Alison M

A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded." There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Long-term negative impact on quality of life in patients with successfully treated Cushing's disease.

PubMed

Heald, Adrian H; Ghosh, Sandip; Bray, Stephanie; Gibson, Christine; Anderson, Simon G; Buckler, Helen; Fowler, Helen L

2004-10-01

A cohort of pituitary tumour patients, who had undergone definitive treatment within a 15-year period at a single neuroscience centre, were investigated as to whether there were differences in psychological well-being and psychosocial functioning, dependent on endocrine pathology and treatment variables. A detailed assessment of 114 patients with benign pituitary tumours in relation to primary diagnosis and mode of treatment was carried out. Psychological rating scales used were: the Hospital Anxiety and Depression Scale--UK version (HADS-UK), the World Health Organization Quality of Life Scale--abbreviated version (WHOQOL-BREF), General Health Questionnaire 28 (GHQ-28), the Functional Assessment of Cancer Therapy (FACT) and the Social Adjustment Scale--modified (SAS1 and SAS2; the former completed by the patient and the latter by another person who knows the patient well). All Cushing's patients were biochemically cured as defined by a normal 24-h urine free cortisol excretion within the previous 6 months. Patients with treated Cushing's disease had significantly impaired psychological well-being and psychosocial functioning across all tested domains compared with all other pituitary tumours, where scores were similar. When participants with Cushing's disease were excluded, patients who had undergone transfrontal surgery scored significantly higher on GHQ and HADS ratings than transsphenoidally treated patients. Cushing's disease even when biochemically stable has long-term adverse effects on mood and social functioning. We hypothesize that this may be related to irreversible changes in central neural function. Further studies are necessary to define the precise pathways involved.

Correlation of Various Biomarkers with Axillary Nodal Metastases: Can a Panel of Such Biomarkers Guide Selective Use of Axillary Surgery in T1 Breast Cancer?

PubMed

Dass, Tufale A; Rakesh, Sharma; Prakash, K Patil; Singh, Chandraveer

2015-12-01

To evaluate the correlation of various clinic-pathological variables with axillary nodal involvement in T1 breast cancer & to identify a sub-group of T1 cancers, on the basis of observed variables, with a low risk of axillary nodal metastases. Clinico-pathological variables observed included tumor size, lymphovascular invasion (LVI), histological grade of tumor, tumor palpability, estrogen/progesterone (ER/PR) & her2/neu receptors, age, family history, histological type of tumor, axillary nodal metastases for 100 patients without clinically palpable nodes who underwent axillary lymph node dissection in Bombay Hospital & Medical Research Center from March, 2009. Data compiled was analyzed by univariate & multivariate analysis. All the variables viz. tumor size, LVI, histological grade, tumor palpability & ER/PR/Her2 receptor profile, which were found to be significantly associated with axillary lymph node involvement (ALNI) on univariate analysis were also found to be independent predictors of ALNI on multivariate analysis. Age of the patient, family history & histological type of tumor were not significantly correlated with ALNI. None of the 12 patients with tumor biomarker profile of T1a-b tumors without LVI & with histological grade I, had ALNI. The risk of ALNI can be predicted by using various tumor biomarker variables. Based on the predicted risk of ALNI, the management strategy for axilla can be individualized. The omission of operative axillary staging may be considered in patients with low predictive risk of ALNI.

Huge intradiploic epidermoid cyst.

PubMed

Turkoglu, Omer Faruk; Ozdol, Cagatay; Gurcan, Oktay; Gurcay, Ahmet Gurhan; Tun, Kagan; Cemil, Berker

2010-01-01

A 60-year-old man presented with an occipital mass under the scalp and complained of headache, nausea, and dizziness. Magnetic resonance imaging showed a well-defined mass in the occipital scalp extending from the scalp through the cranium and several centimetres into the posterior fossa. There were well-defined margins in the deep portion and the mass was totally removed. Histological examination showed that the cystic structure was lined by squamous epithelium containing laminated keratin material. The pathological findings were consistent with the diagnosis of an epidermoid cyst. The patient was discharged free of symptoms.

Development of an Ontology for Rehabilitation: Traumatic Brain Injury

ERIC Educational Resources Information Center

Grove, Michael J.

2013-01-01

Traumatic Brain Injury (TBI) rehabilitation interventions are very heterogeneous due to injury characteristics and pathology, patient demographics, healthcare settings, caregiver variability, and individualized, multi-discipline treatment plans. Consequently, comparing and generalizing the effectiveness of interventions is limited largely due to…

In phyllodes tumour of the breast expression of c-kit but not of ALDH1A1 is associated with adverse clinico-pathological features.

PubMed

Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Kohli, Pavneet Singh; Singh, Gurpreet

2016-12-01

Attempts at identification of an ideal prognostic/predictive biomarker in phyllodes tumour (PT) have not been fruitful so far. Studies evaluating c-kit expression in PT have shown contradictory results. Recently aldehyde dehydrogenase 1A1 (ALDH1A1) was proposed as a stem cell marker for malignant PT but its expression has not been studied in benign and borderline tumours. We aimed to evaluate expression and prognostic significance of c-kit and ALDH1A1 in different grades of PT. Epithelial and stromal c-kit and ALDH1A1 expression were studied in 104 PT cases (86 primary and 18 recurrent tumours) and compared with different clinico-pathological features and recurrence rates. Stromal c-kit expression at 1 % cutoff correlated with increasing tumour grade, larger tumour size, hypercellularity, nuclear atypia, stromal overgrowth, infiltrative margins and mitotic count. These associations, however, were lost with higher (5 or 10 %) cutoffs. Conversely, decreased c-kit expression in the epithelial component correlated with increasing tumour grade, regardless of the cutoffs used. Stromal ALDH1A1 expression did not have significant associations with tumour grade or other adverse clinico-pathological features, regardless of different cutoffs. None of the cases showed significant epithelial ALDH1A1 expression. Expression of c-kit was associated with poorer overall survival (p = 0.011), while ALDH1A1 expression was associated with shorter recurrence-free survival (p = 0.036). In conclusion, c-kit expression was associated with higher tumour grade and adverse clinico-pathological features. However, these associations are cutoff dependent, partly explaining the variability in previously reported studies. ALDH1A1 expression did not have significant correlations with tumour grade and adverse clinico-pathological variables.

Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration.

PubMed

Margulis, Vitaly; Shariat, Shahrokh F; Matin, Surena F; Kamat, Ashish M; Zigeuner, Richard; Kikuchi, Eiji; Lotan, Yair; Weizer, Alon; Raman, Jay D; Wood, Christopher G

2009-03-15

The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified. Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were re-reviewed by genitourinary pathologists according to strict criteria. Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high-grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) -positive. Over a mean follow-up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5-year recurrence-free and cancer-specific survival probabilities (+/-SD) were 69%+/-1% and 73%+/-1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P<.001), advancing pathologic T stage (P-for-trend<.001), LN metastases (HR: 1.8, P<.001), infiltrative growth pattern (HR: 1.5, P<.001), and LVI (HR: 1.2, P=.041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P=.001), high tumor grade (HR: 1.7, P=.001), increasing pathologic T stage (P-for-trend<.001), LN metastases (HR: 1.7, P<.001), sessile architecture (HR: 1.5, P=.002), and LVI (HR: 1.4, P=.02) were independently associated with cancer-specific survival. Radical nephroureterectomy provided durable local control and cancer-specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with oncologic outcomes, which could potentially be used to select patients for adjuvant systemic therapy. Copyright (c) 2009 American Cancer Society.

Functional Assessment of Synoptic Pathology Reporting for Ovarian Cancer.

PubMed

Słodkowska, Janina; Cierniak, Szczepan; Patera, Janusz; Kopik, Jarosław; Baranowski, Włodzimierz; Markiewicz, Tomasz; Murawski, Piotr; Buda, Irmina; Kozłowski, Wojciech

2016-01-01

Ovarian cancer has one of the highest death/incidence rates and is commonly diagnosed at an advanced stage. In the recent WHO classification, new histotypes were classified which respond differently to chemotherapy. The e-standardized synoptic cancer pathology reports offer the clinicians essential and reliable information. The aim of our project was to develop an e-template for the standardized synoptic pathology reporting of ovarian carcinoma [based on the checklist of the College of American Pathologists (CAP) and the recent WHO/FIGO classification] to introduce a uniform and improved quality of cancer pathology reports. A functional and qualitative evaluation of the synoptic reporting was performed. An indispensable module for e-synoptic reporting was developed and integrated into the Hospital Information System (HIS). The electronic pathology system used a standardized structure with drop-down lists of defined elements to ensure completeness and consistency of reporting practices with the required guidelines. All ovarian cancer pathology reports (partial and final) with the corresponding glass slides selected from a 1-year current workflow were revised for the standard structured reports, and 42 tumors [13 borderline tumors and 29 carcinomas (mainly serous)] were included in the study. Analysis of the reports for completeness against the CAP checklist standard showed a lack of pTNM staging in 80% of the partial or final unstructured reports; ICD-O coding was missing in 83%. Much less frequently missed or unstated data were: ovarian capsule infiltration, angioinvasion and implant evaluation. The e-records of ovarian tumors were supplemented with digital macro- and micro-images and whole-slide images. The e-module developed for synoptic ovarian cancer pathology reporting was easily incorporated into HIS.CGM CliniNet and facilitated comprehensive reporting; it also provided open access to the database for concerned recipients. The e-synoptic pathology reports appeared more accurate, clear and conclusive than traditional narrative reports. Standardizing structured reporting and electronic tools allows open access and downstream utilization of pathology data for clinicians and tumor registries. © 2016 S. Karger AG, Basel.

Nuclear magnetic resonance proton imaging of bone pathology

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

Atlan, H.; Sigal, R.; Hadar, H.

Thirty-two patients with diversified pathology were examined with a supraconductive NMR imager using spin echo with different TR and TE to obtain T1 and T2 weighted images. They included 20 tumors (12 primary, eight metastasis), six osteomyelitis, three fractures, two osteonecrosis, and one diffuse metabolic (Gaucher) disease. In all cases except for the stress fractures, the bone pathology was clearly visualized in spite of the normal lack of signal from the compact cortical bone. Nuclear magnetic resonance (NMR) imaging proved to be at least as sensitive as radionuclide scintigraphy but much more accurate than all other imaging procedures including computedmore » tomography (CT) and angiography to assess the extension of the lesions, especially in tumors extended to soft tissue. This is due both to easy acquisition of sagittal and coronal sections and to different patterns of pathologic modifications of T1 and T2 which are beginning to be defined. It is hoped that more experience in clinical use of these patterns will help to discriminate between tumor extension and soft-tissue edema. We conclude that while radionuclide scintigraphy will probably remain the most sensitive and easy to perform screening test for bone pathology, NMR imaging, among noninvasive diagnostic procedures, appears to be at least as specific as CT. In addition, where the extension of the lesions is concerned, NMR imaging is much more informative than CT. In pathology of the spine, the easy visualization of the spinal cord should decrease the need for myelography.« less

Differential and Conditional Activation of PKC-Isoforms Dictates Cardiac Adaptation during Physiological to Pathological Hypertrophy

PubMed Central

Naskar, Shaon; Datta, Kaberi; Mitra, Arkadeep; Pathak, Kanchan; Datta, Ritwik; Bansal, Trisha; Sarkar, Sagartirtha

2014-01-01

A cardiac hypertrophy is defined as an increase in heart mass which may either be beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy). This study was undertaken to establish the role of different protein kinase-C (PKC) isoforms in the regulation of cardiac adaptation during two types of cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of their downstream proteins were studied during physiological and pathological hypertrophy in 24 week male Balb/c mice (Mus musculus) models, by reverse transcriptase-PCR, western blot analysis and M-mode echocardiography for cardiac function analysis. PKC-δ was significantly induced during pathological hypertrophy while PKC-α was exclusively activated during physiological hypertrophy in our study. PKC-δ activation during pathological hypertrophy resulted in cardiomyocyte apoptosis leading to compromised cardiac function and on the other hand, activation of PKC-α during physiological hypertrophy promoted cardiomyocyte growth but down regulated cellular apoptotic load resulting in improved cardiac function. Reversal in PKC-isoform with induced activation of PKC-δ and simultaneous inhibition of phospho-PKC-α resulted in an efficient myocardium to deteriorate considerably resulting in compromised cardiac function during physiological hypertrophy via augmentation of apoptotic and fibrotic load. This is the first report where PKC-α and -δ have been shown to play crucial role in cardiac adaptation during physiological and pathological hypertrophy respectively thereby rendering compromised cardiac function to an otherwise efficient heart by conditional reversal of their activation. PMID:25116170

Guidelines for biomarker testing in gastroenteropancreatic neuroendocrine neoplasms: a national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.

PubMed

García-Carbonero, R; Vilardell, F; Jiménez-Fonseca, P; González-Campora, R; González, E; Cuatrecasas, M; Capdevila, J; Aranda, I; Barriuso, J; Matías-Guiu, X

2014-03-01

The annual incidence of neuroendocrine tumours in the Caucasian population ranges from 2.5 to 5 new cases per 100,000 inhabitants. Gastroenteropancreatic neuroendocrine tumours is a family of neoplasms widely variable in terms of anatomical location, hormone composition, clinical syndromes they cause and in their biological behaviour. This high complexity and clinical heterogeneity, together with the known difficulty of predicting their behaviour from their pathological features, are reflected in the many classifications that have been developed over the years in this field. This article reviews the main tissue and clinical biomarkers and makes recommendations for their use in medical practice. This document represents a consensus reached jointly by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP).

The Added Value of Pathology Review in Vulvar Cancer: Results From a Population-based Cohort Study.

PubMed

Barbera, Lisa; Gien, Lilian T; Sutradhar, Rinku; Thomas, Gillian; Covens, Al; Elit, Laurie; Fyles, Anthony; Rakovitch, Eileen; Liu, Ying; Khalifa, Mahmoud

2017-03-01

We conducted a population-based patterns of care study of vulvar carcinoma. This paper describes the changes in reporting based on pathology review. This is a retrospective population-based cohort study. We obtained all pathology records available from the provincial cancer registry for primary invasive squamous cell carcinoma of the vulva diagnosed between 1998 and 2007. Pathology reviews were conducted centrally by a group of gynecologic pathologists and were identified during abstraction. Corresponding original reports were matched to pathology review reports based on accession numbers. We compared the reported value for presence/absence of invasion, grade, depth, thickness, size, lymphovascular space invasion, peripheral margin status, and deep margin status in the original and review report. A total of 1011 vulvar resection reports were identified. From these, we identified 316 pairs of original/review reports. Missing data were common but improved in the reviews. In total, 55 (17%) reports had at least 1 change from the original to the review based on presence of invasion, depth, lymphovascular space invasion, or margin. When we included reports where a variable was missing in the original but then completed in the review, there were clinically relevant changes in 210 reports (66%). Vulvar carcinoma is a rare diagnosis and pathology reviews resulted in potentially important clinical changes in a significant proportion of cases. Referral pathologists play an important role in contributing to high-quality clinical decisions.

