Dimensional assessment of personality pathology in patients with eating disorders.

PubMed

Goldner, E M; Srikameswaran, S; Schroeder, M L; Livesley, W J; Birmingham, C L

1999-02-22

This study examined patients with eating disorders on personality pathology using a dimensional method. Female subjects who met DSM-IV diagnostic criteria for eating disorder (n = 136) were evaluated and compared to an age-controlled general population sample (n = 68). We assessed 18 features of personality disorder with the Dimensional Assessment of Personality Pathology - Basic Questionnaire (DAPP-BQ). Factor analysis and cluster analysis were used to derive three clusters of patients. A five-factor solution was obtained with limited intercorrelation between factors. Cluster analysis produced three clusters with the following characteristics: Cluster 1 members (constituting 49.3% of the sample and labelled 'rigid') had higher mean scores on factors denoting compulsivity and interpersonal difficulties; Cluster 2 (18.4% of the sample) showed highest scores in factors denoting psychopathy, neuroticism and impulsive features, and appeared to constitute a borderline psychopathology group; Cluster 3 (32.4% of the sample) was characterized by few differences in personality pathology in comparison to the normal population sample. Cluster membership was associated with DSM-IV diagnosis -- a large proportion of patients with anorexia nervosa were members of Cluster 1. An empirical classification of eating-disordered patients derived from dimensional assessment of personality pathology identified three groups with clinical relevance.

Correlation between STK33 and the pathology and prognosis of lung cancer

PubMed Central

Lu, Yi; Tang, Jie; Zhang, Wenmei; Shen, Ce; Xu, Ling; Yang, Danrong

2017-01-01

Correlation between the expression of STK33 and the pathology of lung cancer was investigated, to explore its effects on prognosis. Hundred and two lung cancer patients diagnosed by pathological examinations were randomly selected in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from February, 2012 to February, 2017 to serve as observation group, and the tumor tissues were collected. At the same time, 19 patients with lung benign lesions were selected and lung tissues were also collected to serve as control group. RT-qPCR was used to detect the expression of STK33 mRNA in tissues. Expression levels of STK33 protein were detected and compared by SP immunohistochemistry staining and western blot analysis. Statistical analysis was performed to analyze the correlation between STK33 expression and the pathology and prognosis of lung cancer. Results of PCR showed that expression level of STK33 gene in control group was significantly lower than that in observation group (p<0.05). The expression level of STK33 mRNA in lung adenocarcinoma and squamous cell carcinoma was lower than that in lung small cell carcinoma and large cell carcinoma (p<0.05). Western blot analysis showed that the expression level of STK33 protein in lung small cell carcinoma and large cell carcinoma was significantly higher than that in lung adenocarcinoma and squamous cell carcinoma (p<0.05). Immunohistochemistry staining showed that the positive rate of STK33 in lung large cell carcinoma (100%) and small cell carcinoma (100%) was significantly higher than that in lung adenocarcinoma (88.1%) and squamous cell carcinoma (86.2%) (p<0.05). The 5-year survival rate analysis showed that the recurrence-free survival rate and overall survival rate of STK33 gene high expression level group were significantly lower than those of low expression level group (p<0.05). The differential expression level of STK33 is related to the pathology and prognosis of lung cancer, which is of great value in clinical diagnosis and prognosis evaluation. PMID:29085482

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.

Diffusion-weighted imaging: Apparent diffusion coefficient histogram analysis for detecting pathologic complete response to chemoradiotherapy in locally advanced rectal cancer.

PubMed

Choi, Moon Hyung; Oh, Soon Nam; Rha, Sung Eun; Choi, Joon-Il; Lee, Sung Hak; Jang, Hong Seok; Kim, Jun-Gi; Grimm, Robert; Son, Yohan

2016-07-01

To investigate the usefulness of apparent diffusion coefficient (ADC) values derived from histogram analysis of the whole rectal cancer as a quantitative parameter to evaluate pathologic complete response (pCR) on preoperative magnetic resonance imaging (MRI). We enrolled a total of 86 consecutive patients who had undergone surgery for rectal cancer after neoadjuvant chemoradiotherapy (CRT) at our institution between July 2012 and November 2014. Two radiologists who were blinded to the final pathological results reviewed post-CRT MRI to evaluate tumor stage. Quantitative image analysis was performed using T2 -weighted and diffusion-weighted images independently by two radiologists using dedicated software that performed histogram analysis to assess the distribution of ADC in the whole tumor. After surgery, 16 patients were confirmed to have achieved pCR (18.6%). All parameters from pre- and post-CRT ADC histogram showed good or excellent agreement between two readers. The minimum, 10th, 25th, 50th, and 75th percentile and mean ADC from post-CRT ADC histogram were significantly higher in the pCR group than in the non-pCR group for both readers. The 25th percentile value from ADC histogram in post-CRT MRI had the best diagnostic performance for detecting pCR, with an area under the receiver operating characteristic curve of 0.796. Low percentile values derived from the ADC histogram analysis of rectal cancer on MRI after CRT showed a significant difference between pCR and non-pCR groups, demonstrating the utility of the ADC value as a quantitative and objective marker to evaluate complete pathologic response to preoperative CRT in rectal cancer. J. Magn. Reson. Imaging 2016;44:212-220. © 2015 Wiley Periodicals, Inc.

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

Mood states modulate complexity in heartbeat dynamics: A multiscale entropy analysis

NASA Astrophysics Data System (ADS)

Valenza, G.; Nardelli, M.; Bertschy, G.; Lanata, A.; Scilingo, E. P.

2014-07-01

This paper demonstrates that heartbeat complex dynamics is modulated by different pathological mental states. Multiscale entropy analysis was performed on R-R interval series gathered from the electrocardiogram of eight bipolar patients who exhibited mood states among depression, hypomania, and euthymia, i.e., good affective balance. Three different methodologies for the choice of the sample entropy radius value were also compared. We show that the complexity level can be used as a marker of mental states being able to discriminate among the three pathological mood states, suggesting to use heartbeat complexity as a more objective clinical biomarker for mental disorders.

Quantitative proteomics identify an association between extracellular matrix degradation and immunopathology of genotype VII Newcastle disease virus in the spleen in chickens.

PubMed

Hu, Zenglei; Gu, Han; Hu, Jiao; Hu, Shunlin; Wang, Xiaoquan; Liu, Xiaowen; Jiao, Xinan; Liu, Xiufan

2018-06-15

Pathogenesis of genotype VII Newcastle disease virus (NDV) is characterized with remarkable immunopathology in the spleen in chickens. However, the mechanism for this unique pathological phenotype is not fully understood. Previous transcriptomics data showed that genotype VII NDV JS5/05 caused a greater downregulation of extracellular matrix (ECM) genes than genotype IV virus Herts/33 in the spleen. In this study, the role of ECM in pathology of genotype VII NDV was investigated using quantitative proteomics. Pathology studies showed that JS5/05 caused severe immunopathology characterized with remarkable necrosis in the spleen, whereas Herts/33 only induced mild pathological changes. The ECM was firstly enriched from the spleens and ECM proteins of different categories were identified by LC-MS/MS. Quantitative proteomic analysis showed that JS5/05 caused a significant disruption of ECM integrity and molecular composition compared to Herts/33. Particularly, JS5/05 induced a more remarkable collagen breakdown in the spleen compared to Herts/33. Moreover, matrix metalloproteinase (MMP)-13 and -14 were significantly upregulated by JS5/05 infection. KEGG pathway analysis suggested that differential regulation of ECM proteins by JS5/05 and Herts/33 may impact pathology through different pathways. Therefore, our results suggested that MMP upregulation and consequent ECM degradation contribute to immunopathology of genotype VII NDV in the spleen. Pathogenesis of genotype VII NDV is characterized with severe immunopathology in the spleen in chickens. Elucidating the mechanism of this pathology phenotype is critical to understand pathogenesis of genotype VII NDV. Here, we present the proteomic data of an important non-cellular compartment, the extracellular matrix (ECM), in the spleen from chickens infected with genotype VII and IV NDVs. Our results suggest that significant upregulation of matrix metalloproteinases by genotype VII NDV and consequent disruption of ECM integrity and composition may be associated with immunopathology in the spleen. Moreover, ECM degradation, represented by collagen breakdown, is an important pathology event in the process of genotype VII NDV infection. Our study for the first time presents evidence of ECM regulation by NDV and adds ECM remodeling as a new manifestation for NDV pathology. Our findings also deepen the understanding of NDV pathogenesis. Copyright © 2018. Published by Elsevier B.V.

The General Assessment of Personality Disorder (GAPD): factor structure, incremental validity of self-pathology, and relations to DSM-IV personality disorders.

PubMed

Hentschel, Annett G; Livesley, W John

2013-01-01

Recent developments in the classification of personality disorder, especially moves toward more dimensional systems, create the need to assess general personality disorder apart from individual differences in personality pathology. The General Assessment of Personality Disorder (GAPD) is a self-report questionnaire designed to evaluate general personality disorder. The measure evaluates 2 major components of disordered personality: self or identity problems and interpersonal dysfunction. This study explores whether there is a single factor reflecting general personality pathology as proposed by the Diagnostic and Statistical Manual of Mental Disorders (5th ed.), whether self-pathology has incremental validity over interpersonal pathology as measured by GAPD, and whether GAPD scales relate significantly to Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]) personality disorders. Based on responses from a German psychiatric sample of 149 participants, parallel analysis yielded a 1-factor model. Self Pathology scales of the GAPD increased the predictive validity of the Interpersonal Pathology scales of the GAPD. The GAPD scales showed a moderate to high correlation for 9 of 12 DSM-IV personality disorders.

Relationships between pathologic subjective halitosis, olfactory reference syndrome, and social anxiety in young Japanese women.

PubMed

Tsuruta, Miho; Takahashi, Toru; Tokunaga, Miki; Iwasaki, Masanori; Kataoka, Shota; Kakuta, Satoko; Soh, Inho; Awano, Shuji; Hirata, Hiromi; Kagawa, Masaharu; Ansai, Toshihiro

2017-03-14

Pathologic subjective halitosis is known as a halitosis complaint without objective confirmation of halitosis by others or by halitometer measurements; it has been reported to be associated with social anxiety disorder. Olfactory reference syndrome is a preoccupation with the false belief that one emits a foul and offensive body odor. Generally, patients with olfactory reference syndrome are concerned with multiple body parts. However, the mouth is known to be the most common source of body odor for those with olfactory reference syndrome, which could imply that the two conditions share similar features. Therefore, we investigated potential causal relationships among pathologic subjective halitosis, olfactory reference syndrome, social anxiety, and preoccupations with body part odors. A total of 1360 female students (mean age 19.6 ± 1.1 years) answered a self-administered questionnaire regarding pathologic subjective halitosis, olfactory reference syndrome, social anxiety, and preoccupation with odors of body parts such as mouth, body, armpits, and feet. The scale for pathologic subjective halitosis followed that developed by Tsunoda et al.; participants were divided into three groups based on their scores (i.e., levels of pathologic subjective halitosis). A Bayesian network was used to analyze causal relationships between pathologic subjective halitosis, olfactory reference syndrome, social anxiety, and preoccupations with body part odors. We found statistically significant differences in the results for olfactory reference syndrome and social anxiety among the various levels of pathologic subjective halitosis (P < 0.001). Residual analyses indicated that students with severe levels of pathologic subjective halitosis showed greater preoccupations with mouth and body odors (P < 0.05). Bayesian network analysis showed that social anxiety directly influenced pathologic subjective halitosis and olfactory reference syndrome. Preoccupations with mouth and body odors also influenced pathologic subjective halitosis. Social anxiety may be a causal factor of pathologic subjective halitosis and olfactory reference syndrome.

A CT-rich haplotype in intron 4 of SNCA confers risk for Lewy body pathology in Alzheimer’s disease and affects SNCA expression

PubMed Central

Lutz, Michael W.; Saul, Robert; Linnertz, Colton; Glenn, Omolara-Chinue; Roses, Allen D.; Chiba-Falek, Ornit

2015-01-01

INTRODUCTION We recently showed that tagging-SNPs across the SNCA locus were significantly associated with increased risk for LB pathology in AD cases. However, the actual genetic variant(s) that underlie the observed associations remain elusive. METHODS We used a bioinformatics algorithm to catalogue Structural-Variants in a region of SNCA-intron4, followed by phased-sequencing. We performed a genetic-association analysis in autopsy series of LBV/AD cases compared with AD-only controls. We investigated the biological functions by expression analysis using temporal-cortex samples. RESULTS We identified four distinct haplotypes within a highly-polymorphic-low-complexity CT-rich region. We showed that a specific haplotype conferred risk to develop LBV/AD. We demonstrated that the CT-rich site acts as an enhancer element, where the risk haplotype was significantly associated with elevated levels of SNCA-mRNA. DISCUSSION We have discovered a novel haplotype in a CT-rich region in SNCA that contributes to LB pathology in AD patients, possibly via cis-regulation of the gene expression. PMID:26079410

Screening for Generalized Anxiety Disorder in inpatient psychosomatic rehabilitation: pathological worry and the impact of depressive symptoms

PubMed Central

Salzer, Simone; Stiller, Christian; Tacke-Pook, Achim; Jacobi, Claus; Leibing, Eric

2009-01-01

Objective: Pathological worry is considered to be a defining feature for Generalized Anxiety Disorder (GAD). The Penn State Worry Questionnaire (PSWQ) is an instrument for assessing pathological worry. Two earlier studies demonstrated the suitability of the PSWQ as screening instrument for GAD in outpatient and non-clinical samples. This study examined the suitability of the PSWQ as a screening instrument for GAD in a German inpatient sample (N=237). Furthermore, a comparison of patients with GAD and patients with depression and other anxiety disorders regarding pathological worry and depression was carried out in a sub-sample of N=118 patients. Method: Cut-off scores optimizing sensitivity, optimizing specificity and simultaneously optimizing both sensitivity and specificity were calculated for the PSWQ score by receiver operating characteristic analysis (ROC). Differences regarding pathological worry and depression measured by the PSWQ and the Beck Depression Inventory (BDI) across five diagnostic subgroups were examined by conducting one-way ANOVAs. The influence of depression on pathological worry was controlled by conducting an ANCOVA with BDI score as a covariate. Results: The ROC analysis showed an area under the curve of AUC=.67 (p=0.02) with only 54.4% of the patients correctly classified. Comparison of diagnostic subgroups showed that after controlling the influence of depression, differences referring to pathological worry between diagnostic subgroups no longer existed. Conclusions: Contrary to the earlier results we found that the use of the PSWQ as a screening instrument for GAD at least in a sample of psychotherapy inpatients is not meaningful. Instead of that, the PSWQ can be used to discriminate high from low worriers in clinical samples. Thus, the instrument can be useful in establishing e.g. symptom-oriented group interventions as they are established in behavioural-medicine inpatient settings. Furthermore, our findings stress the influence of (comorbid) depressive symptoms on the process of worrying. PMID:19742048

Screening for Generalized Anxiety Disorder in inpatient psychosomatic rehabilitation: pathological worry and the impact of depressive symptoms.

PubMed

Salzer, Simone; Stiller, Christian; Tacke-Pook, Achim; Jacobi, Claus; Leibing, Eric

2009-07-09

Pathological worry is considered to be a defining feature for Generalized Anxiety Disorder (GAD). The Penn State Worry Questionnaire (PSWQ) is an instrument for assessing pathological worry. Two earlier studies demonstrated the suitability of the PSWQ as screening instrument for GAD in outpatient and non-clinical samples. This study examined the suitability of the PSWQ as a screening instrument for GAD in a German inpatient sample (N=237). Furthermore, a comparison of patients with GAD and patients with depression and other anxiety disorders regarding pathological worry and depression was carried out in a sub-sample of N=118 patients. Cut-off scores optimizing sensitivity, optimizing specificity and simultaneously optimizing both sensitivity and specificity were calculated for the PSWQ score by receiver operating characteristic analysis (ROC). Differences regarding pathological worry and depression measured by the PSWQ and the Beck Depression Inventory (BDI) across five diagnostic subgroups were examined by conducting one-way ANOVAs. The influence of depression on pathological worry was controlled by conducting an ANCOVA with BDI score as a covariate. The ROC analysis showed an area under the curve of AUC=.67 (p=0.02) with only 54.4% of the patients correctly classified. Comparison of diagnostic subgroups showed that after controlling the influence of depression, differences referring to pathological worry between diagnostic subgroups no longer existed. Contrary to the earlier results we found that the use of the PSWQ as a screening instrument for GAD at least in a sample of psychotherapy inpatients is not meaningful. Instead of that, the PSWQ can be used to discriminate high from low worriers in clinical samples. Thus, the instrument can be useful in establishing e.g. symptom-oriented group interventions as they are established in behavioural-medicine inpatient settings. Furthermore, our findings stress the influence of (comorbid) depressive symptoms on the process of worrying.

Study on user interface of pathology picture archiving and communication system.

PubMed

Kim, Dasueran; Kang, Peter; Yun, Jungmin; Park, Sung-Hye; Seo, Jeong-Wook; Park, Peom

2014-01-01

It is necessary to improve the pathology workflow. A workflow task analysis was performed using a pathology picture archiving and communication system (pathology PACS) in order to propose a user interface for the Pathology PACS considering user experience. An interface analysis of the Pathology PACS in Seoul National University Hospital and a task analysis of the pathology workflow were performed by observing recorded video. Based on obtained results, a user interface for the Pathology PACS was proposed. Hierarchical task analysis of Pathology PACS was classified into 17 tasks including 1) pre-operation, 2) text, 3) images, 4) medical record viewer, 5) screen transition, 6) pathology identification number input, 7) admission date input, 8) diagnosis doctor, 9) diagnosis code, 10) diagnosis, 11) pathology identification number check box, 12) presence or absence of images, 13) search, 14) clear, 15) Excel save, 16) search results, and 17) re-search. And frequently used menu items were identified and schematized. A user interface for the Pathology PACS considering user experience could be proposed as a preliminary step, and this study may contribute to the development of medical information systems based on user experience and usability.

The influence of different classification standards of age groups on prognosis in high-grade hemispheric glioma patients.

PubMed

Chen, Jian-Wu; Zhou, Chang-Fu; Lin, Zhi-Xiong

2015-09-15

Although age is thought to correlate with the prognosis of glioma patients, the most appropriate age-group classification standard to evaluate prognosis had not been fully studied. This study aimed to investigate the influence of age-group classification standards on the prognosis of patients with high-grade hemispheric glioma (HGG). This retrospective study of 125 HGG patients used three different classification standards of age-groups (≤ 50 and >50 years old, ≤ 60 and >60 years old, ≤ 45 and 45-65 and ≥ 65 years old) to evaluate the impact of age on prognosis. The primary end-point was overall survival (OS). The Kaplan-Meier method was applied for univariate analysis and Cox proportional hazards model for multivariate analysis. Univariate analysis showed a significant correlation between OS and all three classification standards of age-groups as well as between OS and pathological grade, gender, location of glioma, and regular chemotherapy and radiotherapy treatment. Multivariate analysis showed that the only independent predictors of OS were classification standard of age-groups ≤ 50 and > 50 years old, pathological grade and regular chemotherapy. In summary, the most appropriate classification standard of age-groups as an independent prognostic factor was ≤ 50 and > 50 years old. Pathological grade and chemotherapy were also independent predictors of OS in post-operative HGG patients. Copyright © 2015. Published by Elsevier B.V.

Automated classification of brain tumor type in whole-slide digital pathology images using local representative tiles.

PubMed

Barker, Jocelyn; Hoogi, Assaf; Depeursinge, Adrien; Rubin, Daniel L

2016-05-01

Computerized analysis of digital pathology images offers the potential of improving clinical care (e.g. automated diagnosis) and catalyzing research (e.g. discovering disease subtypes). There are two key challenges thwarting computerized analysis of digital pathology images: first, whole slide pathology images are massive, making computerized analysis inefficient, and second, diverse tissue regions in whole slide images that are not directly relevant to the disease may mislead computerized diagnosis algorithms. We propose a method to overcome both of these challenges that utilizes a coarse-to-fine analysis of the localized characteristics in pathology images. An initial surveying stage analyzes the diversity of coarse regions in the whole slide image. This includes extraction of spatially localized features of shape, color and texture from tiled regions covering the slide. Dimensionality reduction of the features assesses the image diversity in the tiled regions and clustering creates representative groups. A second stage provides a detailed analysis of a single representative tile from each group. An Elastic Net classifier produces a diagnostic decision value for each representative tile. A weighted voting scheme aggregates the decision values from these tiles to obtain a diagnosis at the whole slide level. We evaluated our method by automatically classifying 302 brain cancer cases into two possible diagnoses (glioblastoma multiforme (N = 182) versus lower grade glioma (N = 120)) with an accuracy of 93.1% (p < 0.001). We also evaluated our method in the dataset provided for the 2014 MICCAI Pathology Classification Challenge, in which our method, trained and tested using 5-fold cross validation, produced a classification accuracy of 100% (p < 0.001). Our method showed high stability and robustness to parameter variation, with accuracy varying between 95.5% and 100% when evaluated for a wide range of parameters. Our approach may be useful to automatically differentiate between the two cancer subtypes. Copyright © 2015 Elsevier B.V. All rights reserved.

A convex optimization approach for identification of human tissue-specific interactomes.

PubMed

Mohammadi, Shahin; Grama, Ananth

2016-06-15

Analysis of organism-specific interactomes has yielded novel insights into cellular function and coordination, understanding of pathology, and identification of markers and drug targets. Genes, however, can exhibit varying levels of cell type specificity in their expression, and their coordinated expression manifests in tissue-specific function and pathology. Tissue-specific/tissue-selective interaction mechanisms have significant applications in drug discovery, as they are more likely to reveal drug targets. Furthermore, tissue-specific transcription factors (tsTFs) are significantly implicated in human disease, including cancers. Finally, disease genes and protein complexes have the tendency to be differentially expressed in tissues in which defects cause pathology. These observations motivate the construction of refined tissue-specific interactomes from organism-specific interactomes. We present a novel technique for constructing human tissue-specific interactomes. Using a variety of validation tests (Edge Set Enrichment Analysis, Gene Ontology Enrichment, Disease-Gene Subnetwork Compactness), we show that our proposed approach significantly outperforms state-of-the-art techniques. Finally, using case studies of Alzheimer's and Parkinson's diseases, we show that tissue-specific interactomes derived from our study can be used to construct pathways implicated in pathology and demonstrate the use of these pathways in identifying novel targets. http://www.cs.purdue.edu/homes/mohammas/projects/ActPro.html mohammadi@purdue.edu. © The Author 2016. Published by Oxford University Press.

Progressive supranuclear palsy: neuronal and glial cytoskeletal pathology in the higher order processing autonomic nuclei of the lower brainstem.

PubMed

Rüb, U; Del Tredici, K; Schultz, C; de Vos, R A I; Jansen Steur, E N H; Arai, K; Braak, H

2002-02-01

The medial and lateral parabrachial nuclei (MPB, LPB), the gigantocellular reticular nucleus (GI), the raphes magnus (RMG) and raphes obscurus nuclei (ROB), as well as the intermediate reticular zone (IRZ) represent pivotal subordinate brainstem centres, all of which control autonomic functions. In this study, we investigated the occurrence and severity of the neuronal and glial cytoskeletal pathology in these six brainstem nuclei from 17 individuals with clinically diagnosed and neuropathologically confirmed progressive supranuclear palsy (PSP). The association between the severity of the pathology and the duration of the disease was investigated by means of correlation analysis. The brainstem nuclei in all of the PSP cases were affected by the neuronal cytoskeletal pathology, with the IRZ and GI regularly showing severe involvement, the MPB, RMG, and ROB marked involvement, and the LPB mild involvement. In the six nuclear greys studied, glial cells undergo alterations of their cytoskeleton on an irregular basis, whereby diseased oligodendrocytes predominantly presented as coiled bodies and affected astrocytes as thorn-shaped astrocytes. In all six nuclei, the severity of the neuronal or glial cytoskeletal pathology showed no correlation with the duration of PSP. In view of their functional role, the neuronal pathology in the nuclei studied offers a possible explanation for the autonomic dysfunctions that eventually develop in the course of PSP.

[The Base of the Skull. Rudolf Virchow between Pathology and Anthropology].

PubMed

Seemann, Sophie

2016-01-01

Throughout his scientific career, the pathologist and anthropologist Rudolf Virchow (1821-1902) examined countless skulls, gradually changing his perspective on this object of research. Initially, he was mainly concerned with pathologically deformed skulls. From the 1850s onwards, he gradually developed a more anthropological approach, and anthropology increasingly came to dominate his scientific interest. This article shows how different influences became central for the establishment of his specific and dynamic model of the human skull development and its successful application in anthropology. Crucial for this process were Virchow's collaboration with his teacher Robert Froriep (1804-1861) in the department of pathology of the Charité, his research on cretinism and rickets, as well as his description of the base of the skull as the center of skull development. His research work was attended by and showed a reciprocal interaction with the buildup of large skull collections. This article uses Virchow's original publications on skull pathology as well as his still preserved skull specimens from the collection of the Berlin Museum of Medical History at the Charité for an integrated text and object based analysis.

Microfluidics for rapid cytokeratin immunohistochemical staining in frozen sections.

PubMed

Brajkovic, Saska; Dupouy, Diego G; de Leval, Laurence; Gijs, Martin Am

2017-08-01

Frozen sections (FS) of tumor samples represent a cornerstone of pathological intraoperative consultation and have an important role in the microscopic analysis of specimens during surgery. So far, immunohistochemical (IHC) stainings on FS have been demonstrated for a few markers using manual methods. Microfluidic technologies have proven to bring substantial improvement in many fields of diagnostics, though only a few microfluidic devices have been designed to improve the performance of IHC assays. In this work, we show optimization of a complete pan-cytokeratin chromogenic immunostaining protocol on FS using a microfluidic tissue processor into a protocol taking <12 min. Our results showed specificity and low levels of background. The dimensions of the microfluidic prototype device are compatible with the space constraints of an intraoperative pathology laboratory. We therefore anticipate that the adoption of microfluidic technologies in the field of surgical pathology can significantly improve the way FSs influence surgical procedures.

Microfluidics for rapid cytokeratin immunohistochemical staining in frozen sections

PubMed Central

Brajkovic, Saska; Dupouy, Diego G.; de Leval, Laurence; Gijs, Martin A. M.

2017-01-01

Frozen sections (FS) of tumor samples represent a cornerstone of pathological intraoperative consultation and play an important role in the microscopic analysis of specimens during surgery. So far, immunohistochemical (IHC) stainings on FS have been demonstrated for a few markers using manual methods. Microfluidic technologies have proven to bring substantial improvement in many fields of diagnostics, though only a few microfluidic devices have been designed to improve the performance of IHC assays. In this work, we show optimization of a complete pan-cytokeratin chromogenic immunostaining protocol on FS using a microfluidic tissue processor, into a protocol taking less than 12 minutes. Our results showed specificity and low levels of background. The dimensions of the microfluidic prototype device are compatible with the space constraints of an intraoperative pathology laboratory. We therefore anticipate that the adoption of microfluidic technologies in the field of surgical pathology can significantly improve the way FSs influence surgical procedures. PMID:28553936

Timing and necessity of a flexible sigmoidoscopy in patients with symptoms suggestive of haemorrhoids.

PubMed

Vening, W; Willigendael, E M; Tjeertes, E K M; Hulsewé, K W E; Hoofwijk, A G M

2010-02-01

This study was performed to determine the probability of finding additional pathology, requiring treatment or follow-up, in patients referred with symptoms suggestive of haemorrhoids. Secondly, to determine, at what age a flexible sigmoidoscopy should be performed in these patients. All patients referred for the treatment of haemorrhoids over a period of 5 years were prospectively included in a database. Data included patient characteristics, clinical information, histopathological analysis and the sigmoidoscopy results. Haemorrhoids were present in 961 (95.6%) of 1005 patients. Of these patients, 692 (72.0%) patients were free from any additional pathology, 161 (16%) patients had diverticulosis, in 15 (1.5%) patients the sigmoidoscopy showed signs of colitis, 116 (11.5%) patients had polyps and a malignancy was present in eight (0.8%) patients. In the age group between 30-40 and 40-50, the presence of additional pathology increased significantly (P < 0.05). No malignancies were found under the age of 40. The vast majority of patients referred for the treatment and analysis of haemorrhoids were free from any additional pathology. But, over the age of 40, the incidence of additional pathology increased significantly. Therefore, we suggest that a flexible sigmoidoscopy should be performed in all patients over the age of 40, with clinical signs of haemorrhoids.

Pathologic implications of prostatic anterior fat pad.