Variability of breath condensate pH may contribute to the better understanding of non-allergic seasonal respiratory diseases

NASA Astrophysics Data System (ADS)

Kullmann, Tamás; Szipőcs, Annamária

2017-09-01

The seasonal variability of certain non-allergic respiratory diseases is not clearly understood. Analysis of the breath condensate, the liquid that can be collected by breathing into a cold tube, has been proposed to bring closer to the understanding of airway pathologies. It has been assumed, that (1) airway lining fluid was a stable body liquid and (2) the breath condensate samples were representative of the airway lining fluid. Research was focussed on the identification of biomarkers indicative of respiratory pathologies. Despite 30 years of extended investigations breath condensate analysis has not gained any clinical implementation so far. The pH of the condensate is the characteristic that can be determined with the highest reproducibility. The present paper shows, that contrary to the initial assumptions, breath condensate is not a representative of the airway lining fluid, and the airway lining fluid is not a stable body liquid. Condensate pH shows baseline variability and it is influenced by drinking and by the ambient temperature. The changes in condensate pH are linked to changes in airway lining fluid pH. The variability of airway lining fluid pH may explain seasonal incidence of certain non-allergic respiratory diseases such as the catching of a common cold and the increased incidence of COPD exacerbations and exercise-induced bronchoconstriction in cold periods.

Extracapillary proliferation in IgA nephropathy; recent findings and new ideas

PubMed Central

Nasri, Hamid; Mubarak, Muhammed

2015-01-01

Context: IgA nephropathy (IgAN) is an autoimmune disorder and is the most common form of primary glomerulonephritis (GN) worldwide. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. Results: It is a slowly progressing disorder that leads to end-stage renal disease (ESRD) in up to 50% of the patients within 25 years of the onset of the disease. IgAN is defined by predominant IgA deposition in the mesangial area on immunofluorescence (IF) microscopy. Its histology varies from mild focal segmental proliferation of mesangial cells to severe diffuse global proliferation with extracapillary proliferation (crescent formation). The Oxford classification, designed in 2009, is a new classification for the evaluation of morphologic lesions of IgAN. This classification, containing four pathology variables, was found to have prognostic implications. The variables included are mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S) and the proportion of interstitial fibrosis and tubular atrophy (T). However, crescents were not included in the Oxford classification. Conclusions: In this mini-review, we describe the recent publications about the significance of extracapillary proliferation in IgAN and we conclude that, there is much controversy about the role of extracapillary proliferation as a significant prognostic factor in IgAN. Hence, it is important to re-consider crescents in IgAN patients. Therefore, we suggest further investigations on this aspect of IgAN disease. PMID:25657978

Idiopathic granulomatous mastitis: a heterogeneous disease with variable clinical presentation.

PubMed

Baslaim, Muna M; Khayat, Hind A; Al-Amoudi, Shefaa A

2007-08-01

Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast disease that presents with variable local manifestations. We describe here the different management protocols based on the clinical presentation of these patients. A retrospective review of 20 histopathologic confirmed cases of IGM seen over a period of 10 years was performed. The median age was 34 years (age range: 21-45 years). All were married, parous with history of breast feeding. Ill-defined mass mimicking carcinoma was the commonest presentation (70%); however, with the presence of signs of inflammation like pain (55%), redness (40%), and peau d'orange (40%), an inflammatory process appeared more likely. Axillary lymph node enlargement was infrequently seen (40%). Radiologic findings (mammography and ultrasound) were nonspecific. Histopathology showed the characteristic lobular distribution of granulomatous inflammation in all cases. Surgically, 7 patients had abscess drainage with open biopsy, and 7 patients had lumpectomy. Six patients with diffuse breast involvement were diagnosed by core needle biopsy only. Microbial cultures showed no growth. Antibiotics were given empirically when signs of inflammation where present. Two patients needed further abscess drainage followed by persistent sinus excision 3-6 weeks later. The median follow-up was 24 months (range: 15-42 months). Seventeen patients (85%) were recurrence-free, and 3 patients (15%) were lost to follow-up. Management of IGM cases needs to be tailored according to the clinical presentation. Precise radiologic and pathologic data interpretation by a multidisciplinary breast team will facilitate diagnosis and minimize unnecessary intervention.

Functional connectivity with the retrosplenial cortex predicts cognitive aging in rats.

PubMed

Ash, Jessica A; Lu, Hanbing; Taxier, Lisa R; Long, Jeffrey M; Yang, Yihong; Stein, Elliot A; Rapp, Peter R

2016-10-25

Changes in the functional connectivity (FC) of large-scale brain networks are a prominent feature of brain aging, but defining their relationship to variability along the continuum of normal and pathological cognitive outcomes has proved challenging. Here we took advantage of a well-characterized rat model that displays substantial individual differences in hippocampal memory during aging, uncontaminated by slowly progressive, spontaneous neurodegenerative disease. By this approach, we aimed to interrogate the underlying neural network substrates that mediate aging as a uniquely permissive condition and the primary risk for neurodegeneration. Using resting state (rs) blood oxygenation level-dependent fMRI and a restrosplenial/posterior cingulate cortex seed, aged rats demonstrated a large-scale network that had a spatial distribution similar to the default mode network (DMN) in humans, consistent with earlier findings in younger animals. Between-group whole brain contrasts revealed that aged subjects with documented deficits in memory (aged impaired) displayed widespread reductions in cortical FC, prominently including many areas outside the DMN, relative to both young adults (Y) and aged rats with preserved memory (aged unimpaired, AU). Whereas functional connectivity was relatively preserved in AU rats, they exhibited a qualitatively distinct network signature, comprising the loss of an anticorrelated network observed in Y adults. Together the findings demonstrate that changes in rs-FC are specifically coupled to variability in the cognitive outcome of aging, and that successful neurocognitive aging is associated with adaptive remodeling, not simply the persistence of youthful network dynamics.

Extraction of the human cerebral ventricular system from MRI: inclusion of anatomical knowledge and clinical perspective

NASA Astrophysics Data System (ADS)

Aziz, Aamer; Hu, Qingmao; Nowinski, Wieslaw L.

2004-04-01

The human cerebral ventricular system is a complex structure that is essential for the well being and changes in which reflect disease. It is clinically imperative that the ventricular system be studied in details. For this reason computer assisted algorithms are essential to be developed. We have developed a novel (patent pending) and robust anatomical knowledge-driven algorithm for automatic extraction of the cerebral ventricular system from MRI. The algorithm is not only unique in its image processing aspect but also incorporates knowledge of neuroanatomy, radiological properties, and variability of the ventricular system. The ventricular system is divided into six 3D regions based on the anatomy and its variability. Within each ventricular region a 2D region of interest (ROI) is defined and is then further subdivided into sub-regions. Various strict conditions that detect and prevent leakage into the extra-ventricular space are specified for each sub-region based on anatomical knowledge. Each ROI is processed to calculate its local statistics, local intensity ranges of cerebrospinal fluid and grey and white matters, set a seed point within the ROI, grow region directionally in 3D, check anti-leakage conditions and correct growing if leakage occurs and connects all unconnected regions grown by relaxing growing conditions. The algorithm was tested qualitatively and quantitatively on normal and pathological MRI cases and worked well. In this paper we discuss in more detail inclusion of anatomical knowledge in the algorithm and usefulness of our approach from clinical perspective.

Lymph node ratio may predict relapse free survival and overall survival in patients with stage II & III colorectal carcinoma.

PubMed

Zekri, Jamal; Ahmad, Imran; Fawzy, Ehab; Elkhodary, Tawfik R; Al-Gahmi, Aboelkhair; Hassouna, Ashraf; El Sayed, Mohamed E; Ur Rehman, Jalil; Karim, Syed M; Bin Sadiq, Bakr

2015-01-01

Lymph node ratio (LNR) defined as the number of lymph nodes (LNs) involved with metastases divided by number of LNs examined, has been shown to be an independent prognostic factor in breast, stomach and various other solid tumors. Its significance as a prognostic determinant in colorectal cancer (CRC) is still under investigation. This study investigated the prognostic value of LNR in patients with resected CRC. We retrospectively ex- amined 145 patients with stage II & III CRC diagnosed and treated at a single institution during 9 years pe- riod. Patients were grouped according to LNR in three groups. Group 1; LNR < 0.05, Group 2; LNR = 0.05-0.19 & Group 3 > 0.19. Chi square, life table analysis and multivariate Cox regression were used for statistical analysis. On multivariate analysis, number of involved LNs (NILN) (HR = 1.15, 95% CI 1.055-1.245; P = 0.001) and pathological T stage (P = 0.002) were statistically significant predictors of relapse free survival (RFS). LNR as a continuous variable (but not as a categorical variable) was statistically significant predictor of RFS (P = 0.02). LNR was also a statistically significant predictor of overall survival (OS) (P = 0.02). LNR may predict RFS and OS in patients with resected stage II & III CRC. Studies with larger cohorts and longer follow up are needed to further examine and validate theprognostic value of LNR.

Postoperative seizure outcome-guided machine learning for interictal electrocorticography in neocortical epilepsy.

PubMed

Park, Seong-Cheol; Chung, Chun Kee

2018-06-01

The objective of this study was to introduce a new machine learning guided by outcome of resective epilepsy surgery defined as the presence/absence of seizures to improve data mining for interictal pathological activities in neocortical epilepsy. Electrocorticographies for 39 patients with medically intractable neocortical epilepsy were analyzed. We separately analyzed 38 frequencies from 0.9 to 800 Hz including both high-frequency activities and low-frequency activities to select bands related to seizure outcome. An automatic detector using amplitude-duration-number thresholds was used. Interictal electrocorticography data sets of 8 min for each patient were selected. In the first training data set of 20 patients, the automatic detector was optimized to best differentiate the seizure-free group from not-seizure-free-group based on ranks of resection percentages of activities detected using a genetic algorithm. The optimization was validated in a different data set of 19 patients. There were 16 (41%) seizure-free patients. The mean follow-up duration was 21 ± 11 mo (range, 13-44 mo). After validation, frequencies significantly related to seizure outcome were 5.8, 8.4-25, 30, 36, 52, and 75 among low-frequency activities and 108 and 800 Hz among high-frequency activities. Resection for 5.8, 8.4-25, 108, and 800 Hz activities consistently improved seizure outcome. Resection effects of 17-36, 52, and 75 Hz activities on seizure outcome were variable according to thresholds. We developed and validated an automated detector for monitoring interictal pathological and inhibitory/physiological activities in neocortical epilepsy using a data-driven approach through outcome-guided machine learning. NEW & NOTEWORTHY Outcome-guided machine learning based on seizure outcome was used to improve detections for interictal electrocorticographic low- and high-frequency activities. This method resulted in better separation of seizure outcome groups than others reported in the literature. The automatic detector can be trained without human intervention and no prior information. It is based only on objective seizure outcome data without relying on an expert's manual annotations. Using the method, we could find and characterize pathological and inhibitory activities.

Cellular calcium dynamics in lactation and breast cancer: From physiology to pathology

USDA-ARS?s Scientific Manuscript database

Breast cancer is the second leading cause of cancer mortality in women, estimated at nearly 40,000 deaths and more than 230,000 new cases diagnosed in the U.S. this year alone. One of the defining characteristics of breast cancer is the radiographic presence of microcalcifications. These palpable mi...

An Interpersonal Analysis of Pathological Personality Traits in "DSM-5"

ERIC Educational Resources Information Center

Wright, Aidan G. C.; Pincus, Aaron L.; Hopwood, Christopher J.; Thomas, Katherine M.; Markon, Kristian E.; Krueger, Robert F.

2012-01-01

The proposed changes to the personality disorder section of the "Diagnostic and Statistical Manual of Mental Disorders" (5th ed.) places an increased focus on interpersonal impairment as one of the defining features of personality psychopathology. In addition, a proposed trait model has been offered to provide a means of capturing…

From Intuition to Science: Re-ED and Trauma-Informed Care

ERIC Educational Resources Information Center

Maikoetter, Michelle

2011-01-01

Nicholas Hobbs, a visionary in the field of psychology, believed strongly that how one defines a problem determines in large part the strategies that can be generated to solve it (Hobbs, 1982). He questioned the validity of psychiatric labels and other means of classification that pathologized children, believing that such approaches guided people…

One Fungus, One Name: Defining the genus Fusarium in a scientifically robust way that preserves longstanding use

USDA-ARS?s Scientific Manuscript database

In this letter, we advocate recognizing the genus Fusarium as the sole name for a group that includes virtually all Fusarium species of importance in plant pathology, mycotoxicology, medicine and basic research. This phylogenetically-guided circumscription will free scientists from any obligation to...

Multiple Personality and the Pathological Dissociation of Self.

ERIC Educational Resources Information Center

Price, Reese E.

This paper considers the condition of Multiple Personality Disorder (MPD), which is defined as a separation of alternating personalities by rigid boundaries and amnestic barriers. It is proposed that MPD represents the end of a continuum of a defensive dissociation of the self that can result when a child employs a dissociative splitting of self…

Dwarf mistletoes: Biology, pathology, and systematics

Treesearch

Frank G. Hawksworth; Delbert Wiens

1996-01-01

Arceuthobium (dwarf mistletoes), a well defined but morphologically reduced genus of the family Viscaceae, is parasitic on Pinaceae in the Old and New Worlds and on Cupressaceae in the Old World. Although conifer forests in many parts of the Northern Hemisphere are infested with dwarf mistletoes, those most commonly infested are in western North...

Behavioral Profiles in 4-5 Year-Old Children: Normal and Pathological Variants

ERIC Educational Resources Information Center

Larsson, Jan-Olov; Bergman, Lars R.; Earls, Felton; Rydelius, Per-Anders

2004-01-01

Normal and psychopathological patterns of behavior symptoms in preschool children were described by a classification approach using cluster analysis. The behavior of 406 children, average age 4 years 9 months, from the general population was evaluated at home visits. Seven clusters were identified based on empirically defined dimensions:…

Delineation of the function of a major gamma delta T cell subset during infection.

PubMed

Andrew, Elizabeth M; Newton, Darren J; Dalton, Jane E; Egan, Charlotte E; Goodwin, Stewart J; Tramonti, Daniela; Scott, Philip; Carding, Simon R

2005-08-01

Gammadelta T cells play important but poorly defined roles in pathogen-induced immune responses and in preventing chronic inflammation and pathology. A major obstacle to defining their function is establishing the degree of functional redundancy and heterogeneity among gammadelta T cells. Using mice deficient in Vgamma1+ T cells which are a major component of the gammadelta T cell response to microbial infection, a specific immunoregulatory role for Vgamma1+ T cells in macrophage and gammadelta T cell homeostasis during infection has been established. By contrast, Vgamma1+ T cells play no significant role in pathogen containment or eradication and cannot protect mice from immune-mediated pathology. Pathogen-elicited Vgamma1+ T cells also display different functional characteristics at different stages of the host response to infection that involves unique and different populations of Vgamma1+ T cells. These findings, therefore, identify distinct and nonoverlapping roles for gammadelta T cell subsets in infection and establish the complexity and adaptability of a single population of gammadelta T cells in the host response to infection that is not predetermined, but is, instead, shaped by environmental factors.

Regulated production of free radicals by the mitochondrial electron transport chain: Cardiac ischemic preconditioning.

PubMed

Matsuzaki, Satoshi; Szweda, Pamela A; Szweda, Luke I; Humphries, Kenneth M

2009-11-30

Excessive production of free radicals by mitochondria is associated with, and likely contributes to, the progression of numerous pathological conditions. Nevertheless, the production of free radicals by the mitochondria may have important biological functions under normal or stressed conditions by activating or modulating redox-sensitive cellular signaling pathways. This raises the intriguing possibility that regulated mitochondrial free radical production occurs via mechanisms that are distinct from pathologies associated with oxidative damage. Indeed, the capacity of mitochondria to produce free radicals in a limited manner may play a role in ischemic preconditioning, the phenomenon whereby short bouts of ischemia protect from subsequent prolonged ischemia and reperfusion. Ischemic preconditioning can thus serve as an important model system for defining regulatory mechanisms that allow for transient, signal-inducing, production of free radicals by mitochondria. Defining how these mechanism(s) occur will provide insight into therapeutic approaches that minimize oxidative damage without altering normal cellular redox biology. The aim of this review is to present and discuss evidence for the regulated production of superoxide by the electron transport chain within the ischemic preconditioning paradigm of redox regulation.

Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases.

PubMed

Lucidi, Valerio; Hendlisz, Alain; Van Laethem, Jean-Luc; Donckier, Vincent

2016-04-21

In oncosurgical approach to colorectal liver metastases, surgery remains considered as the only potentially curative option, while chemotherapy alone represents a strictly palliative treatment. However, missing metastases, defined as metastases disappearing after chemotherapy, represent a unique model to evaluate the curative potential of chemotherapy and to challenge current therapeutic algorithms. We reviewed recent series on missing colorectal liver metastases to evaluate incidence of this phenomenon, predictive factors and rates of cure defined by complete pathologic response in resected missing metastases and sustained clinical response when they were left unresected. According to the progresses in the efficacy of chemotherapeutic regimen, the incidence of missing liver metastases regularly increases these last years. Main predictive factors are small tumor size, low marker level, duration of chemotherapy, and use of intra-arterial chemotherapy. Initial series showed low rates of complete pathologic response in resected missing metastases and high recurrence rates when unresected. However, recent reports describe complete pathologic responses and sustained clinical responses reaching 50%, suggesting that chemotherapy could be curative in some cases. Accordingly, in case of missing colorectal liver metastases, the classical recommendation to resect initial tumor sites might have become partially obsolete. Furthermore, the curative effect of chemotherapy in selected cases could lead to a change of paradigm in patients with unresectable liver-only metastases, using intensive first-line chemotherapy to intentionally induce missing metastases, followed by adjuvant surgery on remnant chemoresistant tumors and close surveillance of initial sites that have been left unresected.

Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach.

PubMed

Lai, Ling; Leone, Teresa C; Keller, Mark P; Martin, Ola J; Broman, Aimee T; Nigro, Jessica; Kapoor, Kapil; Koves, Timothy R; Stevens, Robert; Ilkayeva, Olga R; Vega, Rick B; Attie, Alan D; Muoio, Deborah M; Kelly, Daniel P

2014-11-01

An unbiased systems approach was used to define energy metabolic events that occur during the pathological cardiac remodeling en route to heart failure (HF). Combined myocardial transcriptomic and metabolomic profiling were conducted in a well-defined mouse model of HF that allows comparative assessment of compensated and decompensated (HF) forms of cardiac hypertrophy because of pressure overload. The pressure overload data sets were also compared with the myocardial transcriptome and metabolome for an adaptive (physiological) form of cardiac hypertrophy because of endurance exercise training. Comparative analysis of the data sets led to the following conclusions: (1) expression of most genes involved in mitochondrial energy transduction were not significantly changed in the hypertrophied or failing heart, with the notable exception of a progressive downregulation of transcripts encoding proteins and enzymes involved in myocyte fatty acid transport and oxidation during the development of HF; (2) tissue metabolite profiles were more broadly regulated than corresponding metabolic gene regulatory changes, suggesting significant regulation at the post-transcriptional level; (3) metabolomic signatures distinguished pathological and physiological forms of cardiac hypertrophy and served as robust markers for the onset of HF; and (4) the pattern of metabolite derangements in the failing heart suggests bottlenecks of carbon substrate flux into the Krebs cycle. Mitochondrial energy metabolic derangements that occur during the early development of pressure overload-induced HF involve both transcriptional and post-transcriptional events. A subset of the myocardial metabolomic profile robustly distinguished pathological and physiological cardiac remodeling. © 2014 American Heart Association, Inc.

Histopathological subgroups in knee osteoarthritis.

PubMed

Wyatt, L A; Moreton, B J; Mapp, P I; Wilson, D; Hill, R; Ferguson, E; Scammell, B E; Walsh, D A

2017-01-01

Osteoarthritis (OA) is a heterogeneous, multi-tissue disease. We hypothesised that different histopathological features characterise different stages during knee OA progression, and that discrete subgroups can be defined based on validated measures of OA histopathological features. Medial tibial plateaux and synovium were from 343 post-mortem (PM) and 143 OA arthroplasty donations. A 'chondropathy/osteophyte' group (n = 217) was classified as PM cases with osteophytes or macroscopic medial tibiofemoral chondropathy lesions ≥grade 3 to represent pre-surgical (early) OA. 'Non-arthritic' controls (n = 48) were identified from the remaining PM cases. Mankin histopathological scores were subjected to Rasch analysis and supplemented with histopathological scores for subchondral bone marrow replacement and synovitis. Item weightings were derived by principle components analysis (PCA). Histopathological subgroups were sought using latent class analysis (LCA). Chondropathy, synovitis and osteochondral pathology were each associated with OA at arthroplasty, but each was also identified in some 'non-arthritic' controls. Tidemark breaching in the chondropathy/osteophyte group was greater than in non-arthritic controls. Three histopathological subgroups were identified, characterised as 'mild OA', or 'severe OA' with mild or moderate/severe synovitis. Presence and severity of synovitis helps define distinct histopathological OA subgroups. The absence of a discrete 'normal' subgroup indicates a pathological continuum between normality and OA status. Identifying specific pathological processes and their clinical correlates in OA subgroups has potential to accelerate the development of more effective therapies. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

A brief history of prions.

PubMed

Zabel, Mark D; Reid, Crystal

2015-12-01

Proteins were described as distinct biological molecules and their significance in cellular processes was recognized as early as the 18th century. At the same time, Spanish shepherds observed a disease that compelled their Merino sheep to pathologically scrape against fences, a defining clinical sign that led to the disease being named scrapie. In the late 19th century, Robert Koch published his postulates for defining causative agents of disease. In the early 20th century, pathologists Creutzfeldt and Jakob described a neurodegenerative disease that would later be included with scrapie into a group of diseases known as transmissible spongiform encephalopathies (TSEs). Later that century, mounting evidence compelled a handful of scientists to betray the prevailing biological dogma governing pathogen replication that Watson and Crick so convincingly explained by cracking the genetic code just two decades earlier. Because TSEs seemed to defy these new rules, J.S. Griffith theorized mechanisms by which a pathogenic protein could encipher its own replication blueprint without a genetic code. Stanley Prusiner called this proteinaceous infectious pathogen a prion. Here we offer a concise account of the discovery of prions, the causative agent of TSEs, in the wider context of protein biochemistry and infectious disease. We highlight the discovery of prions in yeast and discuss the implication of prions as epigenomic carriers of biological and pathological information. We also consider expanding the prion hypothesis to include other proteins whose alternate isoforms confer new biological or pathological properties. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A brief history of prions

PubMed Central

Zabel, Mark D.; Reid, Crystal

2015-01-01

Proteins were described as distinct biological molecules and their significance in cellular processes was recognized as early as the 18th century. At the same time, Spanish shepherds observed a disease that compelled their Merino sheep to pathologically scrape against fences, a defining clinical sign that led to the disease being named scrapie. In the late 19th century, Robert Koch published his postulates for defining causative agents of disease. In the early 20th century, pathologists Creutzfeldt and Jakob described a neurodegenerative disease that would later be included with scrapie into a group of diseases known as transmissible spongiform encephalopathies (TSEs). Later that century, mounting evidence compelled a handful of scientists to betray the prevailing biological dogma governing pathogen replication that Watson and Crick so convincingly explained by cracking the genetic code just two decades earlier. Because TSEs seemed to defy these new rules, J.S. Griffith theorized mechanisms by which a pathogenic protein could encipher its own replication blueprint without a genetic code. Stanley Prusiner called this proteinaceous infectious pathogen a prion. Here we offer a concise account of the discovery of prions, the causative agent of TSEs, in the wider context of protein biochemistry and infectious disease. We highlight the discovery of prions in yeast and discuss the implication of prions as epigenomic carriers of biological and pathological information. We also consider expanding the prion hypothesis to include other proteins whose alternate isoforms confer new biological or pathological properties. PMID:26449713

Heller Myotomy Versus Heller Myotomy With Dor Fundoplication for Achalasia

PubMed Central

Richards, William O.; Torquati, Alfonso; Holzman, Michael D.; Khaitan, Leena; Byrne, Daniel; Lutfi, Rami; Sharp, Kenneth W.

2004-01-01

Objective: We sought to determine the impact of the addition of Dor fundoplication on the incidence of postoperative gastroesophageal reflux (GER) after Heller myotomy. Summary Background Data: Based only on case series, many surgeons believe that an antireflux procedure should be added to the Heller myotomy. However, no prospective randomized data support this approach. Patients and Methods: In this prospective, randomized, double-blind, institutional review board-approved clinical trial, patients with achalasia were assigned to undergo Heller myotomy or Heller myotomy plus Dor fundoplication. Patients were studied via 24-hour pH study and manometry at 6 months postoperatively. Pathologic GER was defined as distal esophageal time acid exposure time greater than 4.2% per 24-hour period. The outcome variables were analyzed on an intention-to-treat basis. Results: Forty-three patients were enrolled. There were no differences in the baseline characteristics between study groups. Pathologic GER occurred in 10 of 21 patients (47.6%) after Heller and in 2 of 22 patients (9.1%) after Heller plus Dor (P = 0.005). Heller plus Dor was associated with a significant reduction in the risk of GER (relative risk 0.11; 95% confidence interval 0.02–0.59; P = 0.01). Median distal esophageal acid exposure time was lower in the Heller plus Dor (0.4%; range, 0–16.7) compared with the Heller group (4.9%; range, 0.1–43.6; P = 0.001). No significant difference in surgical outcome between the 2 techniques with respect to postoperative lower-esophageal sphincter pressure or postoperative dysphagia score was observed. Conclusions: Heller Myotomy plus Dor Fundoplication was superior to Heller myotomy alone in regard to the incidence of postoperative GER. PMID:15319712

Determinants of physiological uptake of 18F-fluorodeoxyglucose in palatine tonsils.

PubMed

Birkin, Emily; Moore, Katherine S; Huang, Chao; Christopher, Marshall; Rees, John I; Jayaprakasam, Vetrisudar; Fielding, Patrick A

2018-06-01

To determine the extent of physiological variation of uptake of F-flurodeoxyglucose (FDG) within palatine tonsils. To define normal limits for side-to-side variation and characterize factors affecting tonsillar uptake of FDG.Over a period of 16 weeks 299 adult patients at low risk for head and neck pathology, attending our center for FDG positron emission tomography/computed tomography (PET/CT) scans were identified. The maximum standardized uptake value (SUVmax) was recorded for each palatine tonsil. For each patient age, gender, smoking status, scan indication and prior tonsillectomy status as well as weather conditions were noted.There was a wide variation in palatine tonsil FDG uptake with SUVmax values between 1.3 and 11.4 recorded. There was a strong left to right correlation for tonsillar FDG uptake within each patient (P < .01). The right palatine tonsil showed increased FDG uptake (4.63) compared to the left (4.47) (P < .01). In multivariate analysis, gender, scan indication, and prevailing weather had no significant impact of tonsillar FDG uptake. Lower tonsillar uptake was seen in patients with a prior history of tonsillectomy (4.13) than those without this history (4.64) (P < .01). Decreasing tonsillar FDG uptake was seen with advancing age (P < .01). Significantly lower uptake was seen in current smokers (SUVmax 4.2) than nonsmokers (SUV 4.9) (P = .03).Uptake of FDG in palatine tonsils is variable but shows a strong side-to-side correlation. We suggest the left/ right SUVmax ratio as a guide to normality with a first to 99th percentiles of (0.70-1.36) for use in patients not suspected to have tonsillar pathology.

Brain arterial aging and its relationship to Alzheimer dementia

PubMed Central

Honig, Lawrence; Elkind, Mitchell S.V.; Mohr, Jay P.; Goldman, James; Dwork, Andrew J.; Morgello, Susan; Marshall, Randolph S.

2016-01-01

Objective: To test the hypothesis that brain arterial aging is associated with the pathologic diagnosis of Alzheimer disease (AD). Methods: Brain large arteries were assessed for diameter, gaps in the internal elastic lamina (IEL), luminal stenosis, atherosclerosis, and lumen-to-wall ratio. Elastin, collagen, and amyloid were assessed with Van Gieson, trichrome, and Congo red staining intensities, and quantified automatically. Brain infarcts and AD (defined pathologically) were assessed at autopsy. We created a brain arterial aging (BAA) score with arterial characteristics associated with aging after adjusting for demographic and clinical variables using cross-sectional generalized linear models. Results: We studied 194 autopsied brains, 25 (13%) of which had autopsy evidence of AD. Brain arterial aging consisted of higher interadventitial and lumen diameters, thickening of the wall, increased prevalence of IEL gaps, concentric intima thickening, elastin loss, increased amyloid deposition, and a higher IEL proportion without changes in lumen-to-wall ratio. In multivariable analysis, a high IEL proportion (B = 1.96, p = 0.030), thick media (B = 3.50, p = 0.001), elastin loss (B = 6.16, p < 0.001), IEL gaps (B = 3.14, p = 0.023), and concentric intima thickening (B = 7.19, p < 0.001) were used to create the BAA score. Adjusting for demographics, vascular risk factors, atherosclerosis, and brain infarcts, the BAA score was associated with AD (B = 0.022, p = 0.002). Conclusions: Aging of brain large arteries is characterized by arterial dilation with a commensurate wall thickening, elastin loss, and IEL gaps. Greater intensity of arterial aging was associated with AD independently of atherosclerosis and brain infarcts. Understanding the drivers of arterial aging may advance the knowledge of the pathophysiology of AD. PMID:26984942

Brain arterial aging and its relationship to Alzheimer dementia.