PubMed

Jeong, Jeongyun; Choi, Eun Yong; Kang, Dong I; Ercolani, Matt; Lee, Dong Hyeon; Kim, Wun-Jae; Kim, Isaac Yi

2013-01-01

Lymph node status has significant pathologic implications in patients with prostate cancer. In this study, we have performed pathologic analysis of prostatic anterior fat pad (PAFP) excised during robot-assisted radical prostatectomy (RARP) to investigate the potential role of AFP on pathologic staging of prostate cancer. A total of 258 consecutive patients underwent PAFP excision during RARP between July 2007 and June 2009. PAFP was removed and submitted en bloc to the pathology department and evaluated for the presence of lymphoid tissue and metastatic prostate cancer. Retrospective chart review was performed for all patients. Of the 258 patients, 30 (11.6%) had 1 or 2 PAFP lymph nodes and 228 (88.4%) men showed no lymphoid tissue in their PAFPs. Preoperatively, mean PSA level was higher in the former group. There were no significant pathologic differences between the 2 groups. Among the 30 patients with PAFP lymph nodes, 3 were positive for metastatic prostate cancer. All 3 of these patients had high-risk features preoperatively. In 1 patient, the pelvic lymph nodes were negative for metastatic prostate cancer. At 2-year follow-up, PSA level of this patient was undetectable. Herein, we demonstrated that the PAFP contained lymph nodes in over 11% of the patients undergoing RARP at our institution. Prostate cancer was upstaged in 1 patient as a result of PAFP excision. Since this patient is free of biochemical recurrence at 2 years, routine excision and pathologic analysis of PAFP should be considered in prostate cancer patients undergoing radical prostatectomy. Copyright © 2013 Elsevier Inc. All rights reserved.

Pretreatment tables predicting pathologic stage of locally advanced prostate cancer.

PubMed

Joniau, Steven; Spahn, Martin; Briganti, Alberto; Gandaglia, Giorgio; Tombal, Bertrand; Tosco, Lorenzo; Marchioro, Giansilvio; Hsu, Chao-Yu; Walz, Jochen; Kneitz, Burkhard; Bader, Pia; Frohneberg, Detlef; Tizzani, Alessandro; Graefen, Markus; van Cangh, Paul; Karnes, R Jeffrey; Montorsi, Francesco; van Poppel, Hein; Gontero, Paolo

2015-02-01

Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. Retropubic RP and pelvic lymphadenectomy. Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The Effect of Mental Rotation on Surgical Pathological Diagnosis.

PubMed

Park, Heejung; Kim, Hyun Soo; Cha, Yoon Jin; Choi, Junjeong; Minn, Yangki; Kim, Kyung Sik; Kim, Se Hoon

2018-05-01

Pathological diagnosis involves very delicate and complex consequent processing that is conducted by a pathologist. The recognition of false patterns might be an important cause of misdiagnosis in the field of surgical pathology. In this study, we evaluated the influence of visual and cognitive bias in surgical pathologic diagnosis, focusing on the influence of "mental rotation." We designed three sets of the same images of uterine cervix biopsied specimens (original, left to right mirror images, and 180-degree rotated images), and recruited 32 pathologists to diagnose the 3 set items individually. First, the items found to be adequate for analysis by classical test theory, Generalizability theory, and item response theory. The results showed statistically no differences in difficulty, discrimination indices, and response duration time between the image sets. Mental rotation did not influence the pathologists' diagnosis in practice. Interestingly, outliers were more frequent in rotated image sets, suggesting that the mental rotation process may influence the pathological diagnoses of a few individual pathologists. © Copyright: Yonsei University College of Medicine 2018.

Internet Addiction Disorder: Personality characteristics and risk of pathological overuse in adolescents.

PubMed

Munno, Donato; Cappellin, Flora; Saroldi, Marta; Bechon, Elisa; Guglielmucci, Fanny; Passera, Roberto; Zullo, Giuseppina

2017-02-01

Few studies have investigated Internet Addiction (IA) in adolescents in relation to personality characteristics. The aim of this study was to determine whether personality differences exist between adolescents with problematic/pathological Internet use and those with normal Internet use. Our hypothesis was that certain psychopathological personality traits may predispose to the development of maladaptive Internet use. The Internet Addiction Test (IAT) and the Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A) were administered to a sample of 224 high school students. Analysis of IAT scores showed that 24.6% of the students had problematic Internet use and 1.6% had IA. Comparison of the MMPI-A scores between subjects with normal Internet use and those with problematic or pathological use based on the IAT score showed that some subscales, including schizophrenia and bizarre mentation, were strongly associated with problematic/pathological Internet use. Also, male sex, attending a vocational school, and unhappy childhood were found to be risk factors for IA. Certain psychological dimensions regarding mood and the psychotic area, as well as low self-esteem, family, school and conduct problems could represent risk factors. Taken together, our data suggest a personality profile, with problems at various levels in subjects with problematic or pathological Internet use. Copyright © 2016. Published by Elsevier B.V.

Handheld confocal Raman microspectrometer for in-vivo skin cancer measurement

NASA Astrophysics Data System (ADS)

Lieber, Chad A.; Ellis, Darrel L.; Billheimer, D. D.; Mahadevan-Jansen, Anita

2004-07-01

Several studies have demonstrated Raman spectroscopy to be capable of tissue diagnosis with accuracy rivaling that of histopathologic analysis. This technique obtains biochemical-specific information noninvasively, and can eliminate the pain, time, and cost associated with biopsy and pathological analysis. Furthermore, when used in a confocal arrangement, Raman spectra can be obtained from localized regions of the tissue. Skin cancers are an ideal candidate for this emerging technology, due to their obvious accessibility and presentation at specific depths. However, most commercially available confocal Raman microspectrometers are large, rigid systems ill-suited for clinical application. We developed a bench-top confocal Raman microspectrometer using a portable external-cavity diode laser excitation source. This system was used to study several skin lesions in vitro. Results show the depth-resolved Raman spectra can diagnose in vitro skin lesions with 96% sensitivity, 88% specificity, and 86% pathological classification accuracy. Based on the success of this study, a portable Raman system with a handheld confocal microscope was developed for clinical application. Preliminary in vivo data show several distinct spectral differences between skin pathologies. Diagnostic algorithms are planned for this continuing study to assess the capability of Raman spectroscopy for clinical skin cancer diagnosis.

HIV-1 Phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

PubMed Central

Lamers, Susanna L.; Gray, Rebecca R.; Salemi, Marco; Huysentruyt, Leanne C.; McGrath, Michael

2010-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that 1) HIV-1 is clearly capable of migrating out of the brain, 2) the meninges are the most likely primary transport tissues, and 3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. PMID:21055482

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.

Flexner 3.0-Democratization of Medical Knowledge for the 21st Century: Teaching Medical Science Using K-12 General Pathology as a Gateway Course.

PubMed

Weinstein, Ronald S; Krupinski, Elizabeth A; Weinstein, John B; Graham, Anna R; Barker, Gail P; Erps, Kristine A; Holtrust, Angelette L; Holcomb, Michael J

2016-01-01

A medical school general pathology course has been reformatted into a K-12 general pathology course. This new course has been implemented at a series of 7 to 12 grade levels and the student outcomes compared. Typically, topics covered mirrored those in a medical school general pathology course serving as an introduction to the mechanisms of diseases. Assessment of student performance was based on their score on a multiple-choice final examination modeled after an examination given to medical students. Two Tucson area schools, in a charter school network, participated in the study. Statistical analysis of examination performances showed that there were no significant differences as a function of school ( F = 0.258, P = .6128), with students at school A having an average test scores of 87.03 (standard deviation = 8.99) and school B 86.00 (standard deviation = 8.18; F = 0.258, P = .6128). Analysis of variance was also conducted on the test scores as a function of gender and class grade. There were no significant differences as a function of gender ( F = 0.608, P = .4382), with females having an average score of 87.18 (standard deviation = 7.24) and males 85.61 (standard deviation = 9.85). There were also no significant differences as a function of grade level ( F = 0.627, P = .6003), with 7th graders having an average of 85.10 (standard deviation = 8.90), 8th graders 86.00 (standard deviation = 9.95), 9th graders 89.67 (standard deviation = 5.52), and 12th graders 86.90 (standard deviation = 7.52). The results demonstrated that middle and upper school students performed equally well in K-12 general pathology. Student course evaluations showed that the course met the student's expectations. One class voted K-12 general pathology their "elective course-of-the-year."

High-throughput 3D whole-brain quantitative histopathology in rodents

PubMed Central

Vandenberghe, Michel E.; Hérard, Anne-Sophie; Souedet, Nicolas; Sadouni, Elmahdi; Santin, Mathieu D.; Briet, Dominique; Carré, Denis; Schulz, Jocelyne; Hantraye, Philippe; Chabrier, Pierre-Etienne; Rooney, Thomas; Debeir, Thomas; Blanchard, Véronique; Pradier, Laurent; Dhenain, Marc; Delzescaux, Thierry

2016-01-01

Histology is the gold standard to unveil microscopic brain structures and pathological alterations in humans and animal models of disease. However, due to tedious manual interventions, quantification of histopathological markers is classically performed on a few tissue sections, thus restricting measurements to limited portions of the brain. Recently developed 3D microscopic imaging techniques have allowed in-depth study of neuroanatomy. However, quantitative methods are still lacking for whole-brain analysis of cellular and pathological markers. Here, we propose a ready-to-use, automated, and scalable method to thoroughly quantify histopathological markers in 3D in rodent whole brains. It relies on block-face photography, serial histology and 3D-HAPi (Three Dimensional Histology Analysis Pipeline), an open source image analysis software. We illustrate our method in studies involving mouse models of Alzheimer’s disease and show that it can be broadly applied to characterize animal models of brain diseases, to evaluate therapeutic interventions, to anatomically correlate cellular and pathological markers throughout the entire brain and to validate in vivo imaging techniques. PMID:26876372

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.

Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study.

PubMed

Barra, Filipe Ramos; de Souza, Fernanda Freire; Camelo, Rosimara Eva Ferreira Almeida; Ribeiro, Andrea Campos de Oliveira; Farage, Luciano

2017-01-01

To assess the feasibility of contrast-enhanced spectral mammography (CESM) of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC). In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM). We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively). The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886). The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598). Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88). CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent.

Preservation of pathological tissue specimens by freeze-drying for immunohistochemical staining and various molecular biological analyses.

PubMed

Matsuo, S; Sugiyama, T; Okuyama, T; Yoshikawa, K; Honda, K; Takahashi, R; Maeda, S

1999-05-01

Conditions of preserving DNA, RNA and protein in pathological specimens are of great importance as degradation of such macromolecules would critically affect results of molecular biological analysis. The feasibility of freeze-drying as a means of preserving pathological tissue samples for molecular analysis has previously been shown. In the present study, further tests on long-term storage conditions and analyses of freeze-dried samples by polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, western blotting and immunohistochemistry are reported. Rat chromosomal DNA of freeze-dried samples stored for 4 years showed slight degradation while RNA degradation was more prominently seen at an earlier stage of storage. However, these 4 year DNA and RNA samples were still able to serve as a template for some PCR and RT-PCR analyses, respectively. Overexpression of c-erbB-2 and p53 protein was demonstrated by western blotting and immunohistochemical staining using freeze-dried human breast cancer tissues. Although macromolecules in freeze-dried samples degrade to some extent during the preservation period, they should still be of value for certain molecular biological analyses and morphological examination; hence, providing more convenient and inexpensive ways of pathological tissue storage.

Osteosarcoma subtypes: Magnetic resonance and quantitative diffusion weighted imaging criteria.

PubMed

Zeitoun, Rania; Shokry, Ahmed M; Ahmed Khaleel, Sahar; Mogahed, Shaimaa M

2018-03-01

Osteosarcoma (OS) is a primary bone malignancy, characterized by spindle cells producing osteoid. The objective of this study is to describe the magnetic resonance imaging (MRI) features of different OS subtypes, record their attenuation diffusion coefficient (ADC) values and to point to the relation of their pathologic base and their corresponding ADC value. We performed a retrospective observational lesion-based analysis for 31 pathologically proven osteosarcoma subtypes: osteoblastic (n = 9), fibroblastic (n = 8), chondroblastic (n = 6), para-osteal (n = 3), periosteal (n = 1), telangiectatic (n = 2), small cell (n = 1) and extra-skeletal (n = 1). On conventional images we recorded: bone of origin, epicenter, intra-articular extension, and invasion of articulating bones, skip lesions, distant metastases, pathological fractures, ossified matrix, hemorrhage and necrosis. We measured the mean ADC value for each lesion. Among the included OS lesions, 51.6% originated at the femur, 29% showed intra-articular extension, 16% invaded neighboring bone, 9% were associated with pathological fracture and 25.8% were associated with distant metastases. On MRI, all lesions showed ossified matrix, 35.5% showed hemorrhage and 58% showed necrosis. The mean ADC values for OS lesions ranged from 0.74 × 10 -3  mm 2 /s (recorded for conventional osteoblastic OS) to 1.50 × 10 -3  mm 2 /s (recorded for telangiectatic OS) with an average value of 1.16 ± 0.18 × 10 -3  mm 2 /s. Conventional chondroblastic OS recorded higher values compared to the other two conventional subtypes. Osteosarcoma has different pathologic subtypes which correspondingly vary in their imaging criteria and their ADC values. Copyright © 2018. Production and hosting by Elsevier B.V.

APOEε2 is associated with milder clinical and pathological Alzheimer's disease

PubMed Central

Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E.; Betensky, Rebecca A.; Hyman, Bradley T.

2015-01-01

Objective The Alzheimer disease (AD) APOEε4 risk allele associates with an earlier age of onset and increased amyloid-β deposition, whereas the protective APOEε2 allele delays the onset and appears to prevent amyloid-β deposition. Yet the clinical and pathological effects of APOEε2 remain uncertain because of its relative rarity. We investigated the effects of APOE ε2 and ε4 alleles on AD pathology and cognition in a large US dataset of well characterized AD patients. Methods We studied individuals from the National Alzheimer's Coordinating Center (NACC) autopsy cohort across the entire clinico-pathological continuum of AD. Multivariable models were built to examine the associations between APOE alleles and AD neuropathological changes, using the APOEε3/ε3 group as comparator. Mediation analysis was used to estimate the direct and indirect effects of APOE alleles on AD pathology and cognition (CDR-SOB and MMSE). Results Compared to APOEε3/ε3, APOEε2 is independently associated with lower Braak NFT stages and, possibly, fewer neuritic plaques, but has no direct effect on CAA severity, whereas APOEε4 is associated with more neuritic plaques and CAA, but has no independent effect on Braak NFT stage. Unadjusted analyses showed marked differences among APOE genotypes with respect to cognitive performance (ε2>ε3>ε4). Mediation analysis suggests that this is largely explained through effects on pathology. Interpretation Even when adjusted for age of onset, symptom duration and other demographic variables, APOEε2 is associated with milder AD pathology and less severe antemortem cognitive impairment compared to APOE ε3 and ε4 alleles, suggesting a relative neuroprotective effect of APOEε2 in AD. PMID:25623662

Shapelet analysis of pupil dilation for modeling visuo-cognitive behavior in screening mammography

NASA Astrophysics Data System (ADS)

Alamudun, Folami; Yoon, Hong-Jun; Hammond, Tracy; Hudson, Kathy; Morin-Ducote, Garnetta; Tourassi, Georgia

2016-03-01

Our objective is to improve understanding of visuo-cognitive behavior in screening mammography under clinically equivalent experimental conditions. To this end, we examined pupillometric data, acquired using a head-mounted eye-tracking device, from 10 image readers (three breast-imaging radiologists and seven Radiology residents), and their corresponding diagnostic decisions for 100 screening mammograms. The corpus of mammograms comprised cases of varied pathology and breast parenchymal density. We investigated the relationship between pupillometric fluctuations, experienced by an image reader during mammographic screening, indicative of changes in mental workload, the pathological characteristics of a mammographic case, and the image readers' diagnostic decision and overall task performance. To answer these questions, we extract features from pupillometric data, and additionally applied time series shapelet analysis to extract discriminative patterns in changes in pupil dilation. Our results show that pupillometric measures are adequate predictors of mammographic case pathology, and image readers' diagnostic decision and performance with an average accuracy of 80%.

Digital Imaging and Communications in Medicine Whole Slide Imaging Connectathon at Digital Pathology Association Pathology Visions 2017.

PubMed

Clunie, David; Hosseinzadeh, Dan; Wintell, Mikael; De Mena, David; Lajara, Nieves; Garcia-Rojo, Marcial; Bueno, Gloria; Saligrama, Kiran; Stearrett, Aaron; Toomey, David; Abels, Esther; Apeldoorn, Frank Van; Langevin, Stephane; Nichols, Sean; Schmid, Joachim; Horchner, Uwe; Beckwith, Bruce; Parwani, Anil; Pantanowitz, Liron

2018-01-01

As digital pathology systems for clinical diagnostic work applications become mainstream, interoperability between these systems from different vendors becomes critical. For the first time, multiple digital pathology vendors have publicly revealed the use of the digital imaging and communications in medicine (DICOM) standard file format and network protocol to communicate between separate whole slide acquisition, storage, and viewing components. Note the use of DICOM for clinical diagnostic applications is still to be validated in the United States. The successful demonstration shows that the DICOM standard is fundamentally sound, though many lessons were learned. These lessons will be incorporated as incremental improvements in the standard, provide more detailed profiles to constrain variation for specific use cases, and offer educational material for implementers. Future Connectathon events will expand the scope to include more devices and vendors, as well as more ambitious use cases including laboratory information system integration and annotation for image analysis, as well as more geographic diversity. Users should request DICOM features in all purchases and contracts. It is anticipated that the growth of DICOM-compliant manufacturers will likely also ease DICOM for pathology becoming a recognized standard and as such the regulatory pathway for digital pathology products.

[Clinical, pathological and imaging features of primary pelvic Ewing's sarcoma].

PubMed

Liu, J; Chen, Y; Ling, X L; Gong, Y; Ding, J P; Zhang, Z K; Wang, Y J

2016-07-19

To explore the clinical, pathological and imaging features of Ewing's sarcoma in pelvis and to improve knowledge and diagnosis of the disease. A retrospective analysis of the clinical, pathological and imaging data of pathologically confirmed 13 cases of Ewing's sarcoma in pelvis was carried out between May 2008 and March 2016 in the Affiliated Hospital of Hangzhou Normal University, the Third Hospital of Hebei Medical University and the Second Hospital of Hebei Medical University. The median age 13 cases of pelvic primary Ewing's sarcoma was 17 years old.The X-ray and CT imagings showed osteolytic and mixed bone destruction, CT showed mixed type in 10 cases, 8 cases of bone tumors as a flocculent, 10 cases of bone expansion failure, 10 cases of periosteal reaction, the layered 5 cases, radial in 5 cases.Thirteen cases showed soft tissue mass, soft tissue mass was equal or slightly lower density.Four cases showed heterogeneous contrast enhancement.The lesions showed low signal in T1WI and mixed high signal in T2WI of magnetic resonance imaging(MRI). The boundary of the lesions were obscure, and 5 cases had patchy necrosis area, and 9 cases had incomplete false capsule, surrounding soft tissue was violated.Four cases showed heterogeneous contrast enhancement after MRI enhancement scan. The age of onset of Ewing's sarcoma of the pelvis is more concentrated in about 15 years.The imaging feaures are mixed bone destruction and more bone is swelling and permeability damage, soft tissue mass is larger, bone tumor is cloudy or acicular, periosteal reaction in a layered and radial, most cases show that the false envelope is not complete.Combined with clinical and imaging examination, the diagnosis of the disease can be made.

18F Fluorocholine Dynamic Time-of-Flight PET/MR Imaging in Patients with Newly Diagnosed Intermediate- to High-Risk Prostate Cancer: Initial Clinical-Pathologic Comparisons.

PubMed

Choi, Joon Young; Yang, Jaewon; Noworolski, Susan M; Behr, Spencer; Chang, Albert J; Simko, Jeffry P; Nguyen, Hao G; Carroll, Peter R; Kurhanewicz, John; Seo, Youngho

2017-02-01

Purpose To investigate the initial clinical value of fluorine 18 ( 18 F) fluorocholine (FCH) dynamic positron emission tomography (PET)/magnetic resonance (MR) imaging by comparing its parameters with clinical-pathologic findings in patients with newly diagnosed intermediate- to high-risk prostate cancer (PCa) who plan to undergo radical prostatectomy. Materials and Methods The institutional review board approved the study protocol, and informed written consent was obtained from all subjects for this HIPAA-compliant study. Twelve men (mean age ± standard deviation, 61.7 years ± 8.4; range, 46-74 years) with untreated intermediate- to high-risk PCa characterized according to Cancer of the Prostate Risk Assessment (CAPRA) underwent preoperative FCH dynamic PET/MR imaging followed by radical prostatectomy between April and November 2015. PET/MR imaging parameters including average and maximum K1 (delivery rate constant) and standardized uptake values (SUVs) and Prostate Imaging Reporting and Data System (PI-RADS) version 2 scores were measured and compared with clinical-pathologic characteristics. For statistical analysis, the Spearman rank correlation and Mann-Whitney U tests were performed. Results Of the PET parameters, maximum SUV of primary tumors showed significant correlations with several clinical-pathologic parameters including serum prostate-specific antigen level (ρ = 0.71, P = .01), pathologic stage (ρ = 0.59, P = .043), and postsurgical CAPRA score (ρ = 0.72, P = .008). The overall PI-RADS score showed significant correlations with pathologic tumor volume (ρ = 0.81, P < .001), percentage of tumor cells with Gleason scores greater than 3 (ρ = 0.59, P = .02), and postsurgical CAPRA score (ρ = 0.58, P = .046). The high-risk postsurgical CAPRA score patient group had a significantly higher maximum SUV than did the intermediate-risk group. Combined PET and MR imaging showed improved sensitivity (88%) for prediction of pathologic extraprostatic extension compared with that with MR imaging (50%) and PET (75%) performed separately. Conclusion Maximum SUVs and PI-RADS scores from FCH PET/MR imaging show good correlation with clinical-pathologic characteristics, such as postsurgical CAPRA score, which are related to prognosis in patients with newly diagnosed intermediate- to high-risk PCa. © RSNA, 2016 Online supplemental material is available for this article.

A meta-analysis of the relationships between body checking, body image avoidance, body image dissatisfaction, mood, and disordered eating.

PubMed

Walker, D Catherine; White, Emily K; Srinivasan, Vamshek J

2018-04-16

Body checking (BC) and body image avoidance (BIA) have been proposed as etiological and maintaining mechanisms for eating disorder (ED) pathology. To date, no comprehensive review summarizes the relationships of BC and BIA with ED pathology, body image dissatisfaction, or mood/affect. Meta-analyses examined the relationships of BC and BIA with ED pathology, body image dissatisfaction, and mood/affect. Gender, publication status, and presence or absence of ED diagnoses were examined as potential moderators. Results showed strong relationships between BC and ED pathology (ρ = 0.588) and BC and body image dissatisfaction (ρ = 0.631) and a moderate relationship between BC and mood/affect (ρ = 0.385). Similarly, results showed strong relationships between BIA and ED pathology (ρ = 0.553) and BIA and body image dissatisfaction (ρ = 0.543) and a moderate relationship between BIA and mood/affect (ρ = 0.392). Overall, limited evidence supported publication bias; however, publication bias may exist in the relationship between BIA and body image dissatisfaction in the literature. Subgroup moderator analyses suggested that gender moderates the strength of the relationships between BC and ED pathology, body image dissatisfaction, and mood/affect and between BIA and body image dissatisfaction. Results are consistent with cognitive-behavioral models of ED pathology that suggest BC and BIA are behavioral expressions of overvaluation of weight and shape. Notably, more published research has investigated BC than BIA. Future studies, incorporating methods such as meta-analytic structural equation modeling, should examine these variables to further test cognitive-behavioral models of ED development and maintenance. © 2018 Wiley Periodicals, Inc.

IR Spectroscopic signs of malignant neoplasms in the thyroid gland

NASA Astrophysics Data System (ADS)

Tolstorozhev, G. B.; Skornyakov, I. V.; Butra, V. A.

2012-03-01

We use Fourier transform IR spectroscopy to study thyroid tumor tissues which were removed during surgery. The IR spectra of the tissues with pathological foci are compared with data from histologic examination. In the region of N-H, C-H, and C = O stretching vibrations, the IR spectra of the tissues for thyroid cancer are different from the IR spectra of tissues without malignant formations. We identify the spectral signs of thyroid cancer. We show that IR analysis is promising for identification of thyroid pathology at the molecular level.

[Temporary disability in operated spine patients. Preliminary report].

PubMed

Rodríguez-Cabrera, Rafael; Ruiz-García, Diana; Velázquez-Ramírez, Ismael

2013-01-01

The spinal injuries in workers have become a large scale health problem. The purpose of this study is to review the differences in the spine pathologies from incapacity to work, as well as factors that could alter the recovery time and the possibility of returning the patient to work. Statistical preliminary review study in 37 patients enrolled in the Instituto Mexicano del Seguro Social, workers, undertaken to spinal pathology surgery, comparing days of incapacity with proposed internationally, as well as his return to work. The results show that 37% of the patients studied are still active in the social security, 2 years after surgery. The days of disability generated by the pathology in this study group (212.3 days) are significantly higher than what is set on the Medical Disability Advisor (56 days, almost 4 times more). The study shows the need to develop the same analysis in other hospitals, comparing the proportion of cases that return to the work and total disability times for diagnostics.

Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias.

PubMed

Beecham, Gary W; Hamilton, Kara; Naj, Adam C; Martin, Eden R; Huentelman, Matt; Myers, Amanda J; Corneveaux, Jason J; Hardy, John; Vonsattel, Jean-Paul; Younkin, Steven G; Bennett, David A; De Jager, Philip L; Larson, Eric B; Crane, Paul K; Kamboh, M Ilyas; Kofler, Julia K; Mash, Deborah C; Duque, Linda; Gilbert, John R; Gwirtsman, Harry; Buxbaum, Joseph D; Kramer, Patricia; Dickson, Dennis W; Farrer, Lindsay A; Frosch, Matthew P; Ghetti, Bernardino; Haines, Jonathan L; Hyman, Bradley T; Kukull, Walter A; Mayeux, Richard P; Pericak-Vance, Margaret A; Schneider, Julie A; Trojanowski, John Q; Reiman, Eric M; Schellenberg, Gerard D; Montine, Thomas J

2014-09-01

Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs), and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), hippocampal sclerosis of the elderly (HS), and vascular brain injury (VBI). Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE). GalNAc transferase 7 (GALNT7), ATP-Binding Cassette, Sub-Family G (WHITE), Member 1 (ABCG1), and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2) was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1, BIN1, CLU, MS4A6A, PICALM, ABCA7, CD33, PTK2B, SORL1, MEF2C, ZCWPW1, and CASS4 with 9 of these 12 loci showing larger odds ratio in the clinico-pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for NFTs or NPs showed positive correlation, while those for risk of VBI showed a moderate negative correlation. The other co-morbid neuropathologic features showed only nominal association with the known AD loci. Our results discovered new genetic associations with specific neuropathologic features and aligned known genetic risk for AD dementia with specific neuropathologic changes in the largest brain autopsy study of AD and related dementias.

Pathological hypertrophy and cardiac dysfunction are linked to aberrant endogenous unsaturated fatty acid metabolism

PubMed Central

Salomé Campos, Dijon Henrique; Grippa Sant’Ana, Paula; Okoshi, Katashi; Padovani, Carlos Roberto; Masahiro Murata, Gilson; Nguyen, Son; Kolwicz, Stephen C.; Cicogna, Antonio Carlos

2018-01-01

Pathological cardiac hypertrophy leads to derangements in lipid metabolism that may contribute to the development of cardiac dysfunction. Since previous studies, using high saturated fat diets, have yielded inconclusive results, we investigated whether provision of a high-unsaturated fatty acid (HUFA) diet was sufficient to restore impaired lipid metabolism and normalize diastolic dysfunction in the pathologically hypertrophied heart. Male, Wistar rats were subjected to supra-valvar aortic stenosis (SVAS) or sham surgery. After 6 weeks, diastolic dysfunction and pathological hypertrophy was confirmed and both sham and SVAS rats were treated with either normolipidic or HUFA diet. At 18 weeks post-surgery, the HUFA diet failed to normalize decreased E/A ratios or attenuate measures of cardiac hypertrophy in SVAS animals. Enzymatic activity assays and gene expression analysis showed that both normolipidic and HUFA-fed hypertrophied hearts had similar increases in glycolytic enzyme activity and down-regulation of fatty acid oxidation genes. Mass spectrometry analysis revealed depletion of unsaturated fatty acids, primarily linoleate and oleate, within the endogenous lipid pools of normolipidic SVAS hearts. The HUFA diet did not restore linoleate or oleate in the cardiac lipid pools, but did maintain body weight and adipose mass in SVAS animals. Overall, these results suggest that, in addition to decreased fatty acid oxidation, aberrant unsaturated fatty acid metabolism may be a maladaptive signature of the pathologically hypertrophied heart. The HUFA diet is insufficient to reverse metabolic remodeling, diastolic dysfunction, or pathologically hypertrophy, possibly do to preferentially partitioning of unsaturated fatty acids to adipose tissue. PMID:29494668

[The application of stereology in radiology imaging and cell biology fields].