PubMed

Gutierrez, Jose; Honig, Lawrence; Elkind, Mitchell S V; Mohr, Jay P; Goldman, James; Dwork, Andrew J; Morgello, Susan; Marshall, Randolph S

2016-04-19

To test the hypothesis that brain arterial aging is associated with the pathologic diagnosis of Alzheimer disease (AD). Brain large arteries were assessed for diameter, gaps in the internal elastic lamina (IEL), luminal stenosis, atherosclerosis, and lumen-to-wall ratio. Elastin, collagen, and amyloid were assessed with Van Gieson, trichrome, and Congo red staining intensities, and quantified automatically. Brain infarcts and AD (defined pathologically) were assessed at autopsy. We created a brain arterial aging (BAA) score with arterial characteristics associated with aging after adjusting for demographic and clinical variables using cross-sectional generalized linear models. We studied 194 autopsied brains, 25 (13%) of which had autopsy evidence of AD. Brain arterial aging consisted of higher interadventitial and lumen diameters, thickening of the wall, increased prevalence of IEL gaps, concentric intima thickening, elastin loss, increased amyloid deposition, and a higher IEL proportion without changes in lumen-to-wall ratio. In multivariable analysis, a high IEL proportion (B = 1.96, p = 0.030), thick media (B = 3.50, p = 0.001), elastin loss (B = 6.16, p < 0.001), IEL gaps (B = 3.14, p = 0.023), and concentric intima thickening (B = 7.19, p < 0.001) were used to create the BAA score. Adjusting for demographics, vascular risk factors, atherosclerosis, and brain infarcts, the BAA score was associated with AD (B = 0.022, p = 0.002). Aging of brain large arteries is characterized by arterial dilation with a commensurate wall thickening, elastin loss, and IEL gaps. Greater intensity of arterial aging was associated with AD independently of atherosclerosis and brain infarcts. Understanding the drivers of arterial aging may advance the knowledge of the pathophysiology of AD. © 2016 American Academy of Neurology.

Paraduodenal Pancreatitis: Imaging and Pathologic Correlation of 47 Cases Elucidates Distinct Subtypes and the Factors Involved in its Etiopathogenesis.

PubMed

Muraki, Takashi; Kim, Grace E; Reid, Michelle D; Mittal, Pardeep; Bedolla, Gabriela; Memis, Bahar; Pehlivanoglu, Burcin; Freedman, Alexa; Erbarut Seven, Ipek; Choi, Hyejeong; Kooby, David; Maithel, Shishir K; Sarmiento, Juan M; Krasinskas, Alyssa; Adsay, Volkan

2017-10-01

Clinicopathologic characteristics of paraduodenal (groove) pancreatitis (PDP) remain to be fully unraveled. In this study, 47 PDPs with preoperative enhanced images available were subjected to detailed comparative analysis in conjunction with pathologic findings. PDP were predominantly in males (3:1) with a mean age of 50 years, and 60% had a preoperative diagnosis of cancer. Mean lesional size was 3.1 cm. Three distinct subtypes were identified by imaging. Solid-tumoral (type-1) with groove-predominant (type-1A, 36%) forming a distinct solid band between the duodenum and pancreas often with histologic microabscesses (69% vs. 33% in others), and pancreas-involving (type-1B, 19%) forming a pseudotumoral mass spanning into the head-groove area, always diagnosed preoperatively as "cancer," but often lacked parenchymal atrophy of the body (44% vs. 92%). Cyst-forming (type-2) had groove-predominant (type-2A, 15%), often accompanied by Brunner gland hyperplasia, and pancreas-predominant (type-2B, 15%) were in younger (mean: 44 y) females (57% vs. 18%) and had less alcohol/tobacco abuse (50/33% vs. 81/69%). Ill-defined (type-3; 15%) often had main pancreatic duct dilatation (mean: 5.6 vs. 2.8 mm). The capricious presentations of PDP could be attributed to variable effects of different mechanistic and precipitative etiopathogenetic factors such as disturbed accessory duct outflow (dilated Santorini duct, 87%), aggravated by alcohol (77%) with superimposed stasis in the main ampulla (previous cholecystectomy, 47%; choledocholithiasis, 9%), strictured Wirsung duct (68%), and some likely exacerbated by ischemia (hypertension [59%], tobacco abuse [64%], arteriosclerosis in the tissue [23%]). In conclusion, our study identified 3 distinct types of PDP and each may reflect different pathogenetic contributing factors.

Congenital choristomas of the oral cavity in children.

PubMed

Chai, Raymond L; Ozolek, John A; Branstetter, Barton F; Mehta, Deepak K; Simons, Jeffrey P

2011-10-01

To review our institutional experience with oral cavity choristomas in children. Retrospective case series and medical record review. Medical records including clinic notes, operative reports, radiologic studies, and pathology specimens were reviewed. All imaging studies and pathology material were reviewed by a head and neck radiologist and pediatric pathologist, respectively. Sixteen patients (10 males and 6 females) with congenital oral cavity choristomas were identified. Mean age at diagnosis was 1.8 months. Location of the lesions included tongue (n = 9) and floor of mouth (n = 7). Preoperative imaging included magnetic resonance imaging (n = 6), computed tomography (n = 5), plain radiography (n = 1), and no imaging (n = 4). Radiographically, the lesions were consistently lobular with well-defined margins, but other imaging features often mimicked other masses that can arise in the tongue and floor of mouth. Symptoms were present in five of 16 patients and included difficulty feeding, swelling with upper respiratory infection, and partial airway obstruction. Complete surgical excision was performed in 15 of 16 patients; mean age at the time of surgery was 12.7 months. One patient underwent marsupialization. No complications were noted perioperatively. No recurrences of choristoma were seen. On histologic examination, the predominant component was cystic with cyst linings of respiratory epithelium (n = 5), gastric (foveolar) epithelium (n = 1), or both (n = 10). This study supports surgical excision as an effective intervention for children with oral cavity choristomas. Because the etiology of these cysts is unknown and diagnostic terminology is widely variable, we propose a more descriptive diagnosis based on the histology (i.e., lingual choristoma [or lingual developmental cyst] with respiratory epithelium or lingual choristoma [or lingual developmental cyst] with gastric epithelium). Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Cognitive reserve as a predictor of two year neuropsychological performance in early onset first-episode schizophrenia.

PubMed

de la Serna, Elena; Andrés-Perpiñá, Susana; Puig, Olga; Baeza, Inmaculada; Bombin, Igor; Bartrés-Faz, David; Arango, Celso; Gonzalez-Pinto, Ana; Parellada, Mara; Mayoral, María; Graell, Montserrat; Otero, Soraya; Guardia, Joan; Castro-Fornieles, Josefina

2013-01-01

The concept of cognitive reserve (CR) has been defined as individual differences in the efficient utilization of brain networks which allow some people to cope better than others with brain pathology. CR has been developed mainly in the field of aging and dementia after it was observed that there appears to be no direct relationship between the degree of brain pathology and the severity of clinical manifestations of this damage. The present study applies the concept of CR to a sample of children and adolescents with a first episode of schizophrenia, aiming to assess the possible influence of CR on neuropsychological performance after two year follow-up, controlling for the influence of clinical psychopathology. 35 patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder (SSD) and 98 healthy controls (HC) matched for age and gender were included. CR was assessed at baseline, taking into account premorbid IQ, educational-occupational level and leisure activities. Clinical and neuropsychological assessments were completed by all patients at two year follow-up. The CR proxy was able to predict working memory and attention at two year follow-up. Verbal memory and cognitive flexibility were not predicted by any of the variables included in the regression model. The SSD group obtained lower scores than HC on CR. CR measures correctly classified 79.8% of the sample as being SSD or HC. Lower scores on CR were observed in SSD than in HC and the CR measure correctly classified a high percentage of the sample into the two groups. CR may predict SSD performance on working memory and attention tasks. Copyright © 2012 Elsevier B.V. All rights reserved.

Pathological complete response in breast cancer patients receiving anthracycline and taxane-based neoadjuvant chemotherapy: Evaluating the effect of race/ethnicity

PubMed Central

Chavez-MacGregor, Mariana; Litton, Jennifer; Chen, Huiqin; Giordano, Sharon H.; Hudis, Clifford A.; Wolff, Antonio C.; Valero, Vicente; Hortobagyi, Gabriel N.; Bondy, Melissa L.; Gonzalez-Angulo, Ana Maria

2010-01-01

Purpose To evaluate the influence of race/ethnicity and tumor subtype in pathological complete response (pCR) following treatment with neoadjuvant chemotherapy. Methods 2074 patients diagnosed with breast cancer between 1994 and 2008, treated with neoadjuvant anthracycline- and taxane-based chemotherapy, were included. pCR was defined as no residual invasive cancer in the breast and axilla. Kaplan-Meier product-limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome. Results Median age was 50 years, 14.6% patients were black, 15.2% Hispanic, 64.3% White, and 5.9% other race. There were no differences in pCR rates among race/ethnicity: (12.3% in black, 14.2% in Hispanics, 12.3% in whites and 11.5% in others, p=.788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse RFS and OS (p≤.0001). Differences in RFS by race/ethnicity were seen in the patients with hormone receptor-positive disease, p=.007. In multivariate analysis, Hispanics had improved RFS (HR, 95% CI 0.69; 0.49-0.97) and OS (HR, 95% CI 0.63; 0.41-0.97); blacks had a trend to worse outcomes (RFS:HR, 95% CI 1.28; 0.97-1.68, OS:HR, 1.32; 95% CI; 0.97-1.81) when compared to whites. Conclusions In this cohort of patients, race/ethnicity was not significantly associated with pCR rates. In a multivariate analysis we observed improved outcomes in Hispanics and a trend towards worse outcomes in black patients, when compared to whites. Further research is needed to explore the potential differences in biology and outcomes. PMID:20564153

Inter-observer variability in the classification of ovarian cancer cell type using microscopy: a pilot study

NASA Astrophysics Data System (ADS)

Gavrielides, Marios A.; Ronnett, Brigitte M.; Vang, Russell; Seidman, Jeffrey D.

2015-03-01

Studies have shown that different cell types of ovarian carcinoma have different molecular profiles, exhibit different behavior, and that patients could benefit from typespecific treatment. Different cell types display different histopathology features, and different criteria are used for each cell type classification. Inter-observer variability for the task of classifying ovarian cancer cell types is an under-examined area of research. This study served as a pilot study to quantify observer variability related to the classification of ovarian cancer cell types and to extract valuable data for designing a validation study of digital pathology (DP) for this task. Three observers with expertise in gynecologic pathology reviewed 114 cases of ovarian cancer with optical microscopy, with specific guidelines for classifications into distinct cell types. For 93 cases all 3 pathologists agreed on the same cell type, for 18 cases 2 out of 3 agreed, and for 3 cases there was no agreement. Across cell types with a minimum sample size of 10 cases, agreement between all three observers was {91.1%, 80.0%, 90.0%, 78.6%, 100.0%, 61.5%} for the high grade serous carcinoma, low grade serous carcinoma, endometrioid, mucinous, clear cell, and carcinosarcoma cell types respectively. These results indicate that unanimous agreement varied over a fairly wide range. However, additional research is needed to determine the importance of these differences in comparison studies. These results will be used to aid in the design and sizing of such a study comparing optical and digital pathology. In addition, the results will help in understanding the potential role computer-aided diagnosis has in helping to improve the agreement of pathologists for this task.

Intra- and extra-capsular hip fractures in the elderly: Two different pathologies?

PubMed

Dinamarca-Montecinos, J L; Prados-Olleta, N; Rubio-Herrera, R; Castellón-Sánchez del Pino, A; Carrasco-Buvinic, A

2015-01-01

To compare intracapsular (IC) and extracapsular (EC) hip fractures (HIF) in elderly patients in order to determine if they are different pathologies. Longitudinal, observational, descriptive, analytical prospective design, using a non-probabilistic sample from a full sample collection with 647 subjects (male and female), of 60 or more years old, admitted with HIF to the Department of Orthopedics and Traumatology of the Hospital, between January 1, 2010 and December 31, 2012. Follow-up was for 1 year post HIF. Socio-demographic, etiological, developmental, therapeutic and prognostic variables are compared. This is the first study on this subject with Latin American population. EC HIF incidence was superior to IC, contrary to that published in European/American populations. There are significant differences in etiological variables (χ(2)=6.34, p<0.042), with traumatic etiology in EC and non-traumatic in IC. There are also differences in therapeutic interventions performed (osteosynthesis for EC, arthroplasty for IC), with the decision on not to operate being lower in IC (both p<0.0000). The variables associated with the decision on not to perform surgery are age, etiology and postoperative mortality. The results are similar to other studies, adding the IC association with non-traumatic origin, in particular the trend of statistical association between IC and non-primary osteoporotic pathology (neoplasms, renal osteodystrophy, primary hyperparathyroidism). A further analysis was performed on the differences between Latin American and European/American populations in the incidence of either type of HIF. There are important etiological and therapeutic differences between IC and EC HIF; therefore it would be advisable to consider them as distinct disease entities. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

Diagnosis of breast masses from dynamic contrast-enhanced and diffusion-weighted MR: a machine learning approach.

PubMed

Cai, Hongmin; Peng, Yanxia; Ou, Caiwen; Chen, Minsheng; Li, Li

2014-01-01

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly used for breast cancer diagnosis as supplementary to conventional imaging techniques. Combining of diffusion-weighted imaging (DWI) of morphology and kinetic features from DCE-MRI to improve the discrimination power of malignant from benign breast masses is rarely reported. The study comprised of 234 female patients with 85 benign and 149 malignant lesions. Four distinct groups of features, coupling with pathological tests, were estimated to comprehensively characterize the pictorial properties of each lesion, which was obtained by a semi-automated segmentation method. Classical machine learning scheme including feature subset selection and various classification schemes were employed to build prognostic model, which served as a foundation for evaluating the combined effects of the multi-sided features for predicting of the types of lesions. Various measurements including cross validation and receiver operating characteristics were used to quantify the diagnostic performances of each feature as well as their combination. Seven features were all found to be statistically different between the malignant and the benign groups and their combination has achieved the highest classification accuracy. The seven features include one pathological variable of age, one morphological variable of slope, three texture features of entropy, inverse difference and information correlation, one kinetic feature of SER and one DWI feature of apparent diffusion coefficient (ADC). Together with the selected diagnostic features, various classical classification schemes were used to test their discrimination power through cross validation scheme. The averaged measurements of sensitivity, specificity, AUC and accuracy are 0.85, 0.89, 90.9% and 0.93, respectively. Multi-sided variables which characterize the morphological, kinetic, pathological properties and DWI measurement of ADC can dramatically improve the discriminatory power of breast lesions.

Pathologic fracture in childhood and adolescent osteosarcoma: A single-institution experience.

PubMed

Haynes, Lindsay; Kaste, Sue C; Ness, Kirsten K; Wu, Jianrong; Ortega-Laureano, Lucia; Bishop, Michael; Neel, Michael; Rao, Bhaskar; Fernandez-Pineda, Israel

2017-04-01

Pathologic fractures occur in 5-10% of pediatric osteosarcoma (OS) cases and have historically been considered a contraindication to limb salvage. Our purpose was to describe the radiographic features of pathologic fracture and examine its impact on local recurrence rates, functional outcomes, and overall survival. We retrospectively analyzed patients at our institution from 1990 to 2015 with pathologic fracture at diagnosis or during neoadjuvant chemotherapy. We selected a control group of 50 OS patients of similar age and gender without pathologic fracture from 1990 to 2015. Functional outcomes were scored using Musculoskeletal Tumor Society criteria. Chi-square test was used for comparative analysis of groups. Thirty-six patients with 37 pathologic fractures form the study cohort. Of patients who received surgery, 18 of 34 patients with fracture underwent amputation compared to 8 of 48 patients in the nonfracture group (P = 0.007). Indications for amputation in fracture patients were tumor size (n = 7), neurovascular involvement (n = 6), and tumor progression during neoadjuvant chemotherapy (n = 5). Only one patient (2.9%) in the fracture group who underwent limb salvage suffered local recurrence. Of patients who received neoadjuvant chemotherapy, 25 of 34 fracture patients showed poor histological response compared to 24 of 47 nonfracture patients (P = 0.044). There was no statistically significant difference in overall survival (P = 0.96). Functional outcomes were significantly lower in fracture patients (median = 17.5) than nonfracture patients (median = 24) (P = 0.023). Radiographic features of pathologic fractures were highly variable in this population. Limb salvage surgery can be performed without increased risk of local recurrence. Patients with pathologic fracture suffer worse functional outcomes but no decrease in overall survival. © 2016 Wiley Periodicals, Inc.

BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

PubMed

Wunderle, Marius; Gass, Paul; Häberle, Lothar; Flesch, Vivien M; Rauh, Claudia; Bani, Mayada R; Hack, Carolin C; Schrauder, Michael G; Jud, Sebastian M; Emons, Julius; Erber, Ramona; Ekici, Arif B; Hoyer, Juliane; Vasileiou, Georgia; Kraus, Cornelia; Reis, Andre; Hartmann, Arndt; Lux, Michael P; Beckmann, Matthias W; Fasching, Peter A; Hein, Alexander

2018-05-03

BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

An MRI-Based Atlas for Correlation of Imaging and Pathologic Findings in Alzheimer's Disease.

PubMed

Raman, Mekala R; Schwarz, Christopher G; Murray, Melissa E; Lowe, Val J; Dickson, Dennis W; Jack, Clifford R; Kantarci, Kejal

2016-05-01

Pathologic diagnosis is the gold standard in evaluating imaging measures developed as biomarkers for pathologically defined disorders. A brain MRI atlas representing autopsy-sampled tissue can be used to directly compare imaging and pathology findings. Our objective was to develop a brain MRI atlas representing the cortical regions that are routinely sampled at autopsy for the diagnosis of Alzheimer's disease (AD). Subjects (n = 22; ages at death = 70-95) with a range of pathologies and antemortem 3T MRI were included. Histology slides from 8 cortical regions sampled from the left hemisphere at autopsy guided the localization of the atlas regions of interest (ROIs) on each subject's antemortem 3D T1 -weighted MRI. These ROIs were then registered to a common template and combined to form one ROI representing the volume of tissue that was sampled by the pathologists. A subset of the subjects (n = 4; ages at death = 79-95) had amyloid PET imaging. Density of β-amyloid immunostain was quantified from the autopsy-sampled regions in the 4 subjects using a custom-designed ImageScope algorithm. Median uptake values were calculated in each ROI on the amyloid-PET images. We found an association between β-amyloid plaque density in 8 ROIs of the 4 subjects (total ROI n = 32) and median PiB SUVR (r(2) = .64; P < .0001). In an atlas developed for imaging and pathologic correlation studies, we demonstrated that antemortem amyloid burden measured in the atlas ROIs on amyloid PET is strongly correlated with β-amyloid density measured on histology. This atlas can be used in imaging and pathologic correlation studies. © 2016 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.

Optimization of artificial neural network models through genetic algorithms for surface ozone concentration forecasting.

PubMed

Pires, J C M; Gonçalves, B; Azevedo, F G; Carneiro, A P; Rego, N; Assembleia, A J B; Lima, J F B; Silva, P A; Alves, C; Martins, F G

2012-09-01

This study proposes three methodologies to define artificial neural network models through genetic algorithms (GAs) to predict the next-day hourly average surface ozone (O(3)) concentrations. GAs were applied to define the activation function in hidden layer and the number of hidden neurons. Two of the methodologies define threshold models, which assume that the behaviour of the dependent variable (O(3) concentrations) changes when it enters in a different regime (two and four regimes were considered in this study). The change from one regime to another depends on a specific value (threshold value) of an explanatory variable (threshold variable), which is also defined by GAs. The predictor variables were the hourly average concentrations of carbon monoxide (CO), nitrogen oxide, nitrogen dioxide (NO(2)), and O(3) (recorded in the previous day at an urban site with traffic influence) and also meteorological data (hourly averages of temperature, solar radiation, relative humidity and wind speed). The study was performed for the period from May to August 2004. Several models were achieved and only the best model of each methodology was analysed. In threshold models, the variables selected by GAs to define the O(3) regimes were temperature, CO and NO(2) concentrations, due to their importance in O(3) chemistry in an urban atmosphere. In the prediction of O(3) concentrations, the threshold model that considers two regimes was the one that fitted the data most efficiently.

The Diagnostic Accuracy of Incisional Biopsy in the Oral Cavity.

PubMed

Chen, Sara; Forman, Michael; Sadow, Peter M; August, Meredith

2016-05-01

To determine the accuracy of incisional biopsy examination to diagnose oral lesions. This retrospective cohort study was performed to determine the concordance rate between incisional biopsy examination and definitive resection diagnosis for different oral lesions. The study sample was derived from the population of patients who presented to the Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital (Boston, MA) from January 2005 through December 2012. Inclusion criteria were the diagnosis of an oral lesion from an incisional biopsy examination, subsequent diagnosis from the definitive resection of the same lesion, and complete clinical and pathologic patient records. The predictor variables were the origin and size of the lesion. The primary outcome variable was concordance between the provisional incisional biopsy diagnosis and definitive pathologic resection diagnosis. The secondary outcome variable was type of biopsy error for the discordant cases. Incisional biopsy errors were assessed and grouped into 5 categories: 1) sampling error; 2) insufficient tissue for diagnosis; 3) presence of inflammation making diagnosis difficult; 4) artifact; and 5) pathologist discordance. A total of 272 patients met the inclusion criteria. The study sample had a mean age of 47.4 years and 55.7% were women. Of these cases, 242 (88.9%) were concordant when comparing the biopsy and final resection pathology reports. At histologic evaluation, 60.0% of discordant findings were attributed to sampling error, 23.3% to pathologist discrepancy, 13.3% to insufficient tissue provided in the biopsy specimen, and 3.4% to inflammation obscuring diagnosis. Overall, concordant cases had a larger average biopsy volume (1.53 cm(3)) than discordant cases (0.42 cm(3)). The data collected indicate an 88.9% diagnostic concordance with final pathologic results for incisional oral biopsy diagnoses. Sixty percent of discordance was attributed to sampling error when sampled tissue was not representative of the lesion in toto. Multiple-site biopsy specimens and larger-volume samples allowed for a more accurate diagnosis. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Pulmonary asbestosis: radiologic-pathologic brief report.

PubMed

Ahn, C S; Kim, S J; Oh, S J; Park, K J; Kim, H J; Ahn, C M; Kim, H K; Shin, D H; Cho, S H; Yang, K M

1997-10-01

Pulmonary asbestosis is defined as bilateral diffuse interstitial fibrosis of the lungs caused by exposure to asbestos. Many occupations are at risk for asbestos exposure, particularly in the mining, milling, manufacturing, construction, shipbuilding, and automotive industries. Therefore, the prevalence of asbestosis should be fairly widespread. The diagnosis of asbestosis can be made on either clinical or pathological grounds. We recently encountered one case of asbestosis which was confirmed histologically. On HRCT, there was ground-glass opacity with irregular linear shadows, subpleural curvilinear lines and parenchymal bands. Neither plaque nor calcification were noted. The histologic findings observed on open-lung biopsy specimen were well in accord with those in HRCT. Many asbestos-coated bodies were present along with black dust.

Osteosarcoma of the mandible mimicking an odontogenic abscess: a case report and review of the literature.

PubMed

Bhadage, Chetan J; Vaishampayan, Sagar; Kolhe, Swapnil; Umarji, Hemant

2013-04-01

Inflammatory lesions, like periapical/odontogenic abscesses, are by far the most common pathologic condition of the jaws. Radiographically, these lesions commonly manifest as widening of periodontal ligament space, discontinuity of lamina dura and ill-defined periapical radiolucency. There are some rare disorders which could cause similar radiographic changes in the jaw bone. With careful scrutiny of periapical radiolucency, regular periodic follow-up radiographs and histo-pathologic examination, the periapical abscess or infection can be differentiated from rare fatal disorders. This paper highlights the need for vigilant examination of even the commonest, innocuous-appearing periapical changes which sometimes are produced by some rare fatal disorders.

mTOR is a key modulator of ageing and age-related disease

PubMed Central

Johnson, Simon C.; Rabinovitch, Peter S.; Kaeberlein, Matt

2013-01-01

Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans. PMID:23325216

Qualitative and Quantitative Distinctions in Personality Disorder

PubMed Central

Wright, Aidan G. C.

2011-01-01

The “categorical-dimensional debate” has catalyzed a wealth of empirical advances in the study of personality pathology. However, this debate is merely one articulation of a broader conceptual question regarding whether to define and describe psychopathology as a quantitatively extreme expression of normal functioning or as qualitatively distinct in its process. In this paper I argue that dynamic models of personality (e.g., object-relations, cognitive-affective processing system) offer the conceptual scaffolding to reconcile these seemingly incompatible approaches to characterizing the relationship between normal and pathological personality. I propose that advances in personality assessment that sample behavior and experiences intensively provide the empirical techniques, whereas interpersonal theory offers an integrative theoretical framework, for accomplishing this goal. PMID:22804676

[Adult hepatoblastoma. A case report].

PubMed

Goikoetxea Urdiain, A; Sánchez Acedo, P; Mateo Retuerta, J; Tarifa Castilla, A; Zazpe Ripa, C; Herrera Cabezón, J

2016-01-01

Adult hepatoblastoma is a rare pathology. Its pathogeny is not well understood and prognosis is very bad. We pre-sent a case of adult hepatoblastoma treated in our centre. A 65 year-old male, without previous hepatopathy, who consulted due to right hypochondrial pain with a subacute evolution. The pathological diagnosis was adult epithelial hepatoblastoma, with free surgical margins. The patient recei-ved a second surgical intervention 5 months later due to early recurrence and died 10 months after the diagnosis due to a new massive recurrence. His definitive diagnosis is histological. Radical surgery is the only treatment that increases survival, but recurrence is frequent. There are no well-defined patterns of adjuvant chemotherapy nor is there any trans-plant experience.

Intraosseous schwannoma in schwannomatosis.

PubMed

Kashima, T G; Gibbons, M R J P; Whitwell, D; Gibbons, C L M H; Bradley, K M; Ostlere, S J; Athanasou, N A

2013-12-01

This study investigates the clinical, radiological, and pathological features of two cases of intraosseous schwannoma that arose in patients with multiple soft tissue schwannomas. In both cases, the patients were adult females and the tibial bone was affected. Vestibular schwannomas were not identified, indicating that these were not cases of neurofibromatosis 2 (NF2). Radiographs showed a well-defined lytic lesion in the proximal tibia; in one case, this was associated with a pathological fracture. Histologically, both cases showed typical features of benign schwannoma. Molecular analysis of one of the excised tumors showed different alterations in the NF2 gene in keeping with a diagnosis of schwannomatosis. Our findings show for the first time that intraosseous schwannomas can occur in schwannomatosis.

Needs and workflow assessment prior to implementation of a digital pathology infrastructure for the US Air Force Medical Service

PubMed Central

Ho, Jonhan; Aridor, Orly; Glinski, David W.; Saylor, Christopher D.; Pelletier, Joseph P.; Selby, Dale M.; Davis, Steven W.; Lancia, Nicholas; Gerlach, Christopher B.; Newberry, Jonathan; Anthony, Leslie; Pantanowitz, Liron; Parwani, Anil V.

2013-01-01

Background: Advances in digital pathology are accelerating integration of this technology into anatomic pathology (AP). To optimize implementation and adoption of digital pathology systems within a large healthcare organization, initial assessment of both end user (pathologist) needs and organizational infrastructure are required. Contextual inquiry is a qualitative, user-centered tool for collecting, interpreting, and aggregating such detailed data about work practices that can be employed to help identify specific needs and requirements. Aim: Using contextual inquiry, the objective of this study was to identify the unique work practices and requirements in AP for the United States (US) Air Force Medical Service (AFMS) that had to be targeted in order to support their transition to digital pathology. Subjects and Methods: A pathology-centered observer team conducted 1.5 h interviews with a total of 24 AFMS pathologists and histology lab personnel at three large regional centers and one smaller peripheral AFMS pathology center using contextual inquiry guidelines. Findings were documented as notes and arranged into a hierarchal organization of common themes based on user-provided data, defined as an affinity diagram. These data were also organized into consolidated graphic models that characterized AFMS pathology work practices, structure, and requirements. Results: Over 1,200 recorded notes were grouped into an affinity diagram composed of 27 third-level, 10 second-level, and five main-level (workflow and workload distribution, quality, communication, military culture, and technology) categories. When combined with workflow and cultural models, the findings revealed that AFMS pathologists had needs that were unique to their military setting, when compared to civilian pathologists. These unique needs included having to serve a globally distributed patient population, transient staff, but a uniform information technology (IT) structure. Conclusions: The contextual inquiry method helped reveal similarities and key differences with civilian pathologists. Such an analysis helped identify specific instances that would benefit from implementing digital pathology in a military environment. Employing digital pathology to facilitate workload distribution, secondary consultations, and quality assurance (over-reads) could help the AFMS deliver more accurate, efficient, and timely AP services at a global level. PMID:24392246

Optimal inference with suboptimal models: Addiction and active Bayesian inference

PubMed Central

Schwartenbeck, Philipp; FitzGerald, Thomas H.B.; Mathys, Christoph; Dolan, Ray; Wurst, Friedrich; Kronbichler, Martin; Friston, Karl

2015-01-01

When casting behaviour as active (Bayesian) inference, optimal inference is defined with respect to an agent’s beliefs – based on its generative model of the world. This contrasts with normative accounts of choice behaviour, in which optimal actions are considered in relation to the true structure of the environment – as opposed to the agent’s beliefs about worldly states (or the task). This distinction shifts an understanding of suboptimal or pathological behaviour away from aberrant inference as such, to understanding the prior beliefs of a subject that cause them to behave less ‘optimally’ than our prior beliefs suggest they should behave. Put simply, suboptimal or pathological behaviour does not speak against understanding behaviour in terms of (Bayes optimal) inference, but rather calls for a more refined understanding of the subject’s generative model upon which their (optimal) Bayesian inference is based. Here, we discuss this fundamental distinction and its implications for understanding optimality, bounded rationality and pathological (choice) behaviour. We illustrate our argument using addictive choice behaviour in a recently described ‘limited offer’ task. Our simulations of pathological choices and addictive behaviour also generate some clear hypotheses, which we hope to pursue in ongoing empirical work. PMID:25561321

Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies.