PubMed

Hu, Na; Wang, Yan; Feng, Yuanming; Lin, Wang

2012-08-01

Stereology is an interdisciplinary method for 3D morphological study developed from mathematics and morphology. It is widely used in medical image analysis and cell biology studies. Because of its unbiased, simple, fast, reliable and non-invasive characteristics, stereology has been widely used in biomedical areas for quantitative analysis and statistics, such as histology, pathology and medical imaging. Because the stereological parameters show distinct differences in different pathology, many scholars use stereological methods to do quantitative analysis in their studies in recent years, for example, in the areas of the condition of cancer cells, tumor grade, disease development and the patient's prognosis, etc. This paper describes the stereological concept and estimation methods, also illustrates the applications of stereology in the fields of CT images, MRI images and cell biology, and finally reflects the universality, the superiority and reliability of stereology.

Assessment of Renal Pathological Changes in Lupus Nephritis Using Diffusion Weighted Imaging: A Multiple Correspondence Analysis.

PubMed

Zheng, Zhenfeng; Yan, Tiekun; Jia, Junya; Li, Dong; Wei, Li; Shang, Wenya; Zheng, Zhenfeng

2018-05-30

Renal pathological changes affect the motion of water molecules, which can be detected using diffusion-weighted imaging (DWI). The current study was performed to explore the correlation between renal tissue pathological injuries and DWI iconographical parameters in lupus nephritis (LN). Twenty adult patients with LN and 11 healthy volunteers were recruited. Patients with LN received renal biopsies and renal DWI-MRI inspections. The renal biopsy tissues were characterized based on the ISN/RPS 2003 classification. The volunteers, who were of comparable gender and age, only underwent renal DWI-MRI inspection. Four DWI parameters, namely, apparent diffusion coefficient (ADC), pure diffusion coefficient (Dt), pseudo-diffusion coefficient (Dp), and perfusion fraction (fp), were calculated using monoexponential and biexponential functions, respectively. Data from different renal areas and pathological pattern groups were compared. Multiple correspondence analysis (MCA) was performed to explore the correlation between each DWI index and multiple pathological features. ADC, Dt, and fp values were lower in the LN group compared to the controls (P < 0.001) regardless of the renal area in the cortex and medulla. Dp values were higher in the LN group (P = 0.004). A difference in mean DWI parameters was found between three LN subgroups and the healthy volunteers, with the exception of the Dp index in the renal cortex. MCA showed that serious proliferative pathological injuries and lower ADC and Dt values were located in the same quadrant. The MCA plots of Dp and fp provided similar results. Higher Dp and fp values were located in the MCA plot quadrant with more serious proliferative pathological changes. DWI is a noninvasive technique that may be used to detect renal pathophysiological changes. Renal cell proliferation and intestinal fibrosis may impact the movement of water in certain microenvironments. Enhanced perfusion may be a compensatory mechanism that is associated with renal pathological injuries. © 2018 The Author(s). Published by S. Karger AG, Basel.

Identification of ageing-associated naturally occurring peptides in human urine

PubMed Central

Nkuipou-Kenfack, Esther; Bhat, Akshay; Klein, Julie; Jankowski, Vera; Mullen, William; Vlahou, Antonia; Dakna, Mohammed; Koeck, Thomas; Schanstra, Joost P.; Zürbig, Petra; Rudolph, Karl L.; Schumacher, Björn; Pich, Andreas; Mischak, Harald

2015-01-01

To assess normal and pathological peptidomic changes that may lead to an improved understanding of molecular mechanisms underlying ageing, urinary peptidomes of 1227 healthy and 10333 diseased individuals between 20 and 86 years of age were investigated. The diseases thereby comprised diabetes mellitus, renal and cardiovascular diseases. Using age as a continuous variable, 116 peptides were identified that significantly (p < 0.05; |ρ|≥0.2) correlated with age in the healthy cohort. The same approach was applied to the diseased cohort. Upon comparison of the peptide patterns of the two cohorts 112 common age-correlated peptides were identified. These 112 peptides predominantly originated from collagen, uromodulin and fibrinogen. While most fibrillar and basement membrane collagen fragments showed a decreased age-related excretion, uromodulin, beta-2-microglobulin and fibrinogen fragments showed an increase. Peptide-based in silico protease analysis was performed and 32 proteases, including matrix metalloproteinases and cathepsins, were predicted to be involved in ageing. Identified peptides, predicted proteases and patient information were combined in a systems biology pathway analysis to identify molecular pathways associated with normal and/or pathological ageing. While perturbations in collagen homeostasis, trafficking of toll-like receptors and endosomal pathways were commonly identified, degradation of insulin-like growth factor-binding proteins was uniquely identified in pathological ageing. PMID:26431327

Animal inference on human mitochondrial diseases.

PubMed

Nardi, Francesco; Frati, Francesco; Liò, Pietro

2016-06-01

Several pathological mutations in the human mitochondrial genome have been characterized based on medical, genetic and biochemical evidence. The observation that the structure and core functions of the mitochondrial genome are conserved from animals to man suggests that the analysis of animal variation may be informative to further characterize, and possibly predict, human pathological variants. We studied the distribution of sequence site-wise diversity and structural heterogeneity (based on several scales of hydrophobicity and supercomplex classification of mitochondrial genes) at different taxonomic levels in ∼15,000 human and animal genomes. We found that human pathological mutations tend to lay in regions of low diversity and that states that are pathological in humans appear to be extremely rare in animals, with two noticeable exceptions (T10663C and C14568T). Focusing on hydrophobicity, as possibly the most general site-wise functional parameter of a protein, we deploy the observed range of hydrophobicity in mammals as a proxy for the range of permissible states compatible with an efficient functioning of the mitochondrial machinery. We show that, while non pathological human variants tend to fall within the hypothesized range, pathological mutations generally fall outside this range. We further analyzed this distribution quantitatively to show that the estimated probability of observed states can indeed be used to predict the pathogenicity of a mutation in humans. This study provides a proof of principle that animal data can indeed be informative to predict the pathogenicity of a human mutation alongside, or in the absence of, additional evidence. Copyright © 2016 Elsevier Ltd. All rights reserved.

Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study

PubMed Central

Barra, Filipe Ramos; de Souza, Fernanda Freire; Camelo, Rosimara Eva Ferreira Almeida; Ribeiro, Andrea Campos de Oliveira; Farage, Luciano

2017-01-01

Objective To assess the feasibility of contrast-enhanced spectral mammography (CESM) of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC). Materials and methods In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM). We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. Results The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively). The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886). The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598). Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88). Conclusion CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent. PMID:28894329

Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections.

PubMed

Tai, Xin You; Koepp, Matthias; Duncan, John S; Fox, Nick; Thompson, Pamela; Baxendale, Sallie; Liu, Joan Y W; Reeves, Cheryl; Michalak, Zuzanna; Thom, Maria

2016-09-01

SEE BERNASCONI DOI101093/AWW202 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is associated with a high prevalence of cognitive impairment but the responsible underlying pathological mechanisms are unknown. Tau, the microtubule-associated protein, is a hallmark of several neurodegenerative diseases including Alzheimer's disease and chronic traumatic encephalopathy. We hypothesized that hyperphosphorylated tau pathology is associated with cognitive decline in temporal lobe epilepsy and explored this through clinico-pathological study. We first performed pathological examination on tissue from 33 patients who had undergone temporal lobe resection between ages 50 and 65 years to treat drug-refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein using AT8 immunohistochemistry and compared this distribution to Braak patterns of Alzheimer's disease and patterns of chronic traumatic encephalopathy. We quantified tau pathology using a modified tau score created specifically for analysis of temporal lobectomy tissue and the Braak staging, which was limited without extra-temporal brain areas available. Next, we correlated tau pathology with pre- and postoperative cognitive test scores and clinical risk factors including age at time of surgery, duration of epilepsy, history of secondary generalized seizures, history of head injury, handedness and side of surgery. Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage analysis showed 12% of our epilepsy cohort had a Braak staging III-IV compared to an age-matched non-epilepsy control group from the literature (8%). We identified a mixture of tau pathology patterns characteristic of Alzheimer's disease and chronic traumatic encephalopathy. We also found unusual patterns of subpial tau deposition, sparing of the hippocampus and co-localization with mossy fibre sprouting, a feature of temporal lobe epilepsy. We demonstrated that the more extensive the tau pathology, the greater the decline in verbal learning (Spearman correlation, r = -0.63), recall (r = -0.44) and graded naming test scores (r = -0.50) over 1-year post-temporal lobe resection (P < 0.05). This relationship with tau burden was also present when examining decline in verbal learning from 3 months to 1 year post-resection (r = -0.54). We found an association between modified tau score and history of secondary generalized seizures (likelihood-ratio χ(2), P < 0.05) however there was no clear relationship between tau pathology and other clinical risk factors assessed. Our findings suggest an epilepsy-related tauopathy in temporal lobe epilepsy, which contributes to accelerated cognitive decline and has diagnostic and treatment implications. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections

PubMed Central

Tai, Xin You; Koepp, Matthias; Duncan, John S.; Fox, Nick; Thompson, Pamela; Baxendale, Sallie; Liu, Joan Y. W.; Reeves, Cheryl; Michalak, Zuzanna

2016-01-01

Abstract See Bernasconi (doi:10.1093/aww202) for a scientific commentary on this article. Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is associated with a high prevalence of cognitive impairment but the responsible underlying pathological mechanisms are unknown. Tau, the microtubule-associated protein, is a hallmark of several neurodegenerative diseases including Alzheimer’s disease and chronic traumatic encephalopathy. We hypothesized that hyperphosphorylated tau pathology is associated with cognitive decline in temporal lobe epilepsy and explored this through clinico-pathological study. We first performed pathological examination on tissue from 33 patients who had undergone temporal lobe resection between ages 50 and 65 years to treat drug-refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein using AT8 immunohistochemistry and compared this distribution to Braak patterns of Alzheimer’s disease and patterns of chronic traumatic encephalopathy. We quantified tau pathology using a modified tau score created specifically for analysis of temporal lobectomy tissue and the Braak staging, which was limited without extra-temporal brain areas available. Next, we correlated tau pathology with pre- and postoperative cognitive test scores and clinical risk factors including age at time of surgery, duration of epilepsy, history of secondary generalized seizures, history of head injury, handedness and side of surgery. Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage analysis showed 12% of our epilepsy cohort had a Braak staging III-IV compared to an age-matched non-epilepsy control group from the literature (8%). We identified a mixture of tau pathology patterns characteristic of Alzheimer’s disease and chronic traumatic encephalopathy. We also found unusual patterns of subpial tau deposition, sparing of the hippocampus and co-localization with mossy fibre sprouting, a feature of temporal lobe epilepsy. We demonstrated that the more extensive the tau pathology, the greater the decline in verbal learning (Spearman correlation, r = −0.63), recall (r = −0.44) and graded naming test scores (r = −0.50) over 1-year post-temporal lobe resection (P < 0.05). This relationship with tau burden was also present when examining decline in verbal learning from 3 months to 1 year post-resection (r = −0.54). We found an association between modified tau score and history of secondary generalized seizures (likelihood-ratio χ2, P < 0.05) however there was no clear relationship between tau pathology and other clinical risk factors assessed. Our findings suggest an epilepsy-related tauopathy in temporal lobe epilepsy, which contributes to accelerated cognitive decline and has diagnostic and treatment implications. PMID:27497924

Phase 3 study of adjuvant radiotherapy versus wait and see in pT3 prostate cancer: impact of pathology review on analysis.

PubMed

Bottke, Dirk; Golz, Reinhard; Störkel, Stephan; Hinke, Axel; Siegmann, Alessandra; Hertle, Lothar; Miller, Kurt; Hinkelbein, Wolfgang; Wiegel, Thomas

2013-08-01

In a randomised trial, radical prostatectomy (RP) followed by adjuvant radiotherapy (aRT) was compared with RP alone in patients with pT3 pN0 prostate cancer with or without positive margin at local pathology (German Cancer Society trial numbers ARO 96-02/AUO AP 09/95). A pathology review was performed on 85% of RP specimens of patients to investigate the influence of pathology review on the analysis. Patients post-RP (n=385) were randomised before achieving an undetectable prostate-specific antigen (PSA) level to either wait and see (n=192) or 60Gy aRT (n=193). Of 307 patients with undetectable PSA after RP, 262 had pathology review. These results were included prospectively into the analysis. Agreement between local and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic reliability for the different parameters was analysed by Cox regression model. Event-free rates were determined by Kaplan-Meier analysis with a median follow-up of 40 mo for the wait-and-see arm and 38.5 mo for the aRT arm. There was fair concordance between pathology review and local pathologists for seminal vesicle invasion (pT3c: 91%; κ=0.76), surgical margin status (84%; κ=0.65), and for extraprostatic extension (pT3a/b: 75%; κ=0.74). Agreement was much less for Gleason score (47%; κ=0.42), whereby the review pathology resulted in a shift to Gleason score 7. In contrast to the analysis of progression-free survival with local pathology, the multivariate analysis including review pathology revealed PSMs and Gleason score >6 as significant prognostic factors. Phase 3 studies of postoperative treatment of prostate cancer should be accomplished in the future with a pathology review. In daily practice, a second opinion by a pathologist experienced in urogenital pathology would be desirable, in particular, for high-risk patients after RP. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome

PubMed Central

Kamiyoshi, Naohiro; Fu, Xue Jun; Morisada, Naoya; Nozu, Yoshimi; Ye, Ming Juan; Imafuku, Aya; Miura, Kenichiro; Yamamura, Tomohiko; Minamikawa, Shogo; Shono, Akemi; Ninchoji, Takeshi; Morioka, Ichiro; Nakanishi, Koichi; Yoshikawa, Norishige; Kaito, Hiroshi; Iijima, Kazumoto

2016-01-01

Background and objectives Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in collagen 4A3 and/or collagen 4A4 accounts for <5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear. Design, setting, participants, & measurements We conducted a retrospective analysis of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (a total of 72 patients) from 16 unrelated families. Patients with suspected Alport syndrome after pathologic examination who were referred from anywhere in Japan for genetic analysis from 2006 to 2015 were included in this study. Clinical, laboratory, and pathologic data were collected from medical records at the point of registration for genetic diagnosis. Genetic analysis was performed by targeted resequencing of 27 podocyte-related genes, including Alport–related collagen genes, to make a diagnosis of autosomal dominant Alport syndrome and identify modifier genes or double mutations. Clinical data were obtained from medical records. Results The median renal survival time was 70 years, and the median age at first detection of proteinuria was 17 years old. There was one patient with hearing loss and one patient with ocular lesion. Among 16 patients who underwent kidney biopsy, three showed FSGS, and seven showed thinning without lamellation of the glomerular basement membrane. Five of 13 detected mutations were reported to be causative mutations for autosomal recessive Alport syndrome in previous studies. Two families possessed double mutations in both collagen 4A3 and collagen 4A4, but no modifier genes were detected among the other podocyte–related genes. Conclusions The renal phenotype of autosomal dominant Alport syndrome was much milder than that of autosomal recessive Alport syndrome or X–linked Alport syndrome in men. It may, thus, be difficult to make an accurate diagnosis of autosomal dominant Alport syndrome on the basis of clinical or pathologic findings. No modifier genes were identified among the known podocyte–related genes. PMID:27281700

Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome.

PubMed

Kamiyoshi, Naohiro; Nozu, Kandai; Fu, Xue Jun; Morisada, Naoya; Nozu, Yoshimi; Ye, Ming Juan; Imafuku, Aya; Miura, Kenichiro; Yamamura, Tomohiko; Minamikawa, Shogo; Shono, Akemi; Ninchoji, Takeshi; Morioka, Ichiro; Nakanishi, Koichi; Yoshikawa, Norishige; Kaito, Hiroshi; Iijima, Kazumoto

2016-08-08

Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in collagen 4A3 and/or collagen 4A4 accounts for <5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear. We conducted a retrospective analysis of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (a total of 72 patients) from 16 unrelated families. Patients with suspected Alport syndrome after pathologic examination who were referred from anywhere in Japan for genetic analysis from 2006 to 2015 were included in this study. Clinical, laboratory, and pathologic data were collected from medical records at the point of registration for genetic diagnosis. Genetic analysis was performed by targeted resequencing of 27 podocyte-related genes, including Alport-related collagen genes, to make a diagnosis of autosomal dominant Alport syndrome and identify modifier genes or double mutations. Clinical data were obtained from medical records. The median renal survival time was 70 years, and the median age at first detection of proteinuria was 17 years old. There was one patient with hearing loss and one patient with ocular lesion. Among 16 patients who underwent kidney biopsy, three showed FSGS, and seven showed thinning without lamellation of the glomerular basement membrane. Five of 13 detected mutations were reported to be causative mutations for autosomal recessive Alport syndrome in previous studies. Two families possessed double mutations in both collagen 4A3 and collagen 4A4, but no modifier genes were detected among the other podocyte-related genes. The renal phenotype of autosomal dominant Alport syndrome was much milder than that of autosomal recessive Alport syndrome or X-linked Alport syndrome in men. It may, thus, be difficult to make an accurate diagnosis of autosomal dominant Alport syndrome on the basis of clinical or pathologic findings. No modifier genes were identified among the known podocyte-related genes. Copyright © 2016 by the American Society of Nephrology.

HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

PubMed

Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

2011-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

Fuller's earth (montmorillonite) pneumoconiosis.

PubMed Central

Gibbs, A R; Pooley, F D

1994-01-01

A fuller's earth worker developed signs of pneumoconiosis. Pathological examination of the lung tissues showed interstitial collections of dust laden macrophages associated with mild fibrosis. Mineralogical analysis showed a high content of montmorillonite. This study shows that a pneumoconiosis can result from prolonged heavy exposure to calcium montmorillonite (fuller's earth) in the absence of quartz. The disease is relatively mild and associated with little clinical disability. Images Figure 1 Figure 2 PMID:7951799

Estimation of T2* Relaxation Time of Breast Cancer: Correlation with Clinical, Imaging and Pathological Features

PubMed Central

Seo, Mirinae; Jahng, Geon-Ho; Sohn, Yu-Mee; Rhee, Sun Jung; Oh, Jang-Hoon; Won, Kyu-Yeoun

2017-01-01

Objective The purpose of this study was to estimate the T2* relaxation time in breast cancer, and to evaluate the association between the T2* value with clinical-imaging-pathological features of breast cancer. Materials and Methods Between January 2011 and July 2013, 107 consecutive women with 107 breast cancers underwent multi-echo T2*-weighted imaging on a 3T clinical magnetic resonance imaging system. The Student's t test and one-way analysis of variance were used to compare the T2* values of cancer for different groups, based on the clinical-imaging-pathological features. In addition, multiple linear regression analysis was performed to find independent predictive factors associated with the T2* values. Results Of the 107 breast cancers, 92 were invasive and 15 were ductal carcinoma in situ (DCIS). The mean T2* value of invasive cancers was significantly longer than that of DCIS (p = 0.029). Signal intensity on T2-weighted imaging (T2WI) and histologic grade of invasive breast cancers showed significant correlation with T2* relaxation time in univariate and multivariate analysis. Breast cancer groups with higher signal intensity on T2WI showed longer T2* relaxation time (p = 0.005). Cancer groups with higher histologic grade showed longer T2* relaxation time (p = 0.017). Conclusion The T2* value is significantly longer in invasive cancer than in DCIS. In invasive cancers, T2* relaxation time is significantly longer in higher histologic grades and high signal intensity on T2WI. Based on these preliminary data, quantitative T2* mapping has the potential to be useful in the characterization of breast cancer. PMID:28096732

A method for normalizing pathology images to improve feature extraction for quantitative pathology.

PubMed

Tam, Allison; Barker, Jocelyn; Rubin, Daniel

2016-01-01

With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology images by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. ICHE may be a useful preprocessing step a digital pathology image processing pipeline.

Radiologic-Pathologic Analysis of Contrast-enhanced and Diffusion-weighted MR Imaging in Patients with HCC after TACE: Diagnostic Accuracy of 3D Quantitative Image Analysis

PubMed Central

Chapiro, Julius; Wood, Laura D.; Lin, MingDe; Duran, Rafael; Cornish, Toby; Lesage, David; Charu, Vivek; Schernthaner, Rüdiger; Wang, Zhijun; Tacher, Vania; Savic, Lynn Jeanette; Kamel, Ihab R.

2014-01-01

Purpose To evaluate the diagnostic performance of three-dimensional (3Dthree-dimensional) quantitative enhancement-based and diffusion-weighted volumetric magnetic resonance (MR) imaging assessment of hepatocellular carcinoma (HCChepatocellular carcinoma) lesions in determining the extent of pathologic tumor necrosis after transarterial chemoembolization (TACEtransarterial chemoembolization). Materials and Methods This institutional review board–approved retrospective study included 17 patients with HCChepatocellular carcinoma who underwent TACEtransarterial chemoembolization before surgery. Semiautomatic 3Dthree-dimensional volumetric segmentation of target lesions was performed at the last MR examination before orthotopic liver transplantation or surgical resection. The amount of necrotic tumor tissue on contrast material–enhanced arterial phase MR images and the amount of diffusion-restricted tumor tissue on apparent diffusion coefficient (ADCapparent diffusion coefficient) maps were expressed as a percentage of the total tumor volume. Visual assessment of the extent of tumor necrosis and tumor response according to European Association for the Study of the Liver (EASLEuropean Association for the Study of the Liver) criteria was performed. Pathologic tumor necrosis was quantified by using slide-by-slide segmentation. Correlation analysis was performed to evaluate the predictive values of the radiologic techniques. Results At histopathologic examination, the mean percentage of tumor necrosis was 70% (range, 10%–100%). Both 3Dthree-dimensional quantitative techniques demonstrated a strong correlation with tumor necrosis at pathologic examination (R2 = 0.9657 and R2 = 0.9662 for quantitative EASLEuropean Association for the Study of the Liver and quantitative ADCapparent diffusion coefficient, respectively) and a strong intermethod agreement (R2 = 0.9585). Both methods showed a significantly lower discrepancy with pathologically measured necrosis (residual standard error [RSEresidual standard error] = 6.38 and 6.33 for quantitative EASLEuropean Association for the Study of the Liver and quantitative ADCapparent diffusion coefficient, respectively), when compared with non-3Dthree-dimensional techniques (RSEresidual standard error = 12.18 for visual assessment). Conclusion This radiologic-pathologic correlation study demonstrates the diagnostic accuracy of 3Dthree-dimensional quantitative MR imaging techniques in identifying pathologically measured tumor necrosis in HCChepatocellular carcinoma lesions treated with TACEtransarterial chemoembolization. © RSNA, 2014 Online supplemental material is available for this article. PMID:25028783

[A new method to extract time-frequency characteristics of hypertension pathological signal based on pseudo Wigner-Ville distribution].

PubMed

Zhang, Xun; Zhang, Miaomiao; Du, Panpan

2012-02-01

Hypertension, as one of diseases with the highest incidence in the world at present, is an important cause of stroke, coronary heart disease, renal insufficiency and other serious diseases. Based on pseudo Wigner-Ville distribution, this paper makes an analysis on the relevant pulse characteristics by measuring time range of the energy concentration circle. In view of the present situation, that is, about half of the high-normal blood pressure persons are likely to develop hypertension, we explored the pulse characteristics to find the pathological changes in subjects with prehypertension, in order to solve the problems that there are no obvious clinical significant features in prehypertension. The results showed that the duration of high energy circle in signal with hypertension pathological changes was shorter than the duration of healthy signal. Hence, healthy signal and hypertension pathological signal can be effectively distinguished by this method, and this provides a new basis to identify the lesion signal when blood pressure is in critical period.

Pathologic bone tissues in a Turkey vulture and a nonavian dinosaur: implications for interpreting endosteal bone and radial fibrolamellar bone in fossil dinosaurs.

PubMed

Chinsamy, Anusuya; Tumarkin-Deratzian, Allison

2009-09-01

We report on similar pathological bone microstructure in an extant turkey vulture (Cathartes aura) and a nonavian dinosaur from Transylvania. Both these individuals exhibit distinctive periosteal reactive bone deposition accompanied by endosteal bone deposits in the medullary cavity. Our findings have direct implications on the two novel bone tissues recently described among nonavian dinosaurs, radial fibrolamellar bone tissue and medullary bone tissue. On the basis of the observed morphology of the periosteal reactive bone in the turkey vulture and the Transylvanian dinosaur, we propose that the radial fibrolamellar bone tissues observed in mature dinosaurs may have had a pathological origin. Our analysis also shows that on the basis of origin, location, and morphology, pathologically derived endosteal bone tissue can be similar to medullary bone tissues described in nonavian dinosaurs. As such, we caution the interpretation of all endosteally derived bone tissue as homologous to avian medullary bone. (c) 2009 Wiley-Liss, Inc.

Homo floresiensis Contextualized: A Geometric Morphometric Comparative Analysis of Fossil and Pathological Human Samples

PubMed Central

Baab, Karen L.; McNulty, Kieran P.; Harvati, Katerina

2013-01-01

The origin of hominins found on the remote Indonesian island of Flores remains highly contentious. These specimens may represent a new hominin species, Homo floresiensis, descended from a local population of Homo erectus or from an earlier (pre-H. erectus) migration of a small-bodied and small-brained hominin out of Africa. Alternatively, some workers suggest that some or all of the specimens recovered from Liang Bua are pathological members of a small-bodied modern human population. Pathological conditions proposed to explain their documented anatomical features include microcephaly, myxoedematous endemic hypothyroidism (“cretinism”) and Laron syndrome (primary growth hormone insensitivity). This study evaluates evolutionary and pathological hypotheses through comparative analysis of cranial morphology. Geometric morphometric analyses of landmark data show that the sole Flores cranium (LB1) is clearly distinct from healthy modern humans and from those exhibiting hypothyroidism and Laron syndrome. Modern human microcephalic specimens converge, to some extent, on crania of extinct species of Homo. However in the features that distinguish these two groups, LB1 consistently groups with fossil hominins and is most similar to H. erectus. Our study provides further support for recognizing the Flores hominins as a distinct species, H. floresiensis, whose affinities lie with archaic Homo. PMID:23874886

Digital Imaging and Communications in Medicine Whole Slide Imaging Connectathon at Digital Pathology Association Pathology Visions 2017

PubMed Central

Clunie, David; Hosseinzadeh, Dan; Wintell, Mikael; De Mena, David; Lajara, Nieves; Garcia-Rojo, Marcial; Bueno, Gloria; Saligrama, Kiran; Stearrett, Aaron; Toomey, David; Abels, Esther; Apeldoorn, Frank Van; Langevin, Stephane; Nichols, Sean; Schmid, Joachim; Horchner, Uwe; Beckwith, Bruce; Parwani, Anil; Pantanowitz, Liron

2018-01-01

As digital pathology systems for clinical diagnostic work applications become mainstream, interoperability between these systems from different vendors becomes critical. For the first time, multiple digital pathology vendors have publicly revealed the use of the digital imaging and communications in medicine (DICOM) standard file format and network protocol to communicate between separate whole slide acquisition, storage, and viewing components. Note the use of DICOM for clinical diagnostic applications is still to be validated in the United States. The successful demonstration shows that the DICOM standard is fundamentally sound, though many lessons were learned. These lessons will be incorporated as incremental improvements in the standard, provide more detailed profiles to constrain variation for specific use cases, and offer educational material for implementers. Future Connectathon events will expand the scope to include more devices and vendors, as well as more ambitious use cases including laboratory information system integration and annotation for image analysis, as well as more geographic diversity. Users should request DICOM features in all purchases and contracts. It is anticipated that the growth of DICOM-compliant manufacturers will likely also ease DICOM for pathology becoming a recognized standard and as such the regulatory pathway for digital pathology products. PMID:29619278

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.

Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine.

PubMed

Ferro, Matteo; Lucarelli, Giuseppe; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Perruolo, Giuseppe; Marino, Ada; Cosimato, Vincenzo; Giorgio, Emilia; Tagliamonte, Virginia; Bottero, Danilo; De Cobelli, Ottavio; Terracciano, Daniela

2015-02-01

Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS). Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Latent class analysis of gambling subtypes and impulsive/compulsive associations: Time to rethink diagnostic boundaries for gambling disorder?

PubMed

Chamberlain, Samuel R; Stochl, Jan; Redden, Sarah A; Odlaug, Brian L; Grant, Jon E

2017-09-01

Gambling disorder has been associated with cognitive dysfunction and impaired quality of life. The current definition of non-pathological, problem, and pathological types of gambling is based on total symptom scores, which may overlook nuanced underlying presentations of gambling symptoms. The aims of the current study were (i) to identify subtypes of gambling in young adults, using latent class analysis, based on individual responses from the Structured Clinical Interview for Gambling Disorder (SCI-GD); and (ii) to explore relationships between these gambling subtypes, and clinical/cognitive measures. Total 582 non-treatment seeking young adults were recruited from two US cities, on the basis of gambling five or more times per year. Participants undertook clinical and neurocognitive assessment, including stop-signal, decision-making, and set-shifting tasks. Data from individual items of the Structured Clinical Interview for Gambling Disorder (SCI-GD) were entered into latent class analysis. Optimal number of classes representing gambling subtypes was identified using Bayesian Information Criterion and differences between them were explored using multivariate analysis of variance. Three subtypes of gambling were identified, termed recreational gamblers (60.2% of the sample; reference group), problem gamblers (29.2%), and pathological gamblers (10.5%). Common quality of life impairment, elevated Barratt Impulsivity scores, occurrence of mainstream mental disorders, having a first degree relative with an addiction, and impaired decision-making were evident in both problem and pathological gambling groups. The diagnostic item 'chasing losses' most discriminated recreational from problem gamblers, while endorsement of 'social, financial, or occupational losses due to gambling' most discriminated pathological gambling from both other groups. Significantly higher rates of impulse control disorders occurred in the pathological group, versus the problem group, who in turn showed significantly higher rates than the reference group. The pathological group also had higher set-shifting errors and nicotine consumption. Even problem gamblers who had a relatively low total SCI-PG scores (mean endorsement of two items) exhibited impaired quality of life, objective cognitive impairment on decision-making, and occurrence of other mental disorders that did not differ significantly from those seen in the pathological gamblers. Furthermore, problem/pathological gambling was associated with other impulse control disorders, but not increased alcohol use. Groups differed on quality of life when classified using the data-driven approach, but not when classified using DSM cut-offs. Thus, the current DSM-5 approach will fail to discriminate a significant fraction of patients with biologically plausible, functionally impairing illness, and may not be ideal in terms of diagnostic classification. Cognitive distortions related to 'chasing losses' represent a particularly important candidate treatment target for early intervention. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

A comparative study of the svm and k-nn machine learning algorithms for the diagnosis of respiratory pathologies using pulmonary acoustic signals

PubMed Central

2014-01-01

Background Pulmonary acoustic parameters extracted from recorded respiratory sounds provide valuable information for the detection of respiratory pathologies. The automated analysis of pulmonary acoustic signals can serve as a differential diagnosis tool for medical professionals, a learning tool for medical students, and a self-management tool for patients. In this context, we intend to evaluate and compare the performance of the support vector machine (SVM) and K-nearest neighbour (K-nn) classifiers in diagnosis respiratory pathologies using respiratory sounds from R.A.L.E database. Results The pulmonary acoustic signals used in this study were obtained from the R.A.L.E lung sound database. The pulmonary acoustic signals were manually categorised into three different groups, namely normal, airway obstruction pathology, and parenchymal pathology. The mel-frequency cepstral coefficient (MFCC) features were extracted from the pre-processed pulmonary acoustic signals. The MFCC features were analysed by one-way ANOVA and then fed separately into the SVM and K-nn classifiers. The performances of the classifiers were analysed using the confusion matrix technique. The statistical analysis of the MFCC features using one-way ANOVA showed that the extracted MFCC features are significantly different (p < 0.001). The classification accuracies of the SVM and K-nn classifiers were found to be 92.19% and 98.26%, respectively. Conclusion Although the data used to train and test the classifiers are limited, the classification accuracies found are satisfactory. The K-nn classifier was better than the SVM classifier for the discrimination of pulmonary acoustic signals from pathological and normal subjects obtained from the RALE database. PMID:24970564

A comparative study of the SVM and K-nn machine learning algorithms for the diagnosis of respiratory pathologies using pulmonary acoustic signals.

PubMed

Palaniappan, Rajkumar; Sundaraj, Kenneth; Sundaraj, Sebastian

2014-06-27

Pulmonary acoustic parameters extracted from recorded respiratory sounds provide valuable information for the detection of respiratory pathologies. The automated analysis of pulmonary acoustic signals can serve as a differential diagnosis tool for medical professionals, a learning tool for medical students, and a self-management tool for patients. In this context, we intend to evaluate and compare the performance of the support vector machine (SVM) and K-nearest neighbour (K-nn) classifiers in diagnosis respiratory pathologies using respiratory sounds from R.A.L.E database. The pulmonary acoustic signals used in this study were obtained from the R.A.L.E lung sound database. The pulmonary acoustic signals were manually categorised into three different groups, namely normal, airway obstruction pathology, and parenchymal pathology. The mel-frequency cepstral coefficient (MFCC) features were extracted from the pre-processed pulmonary acoustic signals. The MFCC features were analysed by one-way ANOVA and then fed separately into the SVM and K-nn classifiers. The performances of the classifiers were analysed using the confusion matrix technique. The statistical analysis of the MFCC features using one-way ANOVA showed that the extracted MFCC features are significantly different (p < 0.001). The classification accuracies of the SVM and K-nn classifiers were found to be 92.19% and 98.26%, respectively. Although the data used to train and test the classifiers are limited, the classification accuracies found are satisfactory. The K-nn classifier was better than the SVM classifier for the discrimination of pulmonary acoustic signals from pathological and normal subjects obtained from the RALE database.

Flexner 3.0—Democratization of Medical Knowledge for the 21st Century

PubMed Central

Krupinski, Elizabeth A.; Weinstein, John B.; Graham, Anna R.; Barker, Gail P.; Erps, Kristine A.; Holtrust, Angelette L.; Holcomb, Michael J.

2016-01-01

A medical school general pathology course has been reformatted into a K-12 general pathology course. This new course has been implemented at a series of 7 to 12 grade levels and the student outcomes compared. Typically, topics covered mirrored those in a medical school general pathology course serving as an introduction to the mechanisms of diseases. Assessment of student performance was based on their score on a multiple-choice final examination modeled after an examination given to medical students. Two Tucson area schools, in a charter school network, participated in the study. Statistical analysis of examination performances showed that there were no significant differences as a function of school (F = 0.258, P = .6128), with students at school A having an average test scores of 87.03 (standard deviation = 8.99) and school B 86.00 (standard deviation = 8.18; F = 0.258, P = .6128). Analysis of variance was also conducted on the test scores as a function of gender and class grade. There were no significant differences as a function of gender (F = 0.608, P = .4382), with females having an average score of 87.18 (standard deviation = 7.24) and males 85.61 (standard deviation = 9.85). There were also no significant differences as a function of grade level (F = 0.627, P = .6003), with 7th graders having an average of 85.10 (standard deviation = 8.90), 8th graders 86.00 (standard deviation = 9.95), 9th graders 89.67 (standard deviation = 5.52), and 12th graders 86.90 (standard deviation = 7.52). The results demonstrated that middle and upper school students performed equally well in K-12 general pathology. Student course evaluations showed that the course met the student’s expectations. One class voted K-12 general pathology their “elective course-of-the-year.” PMID:28725762

A retrospective analysis of oral and maxillofacial pathology in an Australian paediatric population.

PubMed

Ha, W N; Kelloway, E; Dost, F; Farah, C S

2014-06-01

The prevalence of oral and maxillofacial pathology has not previously been reported in the Australian paediatric population. This study aimed to audit a large pathology service to provide insight into the prevalence of oral and maxillofacial pathology. Written records of a major Australian oral pathology service were imported into an electronic database. Age, gender and histological diagnosis were assessed. Prevalence of histological diagnoses as a percentage of the major diagnostic categories and of the whole sample were calculated, as well as gender predilections and mean age of presentation of disease. A total of 1305 oral pathology specimens, collected from paediatric patients aged 16 and under were included in the analysis. The most common pathology was dental pathology (24.4%), followed by odontogenic cysts (18.5%) and mucosal pathology (17.0%). The most frequently encountered lesion was the dentigerous cyst (9.4%), followed by fibrous hyperplasia (8.3%), radicular cyst (5.2%) and chronic periapical granuloma (5.2%). In the paediatric population, dental pathology and specifically, the dentigerous cyst is the most common pathology type sent for histopathology, suggesting a high prevalence of pathology of dental origin occurring in Australian children. © 2014 Australian Dental Association.

Pathological mechanisms of left main stent failure.

PubMed

Mori, Hiroyoshi; Torii, Sho; Harari, Emanuel; Jinnouchi, Hiroyuki; Brauman, Ryan; Smith, Samantha; Kutys, Robert; Fowler, David; Romero, Maria; Virmani, Renu; Finn, Aloke V

2018-07-15

Despite the increasing use of left main (LM) percutaneous coronary intervention (LM-PCI), there have been no pathological studies devoted to understanding the causes of LM stent failure. We aimed to systematically determine the pathological mechanisms of LM stent failure. From the CVPath Stent registry, a total of 46 lesions were identified to have LM-PCI. Pathologic stent failure (PSF) was defined as stent thrombosis, restenosis and in-stent chronic total occlusion (CTO). Failed and patent LM stented lesions were pathologically assessed to determine predictors of PSF. Malapposition and uncovered struts were numerically greater in the LM ostium, body, and bifurcation while neointimal thickness was relatively greater in bifurcation and proximal circumflex. In this study cohort, half of the lesions (n = 23) showed PSF. Stent thrombosis (ST, n = 18) was the major mode of PSF followed by in-stent CTO (n = 4) and restenosis (n = 1). Failed lesions showed significantly greater prevalence of malapposition >20% of struts/section (65% vs. 13%, P < 0.01), stent struts crossing an ostial side branch >30% of the circumference (48% vs. 13%, P < 0.01) and uncovered struts >30% (57% vs. 18%, P = 0.03). In multivariate analysis, the prevalence of malapposition >20% was the strongest risk factor for PSF (Odds ratio 8.0, 95% confidence interval 1.8-45.4, P < 0.01) followed by struts crossing an ostial side branch >30% (Odds ratio 4.2, 95% confidence interval 0.8-24.7, P = 0.09). Our data demonstrate the main pathological predictors for LM stent failure are malapposition and struts crossing an ostial side branch and suggest that imaging-guided PCI may be important. Copyright © 2018 Elsevier B.V. All rights reserved.

Teamwork: a study of Australian and US student speech-language pathologists.

PubMed

Morrison, Susan C; Lincoln, Michelle A; Reed, Vicki A

2009-05-01

In the discipline of speech-language pathology little is known about the explicit and implicit team skills taught within university curricula. This study surveyed 281 speech-language pathology students to determine a baseline of their perceived ability to participate in interprofessional teams. The students were enrolled in programs in Australia and the USA and were surveyed about their perceptions of their attitudes, knowledge and skills in teamwork. MANCOVA analysis for main effects of age, university program and clinical experience showed that age was not significant, negating the perception that life experiences improve perceived team skills. Clinical experience was significant in that students with more clinical experience rated themselves more highly on their team abilities. Post Hoc analysis revealed that Australian students rated themselves higher than their US counterparts on their knowledge about working on teams, but lower on attitudes to teams; all students perceived that they had the skills to work on teams. These results provide insight about teamwork training components in current speech-language pathology curricula. Implications are discussed with reference to enhancing university training programs.

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.

[Differences between adolescents with pathological Internet use in inpatient and outpatient treatment].

PubMed

Wartberg, Lutz; Moll, Bettina; Baldus, Christiane; Thomsen, Monika; Thomasius, Rainer

2017-07-01

In epidemiological studies high prevalence estimates for pathological Internet use in adolescence were reported. There are only few studies published, reporting data of adolescents seeking treatment concerning their pathological Internet use. Currently, a comparison of patients in inpatient versus outpatient treatment is not available. We investigated 74 adolescents reporting pathological Internet use with standardized questionnaires concerning problematic Internet use, psychopathological symptoms and life satisfaction. Overall, 35 adolescents were treated in an outpatient and another 39 adolescents in an inpatient setting. A substantial portion in both groups showed comorbid mental health problems. There were no differences in the degree of problematic Internet use between the two groups. However, compared to adolescents in an outpatient setting, adolescents in inpatient treatment reported longer average Internet usage times, a lower life satisfaction as well as more anxiety/depressiveness and self-esteem problems. In a multivariate logistic regression analysis Internet usage time and life satisfaction were identified as statistically significant factors for the affiliation to one of the two treatment groups. The results of the present study could be useful as a further description of this group of patients and more general to develop interventions for adolescents reporting pathological Internet use.

Diagnostic efficacy of contrast-enhanced sonography by combined qualitative and quantitative analysis in breast lesions: a comparative study with magnetic resonance imaging.

PubMed

Wang, Lin; Du, Jing; Li, Feng-Hua; Fang, Hua; Hua, Jia; Wan, Cai-Feng

2013-10-01

The purpose of this study was to evaluate the diagnostic efficacy of contrast-enhanced sonography for differentiation of breast lesions by combined qualitative and quantitative analyses in comparison to magnetic resonance imaging (MRI). Fifty-six patients with American College of Radiology Breast Imaging Reporting and Data System category 3 to 5 breast lesions on conventional sonography were evaluated by contrast-enhanced sonography and MRI. A comparative analysis of diagnostic results between contrast-enhanced sonography and MRI was conducted in light of the pathologic findings. Pathologic analysis showed 26 benign and 30 malignant lesions. The predominant enhancement patterns of the benign lesions on contrast-enhanced sonography were homogeneous, centrifugal, and isoenhancement or hypoenhancement, whereas the patterns of the malignant lesions were mainly heterogeneous, centripetal, and hyperenhancement. The detection rates for perfusion defects and peripheral radial vessels in the malignant group were much higher than those in the benign group (P < .05). As to quantitative analysis, statistically significant differences were found in peak and time-to-peak values between the groups (P < .05). With pathologic findings as the reference standard, the sensitivity, specificity, and accuracy of contrast-enhanced sonography and MRI were 90.0%, 92.3%, 91.1% and 96.7%, 88.5%, and 92.9%, respectively. The two methods had a concordant rate of 87.5% (49 of 56), and the concordance test gave a value of κ = 0.75, indicating that there was high concordance in breast lesion assessment between the two diagnostic modalities. Contrast-enhanced sonography provided typical enhancement patterns and valuable quantitative parameters, which showed good agreement with MRI in diagnostic efficacy and may potentially improve characterization of breast lesions.

Predicting neo-adjuvant chemotherapy response and progression-free survival of locally advanced breast cancer using textural features of intratumoral heterogeneity on F-18 FDG PET/CT and diffusion-weighted MR imaging.

PubMed

Yoon, Hai-Jeon; Kim, Yemi; Chung, Jin; Kim, Bom Sahn

2018-03-30

Predicting response to neo-adjuvant chemotherapy (NAC) and survival in locally advanced breast cancer (LABC) is important. This study investigated the prognostic value of tumor heterogeneity evaluated with textural analysis through F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and diffusion-weighted imaging (DWI). We enrolled 83 patients with LABC who had completed NAC and curative surgery. Tumor texture indices from pretreatment FDG PET and DWI were extracted from histogram analysis and 7 different parent matrices: co-occurrence matrix, the voxel-alignment matrix, neighborhood intensity difference matrix, intensity size-zone matrix (ISZM), normalized gray-level co-occurrence matrix (NGLCM), neighboring gray-level dependence matrix (NGLDM), and texture spectrum matrix. The predictive values of textural features were tested regarding both pathologic NAC response and progression-free survival. Among 83 patients, 46 were pathologic responders, while 37 were nonresponders. The PET texture indices from 7 parent matrices, DWI texture indices from histogram, and 1 parent matrix (NGLCM) showed significant differences according to NAC response. On multivariable analysis, number nonuniformity of PET extracted from the NGLDM was an independent predictor of pathologic response (P = .009). During a median follow-up period of 17.3 months, 14 patients experienced recurrence. High-intensity zone emphasis (HIZE) and high-intensity short-zone emphasis (HISZE) from PET extracted from ISZM were significant textural predictors (P = .011 and P = .033). On Cox regression analysis, only HIZE was a significant predictor of recurrence (P = .027), while HISZE showed borderline significance (P = .107). Tumor texture indices are useful for NAC response prediction in LABC. Moreover, PET texture indices can help to predict disease recurrence. © 2018 Wiley Periodicals, Inc.

MR spectroscopy of the fetal brain: is it possible without sedation?

PubMed

Berger-Kulemann, V; Brugger, P C; Pugash, D; Krssak, M; Weber, M; Wielandner, A; Prayer, D

2013-02-01

The quality of spectroscopic studies may be limited because of unrestricted fetal movement. Sedation is recommended to avoid motion artefacts. However, sedation involves side effects. The aim of this study was to assess the feasibility and quality of brain (1)H-MR spectroscopy in unsedated fetuses and to evaluate whether quality is dependent on the type of spectra, fetal presentation, GA, and/or fetal pathology. Seventy-five single-voxel spectroscopic studies of the fetal brain, performed at gestational weeks 19-38 at 1.5T, were evaluated retrospectively. A PRESS (TE = 144 or 35 ms) was used. Fetal presentation, GA, and kind of pathology were recorded. The quality of the spectra was assessed by reviewing the spectral appearance (line width, signal-to-noise) of the creatine resonance obtained relative to concentrations (ratios-to-creatine) of choline, myo-inositol, and NAA. Of 75 studies, 50 (66.6%) were rated as readable: short TE = 17/50 (34%), long TE = 33/50 (66%), cephalic presentation in 36/50 (72%) studies, breech in 10/50 (20%) studies, and "other" presentation in 4/50 (8%) studies (mean GA, 31.0 weeks). Twenty-eight of 50 fetuses (56%) showed normal development (short TE = 12/28, long TE = 16/28), and 22/50 (44%) showed pathology. Of the 75 studies, 25 (33.3%) were not readable: short TE = 14/25 (56%), long TE = 11/25 (44%), cephalic presentation in 20/25 (80%) studies, breech in 4/25 (16%) studies, and other presentation in 1 study (4%) (mean GA, 30.1 week). Thirteen of 25 fetuses (52%) showed normal development; 12/25 (48%) showed pathology. Statistical analysis revealed no impact of the different parameters on the quality of spectra. Single-voxel spectroscopy can be performed in approximately two-thirds of unsedated fetuses, regardless of the type of spectra, fetal presentation, GA, and pathology.

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.

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.

Eating disorder pathology in elite adolescent athletes.

PubMed

Giel, Katrin Elisabeth; Hermann-Werner, Anne; Mayer, Jochen; Diehl, Katharina; Schneider, Sven; Thiel, Ansgar; Zipfel, Stephan

2016-06-01

We aimed to investigate eating disorder pathology in German elite adolescent athletes. Evidence suggests that eating disorder pathology is more common in adult elite sports, especially in female athletes and in sports emphasizing leanness. There is a scarcity of studies in elite adolescent athletes who are in a vulnerable developmental stage and are affected by general as well as sport-specific risk factors. Our data was derived from the German Young Olympic Athletes' Lifestyle and Health Management Study (GOAL) which conducted a survey in 1138 elite adolescent athletes. In this sample, we assessed body weight, weight control behavior, body acceptance and screened overall for core symptoms of eating disorders, depression and anxiety. We performed a tree analysis to identify high risk groups for eating disorder pathology. High risk groups comprised (a) athletes competing in weight dependent sports, and among athletes competing in disciplines other than weight dependent sports (b) athletes who are high on negative affectivity, (c) female athletes and (d) male athletes competing in endurance, technical or power sports. Athletes competing in weight dependent disciplines reported wide spread use of compensatory behaviors to influence body weight. Athletes reporting eating disorder pathology showed higher levels of depression and anxiety than athletes without eating disorder pathology. Increased psychosocial burden in athletes with eating disorder pathology suggests that eating disorder symptoms should not be accepted as an unproblematic and functional part of elite sports. The prevention and management of eating disorder pathology is especially important in weight dependent sports. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:553-562). © 2016 Wiley Periodicals, Inc.

A method for normalizing pathology images to improve feature extraction for quantitative pathology

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

Tam, Allison; Barker, Jocelyn; Rubin, Daniel

Purpose: With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. Methods: To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology imagesmore » by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. Results: The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. Conclusions: ICHE may be a useful preprocessing step a digital pathology image processing pipeline.« less

[A study of the phenomenon of voice intonation: analysis, usage and diagnosis].

PubMed

Kazanecka, E; Pawłowski, Z; Zółtowski, M

1997-01-01

The aim of this work was to study the average rise time (RT) and average flow rate (MRT) in utterance. Data were collected from 48 singers and 44 patients. The group of patients included cases of modulus vocale, polypus laryngis, paresis bilateralis, hemiparesis, and CA laryngis. Various characteristics of utterance were recorded synchronously: the frequency and intensity of the fundamental laryngeal tone were measured with a laryngophone, a microphone was used to monitor acoustic radiation from the mouth, and a pneumotrachometer was applied for the measurement of flow rate. The data were stored and analysed with the use of a computer. Results show that the analysis carried out in the study describes the distinctive characteristics of normal and pathologic utterance. The main findings are as follows: a) rise time (RT) decreases with increasing loudness and pitch of the sound and is also shorter in staccato than inlegato sounds; b) during the initial transient of staccato sounds, the average flow rate in the glottis increases with intensity and pitch of the sound; c) pre-fonation time (TPP) and air volume do not differentiate normal and pathologic utterance; d) in cases of voice pathology, the analysis of utterance described in this study can be used for the evaluation of therapy and rehabilitation.

Recurrent hepatocellular carcinoma after liver transplant: identifying the high-risk patient

PubMed Central

Nissen, Nicholas N; Menon, Vijay; Bresee, Catherine; Tran, Tram T; Annamalai, Alagappan; Poordad, Fred; Fair, Jeffrey H; Klein, Andrew S; Boland, Brendan; Colquhoun, Steven D

2011-01-01

Background Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is rarely curable. However, in view of the advent of new treatments, it is critical that patients at high risk for recurrence are identified. Methods Patients undergoing LT for HCC at a single centre between 2002 and 2010 were reviewed and data on clinical parameters and explant pathology were analysed to determine factors associated with HCC recurrence. All necrotic and viable tumour nodules were included in explant staging. All patients underwent LT according to the United Network for Organ Sharing (UNOS) Model for End-stage Liver Disease (MELD) tumour exception policies. Results Liver transplantation was performed in 122 patients with HCC during this period. Rates of recurrence-free survival in the entire cohort at 1 year and 3 years were 95% and 89%, respectively. Thirteen patients developed HCC recurrence at a median of 14 months post-LT. In univariate analysis the factors associated with HCC recurrence were bilobar tumours, vascular invasion, and stage exceeding either Milan or University of California San Francisco (UCSF) Criteria. Multivariate analysis showed pathology outside UCSF Criteria was the major predictor of recurrence; when pathology outside UCSF Criteria was found in combination with vascular invasion, the predicted 3-year recurrence-free survival was only 26%. Conclusions Explant pathology can be used to predict the risk for recurrent HCC after LT, which may allow for improved adjuvant and management strategies. PMID:21843263

Bibliometric investigation on preventive medicine in North Korea: a coauthor and keyword network analysis.

PubMed

Jung, Minsoo

2013-01-01

This study examined the 2 preventive medicine journals in North Korea by using coauthor and keyword network analysis on the basis of medical informatics and bibliometrics. Used were the Journal of Chosun Medicine (JCM) and the Journal of Preventive Medicine (JPM) (from the first volume of 1997 to the fourth volume of 2006) as data. Extracted were 1734 coauthors from 1104 articles and 1567 coauthors from 1172 articles, respectively. Huge single components were extracted in the coauthor analysis, which indicated a tendency toward structuralization. However, the 2 journals differed in that JPM showed a relative tendency toward specialization, whereas JCM showed one toward generalization. Seventeen and 33 keywords were extracted from each journal in the keyword analysis; JCM mainly concerned pathological research, whereas JPM mainly concerned virus and basic medicine studies that were based on infection and immunity. In contrast to South Korea, North Korea has developed Juche medicine, which came from self-reliance ideology and gratuitous medical service. According to the present study, their ideology was embodied by the discovery of bacteria, study on immune system, and emphasis on pathology, on the basis of experimental epidemiology. However, insufficient research has been conducted thus far on population health and its related determinants.

Identifying biomarkers of papillary renal cell carcinoma associated with pathological stage by weighted gene co-expression network analysis.

PubMed

He, Zhongshi; Sun, Min; Ke, Yuan; Lin, Rongjie; Xiao, Youde; Zhou, Shuliang; Zhao, Hong; Wang, Yan; Zhou, Fuxiang; Zhou, Yunfeng

2017-04-25

Although papillary renal cell carcinoma (PRCC) accounts for 10%-15% of renal cell carcinoma (RCC), no predictive molecular biomarker is currently applicable to guiding disease stage of PRCC patients. The mRNASeq data of PRCC and adjacent normal tissue in The Cancer Genome Atlas was analyzed to identify 1148 differentially expressed genes, on which weighted gene co-expression network analysis was performed. Then 11 co-expressed gene modules were identified. The highest association was found between blue module and pathological stage (r = 0.45) by Pearson's correlation analysis. Functional enrichment analysis revealed that biological processes of blue module focused on nuclear division, cell cycle phase, and spindle (all P < 1e-10). All 40 hub genes in blue module can distinguish localized (pathological stage I, II) from non-localized (pathological stage III, IV) PRCC (P < 0.01). A good molecular biomarker for pathological stage of RCC must be a prognostic gene in clinical practice. Survival analysis was performed to reversely validate if hub genes were associated with pathological stage. Survival analysis unveiled that all hub genes were associated with patient prognosis (P < 0.01).The validation cohort GSE2748 verified that 30 hub genes can differentiate localized from non-localized PRCC (P < 0.01), and 18 hub genes are prognosis-associated (P < 0.01).ROC curve indicated that the 17 hub genes exhibited excellent diagnostic efficiency for localized and non-localized PRCC (AUC > 0.7). These hub genes may serve as a biomarker and help to distinguish different pathological stages for PRCC patients.

Mapping thalamocortical network pathology in temporal lobe epilepsy.

PubMed

Bernhardt, Boris C; Bernasconi, Neda; Kim, Hosung; Bernasconi, Andrea

2012-01-10

Although experimental work has provided evidence that the thalamus is a crucial relay structure in temporal lobe epilepsy (TLE), the relation of the thalamus to neocortical pathology remains unclear. To assess thalamocortical network pathology in TLE, we mapped pointwise patterns of thalamic atrophy and statistically related them to neocortical thinning. We studied cross-sectionally 36 patients with drug-resistant TLE and 19 age- and sex-matched healthy control subjects using high-resolution MRI. To localize thalamic pathology, we converted manual labels into surface meshes using the spherical harmonic description and calculated local deformations relative to a template. In addition, we measured cortical thickness by means of the constrained Laplacian anatomic segmentation using proximity algorithm. Compared with control subjects, patients with TLE showed ipsilateral thalamic atrophy that was located along the medial surface, encompassing anterior, medial, and posterior divisions. Unbiased analysis correlating the degree of medial thalamic atrophy with cortical thickness measurements mapped bilateral frontocentral, lateral temporal, and mesiotemporal cortices. These areas overlapped with those of cortical thinning found when patients were compared with control subjects. Thalamic atrophy intensified with a longer duration of epilepsy and was more severe in patients with a history of febrile convulsions. The degree and distribution of thalamic pathology relates to the topography and extent of neocortical atrophy, lending support to the concept that the thalamus is an important hub in the pathologic network of TLE.

mNos2 deletion and human NOS2 replacement in Alzheimer disease models.

PubMed

Colton, Carol A; Wilson, Joan G; Everhart, Angela; Wilcock, Donna M; Puoliväli, Jukka; Heikkinen, Taneli; Oksman, Juho; Jääskeläinen, Olli; Lehtimäki, Kimmo; Laitinen, Teemu; Vartiainen, Nina; Vitek, Michael P

2014-08-01

Understanding the pathophysiologic mechanisms underlying Alzheimer disease relies on knowledge of disease onset and the sequence of development of brain pathologies. We present a comprehensive analysis of early and progressive changes in a mouse model that demonstrates a full spectrum of characteristic Alzheimer disease-like pathologies. This model demonstrates an altered immune redox state reminiscent of the human disease and capitalizes on data indicating critical differences between human and mouse immune responses, particularly in nitric oxide levels produced by immune activation of the NOS2 gene. Using the APPSwDI(+)/(+)mNos2(-/-) (CVN-AD) mouse strain, we show a sequence of pathologic events leading to neurodegeneration,which include pathologically hyperphosphorylated tau in the perforant pathway at 6 weeks of age progressing to insoluble tau, early appearance of β-amyloid peptides in perivascular deposits around blood vessels in brain regions known to be vulnerable to Alzheimer disease, and progression to damage and overt loss in select vulnerable neuronal populations in these regions. The role of species differences between hNOS2 and mNos2 was supported by generating mice in which the human NOS2 gene replaced mNos2. When crossed with CVN-AD mice, pathologic characteristics of this new strain (APPSwDI(+)/(-)/HuNOS2(tg+)/(+)/mNos2(-/-)) mimicked the pathologic phenotypes found in the CVN-AD strain.