PubMed

Chibnik, L B; White, C C; Mukherjee, S; Raj, T; Yu, L; Larson, E B; Montine, T J; Keene, C D; Sonnen, J; Schneider, J A; Crane, P K; Shulman, J M; Bennett, D A; De Jager, P L

2017-03-21

Tauopathies, including Alzheimer's disease (AD) and other neurodegenerative conditions, are defined by a pathological hallmark: neurofibrillary tangles (NFTs). NFT accumulation is thought to be closely linked to cognitive decline in AD. Here, we perform a genome-wide association study for NFT pathologic burden and report the association of the PTPRD locus (rs560380, P=3.8 × 10 -8 ) in 909 prospective autopsies. The association is replicated in an independent data set of 369 autopsies. The association of PTPRD with NFT is not dependent on the accumulation of amyloid pathology. In contrast, we found that the ZCWPW1 AD susceptibility variant influences NFT accumulation and that this effect is mediated by an accumulation of amyloid β plaques. We also performed complementary analyses to identify common pathways that influence multiple neuropathologies that coexist with NFT and found suggestive evidence that certain loci may influence multiple different neuropathological traits, including tau, amyloid β plaques, vascular injury and Lewy bodies. Overall, these analyses offer an evaluation of genetic susceptibility to NFT, a common end point for multiple different pathologic processes.Molecular Psychiatry advance online publication, 21 March 2017; doi:10.1038/mp.2017.20.

Brain Ultrasonography Findings in Neonatal Seizure; a Cross-sectional Study.

PubMed

Nabavi, Seyed Saeed; Partovi, Parinaz

2017-01-01

Screening of newborns with seizure, who have curable pathologic brain findings, might be able to improve their final outcome by accelerating treatment intervention. The present study aimed to evaluate the brain ultrasonography findings of newborns hospitalized with complaint of seizure. The present cross-sectional study designed to evaluate brain ultrasonography findings of hospitalized newborns complaining seizure. Neonatal seizure was defined as presence of tonic, clonic, myoclonic, and subtle attacks in 1 - 28 day old newborns. 100 newborns with the mean age of 5.82 ± 6.29 days were evaluated (58% male). Most newborns were in the < 10 days age range (76%), term (83%) and with normal birth weight (81%). 22 (22%) of the ultrasonography examinations showed a pathologic finding. A correlation was only found between birth age and probability of the presence of a pathologic problem in the brain as the frequency of these problems was significantly higher in pre-term newborns (p = 0.023). Based on the findings of the present study, frequency of pathologic findings in neonatal brain ultrasonography was 22%. Hemorrhage (12%) and hydrocephaly (7%) were the most common findings. The only factor correlating with increased probability of positive findings was the newborns being pre-term.

[The impact of technology in Pathological Anatomy and the contribution of this speciality to technological development].

PubMed

Puras-Gil, A M; López-Cousillas, A

1999-01-01

It is obvious that technology has contributed throughout history to the development of the different sciences. In this article, we define the concept of Pathology as a medical speciality, and we explain its influence in a hospital, considering very different fields such as education, research, quality control, hospital information, and patient care. This speciality has undergone a considerable evolution, to which technological innovation has undoubtedly contributed. As a basic discipline, it is of great importance in pre and post-graduate training, in the medical education at the hospital or outside it, and in the fields previously mentioned. Its relation with other disciplines such us Chemistry, (fixation and dyeing), Physics (mechanical devices), Mathematics (algorithms, morphometry, statistics...) and Telecommunications (telepathology, image analysis...) is examined and their contribution to Pathology is evaluated. We are also aware of contributions made by Pathology to technological innovation in the evaluation of different diagnostic methods or in the recent therapeutic technologies based on Radiotherapy, Hyperthermia, laser, prothesis, etc.; where histological examination provides accurate information about the therapeutic capacity or side-effects, or the rejection reactions caused, aiding the research to obtain adequate results.

[Computerized acquisition and elaboration of clinical data in Rheumatology during ten years: state of art and prospectives

PubMed

Troise Rioda, W.; Nervetti, A.

2001-01-01

The well known complexity to collect the clinical data of patients and in particular in the area of rheumatology push us to develop a computerized clinical chart in order to facilitate the classification, evaluation and monitoring of these patients. The proposed computerized clinical chart is easy to use but at the same time is a very potent tool that allow the clinicians to organize the classic rheumatological pathologies as well as the more complexes or even rare. The proposed clinical chart is based on a relational database (FileMaker Pro 5.0v1) available for both the actual operative systems implemented on personal computers (Windows and Macintosh); this allow the full compatibility among the two systems, the possibility of exchanging data without any loss of information. The computerized clinical chart is structured on modules for specific pathologies and for homogeneous groups of illnesses. Basically the modules are defined correlated files of data for a specific pathology but that can be used also as a common pool for different pathologies. Our experience, based on ten years of use, indicates in the computerized rheumatological clinical chart an indispensable tool for rheumatologists with a real friendly use.

Characterizing "Adversity" of Pathology Findings in ...

EPA Pesticide Factsheets

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 determined and characterized. The European Society of Toxicologic Pathology (ESTP) therefore coordinated a workshop in June 2015 to review available definitions of adversity, weigh determining and qualifying factors of adversity based on case examples, and recommend a practical approach to define and characterize adversity in toxicology reports. The international group of expert pathologists and toxicologists emphasized that a holistic, weight-of-evidence, case-specific approach should be followed for each adversity assessment. It was recommended that nonclinical adversity should typically be determined at a morphological level (most often the organ) in the pathology report and should refer specifically to the test species. Final adversity calls, integration of target pharmacology/pathway information, and consideration of human translation should generally be made in toxicology overview reports. Differences in interpretation and implications of adversity calls between (agro)chemical and pharmaceutical industries and among world regions were highlighted. The results of this workshop should serve a valuable prerequisite for future organ- or lesion-specific workshops planned by the ESTP. This

Imaging of pulmonary emphysema: A pictorial review

PubMed Central

Takahashi, Masashi; Fukuoka, Junya; Nitta, Norihisa; Takazakura, Ryutaro; Nagatani, Yukihiro; Murakami, Yoko; Otani, Hideji; Murata, Kiyoshi

2008-01-01

The term ‘emphysema’ is generally used in a morphological sense, and therefore imaging modalities have an important role in diagnosing this disease. In particular, high resolution computed tomography (HRCT) is a reliable tool for demonstrating the pathology of emphysema, even in subtle changes within secondary pulmonary lobules. Generally, pulmonary emphysema is classified into three types related to the lobular anatomy: centrilobular emphysema, panlobular emphysema, and paraseptal emphysema. In this pictorial review, we discuss the radiological – pathological correlation in each type of pulmonary emphysema. HRCT of early centrilobular emphysema shows an evenly distributed centrilobular tiny areas of low attenuation with ill-defined borders. With enlargement of the dilated airspace, the surrounding lung parenchyma is compressed, which enables observation of a clear border between the emphysematous area and the normal lung. Because the disease progresses from the centrilobular portion, normal lung parenchyma in the perilobular portion tends to be preserved, even in a case of far-advanced pulmonary emphysema. In panlobular emphysema, HRCT shows either panlobular low attenuation or ill-defined diffuse low attenuation of the lung. Paraseptal emphysema is characterized by subpleural well-defined cystic spaces. Recent topics related to imaging of pulmonary emphysema will also be discussed, including morphometry of the airway in cases of chronic obstructive pulmonary disease, combined pulmonary fibrosis and pulmonary emphysema, and bronchogenic carcinoma associated with bullous lung disease. PMID:18686729

Clinical features of pathological grief reaction in elderly patients.

PubMed

Ishii, H; Tokunaga, Y; Kawatani, D; Nishizono, M

1998-12-01

The present study investigates elderly patients suffering from a pathological grief reaction to bereavement. The subjects were nine elderly inpatients with pathological grief reactions in the Department of Psychiatry in Fukuoka University Hospital between April 1991 and March 1995. Medical records of all patients were investigated retrospectively. The results were as follows: (i) all patients were female; (ii) the deceased were all husbands; (iii) most cases were sudden death; (iv) the period to onset was variable, from immediately after death to 10 years after death; (v) a delay of grief reactions was seen in many patients; (vi) the direct causes were often something other than bereavement, such as conflict with sisters, change of residence, bone fracture and daughter's malignant illness; (vii) although there was no significant difference, the ratio of those who began to live alone after bereavement was high; (viii) the number of children were insignificant; and (ix) many patients suffered the death of a parent in childhood. The paper presents observations on the results, and discusses the psychosocial factors of elderly patients with pathological grief reactions to bereavement.

Peripheral nervous system neuroimmunology seen by a neuro-pathologist.

PubMed

Vallat, J-M

2014-10-01

In most dysimmune neuropathies, historically the microscopical lesions were described prior to immunological studies. The latter along with neuropathological studies have found some immune, albeit incomplete, explanations of the mechanisms of these lesions which we will describe in two main syndromes: the primitive auto-immune inflammatory peripheral polyneuropathies (GBS and CIDP) and polyneuropathies induced by a monoclonal dysglobulinemia. In some patients who have to be discussed case by case pathology (nerve biopsy) will confirm the diagnosis, may help to delineate the molecular anomalies and identify lesional mechanisms. We will review the high variability of nerve lesions which is characteristic of dysimmune neuropathies. Pathological studies confirm that both humoral and cellular immune reactions against Schwann cell and/or axonal antigens are implicated in primitive dysimmune neuropathies due to a dysfunction or failure of immune tolerance mechanisms. In case of a polyneuropathy associated to a monoclonal dysglobulinemia, pathological and immunological studies have shown that in many patients, the dysglobulinemia did harm the peripheral nerve; knowledge of the pathological lesions and their mechanisms is of major interest for orienting specific treatments. Copyright © 2014. Published by Elsevier Masson SAS.

A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

PubMed

Critchley-Thorne, Rebecca J; Duits, Lucas C; Prichard, Jeffrey W; Davison, Jon M; Jobe, Blair A; Campbell, Bruce B; Zhang, Yi; Repa, Kathleen A; Reese, Lia M; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory; DeMarshall, Maureen; Foxwell, Tyler; Zaidi, Ali H; Lansing Taylor, D; Rustgi, Anil K; Bergman, Jacques J G H M; Falk, Gary W

2016-06-01

Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia. We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in ≥1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set. A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6-19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression. We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables. The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958-68. ©2016 AACR. ©2016 American Association for Cancer Research.

On the nature of seizure dynamics

PubMed Central

Stacey, William C.; Quilichini, Pascale P.; Ivanov, Anton I.

2014-01-01

Seizures can occur spontaneously and in a recurrent manner, which defines epilepsy; or they can be induced in a normal brain under a variety of conditions in most neuronal networks and species from flies to humans. Such universality raises the possibility that invariant properties exist that characterize seizures under different physiological and pathological conditions. Here, we analysed seizure dynamics mathematically and established a taxonomy of seizures based on first principles. For the predominant seizure class we developed a generic model called Epileptor. As an experimental model system, we used ictal-like discharges induced in vitro in mouse hippocampi. We show that only five state variables linked by integral-differential equations are sufficient to describe the onset, time course and offset of ictal-like discharges as well as their recurrence. Two state variables are responsible for generating rapid discharges (fast time scale), two for spike and wave events (intermediate time scale) and one for the control of time course, including the alternation between ‘normal’ and ictal periods (slow time scale). We propose that normal and ictal activities coexist: a separatrix acts as a barrier (or seizure threshold) between these states. Seizure onset is reached upon the collision of normal brain trajectories with the separatrix. We show theoretically and experimentally how a system can be pushed toward seizure under a wide variety of conditions. Within our experimental model, the onset and offset of ictal-like discharges are well-defined mathematical events: a saddle-node and homoclinic bifurcation, respectively. These bifurcations necessitate a baseline shift at onset and a logarithmic scaling of interspike intervals at offset. These predictions were not only confirmed in our in vitro experiments, but also for focal seizures recorded in different syndromes, brain regions and species (humans and zebrafish). Finally, we identified several possible biophysical parameters contributing to the five state variables in our model system. We show that these parameters apply to specific experimental conditions and propose that there exists a wide array of possible biophysical mechanisms for seizure genesis, while preserving central invariant properties. Epileptor and the seizure taxonomy will guide future modeling and translational research by identifying universal rules governing the initiation and termination of seizures and predicting the conditions necessary for those transitions. PMID:24919973

10-Minute Delayed Recall from the Modified Mini-Mental State Test Predicts Alzheimer’s Disease Pathology

PubMed Central

Lyness, Scott A.; Lee, Ae Young; Zarow, Chris; Teng, Evelyn L.; Chui, Helena C.

2014-01-01

We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer’s disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0–9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation. PMID:24240637

10-minute delayed recall from the modified mini-mental state test predicts Alzheimer's disease pathology.

PubMed

Lyness, Scott A; Lee, Ae Young; Zarow, Chris; Teng, Evelyn L; Chui, Helena C

2014-01-01

We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer's disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0-9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation.

Toward a consensus definition of pathological video-gaming: a systematic review of psychometric assessment tools.

PubMed

King, Daniel L; Haagsma, Maria C; Delfabbro, Paul H; Gradisar, Michael; Griffiths, Mark D

2013-04-01

Pathological video-gaming, or its proposed DSM-V classification of "Internet Use Disorder", is of increasing interest to scholars and practitioners in allied health disciplines. This systematic review was designed to evaluate the standards in pathological video-gaming instrumentation, according to Cicchetti (1994) and Groth-Marnat's (2009) criteria and guidelines for sound psychometric assessment. A total of 63 quantitative studies, including eighteen instruments and representing 58,415 participants, were evaluated. Results indicated that reviewed instrumentation may be broadly characterized as inconsistent. Strengths of available measures include: (i) short length and ease of scoring, (ii) excellent internal consistency and convergent validity, and (iii) potentially adequate data for development of standardized norms for adolescent populations. However, key limitations included: (a) inconsistent coverage of core addiction indicators, (b) varying cut-off scores to indicate clinical status, (c) a lack of a temporal dimension, (d) untested or inconsistent dimensionality, and (e) inadequate data on predictive validity and inter-rater reliability. An emerging consensus suggests that pathological video-gaming is commonly defined by (1) withdrawal, (2) loss of control, and (3) conflict. It is concluded that a unified approach to assessment of pathological video-gaming is needed. A synthesis of extant research efforts by meta-analysis may be difficult in the context of several divergent approaches to assessment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Field of dreamers and dreamed-up fields: functional and fake perimetry.

PubMed

Thompson, J C; Kosmorsky, G S; Ellis, B D

1996-01-01

Hysterical and malingering patients can manifest visual field defects on perimetry (visual field testing), including defects suggestive of true visual pathway pathology. It has been shown that control subjects can easily imitate some pathologic defects with automated, computed perimetry. The authors sought to determine whether subjects could imitate the same pathologic defect with manual and automated perimetry. Six subjects posed as patients with neurologic problems. They had manual perimetry with both an experienced and inexperienced technician followed by automated perimetry. They were later interviewed about the methods of the technicians and the difficulty of the exercise. Four of six subjects easily imitated the assigned defects with both technicians on manual perimetry and with automated perimetry. These included quadrantic, altitudinal, hemianopic, and enlarged blind-spot defects. Two subjects who were assigned cecocentral and paracentral scotomas instead produced enlarged blind spots by manual perimetry and defects suggestive of chiasmal pathology by automated perimetry. Paradoxically, some subjects found that experienced technicians were easier to fool than inexperienced technicians because of the systematic way in which experienced technicians defined defects. With minimal coaching, some subjects can imitate visual fields with enlarged blind spots, quadrantic, hemianopic, and altitudinal defects with ease and reproducibility by both automated and manual perimetry. Cecocentral and paracentral scotomas are harder to imitate but may be mistaken as representing chiasmal pathology. Paradoxically, experienced technicians may not be better at detecting hysterical or malingering individuals.