Empirical evaluation of the inter-relationship of articular elements involved in the pathoanatomy of knee osteoarthritis using magnetic resonance imaging.

PubMed

Meredith, Dennis S; Losina, Elena; Neumann, Gesa; Yoshioka, Hiroshi; Lang, Philipp K; Katz, Jeffrey N

2009-10-29

In this cross-sectional study, we conducted a comprehensive assessment of all articular elements that could be measured using knee MRI. We assessed the association of pathological change in multiple articular structures involved in the pathoanatomy of osteoarthritis. Knee MRI scans from patients over 45 years old were assessed using a semi-quantitative knee MRI assessment form. The form included six distinct elements: cartilage, bone marrow lesions, osteophytes, subchondral sclerosis, joint effusion and synovitis. Each type of pathology was graded using an ordinal scale with a value of zero indicating no pathology and higher values indicating increasingly severe levels of pathology. The principal dependent variable for comparison was the mean cartilage disease score (CDS), which captured the aggregate extent of involvement of articular cartilage. The distribution of CDS was compared to the individual and cumulative distributions of each articular element using the Chi-squared test. The correlations between pathological change in the various articular structures were assessed in a Spearman correlation table. Data from 140 patients were available for review. The cohort had a median age of 61 years (range 45-89) and was 61% female. The cohort included a wide spectrum of OA severity. Our analysis showed a statistically significant trend towards pathological change involving more articular elements as CDS worsened (p-value for trend < 0.0001). Comparison of CDS to change in the severity of pathology of individual articular elements showed statistically significant trends towards more severe pathology as CDS worsened for osteophytes (p-value for trend < 0.0001), bone marrow lesions (p = 0.0003), and subchondral sclerosis (p = 0.009), but not joint effusion or synovitis. There was a moderate correlation between cartilage damage, osteophytes and BMLs as well as a moderate correlation between joint effusion and synovitis. However, cartilage damage and osteophytes were only weakly associated with synovitis or joint effusion. Our results support an inter-relationship of multiple articular elements in the pathoanatomy of knee OA. Prospective studies of OA pathogenesis in humans are needed to correlate these findings to clinically relevant outcomes such as pain and function.

Attachment Style and Internet Addiction: An Online Survey

PubMed Central

Schott, Markus; Decker, Oliver; Sindelar, Brigitte

2017-01-01

Background One of the clinically relevant problems of Internet use is the phenomenon of Internet addiction. Considering the fact that there is ample evidence for the relationship between attachment style and substance abuse, it stands to reason that attachment theory can also make an important contribution to the understanding of the pathogenesis of Internet addiction. Objective The aim of this study was to examine people’s tendency toward pathological Internet usage in relation to their attachment style. Methods An online survey was conducted. Sociodemographic data, attachment style (Bielefeld questionnaire partnership expectations), symptoms of Internet addiction (scale for online addiction for adults), used Web-based services, and online relationship motives (Cyber Relationship Motive Scale, CRMS-D) were assessed. In order to confirm the findings, a study using the Rorschach test was also conducted. Results In total, 245 subjects were recruited. Participants with insecure attachment style showed a higher tendency to pathological Internet usage compared with securely attached participants. An ambivalent attachment style was particularly associated with pathological Internet usage. Escapist and social-compensatory motives played an important role for insecurely attached subjects. However, there were no significant effects with respect to Web-based services and apps used. Results of the analysis of the Rorschach protocol with 16 subjects corroborated these results. Users with pathological Internet use frequently showed signs of infantile relationship structures in the context of social groups. This refers to the results of the Web-based survey, in which interpersonal relationships were the result of an insecure attachment style. Conclusions Pathological Internet use was a function of insecure attachment and limited interpersonal relationships. PMID:28526662

Odontomas and Supernumerary Teeth: Is There a Common Origin?

PubMed Central

Pippi, Roberto

2014-01-01

The aim of the present work is to analyze all scientific evidence to verify whether similarities supporting a unified explanation for odontomas and supernumerary teeth exist. A literature search was first conducted for epidemiologic studies indexed by PubMed, to verify their worldwide incidence. The analysis of the literature data shows some interesting similarities between odontomas and supernumerary teeth concerning their topographic distribution and pathologic manifestations. There is also some indication of common genetic and immuno-histochemical factors. Although from a nosological point of view, odontomas and supernumeraries are classified as distinct entities, they seem to be the expression of the same pathologic process, either malformative or hamartomatous. PMID:25419174

Histogram analysis of apparent diffusion coefficient maps for assessing thymic epithelial tumours: correlation with world health organization classification and clinical staging.

PubMed

Kong, Ling-Yan; Zhang, Wei; Zhou, Yue; Xu, Hai; Shi, Hai-Bin; Feng, Qing; Xu, Xiao-Quan; Yu, Tong-Fu

2018-04-01

To investigate the value of apparent diffusion coefficients (ADCs) histogram analysis for assessing World Health Organization (WHO) pathological classification and Masaoka clinical stages of thymic epithelial tumours. 37 patients with histologically confirmed thymic epithelial tumours were enrolled. ADC measurements were performed using hot-spot ROI (ADC HS-ROI ) and histogram-based approach. ADC histogram parameters included mean ADC (ADC mean ), median ADC (ADC median ), 10 and 90 percentile of ADC (ADC 10 and ADC 90 ), kurtosis and skewness. One-way ANOVA, independent-sample t-test, and receiver operating characteristic were used for statistical analyses. There were significant differences in ADC mean , ADC median , ADC 10 , ADC 90 and ADC HS-ROI among low-risk thymoma (type A, AB, B1; n = 14), high-risk thymoma (type B2, B3; n = 9) and thymic carcinoma (type C, n = 14) groups (all p-values <0.05), while no significant difference in skewness (p = 0.181) and kurtosis (p = 0.088). ADC 10 showed best differentiating ability (cut-off value, ≤0.689 × 10 -3 mm 2 s -1 ; AUC, 0.957; sensitivity, 95.65%; specificity, 92.86%) for discriminating low-risk thymoma from high-risk thymoma and thymic carcinoma. Advanced Masaoka stages (Stage III and IV; n = 24) tumours showed significant lower ADC parameters and higher kurtosis than early Masaoka stage (Stage I and II; n = 13) tumours (all p-values <0.05), while no significant difference on skewness (p = 0.063). ADC 10 showed best differentiating ability (cut-off value, ≤0.689 × 10 -3 mm 2 s -1 ; AUC, 0.913; sensitivity, 91.30%; specificity, 85.71%) for discriminating advanced and early Masaoka stage epithelial tumours. ADC histogram analysis may assist in assessing the WHO pathological classification and Masaoka clinical stages of thymic epithelial tumours. Advances in knowledge: 1. ADC histogram analysis could help to assess WHO pathological classification of thymic epithelial tumours. 2. ADC histogram analysis could help to evaluate Masaoka clinical stages of thymic epithelial tumours. 3. ADC 10 might be a promising imaging biomarker for assessing and characterizing thymic epithelial tumours.

Alterations in the Emotional Regulation Process in Gambling Addiction: The Role of Anger and Alexithymia.

PubMed

Maniaci, Giuseppe; Picone, Francesca; van Holst, Ruth J; Bolloni, Corinna; Scardina, Silvana; Cannizzaro, Carla

2017-06-01

This study aims at the assessment of alexithymia and anger levels in 100 treatment-seeking pathological gamblers compared with controls, who were matched for age, gender and education. Furthermore a positive correlation between alexithymia, anger and severity of gambling disorder and a relationship between gambling behaviour and anger after controlling for alexithymia, are investigated. Finally the role that gender plays in anger in pathological gamblers was also evaluated. Psychological assessment includes the South Oaks Gambling Screen, State-Trait Anger Expression Inventory-2 and the twenty-item Toronto Alexithymia Scale. Statistical analysis of the results shows a higher level of anger in pathological gamblers than in controls, together with alterations in emotional processing. Severity of gambling behaviour positively correlates with alexithymia scores, state-anger and trait-anger. Moreover, a significant contribution of anger in predicting gambling behaviour was suggested after controlling for alexithymia. In conclusion, anger and alexithymia must be regarded as relevant components of the assessment of pathological gamblers, in order to select the best therapeutical strategies to prevent self-defeating behaviours and to reduce drop-out from treatments.

The preanalytic phase in veterinary clinical pathology.

PubMed

Braun, Jean-Pierre; Bourgès-Abella, Nathalie; Geffré, Anne; Concordet, Didier; Trumel, Cathy

2015-03-01

This article presents the general causes of preanalytic variability with a few examples showing specialists and practitioners that special and improved care should be given to this too often neglected phase. The preanalytic phase of clinical pathology includes all the steps from specimen collection to analysis. It is the phase where most laboratory errors occur in human, and probably also in veterinary clinical pathology. Numerous causes may affect the validity of the results, including technical factors, such as the choice of anticoagulant, the blood vessel sampled, and the duration and conditions of specimen handling. While the latter factors can be defined, influence of biologic and physiologic factors such as feeding and fasting, stress, and biologic and endocrine rhythms can often not be controlled. Nevertheless, as many factors as possible should at least be documented. The importance of the preanalytic phase is often not given the necessary attention, although the validity of the results and consequent clinical decision making and medical management of animal patients would likely be improved if the quality of specimens submitted to the laboratory was optimized. © 2014 American Society for Veterinary Clinical Pathology.

The prognostic significance of the 2014 International Society of Urological Pathology (ISUP) grading system for prostate cancer.

PubMed

Samaratunga, Hemamali; Delahunt, Brett; Gianduzzo, Troy; Coughlin, Geoff; Duffy, David; LeFevre, Ian; Johannsen, Shulammite; Egevad, Lars; Yaxley, John

2015-10-01

The 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system was further amended in 2014 with the establishment of grade groupings (ISUP grading). This study examined the predictive value of ISUP grading, comparing results with recognised prognostic parameters.Of 3700 men undergoing radical prostatectomy (RP) reported at Aquesta Pathology between 2008 and 2013, 2079 also had a positive needle biopsy available for review. We examined the association between needle biopsy 2014 ISUP grade and 2005 modified Gleason score, tumour volume, pathological stage of the subsequent RP tumour, as well as biochemical recurrence-free survival (BRFS). The median age was 62 (range 32-79 years). Median serum prostate specific antigen was 5.9 (range 0.4-69 ng/mL). For needle biopsies, 280 (13.5%), 1031 (49.6%), 366 (17.6%), 77 (3.7%) and 325 (15.6%) were 2014 ISUP grades 1-5, respectively. Needle biopsy 2014 ISUP grade showed a significant association with RP tumour volume (p < 0.001), TNM pT and N stage (p < 0.001) and BRFS (p < 0.001). Multivariate analysis using Cox proportional hazards regression model showed serum prostate specific antigen (PSA) at the time of diagnosis and ISUP grade >2 to be significantly associated with BRFS.This study provides evidence of the prognostic significance of ISUP grading for thin core needle biopsy of prostate.

The American Society for Clinical Pathology resident in-service examination: does resident performance provide insight into the effectiveness of clinical pathology education?

PubMed

McKenna, Barbara J

2007-06-01

The resident in-service examination in pathology is an in-training exercise that is taken by virtually all pathology residents in the United States as well as by some participants in Canada, Ireland, and Lebanon. Although all of the anatomic pathology topics in the examination, with only one exception-forensic pathology, show significant improvement in scores over the 4 years of residency training, three areas of clinical pathology training (laboratory administration, clinical chemistry, and microbiology) show significantly lower improvement in performance over the years of residency training. By contrast, transfusion medicine, hematopathology and the special topics section of the examination all demonstrate improved performance by residents over time. While the reason behind these differences must remain speculative at this time, these findings suggest that measures to improve effectiveness in clinical pathology training might be suggested by examining the differences between residency training practices between higher and lower performing areas of clinical pathology.

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.

Acquiring, recording, and analyzing pathology data from experimental mice: an overview.

PubMed

Scudamore, Cheryl L

2014-03-21

Pathology is often underutilized as an end point in mouse studies in academic research because of a lack of experience and expertise. The use of traditional pathology techniques including necropsy and microscopic analysis can be useful in identifying the basic processes underlying a phenotype and facilitating comparison with equivalent human diseases. This overview aims to provide a guide and reference to the acquisition, recording, and analysis of high-quality pathology data from experimental mice in an academic research setting. Copyright © 2014 John Wiley & Sons, Inc.

Using Networks To Understand Medical Data: The Case of Class III Malocclusions

PubMed Central

Scala, Antonio; Auconi, Pietro; Scazzocchio, Marco; Caldarelli, Guido; McNamara, James A.; Franchi, Lorenzo

2012-01-01

A system of elements that interact or regulate each other can be represented by a mathematical object called a network. While network analysis has been successfully applied to high-throughput biological systems, less has been done regarding their application in more applied fields of medicine; here we show an application based on standard medical diagnostic data. We apply network analysis to Class III malocclusion, one of the most difficult to understand and treat orofacial anomaly. We hypothesize that different interactions of the skeletal components can contribute to pathological disequilibrium; in order to test this hypothesis, we apply network analysis to 532 Class III young female patients. The topology of the Class III malocclusion obtained by network analysis shows a strong co-occurrence of abnormal skeletal features. The pattern of these occurrences influences the vertical and horizontal balance of disharmony in skeletal form and position. Patients with more unbalanced orthodontic phenotypes show preponderance of the pathological skeletal nodes and minor relevance of adaptive dentoalveolar equilibrating nodes. Furthermore, by applying Power Graphs analysis we identify some functional modules among orthodontic nodes. These modules correspond to groups of tightly inter-related features and presumably constitute the key regulators of plasticity and the sites of unbalance of the growing dentofacial Class III system. The data of the present study show that, in their most basic abstraction level, the orofacial characteristics can be represented as graphs using nodes to represent orthodontic characteristics, and edges to represent their various types of interactions. The applications of this mathematical model could improve the interpretation of the quantitative, patient-specific information, and help to better targeting therapy. Last but not least, the methodology we have applied in analyzing orthodontic features can be applied easily to other fields of the medical science. PMID:23028552

GPCALMA: A Tool For Mammography With A GRID-Connected Distributed Database

NASA Astrophysics Data System (ADS)

Bottigli, U.; Cerello, P.; Cheran, S.; Delogu, P.; Fantacci, M. E.; Fauci, F.; Golosio, B.; Lauria, A.; Lopez Torres, E.; Magro, R.; Masala, G. L.; Oliva, P.; Palmiero, R.; Raso, G.; Retico, A.; Stumbo, S.; Tangaro, S.

2003-09-01

The GPCALMA (Grid Platform for Computer Assisted Library for MAmmography) collaboration involves several departments of physics, INFN (National Institute of Nuclear Physics) sections, and italian hospitals. The aim of this collaboration is developing a tool that can help radiologists in early detection of breast cancer. GPCALMA has built a large distributed database of digitised mammographic images (about 5500 images corresponding to 1650 patients) and developed a CAD (Computer Aided Detection) software which is integrated in a station that can also be used to acquire new images, as archive and to perform statistical analysis. The images (18×24 cm2, digitised by a CCD linear scanner with a 85 μm pitch and 4096 gray levels) are completely described: pathological ones have a consistent characterization with radiologist's diagnosis and histological data, non pathological ones correspond to patients with a follow up at least three years. The distributed database is realized throught the connection of all the hospitals and research centers in GRID tecnology. In each hospital local patients digital images are stored in the local database. Using GRID connection, GPCALMA will allow each node to work on distributed database data as well as local database data. Using its database the GPCALMA tools perform several analysis. A texture analysis, i.e. an automated classification on adipose, dense or glandular texture, can be provided by the system. GPCALMA software also allows classification of pathological features, in particular massive lesions (both opacities and spiculated lesions) analysis and microcalcification clusters analysis. The detection of pathological features is made using neural network software that provides a selection of areas showing a given "suspicion level" of lesion occurrence. The performance of the GPCALMA system will be presented in terms of the ROC (Receiver Operating Characteristic) curves. The results of GPCALMA system as "second reader" will also be presented.

Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner

PubMed Central

Stauffer, Brian L.; Dockstader, Karen; Russell, Gloria; Hijmans, Jamie; Walker, Lisa; Cecil, Mackenzie; Demos-Davies, Kimberly; Medway, Allen; McKinsey, Timothy A.; Sucharov, Carmen C.

2015-01-01

YY1 can activate or repress transcription of various genes. In cardiac myocytes in culture YY1 has been shown to regulate expression of several genes involved in myocyte pathology. YY1 can also acutely protect the heart against detrimental changes in gene expression. In this study we show that cardiac over-expression of YY1 induces pathologic cardiac hypertrophy in male mice, measured by changes in gene expression and lower ejection fraction/fractional shortening. In contrast, female animals are protected against pathologic gene expression changes and cardiac dysfunction. Furthermore, we show that YY1 regulates, in a sex-specific manner, the expression of mammalian enable (Mena), a factor that regulates cytoskeletal actin dynamics and whose expression is increased in several models of cardiac pathology, and that Mena expression in humans with heart failure is sex-dependent. Finally, we show that sex differences in YY1 expression are also observed in human heart failure. In summary, this is the first work to show that YY1 has a sex-specific effect in the regulation of cardiac pathology. PMID:25935483

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.

Modulation of microrna in two genetically disparate chicken lines showing different necrotic enteritis disease susceptibility

USDA-ARS?s Scientific Manuscript database

Necrotic enteritis (NE) is a re-emerging disease as a result of an increased restriction on the use of antibiotics in poultry. However, the molecular mechanisms underlying the pathology of NE are unclear. Therefore, we carried out small RNA transcriptome analysis in an experimentally induced NE m...

qpure: A Tool to Estimate Tumor Cellularity from Genome-Wide Single-Nucleotide Polymorphism Profiles

PubMed Central

Song, Sarah; Nones, Katia; Miller, David; Harliwong, Ivon; Kassahn, Karin S.; Pinese, Mark; Pajic, Marina; Gill, Anthony J.; Johns, Amber L.; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Newell, Felicity; Cowley, Mark J.; Wu, Jianmin; Wilson, Peter; Fink, Lynn; Biankin, Andrew V.; Waddell, Nic; Grimmond, Sean M.; Pearson, John V.

2012-01-01

Tumour cellularity, the relative proportion of tumour and normal cells in a sample, affects the sensitivity of mutation detection, copy number analysis, cancer gene expression and methylation profiling. Tumour cellularity is traditionally estimated by pathological review of sectioned specimens; however this method is both subjective and prone to error due to heterogeneity within lesions and cellularity differences between the sample viewed during pathological review and tissue used for research purposes. In this paper we describe a statistical model to estimate tumour cellularity from SNP array profiles of paired tumour and normal samples using shifts in SNP allele frequency at regions of loss of heterozygosity (LOH) in the tumour. We also provide qpure, a software implementation of the method. Our experiments showed that there is a medium correlation 0.42 (-value = 0.0001) between tumor cellularity estimated by qpure and pathology review. Interestingly there is a high correlation 0.87 (-value 2.2e-16) between cellularity estimates by qpure and deep Ion Torrent sequencing of known somatic KRAS mutations; and a weaker correlation 0.32 (-value = 0.004) between IonTorrent sequencing and pathology review. This suggests that qpure may be a more accurate predictor of tumour cellularity than pathology review. qpure can be downloaded from https://sourceforge.net/projects/qpure/. PMID:23049875

Factors associated with resistance to dementia despite high Alzheimer disease pathology.

PubMed

Erten-Lyons, D; Woltjer, R L; Dodge, H; Nixon, R; Vorobik, R; Calvert, J F; Leahy, M; Montine, T; Kaye, J

2009-01-27

Autopsy series have shown that some elderly people remain with normal cognitive function during life despite having high burdens of pathologic lesions associated with Alzheimer disease (AD) at death. Understanding why these individuals show no cognitive decline, despite high AD pathologic burdens, may be key to discovery of neuroprotective mechanisms. A total of 36 subjects who on autopsy had Braak stage V or VI and moderate or frequent neuritic plaque scores based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) standards were included. Twelve had normal cognitive function and 24 a diagnosis of AD before death. Demographic characteristics, clinical and pathologic data, as well as antemortem brain volumes were compared between the groups. In multiple regression analysis, antemortem hippocampal and total brain volumes were significantly larger in the group with normal cognitive function after adjusting for gender, age at MRI, time from MRI to death, Braak stage, CERAD neuritic plaque score, and overall presence of vascular disease. Larger brain and hippocampal volumes were associated with preserved cognitive function during life despite a high burden of Alzheimer disease (AD) pathologic lesions at death. A better understanding of processes that lead to preservation of brain volume may provide important clues for the discovery of mechanisms that protect the elderly from AD.

[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.

Egocentric social network analysis of pathological gambling.

PubMed

Meisel, Matthew K; Clifton, Allan D; Mackillop, James; Miller, Joshua D; Campbell, W Keith; Goodie, Adam S

2013-03-01

To apply social network analysis (SNA) to investigate whether frequency and severity of gambling problems were associated with different network characteristics among friends, family and co-workers is an innovative way to look at relationships among individuals; the current study was the first, to our knowledge, to apply SNA to gambling behaviors. Egocentric social network analysis was used to characterize formally the relationships between social network characteristics and gambling pathology. Laboratory-based questionnaire and interview administration. Forty frequent gamblers (22 non-pathological gamblers, 18 pathological gamblers) were recruited from the community. The SNA revealed significant social network compositional differences between the two groups: pathological gamblers (PGs) had more gamblers, smokers and drinkers in their social networks than did non-pathological gamblers (NPGs). PGs had more individuals in their network with whom they personally gambled, smoked and drank than those with who were NPG. Network ties were closer to individuals in their networks who gambled, smoked and drank more frequently. Associations between gambling severity and structural network characteristics were not significant. Pathological gambling is associated with compositional but not structural differences in social networks. Pathological gamblers differ from non-pathological gamblers in the number of gamblers, smokers and drinkers in their social networks. Homophily within the networks also indicates that gamblers tend to be closer with other gamblers. This homophily may serve to reinforce addictive behaviors, and may suggest avenues for future study or intervention. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

A bioinformatics transcriptome meta-analysis highlights the importance of trophoblast differentiation in the pathology of hydatidiform moles.

PubMed

Desterke, Christophe; Slim, Rima; Candelier, Jean-Jacques

2018-05-01

Hydatidiform mole (HM) is an aberrant human pregnancy with abnormal trophoblastic development, migration/invasion of the extravillous trophoblast in the decidua. These abnormalities are established in a hypoxic environment during the first trimester of gestation. Using text mining, we identified 72 unique genes that are linked to HM (HM-linked genes) that we studied by bioinformatic analysis in publicly available transcriptomes of primary chorionic villous cells (cytotrophoblast, syncytiotrophoblast, extravillous trophoblast, and arterial and venous endothelial) isolated from normal placentas or established trophoblastic cell lines cultured under different oxygen concentrations. We show that the majority of HM-linked genes (75%) are involved in normal trophoblastic differentiation, arranged in clusters, and some of them are implicated in chorionic villous invasion or regulated by oxygen concentrations. Our analysis integrates the various aspects of the pathophysiology of HM and highlights the importance of trophoblastic differentiation in this pathology. Copyright © 2018 Elsevier Ltd. All rights reserved.

Long Noncoding RNA H19 in Digestive System Cancers: A Meta-Analysis of Its Association with Pathological Features.

PubMed

Lin, Yang; Xu, Lijian; Wei, Wei; Zhang, Xiaohui; Ying, Rongchao

2016-01-01

Long noncoding RNA (lncRNA) H19 has been reported to be upregulated in malignant digestive tumors, but its clinical relevance is not yet established. The meta-analysis was to investigate the association between H19 expression and pathological features of digestive system cancers. The databases of PubMed, EMBase, Web of Science, CNKI, and WanFang were searched for the related studies. A total of 478 patients from 6 studies were finally included. The meta-analysis showed that the patient group of high H19 expression had a higher risk of poorly differentiated grade, deep tumor invasion (T2 stage or more), lymph node metastasis, and advanced TNM stage than the group of low H19 expression, although there was no difference between them in terms of distant metastasis. Therefore, the high expression of lncRNA H19 might predict poor oncological outcomes of patients with digestive system cancers.

A study of the human rod and cone electroretinogram a-wave component

NASA Astrophysics Data System (ADS)

Barraco, R.; Persano Adorno, D.; Bellomonte, L.; Brai, M.

2009-03-01

The study of the electrical response of the retina to a luminous stimulus is one of the main fields of research in ocular electrophysiology. The features of the first component (a-wave) of the retinal response reflect the functional integrity of the two populations of photoreceptors: rods and cones. We fit the a-wave for pathological subjects with functions that account for possible mechanisms governing the kinetics of the photoreceptors. The paper extends a previous analysis, carried out for normal subjects, in which both populations are active, to patients affected by two particular diseases that reduce the working populations to only one. The pathologies investigated are Achromatopsia, a cone disease, and Congenital Stationary Night Blindness, a rod problem. We present evidence that the analysis of a pathological a-wave can be employed to quantitatively measure either cone or rod activities and to test hypotheses about their responses. The results show that the photoreceptoral responses differ in the two cases and functions implying a different number of photocascade stages are necessary to achieve a correct modeling of the early phototransduction process. Numerical values of the parameters characterizing the best-fit functions are given and discussed.

A systematic review and meta-analysis on the longitudinal relationship between eating pathology and depression.

PubMed

Puccio, Francis; Fuller-Tyszkiewicz, Matthew; Ong, Deborah; Krug, Isabel

2016-05-01

Undertake a meta-analysis to provide a quantitative synthesis of longitudinal studies that assessed the direction of effects between eating pathology and depression. A second aim was to use meta-regression to account for heterogeneity in terms of study-level effect modifiers. A systematic review was conducted on 42 studies that assessed the longitudinal relationship between eating pathology and depression. Of these 42 studies, multilevel random-effects meta-analyses were conducted on 30 eligible studies. Meta-analysis results showed that eating pathology was a risk factor for depression (rm  = 0.13) and that depression was a risk factor for eating pathology (rm  = 0.16). Meta-regression analyses showed that these effects were significantly stronger for studies that operationalized eating pathology as an eating disorder diagnosis versus eating pathology symptoms, and for studies that operationalized the respective outcome measure as a categorical variable (e.g., a diagnosis of a disorder or where symptoms were "present"/"absent") versus a continuous measure. Results also showed that in relation to eating pathology type, the effect of an eating disorder diagnosis and bulimic symptoms on depression was significantly stronger for younger participants. Eating pathology and depression are concurrent risk factors for each other, suggesting that future research would benefit from identifying factors that are etiological to the development of both constructs. Llevar a cabo un meta-análisis para proporcionar una síntesis cuantitativa de los estudios longitudinales que evaluaron la dirección de los efectos entre la alimentación patológica y la depresión. Un segundo objetivo fue utilizar la meta-regresión para dar cuenta de la heterogeneidad en términos de modificadores del efecto a nivel de estudio. MÉTODO: Una revisión sistemática se llevó a cabo en 42 estudios que evaluaron la relación longitudinal entre la alimentación patológica y la depresión. De estos 42 estudios, se realizaron meta-análisis de multinivel de efectos aleatorios en 30 estudios elegibles. Los resultados del meta-análisis mostraron que la alimentación patológica era un factor de riesgo para depresión (rm=0.13) y que la depresión era un factor de riesgo para la alimentación patológica (rm=0.16). Los análisis de meta-regresión mostraron que estos efectos eran significativamente más fuertes para estudios que operacionalizaban la alimentación patológica como un diagnóstico de trastorno de la conducta alimentaria versus síntomas de alimentación patológica, y para los estudios que operacionalizaban la medida respectiva de resultado como una variable categórica (e.g., un diagnóstico de trastorno o cuando los síntomas estaban "presentes"/"ausentes") versus una medida continua. Los resultados mostraron que en relación al tipo de alimentación patológica, el efecto de un diagnóstico de trastorno de la conducta alimentaria y síntomas bulímicos en la depresión era significativamente más fuerte para participantes más jóvenes. DISCUSIÓN: La alimentación patológica y la depresión son factores de riesgo concurrentes uno para el otro, lo que sugiere que la investigación futura se beneficiaría de identificar factores que son etiológicos al desarrollo de ambos constructos. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016;49:439-454). © 2015 Wiley Periodicals, Inc.

Different Achilles Tendon Pathologies Show Distinct Histological and Molecular Characteristics

PubMed Central

Minkwitz, Susann; Schmock, Aysha; Bormann, Nicole; Kurtoglu, Alper; Tsitsilonis, Serafeim; Manegold, Sebastian

2018-01-01

Reasons for the development of chronic tendon pathologies are still under debate and more basic knowledge is needed about the different diseases. The aim of the present study was therefore to characterize different acute and chronic Achilles tendon disorders. Achilles tendon samples from patients with chronic tendinopathy (n = 7), chronic ruptures (n = 6), acute ruptures (n = 13), and intact tendons (n = 4) were analyzed. The histological score investigating pathological changes was significantly increased in tendinopathy and chronic ruptures compared to acute ruptures. Inflammatory infiltration was detected by immunohistochemistry in all tendon pathology groups, but was significantly lower in tendinopathy compared to chronic ruptures. Quantitative real-time PCR (qRT-PCR) analysis revealed significantly altered expression of genes related to collagens and matrix modeling/remodeling (matrix metalloproteinases, tissue inhibitors of metalloproteinases) in tendinopathy and chronic ruptures compared to intact tendons and/or acute ruptures. In all three tendon pathology groups markers of inflammation (interleukin (IL) 1β, tumor necrosis factor α, IL6, IL10, IL33, soluble ST2, transforming growth factor β1, cyclooxygenase 2), inflammatory cells (cluster of differentaition (CD) 3, CD68, CD80, CD206), fat metabolism (fatty acid binding protein 4, peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, adiponectin), and innervation (protein gene product 9.5, growth associated protein 43, macrophage migration inhibitory factor) were detectable, but only in acute ruptures significantly regulated compared to intact tendons. The study gives an insight into structural and molecular changes of pathological processes in tendons and might be used to identify targets for future therapy of tendon pathologies. PMID:29385715

Pathology economic model tool: a novel approach to workflow and budget cost analysis in an anatomic pathology laboratory.

PubMed

Muirhead, David; Aoun, Patricia; Powell, Michael; Juncker, Flemming; Mollerup, Jens

2010-08-01

The need for higher efficiency, maximum quality, and faster turnaround time is a continuous focus for anatomic pathology laboratories and drives changes in work scheduling, instrumentation, and management control systems. To determine the costs of generating routine, special, and immunohistochemical microscopic slides in a large, academic anatomic pathology laboratory using a top-down approach. The Pathology Economic Model Tool was used to analyze workflow processes at The Nebraska Medical Center's anatomic pathology laboratory. Data from the analysis were used to generate complete cost estimates, which included not only materials, consumables, and instrumentation but also specific labor and overhead components for each of the laboratory's subareas. The cost data generated by the Pathology Economic Model Tool were compared with the cost estimates generated using relative value units. Despite the use of automated systems for different processes, the workflow in the laboratory was found to be relatively labor intensive. The effect of labor and overhead on per-slide costs was significantly underestimated by traditional relative-value unit calculations when compared with the Pathology Economic Model Tool. Specific workflow defects with significant contributions to the cost per slide were identified. The cost of providing routine, special, and immunohistochemical slides may be significantly underestimated by traditional methods that rely on relative value units. Furthermore, a comprehensive analysis may identify specific workflow processes requiring improvement.

The Geropathology Research Network: An Interdisciplinary Approach for Integrating Pathology Into Research on Aging

PubMed Central

Ikeno, Yuji; Niedernhofer, Laura; McIndoe, Richard A.; Ciol, Marcia A.; Ritchey, Jerry; Liggitt, Denny

2016-01-01

Geropathology is the study of aging and age-related lesions and diseases in the form of whole necropsies/autopsies, surgical biopsies, histology, and molecular biomarkers. It encompasses multiple subspecialties of geriatrics, anatomic pathology, molecular pathology, clinical pathology, and gerontology. In order to increase the consistency and scope of communication in the histologic and molecular pathology assessment of tissues from preclinical and clinical aging studies, a Geropathology Research Network has been established consisting of pathologists and scientists with expertise in the comparative pathology of aging, the design of aging research studies, biostatistical methods for analysis of aging data, and bioinformatics for compiling and annotating large sets of data generated from aging studies. The network provides an environment to promote learning and exchange of scientific information and ideas for the aging research community through a series of symposia, the development of uniform ways of integrating pathology into aging studies, and the statistical analysis of pathology data. The efforts of the network are ultimately expected to lead to a refined set of sentinel biomarkers of molecular and anatomic pathology that could be incorporated into preclinical and clinical aging intervention studies to increase the relevance and productivity of these types of investigations. PMID:26243216

Epilepsy-related sudden unexpected death: targeted molecular analysis of inherited heart disease genes using next-generation DNA sequencing.

PubMed

Hata, Yukiko; Yoshida, Koji; Kinoshita, Koshi; Nishida, Naoki

2017-05-01

Inherited heart disease causing electric instability in the heart has been suggested to be a risk factor for sudden unexpected death in epilepsy (SUDEP). The purpose of this study was to reveal the correlation between epilepsy-related sudden unexpected death (SUD) and inherited heart disease. Twelve epilepsy-related SUD cases (seven males and five females, aged 11-78 years) were examined. Nine cases fulfilled the criteria of SUDEP, and three cases died by drowning. In addition to examining three major epilepsy-related genes, we used next-generation sequencing (NGS) to examine 73 inherited heart disease-related genes. We detected both known pathogenic variants and rare variants with minor allele frequencies of <0.5%. The pathogenicity of these variants was evaluated and graded by eight in silico predictive algorithms. Six known and six potential rare variants were detected. Among these, three known variants of LDB3, DSC2 and KCNE1 and three potential rare variants of MYH6, DSP and DSG2 were predicted by in silico analysis as possibly highly pathogenic in three of the nine SUDEP cases. Two of three cases with desmosome-related variants showed mild but possible significant right ventricular dysplasia-like pathology. A case with LDB3 and MYH6 variants showed hypertrabeculation of the left ventricle and severe fibrosis of the cardiac conduction system. In the three drowning death cases, one case with mild prolonged QT interval had two variants in ANK2. This study shows that inherited heart disease may be a significant risk factor for SUD in some epilepsy cases, even if pathological findings of the heart had not progressed to an advanced stage of the disease. A combination of detailed pathological examination of the heart and gene analysis using NGS may be useful for evaluating arrhythmogenic potential of epilepsy-related SUD. © 2016 International Society of Neuropathology.

A Bayesian approach to meta-analysis of plant pathology studies.

PubMed

Mila, A L; Ngugi, H K

2011-01-01

Bayesian statistical methods are used for meta-analysis in many disciplines, including medicine, molecular biology, and engineering, but have not yet been applied for quantitative synthesis of plant pathology studies. In this paper, we illustrate the key concepts of Bayesian statistics and outline the differences between Bayesian and classical (frequentist) methods in the way parameters describing population attributes are considered. We then describe a Bayesian approach to meta-analysis and present a plant pathological example based on studies evaluating the efficacy of plant protection products that induce systemic acquired resistance for the management of fire blight of apple. In a simple random-effects model assuming a normal distribution of effect sizes and no prior information (i.e., a noninformative prior), the results of the Bayesian meta-analysis are similar to those obtained with classical methods. Implementing the same model with a Student's t distribution and a noninformative prior for the effect sizes, instead of a normal distribution, yields similar results for all but acibenzolar-S-methyl (Actigard) which was evaluated only in seven studies in this example. Whereas both the classical (P = 0.28) and the Bayesian analysis with a noninformative prior (95% credibility interval [CRI] for the log response ratio: -0.63 to 0.08) indicate a nonsignificant effect for Actigard, specifying a t distribution resulted in a significant, albeit variable, effect for this product (CRI: -0.73 to -0.10). These results confirm the sensitivity of the analytical outcome (i.e., the posterior distribution) to the choice of prior in Bayesian meta-analyses involving a limited number of studies. We review some pertinent literature on more advanced topics, including modeling of among-study heterogeneity, publication bias, analyses involving a limited number of studies, and methods for dealing with missing data, and show how these issues can be approached in a Bayesian framework. Bayesian meta-analysis can readily include information not easily incorporated in classical methods, and allow for a full evaluation of competing models. Given the power and flexibility of Bayesian methods, we expect them to become widely adopted for meta-analysis of plant pathology studies.

Clinical map document based on XML (cMDX): document architecture with mapping feature for reporting and analysing prostate cancer in radical prostatectomy specimens.

PubMed

Eminaga, Okyaz; Hinkelammert, Reemt; Semjonow, Axel; Neumann, Joerg; Abbas, Mahmoud; Koepke, Thomas; Bettendorf, Olaf; Eltze, Elke; Dugas, Martin

2010-11-15

The pathology report of radical prostatectomy specimens plays an important role in clinical decisions and the prognostic evaluation in Prostate Cancer (PCa). The anatomical schema is a helpful tool to document PCa extension for clinical and research purposes. To achieve electronic documentation and analysis, an appropriate documentation model for anatomical schemas is needed. For this purpose we developed cMDX. The document architecture of cMDX was designed according to Open Packaging Conventions by separating the whole data into template data and patient data. Analogue custom XML elements were considered to harmonize the graphical representation (e.g. tumour extension) with the textual data (e.g. histological patterns). The graphical documentation was based on the four-layer visualization model that forms the interaction between different custom XML elements. Sensible personal data were encrypted with a 256-bit cryptographic algorithm to avoid misuse. In order to assess the clinical value, we retrospectively analysed the tumour extension in 255 patients after radical prostatectomy. The pathology report with cMDX can represent pathological findings of the prostate in schematic styles. Such reports can be integrated into the hospital information system. "cMDX" documents can be converted into different data formats like text, graphics and PDF. Supplementary tools like cMDX Editor and an analyser tool were implemented. The graphical analysis of 255 prostatectomy specimens showed that PCa were mostly localized in the peripheral zone (Mean: 73% ± 25). 54% of PCa showed a multifocal growth pattern. cMDX can be used for routine histopathological reporting of radical prostatectomy specimens and provide data for scientific analysis.

Clinical map document based on XML (cMDX): document architecture with mapping feature for reporting and analysing prostate cancer in radical prostatectomy specimens

PubMed Central

2010-01-01

Background The pathology report of radical prostatectomy specimens plays an important role in clinical decisions and the prognostic evaluation in Prostate Cancer (PCa). The anatomical schema is a helpful tool to document PCa extension for clinical and research purposes. To achieve electronic documentation and analysis, an appropriate documentation model for anatomical schemas is needed. For this purpose we developed cMDX. Methods The document architecture of cMDX was designed according to Open Packaging Conventions by separating the whole data into template data and patient data. Analogue custom XML elements were considered to harmonize the graphical representation (e.g. tumour extension) with the textual data (e.g. histological patterns). The graphical documentation was based on the four-layer visualization model that forms the interaction between different custom XML elements. Sensible personal data were encrypted with a 256-bit cryptographic algorithm to avoid misuse. In order to assess the clinical value, we retrospectively analysed the tumour extension in 255 patients after radical prostatectomy. Results The pathology report with cMDX can represent pathological findings of the prostate in schematic styles. Such reports can be integrated into the hospital information system. "cMDX" documents can be converted into different data formats like text, graphics and PDF. Supplementary tools like cMDX Editor and an analyser tool were implemented. The graphical analysis of 255 prostatectomy specimens showed that PCa were mostly localized in the peripheral zone (Mean: 73% ± 25). 54% of PCa showed a multifocal growth pattern. Conclusions cMDX can be used for routine histopathological reporting of radical prostatectomy specimens and provide data for scientific analysis. PMID:21078179

Protein Kinase Activity Decreases with Higher Braak Stages of Alzheimer’s Disease Pathology

PubMed Central

Rosenberger, Andrea F.N.; Hilhorst, Riet; Coart, Elisabeth; García Barrado, Leandro; Naji, Faris; Rozemuller, Annemieke J.M.; van der Flier, Wiesje M.; Scheltens, Philip; Hoozemans, Jeroen J.M.; van der Vies, Saskia M.

2015-01-01

Alzheimer’s disease (AD) is characterized by a long pre-clinical phase (20–30 years), during which significant brain pathology manifests itself. Disease mechanisms associated with pathological hallmarks remain elusive. Most processes associated with AD pathogenesis, such as inflammation, synaptic dysfunction, and hyper-phosphorylation of tau are dependent on protein kinase activity. The objective of this study was to determine the involvement of protein kinases in AD pathogenesis. Protein kinase activity was determined in postmortem hippocampal brain tissue of 60 patients at various stages of AD and 40 non-demented controls (Braak stages 0-VI) using a peptide-based microarray platform. We observed an overall decrease of protein kinase activity that correlated with disease progression. The phosphorylation of 96.7% of the serine/threonine peptides and 37.5% of the tyrosine peptides on the microarray decreased significantly with increased Braak stage (p-value <0.01). Decreased activity was evident at pre-clinical stages of AD pathology (Braak I-II). Increased phosphorylation was not observed for any peptide. STRING analysis in combination with pathway analysis and identification of kinases responsible for peptide phosphorylation showed the interactions between well-known proteins in AD pathology, including the Ephrin-receptor A1 (EphA1), a risk gene for AD, and sarcoma tyrosine kinase (Src), which is involved in memory formation. Additionally, kinases that have not previously been associated with AD were identified, e.g., protein tyrosine kinase 6 (PTK6/BRK), feline sarcoma oncogene kinase (FES), and fyn-associated tyrosine kinase (FRK). The identified protein kinases are new biomarkers and potential drug targets for early (pre-clinical) intervention. PMID:26519433

Quantification of knee vibroarthrographic signal irregularity associated with patellofemoral joint cartilage pathology based on entropy and envelope amplitude measures.

PubMed

Wu, Yunfeng; Chen, Pinnan; Luo, Xin; Huang, Hui; Liao, Lifang; Yao, Yuchen; Wu, Meihong; Rangayyan, Rangaraj M

2016-07-01

Injury of knee joint cartilage may result in pathological vibrations between the articular surfaces during extension and flexion motions. The aim of this paper is to analyze and quantify vibroarthrographic (VAG) signal irregularity associated with articular cartilage degeneration and injury in the patellofemoral joint. The symbolic entropy (SyEn), approximate entropy (ApEn), fuzzy entropy (FuzzyEn), and the mean, standard deviation, and root-mean-squared (RMS) values of the envelope amplitude, were utilized to quantify the signal fluctuations associated with articular cartilage pathology of the patellofemoral joint. The quadratic discriminant analysis (QDA), generalized logistic regression analysis (GLRA), and support vector machine (SVM) methods were used to perform signal pattern classifications. The experimental results showed that the patients with cartilage pathology (CP) possess larger SyEn and ApEn, but smaller FuzzyEn, over the statistical significance level of the Wilcoxon rank-sum test (p<0.01), than the healthy subjects (HS). The mean, standard deviation, and RMS values computed from the amplitude difference between the upper and lower signal envelopes are also consistently and significantly larger (p<0.01) for the group of CP patients than for the HS group. The SVM based on the entropy and envelope amplitude features can provide superior classification performance as compared with QDA and GLRA, with an overall accuracy of 0.8356, sensitivity of 0.9444, specificity of 0.8, Matthews correlation coefficient of 0.6599, and an area of 0.9212 under the receiver operating characteristic curve. The SyEn, ApEn, and FuzzyEn features can provide useful information about pathological VAG signal irregularity based on different entropy metrics. The statistical parameters of signal envelope amplitude can be used to characterize the temporal fluctuations related to the cartilage pathology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clinical Features and Related Factors of Poststroke Pathological Laughing and Crying: A Case-Control Study.

PubMed

Wang, Geying; Teng, Fei; Chen, Yuhui; Liu, Yuanhua; Li, Yancheng; Cai, Li; Zhang, Xu; Nie, Zhiyu; Jin, Lingjing

2016-03-01

The purpose of this study was to analyze clinical features and related factors of poststroke pathological laughing and crying (PSPLC) and to differentiate PSPLC patients with and without pseudobulbar signs. We performed a case-control study in which 56 patients with PSPLC were matched to 56 control stroke patients by age and gender. The pathological laughing and crying scale was used to identify patients with PSPLC. Characteristics of PSPLC outbursts, presence of pseudobulbar signs and autonomic symptoms, lesion locations, and different clinical data were analyzed. Mild cognitive impairment (MCI) was evaluated by the Montreal Cognitive Assessment. Poststroke anger proneness (PSAP) was evaluated by comparison of the patients' premorbid states. Significantly more patients in the PSPLC group showed MCI, PSAP, and pseudobulbar signs than those in the control group. Most patients with PSPLC showed bilateral multiple lesions and the pons (especially the bilateral paramedian basal and basal-tegmental areas) stood out as the most important lesion location. Logistic regression analysis showed that pontine lesion, MCI, and PSAP were independently related to PSPLC; however, the presence of pseudobulbar signs was not related. PSPLC patients with pseudobulbar signs showed more recurrent strokes in the previous 2 years, more severe neurological deficits, as well as higher severity of PSPLC. In addition, more patients in the group with pseudobulbar signs showed concomitant autonomic symptoms. PSPLC, MCI, and PSAP could be manifestations of a more general disorder, in which pontine lesion plays an important role. PSPLC patients with pseudobulbar signs and those without show different features. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Analysis of pathology department Web sites and practical recommendations.

PubMed

Nero, Christopher; Dighe, Anand S

2008-09-01

There are numerous customers for pathology departmental Web sites, including pathology department staff, clinical staff, residency applicants, job seekers, and other individuals outside the department seeking department information. Despite the increasing importance of departmental Web sites as a means of distributing information, no analysis has been done to date of the content and usage of pathology department Web sites. In this study, we analyzed pathology department Web sites to examine the elements present on each site and to evaluate the use of search technology on these sites. Further, we examined the usage patterns of our own departmental Internet and internet Web sites to better understand the users of pathology Web sites. We reviewed selected departmental pathology Web sites and analyzed their content and functionality. Our institution's departmental pathology Web sites were modified to enable detailed information to be stored regarding users and usage patterns, and that information was analyzed. We demonstrate considerable heterogeneity in departmental Web sites with many sites lacking basic content and search features. In addition, we demonstrate that increasing the traffic of a department's informational Web sites may result in reduced phone inquiries to the laboratory. We propose recommendations for pathology department Web sites to maximize promotion of a department's mission. A departmental pathology Web site is an essential communication tool for all pathology departments, and attention to the users and content of the site can have operational impact.

[Forensic Analysis of 20 Dead Cases Related to Heroin Abuse].

PubMed

Huang, W Q; Li, L H; Li, Z; Hong, S J

2016-08-01

To perform retrospective analysis on 20 dead cases related to heroin abuse, and to provide references for the forensic assessment of correlative cases. Among 20 dead cases related to heroin abuse, general situation, using method of drug, cause of death and result of forensic examination were analyzed by statistical analysis for summarizing the cause of death and pathologic changes. The dead were mostly young adults, with more male than female. The results of histopathological examinations showed non-specific pathological changes. There were four leading causes of death, including acute poisoning of heroin abuse or leakage （13 cases, 65%）, concurrent diseases caused by heroin abuse （3 cases, 15%）, inspiratory asphyxia caused by taking heroin （2 cases, 10%）, and heroin withdrawal syndrome （2 cases, 10%）. The forensic identification on dead related to heroin abuse must base on the comprehensive autopsy, and combine with the qualitative and quantitative analysis of heroin and its metabolites in death and the case information, as well as the scene investigation. Copyright© by the Editorial Department of Journal of Forensic Medicine

Intrahepatic, peri-hilar and distal cholangiocarcinoma: Three different locations of the same tumor or three different tumors?

PubMed

Ercolani, G; Dazzi, A; Giovinazzo, F; Ruzzenente, A; Bassi, C; Guglielmi, A; Scarpa, A; D'Errico, A; Pinna, A D

2015-09-01

Few papers deal with pathologic characteristics and outcome of the 3 different cholangiocarcinomas based on location (intrahepatic, peri-hilar, distal). There is little evidence regarding similarity and differences. From two tertiary referral Italian Centers (in Bologna and Verona), 479 patients with cholangiocarcinoma were evaluated between 1980 and 2011. Several pathologic characteristics and their impact on survival were analyzed among resected patients for cholangiocarcinomas depending on the site of origin. Tumour location was intrahepatic in 172 cases (36%), peri-hilar in 243 (51) and distal in 64(13%). Curative resection was performed in 339 (70%) patients. Intrahepatic cholangiocarcinoma showed higher probability to achieve R0 resection (81%), but was more frequently associated with presence of microvascular invasion (71%). Distal cholangiocarcinoma presented less R0 resections (58%), higher lymphnode involvement (60%) and lower microvascular invasion (49%). Hilar cholangiocarcinoma had intermediate characteristics (R0: 65% of cases). Median follow up was 30.2 ± 38 months; the 5 years overall survival was 31% in the resected population. Overall survival curves were similar among the three groups. At univariate analysis surgical margins, lymphnode status, perineural invasion, T category, TNM stage, microvascular invasion, tumour grading had significant impact on survival. At multivariate analysis, only microvascular invasion was significantly related to long term results (HR = 1,7; 95% CI = 1,0-2,5)". Micro-vascular invasion has the strongest impact on survival in all three types of cholangiocarcinoma. In case of comparable pathologic characteristics and stage, the three tumors show similar outcome; depending on location, it shows a different tendency to invade bordering structures which affect the outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

MOVING BEYOND COLOR: THE CASE FOR MULTISPECTRAL IMAGING IN BRIGHTFIELD PATHOLOGY.

PubMed

Cukierski, William J; Qi, Xin; Foran, David J

2009-01-01

A multispectral camera is capable of imaging a histologic slide at narrow bandwidths over the range of the visible spectrum. While several uses for multispectral imaging (MSI) have been demonstrated in pathology [1, 2], there is no unified consensus over when and how MSI might benefit automated analysis [3, 4]. In this work, we use a linear-algebra framework to investigate the relationship between the spectral image and its standard-image counterpart. The multispectral "cube" is treated as an extension of a traditional image in a high-dimensional color space. The concept of metamers is introduced and used to derive regions of the visible spectrum where MSI may provide an advantage. Furthermore, histological stains which are amenable to analysis by MSI are reported. We show the Commission internationale de l'éclairage (CIE) 1931 transformation from spectrum to color is non-neighborhood preserving. Empirical results are demonstrated on multispectral images of peripheral blood smears.

Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials.

PubMed

Kroep, J R; Charehbili, A; Coleman, R E; Aft, R L; Hasegawa, Y; Winter, M C; Weilbaecher, K; Akazawa, K; Hinsley, S; Putter, H; Liefers, G J; Nortier, J W R; Kohno, N

2016-02-01

The addition of bisphosphonates to adjuvant therapy improves survival in postmenopausal breast cancer (BC) patients. We report a meta-analysis of four randomised trials of neoadjuvant chemotherapy (CT) +/- zoledronic acid (ZA) in stage II/III BC to investigate the potential for enhancing the pathological response. Individual patient data from four prospective randomised clinical trials reporting the effect of the addition of ZA on the pathological response after neoadjuvant CT were pooled. Primary outcomes were pathological complete response in the breast (pCRb) and in the breast and lymph nodes (pCR). Trial-level and individual patient data meta-analyses were done. Predefined subgroup-analyses were performed for postmenopausal women and patients with triple-negative BC. pCRb and pCR data were available in 735 and 552 patients respectively. In the total study population ZA addition to neoadjuvant CT did not increase pCRb or pCR rates. However, in postmenopausal patients, the addition of ZA resulted in a significant, near doubling of the pCRb rate (10.8% for CT only versus 17.7% with CT+ZA; odds ratio [OR] 2.14, 95% confidence interval [CI] 1.01-4.55) and a non-significant benefit of the pCR rate (7.8% for CT only versus 14.6% with CT+ZA; OR 2.62, 95% CI 0.90-7.62). In patients with triple-negative BC a trend was observed favouring CT+ZA. This meta-analysis shows no impact from the addition of ZA to neoadjuvant CT on pCR. However, as has been seen in the adjuvant setting, the addition of ZA to neoadjuvant CT may augment the effects of CT in postmenopausal patients with BC. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Determining the best treatment for simple bone cyst: a decision analysis.

PubMed

Lee, Seung Yeol; Chung, Chin Youb; Lee, Kyoung Min; Sung, Ki Hyuk; Won, Sung Hun; Choi, In Ho; Cho, Tae-Joon; Yoo, Won Joon; Yeo, Ji Hyun; Park, Moon Seok

2014-03-01

The treatment of simple bone cysts (SBC) in children varies significantly among physicians. This study examined which procedure is better for the treatment of SBC, using a decision analysis based on current published evidence. A decision tree focused on five treatment modalities of SBC (observation, steroid injection, autologous bone marrow injection, decompression, and curettage with bone graft) were created. Each treatment modality was further branched, according to the presence and severity of complications. The probabilities of all cases were obtained by literature review. A roll back tool was utilized to determine the most preferred treatment modality. One-way sensitivity analysis was performed to determine the threshold value of the treatment modalities. Two-way sensitivity analysis was utilized to examine the joint impact of changes in probabilities of two parameters. The decision model favored autologous bone marrow injection. The expected value of autologous bone marrow injection was 0.9445, while those of observation, steroid injection, decompression, and curettage and bone graft were 0.9318, 0.9400, 0.9395, and 0.9342, respectively. One-way sensitivity analysis showed that autologous bone marrow injection was better than that of decompression for the expected value when the rate of pathologic fracture, or positive symptoms of SBC after autologous bone marrow injection, was lower than 20.4%. In our study, autologous bone marrow injection was found to be the best choice of treatment of SBC. However, the results were sensitive to the rate of pathologic fracture after treatment of SBC. Physicians should consider the possibility of pathologic fracture when they determine a treatment method for SBC.

Effects of vehicle-ride exposure on cervical pathology: a meta-analysis

PubMed Central

KOLLOCK, Roger; GAMES, Kenneth; WILSON, Alan E.; SEFTON, JoEllen M.

2015-01-01

Research to date on the effect vehicle-ride exposure has on the development of cervical pathologies in mounted Warfighters is conflicting. The purpose of this study was to determine if the literature suggests a definite effect of vehicle-ride exposure on cervical pathology. Databases were searched using multiple combinations of select terms. Twelve studies meeting the inclusion criteria were included in the meta-analysis. The results of the meta-analysis revealed that overall vehicle-ride exposure was likely to increase cervical pathology (p=0.01, odds ratio=1.59, 95% CI=1.16−2.17). Using vehicle type as a moderator it was found that vehicle-ride exposure in ground-based vehicles (p=0.01, odds ratio=2.33, 95% CI=1.41−3.85) and fixed-wing aircraft (p=0.01, odds ratio =1.59, 95% CI=1.13−2.23) were likely to increase cervical pathology. Using operator/other personnel moderator it was found that in the populations tested, fighter pilots or fighter jet weapons systems operators were more likely to develop a cervical pathology (p<0.001, odds ratio=1.78, 95% CI=1.26−2.50). The available studies indicate an increase in cervical pathology for personnel exposed to ground-based vehicles and fixed-wing aircraft. PMID:25739897

Prognostic signature of protocadherin 10 methylation in curatively resected pathological stage I non-small-cell lung cancer.

PubMed

Harada, Hiroaki; Miyamoto, Kazuaki; Yamashita, Yoshinori; Taniyama, Kiyomi; Mihara, Kazuko; Nishimura, Mitsuki; Okada, Morihito

2015-10-01

Although curative resection is the current treatment of choice for localized non-small-cell lung cancer (NSCLC), patients show a wide spectrum of survival even after complete resection of pathological stage I NSCLC. Thus, identifying molecular biomarkers that help to accurately select patients at high risk of relapse is an important key to improving the treatment strategy. The purpose of this study was to evaluate the prognostic signature of protocadherin 10 (PCDH10) promoter methylation in curatively resected pathological stage I NSCLC. Using methylation-specific polymerase chain reaction assays, methylation of PCDH10 promoter was assessed in cancer tissues of 109 patients who underwent curative resection of pathological stage I NSCLC. Associations between PCDH10 methylation status and disease outcome was analyzed. PCDH10 promoter methylation was detected in 46/109 patients (42.2%). Patients with methylated PCDH10 showed significantly worse recurrence-free, overall, and disease-specific survival compared with those without methylation (P < 0.0001, P = 0.0004, P = 0.0002, respectively). Multivariate Cox proportional hazard regression analysis revealed that adjusted hazard ratios of methylated PCDH10 were 5.159 for recurrence-free, 1.817 for overall, and 5.478 for disease-specific survival (P = 0.0005, P = 0.1475, P = 0.0109, respectively). The pattern of recurrence was not significantly different between patients with and without PCDH10 methylation (P = 0.5074). PCDH10 methylation is a potential biomarker that predicts a poor prognosis after curative resection of pathological stage I NSCLC. Assessment of PCDH10 methylation status might assist in patient stratification for determining an appropriate adjuvant treatment and follow-up strategy. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The clinical and pathological characteristics of nephropathies in connective tissue diseases in the Japan Renal Biopsy Registry (J-RBR).