Retrospective review of treatment retention in pathological gambling.

PubMed

Grant, Jon E; Kim, Suck Won; Kuskowski, Michael

2004-01-01

Although research on pathological gambling is increasing, there are few studies examining correlates of treatment retention. In the current study, 50 outpatients with a primary DSM-IV diagnosis of pathological gambling treated in a clinical practice were assessed by chart review. Standard scales were used to rate subjects at baseline and at 2-month intervals. Subjects who dropped out of treatment were contacted by telephone to determine reasons for discontinuation of treatment. The mean duration of follow-up was 360.4 +/- 352.2 days. Twenty-four (48%) of the subjects discontinued treatment, including 14 (36.8%) of those subjects who were responders (defined as Clinical Global Impression [CGI] scale of "very much" or "much" improved) during at least one assessment point. Of those who discontinued treatment, 41.7% reported missing the thrill of gambling and 20.8% reported feeling certain that they could win and relieve financial burdens. Predictors of treatment continuation were responding to treatment within 8 weeks (odds ratio [OR], 6.00; 95% confidence interval [CI], 1.13 to 32.00; P =.04) and having a supportive environment (OR, 22.99; 95% CI, 5.04 to 104.76; P <.001). We conclude that a large percentage of patients with pathological gambling discontinue treatment. Predictors of treatment continuation may have clinical importance. Prospective longitudinal studies are needed to further elucidate the course of pathological gambling.

Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection

PubMed Central

Stewart, Laurel M.; Koenig, Michelle; Semler, Matthew; Breitbach, Meghan E.; Zeng, Xiankun; Weiler, Andrea M.; Barry, Gabrielle L.; Thoong, Troy H.; Wiepz, Gregory J.; Dudley, Dawn M.; Simmons, Heather A.; Mejia, Andres; Morgan, Terry K.; Salamat, M. Shahriar; Kohn, Sarah; Antony, Kathleen M.; Mohns, Mariel S.; Hayes, Jennifer M.; Schultz-Darken, Nancy; Schotzko, Michele L.; Peterson, Eric; Capuano, Saverio; Osorio, Jorge E.; O’Connor, Shelby L.; O’Connor, David H.; Golos, Thaddeus G.

2018-01-01

Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection. PMID:29381706

Megestrol acetate for treatment of anorexia-cachexia syndrome.

PubMed

Ruiz Garcia, Vicente; López-Briz, Eduardo; Carbonell Sanchis, Rafael; Gonzalvez Perales, Jose Luis; Bort-Marti, Sylvia

2013-03-28

This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation. To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies. We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012. Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology. Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables. We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied. This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.

Barriers and facilitators to adoption of soft copy interpretation from the user perspective: Lessons learned from filmless radiology for slideless pathology

PubMed Central

Patterson, Emily S.; Rayo, Mike; Gill, Carolina; Gurcan, Metin N.

2011-01-01

Background: Adoption of digital images for pathological specimens has been slower than adoption of digital images in radiology, despite a number of anticipated advantages for digital images in pathology. In this paper, we explore the factors that might explain this slower rate of adoption. Materials and Method: Semi-structured interviews on barriers and facilitators to the adoption of digital images were conducted with two radiologists, three pathologists, and one pathologist's assistant. Results: Barriers and facilitators to adoption of digital images were reported in the areas of performance, workflow-efficiency, infrastructure, integration with other software, and exposure to digital images. The primary difference between the settings was that performance with the use of digital images as compared to the traditional method was perceived to be higher in radiology and lower in pathology. Additionally, exposure to digital images was higher in radiology than pathology, with some radiologists exclusively having been trained and/or practicing with digital images. The integration of digital images both improved and reduced efficiency in routine and non-routine workflow patterns in both settings, and was variable across the different organizations. A comparison of these findings with prior research on adoption of other health information technologies suggests that the barriers to adoption of digital images in pathology are relatively tractable. Conclusions: Improving performance using digital images in pathology would likely accelerate adoption of innovative technologies that are facilitated by the use of digital images, such as electronic imaging databases, electronic health records, double reading for challenging cases, and computer-aided diagnostic systems. PMID:21383925

Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus

PubMed Central

Noble, Fergus; Nolan, Luke; Bateman, Adrian C; Byrne, James P; Kelly, Jamie J; Bailey, Ian S; Sharland, Donna M; Rees, Charlotte N; Iveson, Timothy J; Underwood, Tim J; Bateman, Andrew R

2013-01-01

AIM: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy. METHODS: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ≤ 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics. RESULTS: Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to NAC was associated with significantly increased DFS (mean DFS; TRG 1-2: 5.1 years, 95%CI: 4.6-5.6 vs TRG 3-5: 2.8 years, 95%CI: 2.2-3.3, P < 0.0001). Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC (median DFS; TRG 3-5 and nodal down-staging: 5.533 years, 95%CI: 3.558-7.531 vs TRG 3-5 and no nodal down-staging: 1.114 years, 95%CI: 0.961-1.267, P < 0.0001). CONCLUSION: Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS. PMID:24409055

Digital image analysis in pathology: benefits and obligation.

PubMed

Laurinavicius, Arvydas; Laurinaviciene, Aida; Dasevicius, Darius; Elie, Nicolas; Plancoulaine, Benoît; Bor, Catherine; Herlin, Paulette

2012-01-01

Pathology has recently entered the era of personalized medicine. This brings new expectations for the accuracy and precision of tissue-based diagnosis, in particular, when quantification of histologic features and biomarker expression is required. While for many years traditional pathologic diagnosis has been regarded as ground truth, this concept is no longer sufficient in contemporary tissue-based biomarker research and clinical use. Another major change in pathology is brought by the advancement of virtual microscopy technology enabling digitization of microscopy slides and presenting new opportunities for digital image analysis. Computerized vision provides an immediate benefit of increased capacity (automation) and precision (reproducibility), but not necessarily the accuracy of the analysis. To achieve the benefit of accuracy, pathologists will have to assume an obligation of validation and quality assurance of the image analysis algorithms. Reference values are needed to measure and control the accuracy. Although pathologists' consensus values are commonly used to validate these tools, we argue that the ground truth can be best achieved by stereology methods, estimating the same variable as an algorithm is intended to do. Proper adoption of the new technology will require a new quantitative mentality in pathology. In order to see a complete and sharp picture of a disease, pathologists will need to learn to use both their analogue and digital eyes.

Digital Pathology: Data-Intensive Frontier in Medical Imaging

PubMed Central

Cooper, Lee A. D.; Carter, Alexis B.; Farris, Alton B.; Wang, Fusheng; Kong, Jun; Gutman, David A.; Widener, Patrick; Pan, Tony C.; Cholleti, Sharath R.; Sharma, Ashish; Kurc, Tahsin M.; Brat, Daniel J.; Saltz, Joel H.

2013-01-01

Pathology is a medical subspecialty that practices the diagnosis of disease. Microscopic examination of tissue reveals information enabling the pathologist to render accurate diagnoses and to guide therapy. The basic process by which anatomic pathologists render diagnoses has remained relatively unchanged over the last century, yet advances in information technology now offer significant opportunities in image-based diagnostic and research applications. Pathology has lagged behind other healthcare practices such as radiology where digital adoption is widespread. As devices that generate whole slide images become more practical and affordable, practices will increasingly adopt this technology and eventually produce an explosion of data that will quickly eclipse the already vast quantities of radiology imaging data. These advances are accompanied by significant challenges for data management and storage, but they also introduce new opportunities to improve patient care by streamlining and standardizing diagnostic approaches and uncovering disease mechanisms. Computer-based image analysis is already available in commercial diagnostic systems, but further advances in image analysis algorithms are warranted in order to fully realize the benefits of digital pathology in medical discovery and patient care. In coming decades, pathology image analysis will extend beyond the streamlining of diagnostic workflows and minimizing interobserver variability and will begin to provide diagnostic assistance, identify therapeutic targets, and predict patient outcomes and therapeutic responses. PMID:25328166

Gambling, Drinking and Quality of Life: Evidence from Macao and Australia.

PubMed

Loo, Jasmine M Y; Shi, Yongdong; Pu, Xiaohong

2016-06-01

The investigation of the interface between psychological constructs, compulsive consumption of alcohol and pathological gambling is an important avenue for development of future initiatives in social marketing or prevention programs. This cross-cultural study attempts to bridge the gap in literature by providing an evaluation of the predictive ability of psychological variables such as gambling urge, gambling-related erroneous cognitions and comorbid alcohol consumption on pathological gambling behaviour and its impact on overall quality of life indicators. Participants consist of 445 Macao and Australian young adults (Mean age = 23 years). Results indicate that probable pathological gamblers as compared with non-gamblers reported significantly lower quality of life in all domains-physical health, psychological well-being, social relationships and environment. Adults who drank more alcohol and have stronger erroneous cognitions evidenced higher pathological gambling behavior. Our research model fits both cohorts and interestingly, erroneous gambling-related cognitions serve as a full mediator for the predictive relationship between gambling urge and pathological gambling in the Macao sample, but serve as a partial mediator in the Australian sample. Targeting erroneous cognitions in future social marketing or preventive campaigns should demonstrate to be an important strategy in reducing the effects of urge to gamble among at-risk individuals. Further implications for the industry, marketing and governmental strategies are discussed.

Modeling the Association between 43 Different Clinical and Pathological Variables and the Severity of Cognitive Impairment in a Large Autopsy Cohort of Elderly Persons

PubMed Central

Nelson, Peter T.; Abner, Erin L.; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Davis, Daron G.; Poduska, John W.; Patel, Ela; Mendiondo, Marta S.; Markesbery, William R.

2009-01-01

We evaluated the association between mini-mental status examination (MMSE) scores proximal to death and the values of 43 different clinical and pathological parameters. Studies were performed using data from 334 elderly, longitudinally evaluated research subjects who had undergone autopsy and satisfied inclusion criteria from an initial study group of 501. Interindividual variance in MMSE scores was used as a surrogate for the severity of cognitive impairment linked to aging (CILA). A statistical linear regression-based model provided a framework for assessing the parameters with significant, direct impact on CILA severity. Strong association between CILA and Alzheimer’s disease (AD) pathology, especially isocortical neurofibrillary tangles, was evident. The pattern of association between AD lesion densities with cognitive impairment severity was biologically informative, with neuritic plaques having more impact in relatively high-functioning individuals. Abundant isocortical Lewy bodies tended to be an additive pathology correlating with final MMSE scores approximately 10 points lower. In a subset of cases we found evidence for association between TDP-43-related pathology and CILA severity, independent of AD or hippocampal sclerosis. There was no support for independent association between CILA severity and most evaluated indices including diffuse plaques, argyrophilic grains, heart disease, education level, apolipoprotein E alleles or diabetes. PMID:19021630

Finding and Developing Moderators and Directional Keys by Regression Analysis.

ERIC Educational Resources Information Center

Kokosh, John

A procedure for rapid screening of variables as potential moderators is presented and discussed. A moderator is defined as any variable which can be used to identify differentially predictable persons; or defined statistically by stating that if a predictor and a moderator are each divided into three or more categories and used as independent…

The effect of pathological gambling on families, marriages, and children.

PubMed

Shaw, Martha C; Forbush, Kelsie T; Schlinder, Jessica; Rosenman, Eugene; Black, Donald W

2007-08-01

Pathological gambling (PG) is widely reported to have negative consequences on marriages, families, and children. Empirical evidence is only now accumulating but when put together with anecdotal information, the extent of these problems is clear. PG contributes to chaos and dysfunction within the family unit, disrupts marriages, leading to high rates of separation and divorce, and is associated with child abuse and neglect. Divorce rates are high, not surprising in light of reports that these marriages are often abusive. Research shows that the families of pathological gamblers are filled with members who gamble excessively, suffer from depressive or anxiety disorders, and misuse alcohol, drugs, or both. Families of persons with PG are also large, a variable independently related to family dysfunction. The authors review the evidence on the impact of PG on families, marriages, and offspring, and make recommendations for future research targeting these problems.

Sleep Paralysis Among Egyptian College Students: Association With Anxiety Symptoms (PTSD, Trait Anxiety, Pathological Worry).

PubMed

Jalal, Baland; Hinton, Devon E

2015-11-01

Among Egyptian college students in Cairo (n = 100), this study examined the relationship between sleep paralysis (SP) and anxiety symptoms, viz., posttraumatic stress disorder (PTSD), trait anxiety, and pathological worry. SP rates were high; 43% of participants reported at least one lifetime episode of SP, and 24% of those who reported at least one lifetime episode had experienced four or more episodes during the previous year. Fourteen percent of men had experienced SP as compared to 86% of women. As hypothesized, relative to non-SP experiencers, participants who had SP reported higher symptoms of PTSD, trait anxiety, and pathological worry. Also, as hypothesized, the experiencing of hypnogogic/hypnopompic hallucinations during SP, even after controlling for negative affect, was highly correlated with symptoms of PTSD and trait anxiety. The study also investigated possible mechanisms by examining the relationship of hallucinations to anxiety variables.

Physical health correlates of pathological and healthy dependency in urban women.

PubMed

Porcerelli, John H; Bornstein, Robert F; Markova, Tsveti; Huprich, Steven K

2009-10-01

This study assessed the relationship between dependency and indicators of health/illness, healthcare costs, and utilization. Dependency ratings were obtained using the Relationship Profile Test (Bornstein and Languirand, 2003), a questionnaire that assesses healthy and pathological dependency: destructive overdependence (DO), dysfunctional detachment (DD), and healthy dependency (HD). The sample consisted of primarily low-income, African-American, and female primary care patients (N = 110). DO and DD were significantly associated with indices of increased illness, with DO evidencing slightly larger effect sizes than DD. HD was significantly (negatively) associated with 1 health/illness variable. DD and DO were associated with higher total outpatient costs with DD also being associated with average costs per visit. DO and HD were associated with utilization (increased hospital days and fewer emergency room visits, respectively). Further research is recommended to inform researchers and clinicians about the dependency-illness relationship and to develop interventions that maximize HD and minimize pathological dependency.