PubMed

Ichikawa, Kazunobu; Konta, Tsuneo; Sato, Hiroshi; Ueda, Yoshihiko; Yokoyama, Hitoshi

2017-12-01

In connective tissue diseases, a wide variety of glomerular, tubulointerstitial, and vascular lesions of the kidney are observed. Nonetheless, recent information is limited regarding renal lesions in connective tissue diseases, except in systemic lupus erythematosus (SLE). In this study, we used a nationwide database of biopsy-confirmed renal diseases in Japan (J-RBR) (UMIN000000618). In total, 20,523 registered patients underwent biopsy between 2007 and 2013; from 110 patients with connective tissue diseases except SLE, we extracted data regarding the clinico-pathological characteristics of the renal biopsy. Our analysis included patients with rheumatoid arthritis (RA) (n = 52), Sjögren's syndrome (SjS) (n = 35), scleroderma (n = 10), mixed connective tissue disease (MCTD; n = 5), anti-phospholipid syndrome (APS; n = 3), polymyositis/dermatomyositis (PM/DM; n = 1), Behçet's disease (n = 1) and others (n = 3). The clinico-pathological features differed greatly depending on the underlying disease. The major clinical diagnosis was nephrotic syndrome in RA; chronic nephritic syndrome with mild proteinuria and reduced renal function in SjS; rapidly progressive nephritic syndrome in scleroderma. The major pathological diagnosis was membranous nephropathy (MN) and amyloidosis in RA; tubulointerstitial nephritis in SjS; proliferative obliterative vasculopathy in scleroderma; MN in MCTD. In RA, most patients with nephrosis were treated using bucillamine, and showed membranous nephropathy. Using the J-RBR database, our study revealed that biopsy-confirmed cases of connective tissue diseases such as RA, SjS, scleroderma, and MCTD show various clinical and pathological characteristics, depending on the underlying diseases and the medication used.

Attachment Style and Internet Addiction: An Online Survey.

PubMed

Eichenberg, Christiane; Schott, Markus; Decker, Oliver; Sindelar, Brigitte

2017-05-17

One of the clinically relevant problems of Internet use is the phenomenon of Internet addiction. Considering the fact that there is ample evidence for the relationship between attachment style and substance abuse, it stands to reason that attachment theory can also make an important contribution to the understanding of the pathogenesis of Internet addiction. The aim of this study was to examine people's tendency toward pathological Internet usage in relation to their attachment style. An online survey was conducted. Sociodemographic data, attachment style (Bielefeld questionnaire partnership expectations), symptoms of Internet addiction (scale for online addiction for adults), used Web-based services, and online relationship motives (Cyber Relationship Motive Scale, CRMS-D) were assessed. In order to confirm the findings, a study using the Rorschach test was also conducted. In total, 245 subjects were recruited. Participants with insecure attachment style showed a higher tendency to pathological Internet usage compared with securely attached participants. An ambivalent attachment style was particularly associated with pathological Internet usage. Escapist and social-compensatory motives played an important role for insecurely attached subjects. However, there were no significant effects with respect to Web-based services and apps used. Results of the analysis of the Rorschach protocol with 16 subjects corroborated these results. Users with pathological Internet use frequently showed signs of infantile relationship structures in the context of social groups. This refers to the results of the Web-based survey, in which interpersonal relationships were the result of an insecure attachment style. Pathological Internet use was a function of insecure attachment and limited interpersonal relationships. ©Christiane Eichenberg, Markus Schott, Oliver Decker, Brigitte Sindelar. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 17.05.2017.

Positive surgical margins in robot-assisted partial nephrectomy: a multi-institutional analysis of oncologic outcomes (leave no tumor behind).

PubMed

Khalifeh, Ali; Kaouk, Jihad H; Bhayani, Sam; Rogers, Craig; Stifelman, Michael; Tanagho, Youssef S; Kumar, Ramesh; Gorin, Michael A; Sivarajan, Ganesh; Samarasekera, Dinesh; Allaf, Mohamad E

2013-11-01

Expanding indications for robot-assisted partial nephrectomy raise major oncologic concerns for positive surgical margins. Previous reports showed no correlation between positive surgical margins and oncologic outcomes. We report a multi-institutional experience with the oncologic outcomes of positive surgical margins on robot-assisted partial nephrectomy. Pathological and clinical followup data were reviewed from an institutional review board approved, prospectively maintained joint database from 5 institutions. Tumors with malignant pathology were isolated and statistically analyzed for demographics and oncologic followup. The log rank test was used to compare recurrence-free and metastasis-free survival between patients with positive and negative surgical margins. The proportional hazards method was used to assess the influence of multiple factors, including positive surgical margins, on recurrence and metastasis. A total of 943 robot-assisted partial nephrectomies for malignant tumors were successfully completed. Of the patients 21 (2.2%) had positive surgical margins on final pathological assessment, resulting in 2 groups, including the 21 with positive surgical margins and 922 with negative surgical margins. Positive surgical margin cases had higher recurrence and metastasis rates (p<0.001). As projected by the Kaplan-Meier method in the population as a whole at followup out to 63.6 months, 5-year recurrence-free and metastasis-free survival was 94.8% and 97.5%, respectively. There was a statistically significant difference in recurrence-free and metastasis-free survival between patients with positive and negative surgical margins (log rank test<0.001), which favored negative surgical margins. Positive surgical margins showed an 18.4-fold higher HR for recurrence when adjusted for multiple tumors, tumor size, tumor growth pattern and pathological stage. Positive surgical margins on final pathological evaluation increase the HR of recurrence and metastasis. In addition to pathological and molecular tumor characteristics, this should be considered to plan appropriate management. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier 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.

Robot-assisted laparoscopic adenomyomectomy of adenomyotic nodule implanted in the uterine endometrium manifesting as endometrial cancer: a case report and literature review.

PubMed

Jeon, J H; Jeong, K; Moon, H S

2017-01-01

Thickened uterine endometrium with abnormal uterine bleeding highly suggests endometrial hyperplasia or endometrial carcinoma. A case of 35-year-old nulliparous woman came to our department with endometrial mass manifesting as endometrial cancer. Transrectal ultrasonography and magnetic resonance imaging (MRI) showed an 8x6 cm multicystic, ill-defined mass compacted at the uterine endometrium, the anterior wall of the uterus, and 3x3 cm heterogenous mass at the left adnexa. The edometrial mass showed multiple septations with enhancement and low-signal intensity on T2-weighted images. After endometrial biopsy was done and simple hyperplasia without atypia was observed at the histopathologic finding, the patient underwent robot-assisted laparoscopy and diagnosed as adenomyoma at the frozen pathology. After adenomyomectomy, permanent pathologic analysis revealed the same result and she recovered without any complications and responded well to gonadotropin-releasing hormone (GnRH) agonist therapy.

A Computer-Aided Distinction Method of Borderline Grades of Oral Cancer

NASA Astrophysics Data System (ADS)

Sami, Mustafa M.; Saito, Masahisa; Muramatsu, Shogo; Kikuchi, Hisakazu; Saku, Takashi

We have developed a new computer-aided diagnostic system for differentiating oral borderline malignancies in hematoxylin-eosin stained microscopic images. Epithelial dysplasia and carcinoma in-situ (CIS) of oral mucosa are two different borderline grades similar to each other, and it is difficult to distinguish between them. A new image processing and analysis method has been applied to a variety of histopathological features and shows the possibility for differentiating the oral cancer borderline grades automatically. The method is based on comparing the drop-shape similarity level in a particular manually selected pair of neighboring rete ridges. It was found that the considered similarity level in dysplasia was higher than those in epithelial CIS, of which pathological diagnoses were conventionally made by pathologists. The developed image processing method showed a good promise for the computer-aided pathological assessment of oral borderline malignancy differentiation in clinical practice.

Delusions as harmful malfunctioning beliefs.

PubMed

Miyazono, Kengo

2015-05-01

Delusional beliefs are typically pathological. Being pathological is clearly distinguished from being false or being irrational. Anna might falsely believe that his husband is having an affair but it might just be a simple mistake. Again, Sam might irrationally believe, without good evidence, that he is smarter than his colleagues, but it might just be a healthy self-deceptive belief. On the other hand, when a patient with brain damage caused by a car accident believes that his father was replaced by an imposter or another patient with schizophrenia believes that "The Organization" painted the shops on a street in red and green to convey a message, these beliefs are not merely false or irrational. They are pathological. What makes delusions pathological? This paper explores the negative features because of which delusional beliefs are pathological. First, I critically examine the proposals according to which delusional beliefs are pathological because of (1) their strangeness, (2) their extreme irrationality, (3) their resistance to folk psychological explanations or (4) impaired responsibility-grounding capacities of people with them. I present some counterexamples as well as theoretical problems for these proposals. Then, I argue, following Wakefield's harmful dysfunction analysis of disorder, that delusional beliefs are pathological because they involve some sorts of harmful malfunctions. In other words, they have a significant negative impact on wellbeing (=harmful) and, in addition, some psychological mechanisms, directly or indirectly related to them, fail to perform the jobs for which they were selected in the past (=malfunctioning). An objection to the proposal is that delusional beliefs might not involve any malfunctions. For example, they might be playing psychological defence functions properly. Another objection is that a harmful malfunction is not sufficient for something to be pathological. For example, false beliefs might involve some malfunctions according to teleosemantics, a popular naturalist account of mental content, but harmful false beliefs do not have to be pathological. I examine those objections in detail and show that they should be rejected after all. Copyright © 2014. Published by Elsevier Inc.

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.

Systematic review and meta-analysis of prognostic role of splenic vessels infiltration in resectable pancreatic cancer.

PubMed

Crippa, Stefano; Cirocchi, Roberto; Maisonneuve, Patrick; Partelli, Stefano; Pergolini, Ilaria; Tamburrino, Domenico; Aleotti, Francesca; Reni, Michele; Falconi, Massimo

2018-01-01

Identification of factors associated with dismal survival after surgery in resectable pancreatic ductal adenocarcinoma is important to select patients for neoadjuvant treatment. The present meta-analysis aimed to compare the results of distal pancreatectomy for resectable adenocarcinoma of the pancreatic body-tail with and without splenic vessels infiltration. A systematic search was performed of PubMed, Embase and the Cochrane Library in accordance with PRISMA guidelines. The inclusion criteria were studies including patients who underwent distal pancreatectomy for pancreatic cancer with or without splenic vessels infiltration. 5-year overall survival (OS) was the primary outcomes. Meta-analysis was carried out applying time-to-event method. Six articles with 423 patients were analysed. Patients with pathological splenic artery invasion had a worse survival compared with those without infiltration (Hazard ratio 1.76, 95% CI 1.36-2.28; P < 0.0001). A similar results was found when considering pathological splenic vessels infiltration, showing that survival was significantly poorer when splenic vein infiltration was present (Hazard ratio 1.51, 95% CI 1.19-1.93; P = 0.0009). This meta-analysis showed worse survival for patients with splenic vessels infiltration undergoing distal pancreatectomy for pancreatic cancer. Splenic vessels infiltration represents the stigmata of a more aggressive disease, although resectable. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Video Games Related to Young Adults: Mapping Research Interest

ERIC Educational Resources Information Center

Piotrowski, Chris

2015-01-01

This study attempts to identify the typological-research domain of the extant literature on video games related to college-age samples (18-29 years-of-age). A content analysis of 264 articles, from PsycINFO for these identifiers, was performed. Findings showed that negative or pathological aspects of video gaming, i.e., violence potential,…

Primary Adenocarcinoma of Intestinal Type Arising From a Vaginal Mass: A Case Report.

PubMed

Morrell, Lindsay H; Matthews, Kirk J; Chafe, Weldon E

2015-07-01

A patient with a history of a severe vaginal laceration during vaginal birth, unknown degree, presented with recurrent vaginal discharge and was found to have a vaginal mass. Pathologic analysis showed squamous mucosa transitioning into colonic type of mucosa with adenocarcinoma developed from colonic type of mucosa, reminiscent of anorectal junction.

Metabolomic analysis reveals altered metabolic pathways in a rat model of gastric carcinogenesis.

PubMed

Gu, Jinping; Hu, Xiaomin; Shao, Wei; Ji, Tianhai; Yang, Wensheng; Zhuo, Huiqin; Jin, Zeyu; Huang, Huiying; Chen, Jiacheng; Huang, Caihua; Lin, Donghai

2016-09-13

Gastric cancer (GC) is one of the most malignant tumors with a poor prognosis. Alterations in metabolic pathways are inextricably linked to GC progression. However, the underlying molecular mechanisms remain elusive. We performed NMR-based metabolomic analysis of sera derived from a rat model of gastric carcinogenesis, revealed significantly altered metabolic pathways correlated with the progression of gastric carcinogenesis. Rats were histologically classified into four pathological groups (gastritis, GS; low-grade gastric dysplasia, LGD; high-grade gastric dysplasia, HGD; GC) and the normal control group (CON). The metabolic profiles of the five groups were clearly distinguished from each other. Furthermore, significant inter-metabolite correlations were extracted and used to reconstruct perturbed metabolic networks associated with the four pathological stages compared with the normal stage. Then, significantly altered metabolic pathways were identified by pathway analysis. Our results showed that oxidative stress-related metabolic pathways, choline phosphorylation and fatty acid degradation were continually disturbed during gastric carcinogenesis. Moreover, amino acid metabolism was perturbed dramatically in gastric dysplasia and GC. The GC stage showed more changed metabolite levels and more altered metabolic pathways. Two activated pathways (glycolysis; glycine, serine and threonine metabolism) substantially contributed to the metabolic alterations in GC. These results lay the basis for addressing the molecular mechanisms underlying gastric carcinogenesis and extend our understanding of GC progression.

Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: Case report and literature review

PubMed Central

Ogaki, Kotaro; Koga, Shunsuke; Aoki, Naoya; Lin, Wenlang; Suzuki, Kinuko; Ross, Owen A.; Dickson, Dennis W.

2015-01-01

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy confirmed cases exceedingly rare. We report a 69-year-old white man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison’s disease. His initial symptom was temporary loss of eyesight at age 34 years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities, and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss, and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69 years with a diagnosis of multiple system atrophy. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be considered in the differential diagnosis of MSA. PMID:26227820

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.

Fluorine-18-fluorodeoxyglucose positron emission tomography as an objective substitute for CT morphologic response criteria in patients undergoing chemotherapy for colorectal liver metastases.

PubMed

Nishioka, Yujiro; Yoshioka, Ryuji; Gonoi, Wataru; Sugawara, Toshitaka; Yoshida, Shuntaro; Hashimoto, Masaji; Shindoh, Junichi

2018-05-01

The computed tomography (CT) morphologic response of colorectal liver metastases (CLM) after chemotherapy is reportedly correlated with pathologic response and survival outcomes of patients undergoing surgery. However, they are rather subjective criteria and not evaluable without adequate quality of contrast-enhanced CT images. This study sought the potential use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) as an objective substitute for predicting pathological viability of CLM after chemotherapy. Predictive ability of tumor viability of ≤10% was compared between FDG-PET/CT and contrast-enhanced CT in 34 patients who underwent curative surgical resection for CLM after chemotherapy. The CT morphology and response were defined according to the reported criteria (Chun YS, JAMA 2009). The mean standard uptake value (SUV-mean) in CLM was significantly lower in patients with group 1 and group 2 CT morphology (median, 2.53 and 3.00, respectively) than in group 3 (median, 3.32). The tumor SUV-mean showed moderate correlation with the tumor pathologic viability (r = 0.660, P < 0.0001). A receiver operating characteristic curve analysis revealed that both the tumor SUV-mean (area under the curve [AUC], 0.916; the cut-off value, 3.00) and the CT morphology (AUC, 0.882) have excellent predictive power for ≤10% of tumor viability, while degree of tumor shrinkage showed lower predictive power (AUC, 0.692). FDG-PET shows significant correlation with pathologic viability of CLM after chemotherapy and may offer additional objective information for estimating tumor viability when the CT morphologic response is not evaluable.

Egocentric Social Network Analysis of Pathological Gambling

PubMed Central

Meisel, Matthew K.; Clifton, Allan D.; MacKillop, James; Miller, Joshua D.; Campbell, W. Keith; Goodie, Adam S.

2012-01-01

Aims To apply social network analysis (SNA) to investigate whether frequency and severity of gambling problems were associated with different network characteristics among friends, family, and co-workers. is an innovative way to look at relationships among individuals; the current study was the first to our knowledge to apply SNA to gambling behaviors. Design Egocentric social network analysis was used to formally characterize the relationships between social network characteristics and gambling pathology. Setting Laboratory-based questionnaire and interview administration. Participants Forty frequent gamblers (22 non-pathological gamblers, 18 pathological gamblers) were recruited from the community. Findings The SNA revealed significant social network compositional differences between the two groups: pathological gamblers (PGs) had more gamblers, smokers, and drinkers in their social networks than did nonpathological gamblers (NPGs). PGs had more individuals in their network with whom they personally gambled, smoked, and drank with than those with who were NPG. Network ties were closer to individuals in their networks who gambled, smoked, and drank more frequently. Associations between gambling severity and structural network characteristics were not significant. Conclusions Pathological gambling is associated with compositional but not structural differences in social networks. Pathological gamblers differ from non-pathological gamblers in the number of gamblers, smokers, and drinkers in their social networks. Homophily within the networks also indicates that gamblers tend to be closer with other gamblers. This homophily may serve to reinforce addictive behaviors, and may suggest avenues for future study or intervention. PMID:23072641

[Clinical analysis of 6 cases of Bartter syndrome].

PubMed

Yin, Fang-mei; Zheng, Fang-qiu; Zhang, Xin; Wu, Mei-jun; Wei, Hong-yan; Ma, Zhong-shu; Lu, Biao; Qiu, Ming-cai

2011-03-01

To summarize the clinical characteristics of Bartter syndrome and investigate its pathogenesis. The clinical data of 6 cases of Bartter syndrome at our hospital from November 2006 to May 2010 were analyzed retrospectively. The onset age of Bartter syndrome was 13-35 years old. The main symptoms included weakness (6/6), paralysis (1/6), numbness (5/6) and tetany (4/6). All patients had normal blood pressure. The biochemical tests showed persistent hypokalemia, metabolic alkalosis (6/6) and hyperreninemia. The pathological examination of deltoid muscle biopsy showed the swelling, degeneration and necrosis of myocytes and the deposition of immunocomplex in myolemma. And the pathological examination of renal biopsy showed the hyperplasia of juxtaglomerular apparatus (5/6) and the deposition of immunocomplex. All symptoms were relieved after a therapy of potassium supplementation or a combination of indomethacin, spironolactone and immunosuppressant. When such clinical features as weakness, paralysis, tetany, hypokalemic alkalosis and normotension are encountered, Bartter syndrome should be suspected. Serum electrolytes, blood gas analysis and activation of the renin-angiotensin-aldosterone system should be examined for a definite diagnosis. The treatment of choice includes potassium and magnesium supplementation or in combination with prostaglandin synthetase inhibitor, aldosterone antagonist and immunosuppressant. Immunologic mechanism may participate in the course of Bartter syndrome.

Establishment and characterization of a novel dedifferentiated liposarcoma cell line, NDDLS-1.

PubMed

Ariizumi, Takashi; Ogose, Akira; Kawashima, Hiroyuki; Hotta, Tetsuo; Li, Guidong; Xu, Yongjun; Hirose, Takanori; Endo, Naoto

2011-08-01

We established a dedifferentiated liposarcoma cell line (NDDLS-1) that produces interleukin-6 (IL-6) and granulocyte-colony stimulating factor (G-CSF). The parental tumor showed high leukemoid reactions. The NDDLS-1 cell line was established from a pleural effusion associated with a lung metastasis. Pleomorphic tumor cells arranged in a haphazard growth pattern were seen in xenograft tumors. Numerous inflammatory cells including neutrophils or eosinophils were present throughout the tumor cells. This finding resembled the dedifferentiated area of the parental tumor. The mice bearing NDDLS-1 showed marked leukocytosis. In addition, the NDDLS-1 cells expressed IL-6 and G-CSF at both the mRNA and protein levels, while the NDDLS-1 cells produced near normal levels of tumor necrosis factor alpha (TNF-α). In the cytogenetic analysis, both the parental tumor and the NDDLS-1 cells showed a ring or giant marker chromosomes. The NDDLS-1 cell line demonstrated the amplification and expression of both MDM2 and CDK4 by fluorescence in situ hybridization and immunohistochemical analysis. The NDDLS-1 cell line is consistent with the parental dedifferentiated liposarcoma, and it should therefore be useful for further investigations of human dedifferentiated liposarcomas. © 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

Long Circulating Enzyme Replacement Therapy Rescues Bone Pathology in Mucopolysaccharidosis VII Murine Model

PubMed Central

Rowan, Daniel J.; Tomatsu, Shunji; Grubb, Jeffrey H.; Haupt, Bisong; Montaño, Adriana M.; Oikawa, Hirotaka; Sosa, Catalina; Chen, Anping; Sly, William S.

2012-01-01

Mucopolysaccharidosis (MPS) type VII is a lysosomal storage disease caused by deficiency of the lysosomal enzyme β-glucuronidase (GUS), leading to accumulation of glycosaminoglycans (GAGs). Enzyme replacement therapy (ERT) effectively clears GAG storage in the viscera. Recent studies showed that a chemically modified form of GUS (PerT-GUS), which escaped clearance by mannose 6-phosphate and mannose receptors and showed prolonged circulation, reduced CNS storage more effectively than native GUS. Clearance of storage in bone has been limited due to the avascularity of the growth plate. To evaluate the effectiveness of long-circulating PerT-GUS in reducing the skeletal pathology, we treated MPS VII mice for 12 weeks beginning at 5 weeks of age with PerT-GUS or native GUS and used micro-CT, radiographs, and quantitative histopathological analysis for assessment of bones. Micro-CT findings showed PerT-GUS treated mice had a significantly lower BMD. Histopathological analysis also showed reduced storage material and a more organized growth plate in PerT-GUS treated mice compared with native GUS treated mice. Long term treatment with PerT-GUS from birth up to 57 weeks also significantly improved bone lesions demonstrated by micro-CT, radiographs and quantitative histopathological assay. In conclusion, long-circulating PerT-GUS provides a significant impact to rescue of bone lesions and CNS involvement. PMID:22902520

[Application of digital pathology tools. An unusual case of non-Hodgkin lymphoma].

PubMed

Meyer, A-S K; Dallenbach, F E; Lienert, G; Möller, P; Lennerz, J K

2012-11-01

Currently, lymphoma diagnosis is based on a combination of morphology, immunophenotyping, and molecular testing. Using the example of an unusual case of malignant non-Hodgkin lymphoma, we show that improved visualization using digital pathology contributes to the convergence of these complementary diagnostic modalities. A 45-year-old woman presented with skin rash and cervical lymphadenopathy. Histological workup of an excised lymph node showed loss of normal architecture with diffuse infiltration and increased mitotic activity. Immunohistochemistry for CD3/CD5 showed atypical arrangement and infiltration of a T-cell population that dominated over regionally dense, MUM1-positive plasmacellular infiltrates. Expanded CD21/CD23-positive meshworks of follicular dendritic cells were present within and between regressed follicles and the T-cell infiltrate; staining for CD56 and cyclin-D1 was negative. Quantification of Ki-67 staining within the T-, B- and plasmacellular compartments was achieved by digital image conversion, overlay and subsequent quantification algorithms that revealed proliferation within more than 60% of T-cells, over 50% of plasma cells and only 20% of B-cells. Clonality analysis by PCR revealed monoclonal rearrangement for both T-cell receptor gamma chains and immunoglobulin heavy chains. Taken together, we present an unusual combination of an angioimmunoblastic T-cell lymphoma (AITL) and simultaneous plasmacellular lymphoma. This report demonstrates how application of modern tools of digital pathology can visually integrate unusual morphological and molecular findings.

[Feasibility study of dynamic contrast enhanced magnetic resonance imaging qualitative diagnosis of musculoskeletal tumors].

PubMed

Zhang, J; Zuo, P L; Cheng, K B; Yu, A H; Cheng, X G

2016-04-18

To investigate the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in differentiating musculoskeletal tumors with different behaviours of pathological findings before therapy. A total of 34 subjects of musculoskeletal tumors were involved in this retrospective analysis. DCE-MRI was performed using a fat-saturated 3D VIBE (volumetric interpolated breath-hold exam) imaging sequence with following parameters: FA, 10 degree; TR/TE, 5.6/2.4 ms; slice thickness, 4.0 mm with no intersection gap; field of view, 310 mm×213 mm; matrix, 256×178; voxel size, 1.2 mm×1.2 mm×4.0 mm; parallel imaging acceleration factor. The actuation time for the DCE-MRI sequence was 255 s with a temporal resolution of 5 s and 40 image volumes. Using pathological results as a gold standard, tumors were divided into benign, borderline and malignant tumors. Toft's model was used for calculation of K(trans) (volume transfer constant), Ve (extravascular extracellular space distribute volume per unit tissue volume) and Kep (microvascular permeability reflux constant). Those parameters were compared between the lesions and the control tissues using paired t tests. The one-way analysis of variance was used to assess the difference among benign, borderline and malignant tumors. P values <0.05 difference was statistically significant. Based on the WHO Classification of Tumours of Soft Tissue and Bone(2012) criteria, 34 patients were divided into three groups: 11 for benign tumors, 12 for borderline tumors, and 11 for malignancies. Compared with control tissues, K(trans) and Kep showed no difference, but Ve was increased in benign tumors, Kep showed no difference, but K(trans) and Ve were increased in borderline tumors,K(trans), Kep and Ve were increased in malignant tumors. K(trans) (P<0.001) and Kep (P<0.01) were significantly higher in malignant tumors than in benign and borderline tumors, but did not show any difference between benign tumors and borderline tumors. Ve was significantly higher in malignant tumors than in benign (P<0.05), but did not show any difference between malignant and borderline tumors, benign tumors and borderline tumors (P>0.05). DCE-MRI technique is useful to evaluate the pathological behaviour of musculoskeletal tumors. The quantitative analysis of DCE parameters in conjunction with conventional MR images can improve the accuracy of musculoskeletal tumor qualitative analysis.

Role of genetic polymorphisms in NFKB-mediated inflammatory pathways in response to primary chemoradiation therapy for rectal cancer.

PubMed

Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

2014-11-01

To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Dzhugashvili, Maia; Department of Radiation Oncology, Madrid Oncology Institute; Luengo-Gil, Ginés

Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95%more » confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment.« less

Risk of Pathologic Upgrading or Locally Advanced Disease in Early Prostate Cancer Patients Based on Biopsy Gleason Score and PSA: A Population-Based Study of Modern Patients

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

Caster, Joseph M.; Falchook, Aaron D.; Hendrix, Laura H.

Purpose: Radiation oncologists rely on available clinical information (biopsy Gleason score and prostate-specific antigen [PSA]) to determine the optimal treatment regimen for each prostate cancer patient. Existing published nomograms correlating clinical to pathologic extent of disease were based on patients treated in the 1980s and 1990s at select academic institutions. We used the Surveillance, Epidemiology, and End Results (SEER) database to examine pathologic outcomes (Gleason score and cancer stage) in early prostate cancer patients based on biopsy Gleason score and PSA concentration. Methods and Materials: This analysis included 25,858 patients whose cancer was diagnosed between 2010 and 2011, with biopsymore » Gleason scores of 6 to 7 and clinical stage T1 to T2 disease, who underwent radical prostatectomy. In subgroups based on biopsy Gleason score and PSA level, we report the proportion of patients with pathologically advanced disease (positive surgical margin or pT3-T4 disease) or whose Gleason score was upgraded. Logistic regression was used to examine factors associated with pathologic outcomes. Results: For patients with biopsy Gleason score 6 cancers, 84% of those with PSA <10 ng/mL had surgical T2 disease with negative margins; this decreased to 61% in patients with PSA of 20 to 29.9 ng/mL. Gleason score upgrading was seen in 43% (PSA: <10 ng/mL) to 61% (PSA: 20-29.9 ng/mL) of biopsy Gleason 6 patients. Patients with biopsy Gleason 7 cancers had a one-third (Gleason 3 + 4; PSA: <10 ng/mL) to two-thirds (Gleason 4 + 3; PSA: 20-29.9 ng/mL) probability of having pathologically advanced disease. Gleason score upgrading was seen in 11% to 19% of patients with biopsy Gleason 4 + 3 cancers. Multivariable analysis showed that higher PSA and older age were associated with Gleason score upgrading and pathologically advanced disease. Conclusions: This is the first population-based study to examine pathologic extent of disease and pathologic Gleason score upgrading based on clinically available information in modern patients. These data inform the selection of radiation therapy strategies and an understanding of whether prostatectomy alone is likely to be curative for patients with early prostate cancers.« less

Deciphering Sources of Variability in Clinical Pathology.