Pathology in Continuous Infusion Studies in Rodents and Non-Rodents and ITO (Infusion Technology Organisation)-Recommended Protocol for Tissue Sampling and Terminology for Procedure-Related Lesions

PubMed Central

Weber, Klaus; Mowat, Vasanthi; Hartmann, Elke; Razinger, Tanja; Chevalier, Hans-Jörg; Blumbach, Kai; Green, Owen P.; Kaiser, Stefan; Corney, Stephen; Jackson, Ailsa; Casadesus, Agustin

2011-01-01

Many variables may affect the outcome of continuous infusion studies. The results largely depend on the experience of the laboratory performing these studies, the technical equipment used, the choice of blood vessels and hence the surgical technique as well the quality of pathological evaluation. The latter is of major interest due to the fact that the pathologist is not involved until necropsy in most cases, i.e. not dealing with the complicated surgical or in-life procedures of this study type. The technique of tissue sampling during necropsy and the histology processing procedures may influence the tissues presented for evaluation, hence the pathologist may be a source of misinterpretation. Therefore, ITO proposes a tissue sampling procedure and a standard nomenclature for pathological lesions for all sites and tissues in contact with the port-access and/or catheter system. PMID:22272050

Efficient field-theoretic simulation of polymer solutions

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

Villet, Michael C.; Fredrickson, Glenn H., E-mail: ghf@mrl.ucsb.edu; Department of Materials, University of California, Santa Barbara, California 93106

2014-12-14

We present several developments that facilitate the efficient field-theoretic simulation of polymers by complex Langevin sampling. A regularization scheme using finite Gaussian excluded volume interactions is used to derive a polymer solution model that appears free of ultraviolet divergences and hence is well-suited for lattice-discretized field theoretic simulation. We show that such models can exhibit ultraviolet sensitivity, a numerical pathology that dramatically increases sampling error in the continuum lattice limit, and further show that this pathology can be eliminated by appropriate model reformulation by variable transformation. We present an exponential time differencing algorithm for integrating complex Langevin equations for fieldmore » theoretic simulation, and show that the algorithm exhibits excellent accuracy and stability properties for our regularized polymer model. These developments collectively enable substantially more efficient field-theoretic simulation of polymers, and illustrate the importance of simultaneously addressing analytical and numerical pathologies when implementing such computations.« less

Dynamic of Change in Pathological Personality Trait Dimensions: A Latent Change Analysis Among at-Risk Women

PubMed Central

Barbot, Baptiste; Hunter, Scott R.; Grigorenko, Elena L.; Luthar, Suniya S.

2012-01-01

This study explores longitudinally a four-factor structure of pathological personality trait dimensions (PPTDs) to examine both its structural stability and intra-individual changes among PPTDs over time. Personality Disorder (PD) scales of the Millon Clinical Multiaxial Inventory-III were administered to 361 low-income women with various psychiatric conditions (drug dependence, depression), who were followed in a two-wave study over 5-years. Cross-sectional and longitudinal factor analyses outlined a robust factorial structure of PPTDs, extrinsically invariant over time, representing Negative Emotionality, Introversion, Antagonism and Impulsivity. Despite moderate rank-order stability in the PPTDs, results also indicated substantial intra-individual variability in the degree and direction of change, consistent with trajectories of change in participants’ clinical diagnoses. Results are discussed in light of current debates on the structure and dynamic of pathological personality. PMID:23710108

A study of renal blood flow regulation using the discrete wavelet transform

NASA Astrophysics Data System (ADS)

Pavlov, Alexey N.; Pavlova, Olga N.; Mosekilde, Erik; Sosnovtseva, Olga V.

2010-02-01

In this paper we provide a way to distinguish features of renal blood flow autoregulation mechanisms in normotensive and hypertensive rats based on the discrete wavelet transform. Using the variability of the wavelet coefficients we show distinctions that occur between the normal and pathological states. A reduction of this variability in hypertension is observed on the microscopic level of the blood flow in efferent arteriole of single nephrons. This reduction is probably associated with higher flexibility of healthy cardiovascular system.

Wavelet and receiver operating characteristic analysis of heart rate variability

NASA Astrophysics Data System (ADS)

McCaffery, G.; Griffith, T. M.; Naka, K.; Frennaux, M. P.; Matthai, C. C.

2002-02-01

Multiresolution wavelet analysis has been used to study the heart rate variability in two classes of patients with different pathological conditions. The scale dependent measure of Thurner et al. was found to be statistically significant in discriminating patients suffering from hypercardiomyopathy from a control set of normal subjects. We have performed Receiver Operating Characteristc (ROC) analysis and found the ROC area to be a useful measure by which to label the significance of the discrimination, as well as to describe the severity of heart dysfunction.

Evaluating the Patterns of Aging-Related Tau Astrogliopathy Unravels Novel Insights Into Brain Aging and Neurodegenerative Diseases.

PubMed

Kovacs, Gabor G; Robinson, John L; Xie, Sharon X; Lee, Edward B; Grossman, Murray; Wolk, David A; Irwin, David J; Weintraub, Dan; Kim, Christopher F; Schuck, Theresa; Yousef, Ahmed; Wagner, Stephanie T; Suh, Eunran; Van Deerlin, Vivianna M; Lee, Virginia M-Y; Trojanowski, John Q

2017-04-01

The term "aging-related tau astrogliopathy" (ARTAG) describes pathological accumulation of abnormally phosphorylated tau protein in astrocytes. We evaluated the correlates of ARTAG types (i.e., subpial, subependymal, white and gray matter, and perivascular) in different neuroanatomical regions. Clinical, neuropathological, and genetic (eg, APOE ε4 allele, MAPT H1/H2 haplotype) data from 628 postmortem brains from subjects were investigated; most of the patients had been longitudinally followed at the University of Pennsylvania. We found that (i) the amygdala is a hotspot for all ARTAG types; (ii) age at death, male sex, and presence of primary frontotemporal lobar degeneration (FTLD) tauopathy are significantly associated with ARTAG; (iii) age at death, greater degree of brain atrophy, ventricular enlargement, and Alzheimer disease (AD)-related variables are associated with subpial, white matter, and perivascular ARTAG types; (iv) AD-related variables are associated particularly with lobar white matter ARTAG; and (v) gray matter ARTAG in primary FTLD-tauopathies appears in areas without neuronal tau pathology. We provide a reference map of ARTAG types and propose at least 5 constellations of ARTAG. Furthermore, we propose a conceptual link between primary FTLD-tauopathy and ARTAG-related astrocytic tau pathologies. Our observations serve as a basis for etiological stratification and definition of progression patterns of ARTAG. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Gait disorders in the elderly and dual task gait analysis: a new approach for identifying motor phenotypes.

PubMed

Auvinet, Bernard; Touzard, Claude; Montestruc, François; Delafond, Arnaud; Goeb, Vincent

2017-01-31

Gait disorders and gait analysis under single and dual-task conditions are topics of great interest, but very few studies have looked for the relevance of gait analysis under dual-task conditions in elderly people on the basis of a clinical approach. An observational study including 103 patients (mean age 76.3 ± 7.2, women 56%) suffering from gait disorders or memory impairment was conducted. Gait analysis under dual-task conditions was carried out for all patients. Brain MRI was performed in the absence of contra-indications. Three main gait variables were measured: walking speed, stride frequency, and stride regularity. For each gait variable, the dual task cost was computed and a quartile analysis was obtained. Nonparametric tests were used for all the comparisons (Wilcoxon, Kruskal-Wallis, Fisher or Chi 2 tests). Four clinical subgroups were identified: gait instability (45%), recurrent falls (29%), memory impairment (18%), and cautious gait (8%). The biomechanical severity of these subgroups was ordered according to walking speed and stride regularity under both conditions, from least to most serious as follows: memory impairment, gait instability, recurrent falls, cautious gait (p < 0.01 for walking speed, p = 0.05 for stride regularity). According to the established diagnoses of gait disorders, 5 main pathological subgroups were identified (musculoskeletal diseases (n = 11), vestibular diseases (n = 6), mild cognitive impairment (n = 24), central nervous system pathologies, (n = 51), and without diagnosis (n = 8)). The dual task cost for walking speed, stride frequency and stride regularity were different among these subgroups (p < 0.01). The subgroups mild cognitive impairment and central nervous system pathologies both showed together a higher dual task cost for each variable compared to the other subgroups combined (p = 0.01). The quartile analysis of dual task cost for stride frequency and stride regularity allowed the identification of 3 motor phenotypes (p < 0.01), without any difference for white matter hyperintensities, but with an increased Scheltens score from the first to the third motor phenotype (p = 0.05). Gait analysis under dual-task conditions in elderly people suffering from gait disorders or memory impairment is of great value in assessing the severity of gait disorders, differentiating between peripheral pathologies and central nervous system pathologies, and identifying motor phenotypes. Correlations between motor phenotypes and brain imaging require further studies.

Cognitive Reserve in Healthy Aging and Alzheimer's Disease: A Meta-Analysis of fMRI Studies.

PubMed

Colangeli, Stefano; Boccia, Maddalena; Verde, Paola; Guariglia, Paola; Bianchini, Filippo; Piccardi, Laura

2016-08-01

Cognitive reserve (CR) has been defined as the ability to optimize or maximize performance through differential recruitment of brain networks. In the present study, we aimed at providing evidence for a consistent brain network underpinning CR in healthy and pathological aging. To pursue this aim, we performed a coordinate-based meta-analysis of 17 functional magnetic resonance imaging studies on CR proxies in healthy aging, Alzheimer's disease (AD), and mild cognitive impairment (MCI). We found that different brain areas were associated with CR proxies in healthy and pathological aging. A wide network of areas, including medial and lateral frontal areas, that is, anterior cingulate cortex and dorsolateral prefrontal cortex, as well as precuneus, was associated with proxies of CR in healthy elderly patients. The CR proxies in patients with AD and amnesic-MCI were associated with activation in the anterior cingulate cortex. These results were discussed hypothesizing the existence of possible compensatory mechanisms in healthy and pathological aging. © The Author(s) 2016.

Progress in understanding the pathogenesis of Langerhans cell histiocytosis: back to Histiocytosis X?

PubMed Central

Berres, Marie-Luise; Merad, Miriam; Allen, Carl E.

2016-01-01

Summary Langerhans cell histiocytosis (LCH), the most common histiocytic disorder, is characterized by the accumulation of CD1A+/CD207+ mononuclear phagocytes within granulomatous lesions that can affect nearly all organ systems. Historically, LCH has been presumed to arise from transformed or pathologically activated epidermal dendritic cells called Langerhans cells. However, new evidence supports a model in which LCH occurs as a consequence of a misguided differentiation programme of myeloid dendritic cell precursors. Genetic, molecular and functional data implicate activation of the ERK signalling pathway at critical stages in myeloid differentiation as an essential and universal driver of LCH pathology. Based on these findings, we propose that LCH should be re-defined as an inflammatory myeloid neoplasia. Increased understanding of LCH pathogenesis will provide opportunities to optimize and personalize therapy through improved risk-stratification, targeted therapy and assessment of therapy response based on specific molecular features and origin of the pathological myeloid cells. PMID:25430560

Pathological Overeating: Emerging Evidence for a Compulsivity Construct

PubMed Central

Moore, Catherine F; Sabino, Valentina; Koob, George F; Cottone, Pietro

2017-01-01

Compulsive eating behavior is a transdiagnostic construct that is characteristic of medical and psychiatric conditions such as forms of obesity and eating disorders. Although feeding research is moving toward a better understanding of the proposed addictive properties of food, the components and the mechanisms contributing to compulsive eating are not yet clearly defined or understood. Current understanding highlights three elements of compulsive behavior as it applies to pathological overeating: (1) habitual overeating; (2) overeating to relieve a negative emotional state; and (3) overeating despite aversive consequences. These elements emerge through mechanisms involving pathological habit formation through an aberrant learning process, the emergence of a negative emotional state, and dysfunctions in behavioral control. Dysfunctions in systems within neurocircuitries that comprise the basal ganglia, the extended amygdala, and the prefrontal cortex result in compulsive eating behaviors. Here, we present evidence to relate compulsive eating behavior and addiction and to characterize their underlying neurobiological mechanisms. A major need to improve understanding of compulsive eating through the integration of complex motivational, emotional, and cognitive constructs is warranted. PMID:27922596

Pathology and medical malpractice. Academic and trainee empirical review of cases by State of Texas physicians.

PubMed

Allen, Timothy Craig; Stafford, Mehary; Liang, Bryan A

2014-04-01

This study examines whether the assumptions that pathologists understand the medical malpractice negligence rule and have a clear single standard of care are reasonable. Two hundred eighty-one Texas academic pathologists and trainees were presented 10 actual pathology malpractice cases from publicly available sources, representing the tort system's signal. Of the respondents, 55.52% were trainees, and 44.48% were pathology faculty. Only in two cases did more than 50% of respondents correctly identify the behavior of pathologists as defined by legal outcomes. In only half of the cases did more than 50% of pathologists concur with the jury verdict. This study provides further evidence that physicians do not understand the legal rule of negligence. Pathologists have a poor understanding of negligence and cannot accurately predict a jury verdict. There is significant divergence from the single standard of care assumption. Alternative methods to provide appropriate compensation and to establish physician accountability should be explored. Additional education about medical negligence is needed.

Pathological Overeating: Emerging Evidence for a Compulsivity Construct.

PubMed

Moore, Catherine F; Sabino, Valentina; Koob, George F; Cottone, Pietro

2017-06-01

Compulsive eating behavior is a transdiagnostic construct that is characteristic of medical and psychiatric conditions such as forms of obesity and eating disorders. Although feeding research is moving toward a better understanding of the proposed addictive properties of food, the components and the mechanisms contributing to compulsive eating are not yet clearly defined or understood. Current understanding highlights three elements of compulsive behavior as it applies to pathological overeating: (1) habitual overeating; (2) overeating to relieve a negative emotional state; and (3) overeating despite aversive consequences. These elements emerge through mechanisms involving pathological habit formation through an aberrant learning process, the emergence of a negative emotional state, and dysfunctions in behavioral control. Dysfunctions in systems within neurocircuitries that comprise the basal ganglia, the extended amygdala, and the prefrontal cortex result in compulsive eating behaviors. Here, we present evidence to relate compulsive eating behavior and addiction and to characterize their underlying neurobiological mechanisms. A major need to improve understanding of compulsive eating through the integration of complex motivational, emotional, and cognitive constructs is warranted.

Ethics in the practice of speech-language pathology in health care settings.

PubMed

Kummer, Ann W; Turner, Jan

2011-11-01

ETHICS refers to a moral philosophy or a set of moral principles that determine appropriate behavior in a society. Medical ethics includes a set of specific values that are considered in determining appropriate conduct in the practice of medicine or health care. Because the practice of medicine and medical speech-language pathology affects the health, well-being, and quality of life of individuals served, adherence to a code of ethical conduct is critically important in the health care environment. When ethical dilemmas arise, consultation with a bioethics committee can be helpful in determining the best course of action. This article will help to define medical ethics and to discuss the six basic values that are commonly considered in discussions of medical ethics. Common ethical mistakes in the practice of speech-language pathology will be described. Finally, the value of a bioethics consultation for help in resolving complex ethical issues will be discussed. © Thieme Medical Publishers.

The demand for speech pathology services for children: Do we need more or just different?

PubMed

Reilly, Sheena; Harper, Megan; Goldfeld, Sharon

2016-12-01

An inability or difficulty communicating can have a profound impact on a child's future ability to participate in society as a productive adult. Over the past few years the number of interventions for children with speech and language problems has almost doubled; the majority are targeted interventions delivered by speech pathologists. In this paper we examine the distribution of speech pathology services in metropolitan Melbourne and how these are aligned with need as defined by vulnerability in language and social disadvantage. We identified three times as many private sector services compared to public services for the 0-5 year age group. Overall there was poorer availability of services in some of the most vulnerable areas. The profound and long-term impact of impoverished childhood language, coupled with the considerable limitations on public spending, provide a strong impetus to deliver more equitably distributed speech pathology services. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).