PubMed

Tripathi, Niraj K; Everds, Nancy E; Schultze, A Eric; Irizarry, Armando R; Hall, Robert L; Provencher, Anne; Aulbach, Adam

2017-01-01

The objectives of this session were to explore causes of variability in clinical pathology data due to preanalytical and analytical variables as well as study design and other procedures that occur in toxicity testing studies. The presenters highlighted challenges associated with such variability in differentiating test article-related effects from the effects of experimental procedures and its impact on overall data interpretation. These presentations focused on preanalytical and analytical variables and study design-related factors and their influence on clinical pathology data, and the importance of various factors that influence data interpretation including statistical analysis and reference intervals. Overall, these presentations touched upon potential effect of many variables on clinical pathology parameters, including animal physiology, sample collection process, specimen handling and analysis, study design, and some discussion points on how to manage those variables to ensure accurate interpretation of clinical pathology data in toxicity studies. This article is a brief synopsis of presentations given in a session entitled "Deciphering Sources of Variability in Clinical Pathology-It's Not Just about the Numbers" that occurred at the 35th Annual Symposium of the Society of Toxicologic Pathology in San Diego, California.

CFTR expression and organ damage in cystic fibrosis

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

Tizzano, E.; Chitayat, D.; Buchwald, M.

1994-09-01

To assist our understanding of the origin of organ damage caused by cystic fibrosis (CF) disease, we have analyzed the pattern of expression of the CF gene (CFTR). mRNA in situ hybridization analysis was carried out in human fetal, newborn, infant and adult tissues and the abundance of the mRNA was correlated with the known pathology at the various stages of human development. Analysis of the pattern of expression indicates a constitutive level of mRNA in gastrointestinal tissues starting during early development and maintained throughout life. Prenatal respiratory tissues show qualitative and quantitative major differences in comparison to postnatal lungmore » samples. Male reproductive tissues show high levels of expression in the head of the epididymis compared with the rest of the male ducts. Female reproductive tissues show a variable pattern of expression at different stages during fetal development and during puberty probably due to changes in hormonal levels. Gastrointestinal and male reproductive tissues have a consistent pathology at birth, whereas no lung abnormalities have been described in newborns affected by CF. Our results show that there is no exact correlations between organ damage present at birth and the degree of CFTR expression. To explain these observations, we hypothesize that the pathogenesis of organ damage in CF depend on at least three factors: the rate of CFTR-mediated fluid secretion, differences in genotype and environmental factors, such as the amount of macromolecules in the lumen of the ducts. This last element predicts that damage will occur in tissues with high protein loads and low flow rates (e.g. pancreas, epididymis), where the absence of CFTR function leads to obstruction and pathology. Organs that express CFTR but with no significant damage (e.g. prenatal lung, female reproductive tissues), will have a low protein load and a high flow rates.« less

Comparative analysis of whole mount processing and systematic sampling of radical prostatectomy specimens: pathological outcomes and risk of biochemical recurrence.

PubMed

Salem, Shady; Chang, Sam S; Clark, Peter E; Davis, Rodney; Herrell, S Duke; Kordan, Yakup; Wills, Marcia L; Shappell, Scott B; Baumgartner, Roxelyn; Phillips, Sharon; Smith, Joseph A; Cookson, Michael S; Barocas, Daniel A

2010-10-01

Whole mount processing is more resource intensive than routine systematic sampling of radical retropubic prostatectomy specimens. We compared whole mount and systematic sampling for detecting pathological outcomes, and compared the prognostic value of pathological findings across pathological methods. We included men (608 whole mount and 525 systematic sampling samples) with no prior treatment who underwent radical retropubic prostatectomy at Vanderbilt University Medical Center between January 2000 and June 2008. We used univariate and multivariate analysis to compare the pathological outcome detection rate between pathological methods. Kaplan-Meier curves and the log rank test were used to compare the prognostic value of pathological findings across pathological methods. There were no significant differences between the whole mount and the systematic sampling groups in detecting extraprostatic extension (25% vs 30%), positive surgical margins (31% vs 31%), pathological Gleason score less than 7 (49% vs 43%), 7 (39% vs 43%) or greater than 7 (12% vs 13%), seminal vesicle invasion (8% vs 10%) or lymph node involvement (3% vs 5%). Tumor volume was higher in the systematic sampling group and whole mount detected more multiple surgical margins (each p <0.01). There were no significant differences in the likelihood of biochemical recurrence between the pathological methods when patients were stratified by pathological outcome. Except for estimated tumor volume and multiple margins whole mount and systematic sampling yield similar pathological information. Each method stratifies patients into comparable risk groups for biochemical recurrence. Thus, while whole mount is more resource intensive, it does not appear to result in improved detection of clinically important pathological outcomes or prognostication. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Improving patient safety through quality assurance.

PubMed

Raab, Stephen S

2006-05-01

Anatomic pathology laboratories use several quality assurance tools to detect errors and to improve patient safety. To review some of the anatomic pathology laboratory patient safety quality assurance practices. Different standards and measures in anatomic pathology quality assurance and patient safety were reviewed. Frequency of anatomic pathology laboratory error, variability in the use of specific quality assurance practices, and use of data for error reduction initiatives. Anatomic pathology error frequencies vary according to the detection method used. Based on secondary review, a College of American Pathologists Q-Probes study showed that the mean laboratory error frequency was 6.7%. A College of American Pathologists Q-Tracks study measuring frozen section discrepancy found that laboratories improved the longer they monitored and shared data. There is a lack of standardization across laboratories even for governmentally mandated quality assurance practices, such as cytologic-histologic correlation. The National Institutes of Health funded a consortium of laboratories to benchmark laboratory error frequencies, perform root cause analysis, and design error reduction initiatives, using quality assurance data. Based on the cytologic-histologic correlation process, these laboratories found an aggregate nongynecologic error frequency of 10.8%. Based on gynecologic error data, the laboratory at my institution used Toyota production system processes to lower gynecologic error frequencies and to improve Papanicolaou test metrics. Laboratory quality assurance practices have been used to track error rates, and laboratories are starting to use these data for error reduction initiatives.

Chewing and spitting out food as a compensatory behavior in patients with eating disorders.

PubMed

Song, Youn Joo; Lee, Jung-Hyun; Jung, Young-Chul

2015-10-01

Recent studies suggest that chewing and spitting out food may be associated with severe eating-related pathology. The purpose of this study was to investigate the relationship between chewing and spitting, and other symptoms of eating disorders. We hypothesized that patients who chew and spit as a compensatory behavior have more severe eating-related pathology than patients who have never engaged in chewing and spitting behavior. We divided 359 patients with eating disorders into two groups according to whether they engaged in chewing and spitting as a compensatory behavior to lose weight or not. After comparing eating-related pathology between the two groups, we examined factors associated with pathologic eating behaviors using logistic regression analysis. Among our 359 participants, 24.5% reported having engaged in chewing and spitting as a compensatory behavior. The chewing and spitting (CHSP+) group showed more severe eating disorder symptoms and suicidal behaviors. This group also had significantly higher scores on subscales that measured drive for thinness, bulimia, and impulse regulation on the EDI-2, Food Craving Questionnaire, Body Shape Questionnaire, Beck Depression Inventory, Beck Anxiety Inventory, and Maudsley Obsessive Compulsive Inventory. Chewing and spitting is a common compensatory behavior among patients with eating disorders and is associated with more-pathologic eating behaviors and higher scores on psychometric tests. Copyright © 2015 Elsevier Inc. All rights reserved.

The Relationship between Money Attitudes and Overall Pathology.

ERIC Educational Resources Information Center

McClure, Robert F.

1984-01-01

Surveyed adults (N=159) about money attitudes and general pathological tendencies of anxiety, neuroticism, and introversion. Results showed that problem money attitudes were significantly related to general pathological attitudes but not to each other. (LLL)

[Phoneme analysis and phoneme discrimination of juvenile speech therapy school students].

PubMed

Franz, S; Rosanowski, F; Eysholdt, U; Hoppe, U

2011-05-01

Phoneme analysis and phoneme discrimination, important factors in acquiring spoken and written language, have been evaluated in juvenile speech therapy school students. The results have been correlated with the results of a school achievement test. The following questions were of interest: Do students in the lower verbal skill segment show pathological phoneme analysis and phoneme discrimination skills? Do the results of the school achievement test differ from the results by students visiting German "Hauptschule"? How does phoneme analysis and phoneme discrimination performance correlate to other tested parameters? 74 students of a speech therapy school ranging from 7 (th) to 9 (th) grade were examined (ages 12;10-17;04) with the Heidelberg Phoneme Discrimination Test H-LAD and the school achievement test "Prüfsystem für Schul- und Bildungsberatung PSB-R 6-13". Compared to 4 (th) graders the juvenile speech therapy school students showed worse results in the H-LAD test with good differentiation in the lower measuring range. In the PSB-R 6-13 test the examined students did worse compared to students visiting German "Hauptschule" for all grades except 9 (th) grade. Comparing H-LAD and PSB-R 6-13 shows a significant correlation for the sub-tests covering language competence and intelligence but not for the concentration tests. Pathological phoneme analysis and phoneme discrimination skills suggest elevated need for counseling, but this needs to corroborated through additional linguistic parameters and measuring non-verbal intelligence. Further trails are needed in order to clarify whether the results can lead to sophisticated therapy algorithms for educational purposes. © Georg Thieme Verlag KG Stuttgart · New York.

Histogram and gray level co-occurrence matrix on gray-scale ultrasound images for diagnosing lymphocytic thyroiditis.

PubMed

Shin, Young Gyung; Yoo, Jaeheung; Kwon, Hyeong Ju; Hong, Jung Hwa; Lee, Hye Sun; Yoon, Jung Hyun; Kim, Eun-Kyung; Moon, Hee Jung; Han, Kyunghwa; Kwak, Jin Young

2016-08-01

The objective of the study was to evaluate whether texture analysis using histogram and gray level co-occurrence matrix (GLCM) parameters can help clinicians diagnose lymphocytic thyroiditis (LT) and differentiate LT according to pathologic grade. The background thyroid pathology of 441 patients was classified into no evidence of LT, chronic LT (CLT), and Hashimoto's thyroiditis (HT). Histogram and GLCM parameters were extracted from the regions of interest on ultrasound. The diagnostic performances of the parameters for diagnosing and differentiating LT were calculated. Of the histogram and GLCM parameters, the mean on histogram had the highest Az (0.63) and VUS (0.303). As the degrees of LT increased, the mean decreased and the standard deviation and entropy increased. The mean on histogram from gray-scale ultrasound showed the best diagnostic performance as a single parameter in differentiating LT according to pathologic grade as well as in diagnosing LT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Urine metabolic profiling for the pathogenesis research of erosive oral lichen planus.

PubMed

Li, Xu-Zhao; Yang, Xu-Yan; Wang, Yu; Zhang, Shuai-Nan; Zou, Wei; Wang, Yan; Li, Xiao-Nan; Wang, Ling-Shu; Zhang, Zhi-Gang; Xie, Liang-Zhen

2017-01-01

Oral lichen planus (OLP) is a relatively common chronic immune-pathological and inflammatory disease and potentially oral precancerous lesion. Erosive OLP patients show the higher rate of malignant transformation than patients with non-erosive OLP. Identifying the potential biomarkers related to erosive OLP may help to understand the pathogenesis of the diseases. Metabolic profiles were compared in control and patient subjects with erosive OLP by using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods An integrative analysis was used to identify the perturbed metabolic pathways and pathological processes that may be associated with the disease. In total, 12 modulated metabolites were identified and considered as the potential biomarkers of erosive OLP. Multiple metabolic pathways and pathological processes were involved in erosive OLP. The dysregulations of these metabolites could be used to explain the pathogenesis of the disease, which could also be the potential therapeutic targets for the disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

New Trends of Emerging Technologies in Digital Pathology.

PubMed

Bueno, Gloria; Fernández-Carrobles, M Milagro; Deniz, Oscar; García-Rojo, Marcial

2016-01-01

The future paradigm of pathology will be digital. Instead of conventional microscopy, a pathologist will perform a diagnosis through interacting with images on computer screens and performing quantitative analysis. The fourth generation of virtual slide telepathology systems, so-called virtual microscopy and whole-slide imaging (WSI), has allowed for the storage and fast dissemination of image data in pathology and other biomedical areas. These novel digital imaging modalities encompass high-resolution scanning of tissue slides and derived technologies, including automatic digitization and computational processing of whole microscopic slides. Moreover, automated image analysis with WSI can extract specific diagnostic features of diseases and quantify individual components of these features to support diagnoses and provide informative clinical measures of disease. Therefore, the challenge is to apply information technology and image analysis methods to exploit the new and emerging digital pathology technologies effectively in order to process and model all the data and information contained in WSI. The final objective is to support the complex workflow from specimen receipt to anatomic pathology report transmission, that is, to improve diagnosis both in terms of pathologists' efficiency and with new information. This article reviews the main concerns about and novel methods of digital pathology discussed at the latest workshop in the field carried out within the European project AIDPATH (Academia and Industry Collaboration for Digital Pathology). © 2016 S. Karger AG, Basel.

Gene Expression Profile Change and Associated Physiological and Pathological Effects in Mouse Liver Induced by Fasting and Refeeding

PubMed Central

Zhang, Fang; Xu, Xiang; Zhou, Ben; He, Zhishui; Zhai, Qiwei

2011-01-01

Food availability regulates basal metabolism and progression of many diseases, and liver plays an important role in these processes. The effects of food availability on digital gene expression profile, physiological and pathological functions in liver are yet to be further elucidated. In this study, we applied high-throughput sequencing technology to detect digital gene expression profile of mouse liver in fed, fasted and refed states. Totally 12162 genes were detected, and 2305 genes were significantly regulated by food availability. Biological process and pathway analysis showed that fasting mainly affected lipid and carboxylic acid metabolic processes in liver. Moreover, the genes regulated by fasting and refeeding in liver were mainly enriched in lipid metabolic process or fatty acid metabolism. Network analysis demonstrated that fasting mainly regulated Drug Metabolism, Small Molecule Biochemistry and Endocrine System Development and Function, and the networks including Lipid Metabolism, Small Molecule Biochemistry and Gene Expression were affected by refeeding. In addition, FunDo analysis showed that liver cancer and diabetes mellitus were most likely to be affected by food availability. This study provides the digital gene expression profile of mouse liver regulated by food availability, and demonstrates the main biological processes, pathways, gene networks and potential hepatic diseases regulated by fasting and refeeding. These results show that food availability mainly regulates hepatic lipid metabolism and is highly correlated with liver-related diseases including liver cancer and diabetes. PMID:22096593

Gene expression profile change and associated physiological and pathological effects in mouse liver induced by fasting and refeeding.

PubMed

Zhang, Fang; Xu, Xiang; Zhou, Ben; He, Zhishui; Zhai, Qiwei

2011-01-01

Food availability regulates basal metabolism and progression of many diseases, and liver plays an important role in these processes. The effects of food availability on digital gene expression profile, physiological and pathological functions in liver are yet to be further elucidated. In this study, we applied high-throughput sequencing technology to detect digital gene expression profile of mouse liver in fed, fasted and refed states. Totally 12162 genes were detected, and 2305 genes were significantly regulated by food availability. Biological process and pathway analysis showed that fasting mainly affected lipid and carboxylic acid metabolic processes in liver. Moreover, the genes regulated by fasting and refeeding in liver were mainly enriched in lipid metabolic process or fatty acid metabolism. Network analysis demonstrated that fasting mainly regulated Drug Metabolism, Small Molecule Biochemistry and Endocrine System Development and Function, and the networks including Lipid Metabolism, Small Molecule Biochemistry and Gene Expression were affected by refeeding. In addition, FunDo analysis showed that liver cancer and diabetes mellitus were most likely to be affected by food availability. This study provides the digital gene expression profile of mouse liver regulated by food availability, and demonstrates the main biological processes, pathways, gene networks and potential hepatic diseases regulated by fasting and refeeding. These results show that food availability mainly regulates hepatic lipid metabolism and is highly correlated with liver-related diseases including liver cancer and diabetes.

Atlas of neuroanatomy with radiologic correlation and pathologic illustration

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

Dublin, A.B.; Dublin, W.B.

1982-01-01

This atlas correlates gross neuroanatomic specimens with radiographs and computed tomographic scans. Pathologic specimens and radiographs are displayed in a similar manner. The first chapter, on embryology, shows the development of the telencephalon, diencephalon, mesencephalon, and metencephalon through a series of overlays. The anatomical section shows the surface of the brain, the ventricles and their adjacent structures, and the vascular system. CT anatomy is demonstrated by correlating CT scans with pathologic brain specimens cut in the axial plane. Pathologic changes associated with congenital malformations, injections, injuries, tumors, and other causes are demonstrated in the last six chapters.

Evaluation of genotoxicity and subclinical toxicity of Agaricus blazei Murrill in the Ames test and in histopathological and biochemical analysis.

PubMed

Chang, Jin-Biou; Lu, Hsu-Feng; Liao, Nien-Chieh; Lee, Ching-Sung; Yeh, Ming-Yang; Liu, Chi-Ming; Chung, Ming-Teng; Man-Kuan, Au; Lin, Jen-Jyh; Wu, Ming-Fang; Chung, Jing-Gung

2012-01-01

This study was conducted in order to assess the safety and tolerability of Agaricus blazei Murrill (ABM) in general toxicological studies by Ames tests in vitro and in 28-day feeding toxicity experiments. There were no dose-dependent increases or decreases in the number of revertant colonies both with and without metabolic activation in Ames tests. Doses of 10, 5 and 0.1 mg/per mouse of ABM daily were administered by oral gavage to mice (n=10) for 28 days. The effects on clinical observations, clinical pathology, and histopathology were evaluated. There were no significant changes in the brain, heart, kidney, liver, spleen, adrenal gland, testes or ovaries visually. With increasing doses, male and female treated mice did not show any gradual elevation of serum concentration in any of the nine items we examined, except for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in females. The AST levels of the treatment by medium or high dose and the ALT levels of the treatment by high dose in females were abnormal in comparison to those of the baseline control group, with significant differences. On studying the histological changes in mice, tissue sections of negative control and experimental groups exhibited no apparent pathological alterations. In summary, the Ames test, pathology determinations, biochemical analysis and routine blood parameters were all normal, except for AST and ALT in females. Results showed that the statistical differences observed in one sex were not observed in the other and were not dose dependent.

Genetic variation in CDH13 gene was associated with non-small cell lung cancer (NSCLC): A population-based case-control study

PubMed Central

Li, Yingfu; Li, Chuanyin; Ma, Qianli; Zhang, Yu; Yao, Yueting; Liu, Shuyuan; Zhang, Xinwen; Hong, Chao; Tan, Fang; Shi, Li; Yao, Yufeng

2018-01-01

Cadherin 13 (CDH13, T-cadherin, H-cadherin) has been identified as an anti-oncogene in various cancers. Recent studies have reported that downregulation of H-cadherin in cancers is associated with CDH13 promoter hypermethylation, which could be affected by the single nucleotide polymorphisms (SNPs) near CpG sites in the CDH13 promoter. In the current study, we investigated and analyzed the association of seven SNPs (rs11646213, rs12596316, rs3865188, rs12444338, rs4783244, rs12051272 and rs7195409) with non-small cell lung cancer (NSCLC) using logistic regression analysis. SNPs rs11646213, rs12596316, rs3865188 and rs12444338 are located in the promoter region, rs4783244 and rs12051272 are located in intron 1, and rs7195409 is located in intron 7. A total of 454 patients with NSCLC were placed into a NSCLC group and 444 healthy controls were placed into a control group, all participants were recruited to genotype the SNPs using Taqman assay. Our results showed that the allelic frequencies of rs11646213 were significantly different between NSCLC and control groups (P = 0.006). In addition, the association analysis of these SNPs stratified into NSCLC pathologic stages I+II and III+IV showed that the allelic frequencies rs7195409 had a significant difference between NSCLC pathologic stages I+II and III+IV (P = 0.006). Our results indicated that the rs11646213 and rs7195409 in CDH13 could be associated with NSCLC or its pathologic stages in the Chinese Han population. PMID:29416663

An Annotated Bibliography of Articles in the "Journal of Speech and Language Pathology-Applied Behavior Analysis"

ERIC Educational Resources Information Center

Esch, Barbara E.; Forbes, Heather J.

2017-01-01

The open-source "Journal of Speech and Language Pathology-Applied Behavior Analysis" ("JSLP-ABA") was published online from 2006 to 2010. We present an annotated bibliography of 80 articles published in the now-defunct journal with the aim of representing its scholarly content to readers of "The Analysis of Verbal…

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.

Clinical features, endoscopic polypectomy and STK11 gene mutation in a nine-month-old Peutz-Jeghers syndrome Chinese infant

PubMed Central

Huang, Zhi-Heng; Song, Zai; Zhang, Ping; Wu, Jie; Huang, Ying

2016-01-01

AIM: To investigate multiple polyps in a Chinese Peutz-Jeghers syndrome (PJS) infant. METHODS: A nine-month-old PJS infant was admitted to our hospital for recurrent prolapsed rectal polyps for one month. The clinical characteristics, a colonoscopic image, the pathological characteristics of the polyps and X-ray images of the intestinal perforation were obtained. Serine threonine-protein kinase 11 (STK11) gene analysis was also performed using a DNA sample from this infant. RESULTS: Here we describe the youngest known Chinese infant with PJS. Five polyps, including a giant polyp of approximately 4 cm × 2 cm in size, were removed from the infant’s intestine. Laparotomy was performed to repair a perforation caused by pneumoperitoneum. The pathological results showed that this child had PJS. Molecular analysis of the STK11 gene further revealed a novel frameshift mutation (c.64_65het_delAT) in exon 1 in this PJS infant. CONCLUSION: The appropriate treatment method for multiple polyps in an infant must be carefully considered. Our results also show that the STK11 gene mutation is the primary cause of PJS. PMID:27004004

Twenty-Year Systematic Review of the Hip Pathology, Risk Factors, Treatment, and Clinical Outcomes in Artistic Athletes-Dancers, Figure Skaters, and Gymnasts.

PubMed

Bolia, Ioanna; Utsunomiya, Hajime; Locks, Renato; Briggs, Karen; Philippon, Marc J

2018-01-01

To identify (1) the predominant level of evidence of the clinical studies regarding the hip pathology, risk factors, treatment, and clinical outcomes in artistic athletes (dancers, figure skaters, and gymnasts) (2) the most commonly reported hip pathology, risk factors, treatments, and clinical outcomes in dancers, figure skaters, and gymnasts. To conduct this systematic review PubMed, EMBASE, and Scopus databases were searched for relevant studies and pertinent data were collected from the eligible articles. Included were studies which reported hip injuries in artistic athletes, the risk factors, treatment, and/or the clinical outcomes. We excluded case reports or irrelevant studies. No meta-analysis was performed because of study heterogeneity. The methodical index for nonrandomized studies (MINORS) criteria were used for quality control. Thirty-eight studies were included in the analysis. The mean MINORS score was 13.6 ± 4.6 points indicating fair quality of evidence of the included articles. The predominant level of evidence was level IV. Chondrolabral pathology and muscle injuries were the most commonly reported pathologies. We found only 2 risk factor analysis studies; however, many studies reported risk correlation between artistic sports or imaging findings and hip pathology. Treatment strategies were reported in only 7 studies, clinical outcomes are significantly underreported. Chondrolabral pathology was the most commonly reported hip pathology in artistic athletes, however, prospective cohort studies are necessary to really understand these injuries and their associated risk factors. The lack of clinical outcomes is significant and future data collection is required to assess the effectiveness of the various treatments.

Temporal lobe epilepsy: analysis of patients with dual pathology.

PubMed

Salanova, V; Markand, O; Worth, R

2004-02-01

To determine the frequency and types of dual pathology in patients with temporal lobe epilepsy (TLE) and to analyze the clinical manifestations and surgical outcome. A total of 240 patients with TLE underwent temporal resections following a comprehensive pre-surgical evaluation. Thirty-seven (15.4%) of these had hippocampal sclerosis (HS) or temporal lobe gliosis in association with another lesion (dual pathology). Eighteen of 37 patients with dual pathology had heterotopia of the temporal lobe, nine had cortical dysplasia, four had cavernous angiomas or arteriovenous malformations, one had a dysembryoplastic neuroepithelial tumor, one had a contusion and four patients had cerebral infarctions in childhood. 68.5% had abnormal head magnetic resonance imagings, 91.3% had abnormal positron emission tomography scans, and 96% had abnormal ictal SPECT. The intracarotid amobarbital procedure (IAP) showed impaired memory of the epileptogenic side in 72% of the patients. Twenty patients had left and 17 had right-sided en bloc temporal resections, including the lesion and mesial temporal structures. Twenty-six (70.2%) became seizure-free, eight (21.6%) had rare seizures, two (5.4%) had worthwhile seizure reduction and one (2.7%) had no improvement (range of follow-up 1-16 years, mean = 7.4 years). 15.4% had dual pathology. The dual pathology was almost exclusively seen in patients whose lesions were congenital, or occurred early in life, suggesting that the hippocampus is more vulnerable and more readily develops HS in early childhood. Resections, including the lateral and mesial temporal structures led to a favorable outcome with no mortality and little morbidity.

Activity-based costing for pathology examinations and comparison with the current pricing system in Turkey.

PubMed

Ergün, Ferda A K; Ağirbaş, Ismail; Kuzu, Işınsu

2013-01-01

To demonstrate the real cost data of the pathology examinations by using the activity-based costing method and to contribute to the financial planning of the departments, health managers and also the social security institution. Forty-four examinations selected from the Healthcare Implementation Notification system list and performed at the Ankara University Faculty of Medicine Pathology Department during September 2010 were studied. The analysis and the real cost calculations were done according to the duration of the procedures. Calculated costs were compared with the Healthcare Implementation Notification system and Medicare price lists. The costs of the pathology tests listed within the same pricing levels in the Healthcare Implementation Notification system list showed great differences. The minimum and maximum costs in level 1, 2, 3, and 4 were 15,98-80,15 TL, 15,95-258,59 TL, 42,38- 236,87 TL, and 124,42-406,76 TL, respectively. Medicare price levels were more consistent with the real costs of the examinations compared to the Healthcare Implementation Notification system price list. The prices of the pathology examination listed at different levels in the Healthcare Implementation Notification system lists do not cover the real costs of the work done. The principal parameters of Activity-Based Costing system are more suitable for making the most realistic cost categorization. Although the prices could differ between countries, the Medicare system categories are more realistic than the Healthcare Implementation Notification system. The Healthcare Implementation Notification system list needs to be revised in order to reflect the real costs of the pathology examinations.

Periodontal disease burden and pathological changes in organs of dogs.

PubMed

Pavlica, Zlatko; Petelin, Milan; Juntes, Polona; Erzen, Damjan; Crossley, David A; Skaleric, Uros

2008-06-01

Bacterial plaque associated periodontal disease is the most common chronic infection in man and dogs. In man, there is an association between periodontal disease and myocardial infarction and stroke, while in dogs it has also been associated with changes in internal organs. Inflamed periodontal tissues present a 'periodontal disease burden' to the host and the extent of this inflammatory disease burden is likely to affect the degree of associated pathological change in distant organs. This hypothesis was investigated in dogs with naturally occurring periodontal disease. Post-mortem investigations including periodontal assessment, standard necropsy, and organ histology were performed on 44 mature toy and miniature Poodles (related, periodontitis predisposed breeds) that died naturally or were euthanized based on clinical disease. Animals with gross primary organ pathology were excluded. The periodontal disease burden was estimated from the total surface area of periodontal pocket epithelium using six measurements of probing depth for each tooth and the tooth circumferences. Ordinal logistic regression (OR) analysis established that for each square centimeter of periodontal disease burden there was a 1.4-times higher likelihood of greater changes being present in the left atrio-ventricular valves (OR = 1.43), plus 1.2 and 1.4 times higher likelihoodfor greater liver and kidney pathology (OR = 1.21; OR = 1.42), respectively The results show that there is a link between the estimated 'periodontal disease burden' resulting from plaque-bacteria associated periodontal disease and the level of internal pathology in this population, implying that periodontitis might contribute to the development of systemic pathology in dogs.

Cascade of convolutional neural networks for lung texture classification: overcoming ontological overlapping

NASA Astrophysics Data System (ADS)

Tarando, Sebastian Roberto; Fetita, Catalin; Brillet, Pierre-Yves

2017-03-01

The infiltrative lung diseases are a class of irreversible, non-neoplastic lung pathologies requiring regular follow-up with CT imaging. Quantifying the evolution of the patient status imposes the development of automated classification tools for lung texture. Traditionally, such classification relies on a two-dimensional analysis of axial CT images. This paper proposes a cascade of the existing CNN based CAD system, specifically tuned-up. The advantage of using a deep learning approach is a better regularization of the classification output. In a preliminary evaluation, the combined approach was tested on a 13 patient database of various lung pathologies, showing an increase of 10% in True Positive Rate (TPR) with respect to the best suited state of the art CNN for this task.

Twinkle artefact in the ultrasound diagnosis of superficial epidermoid cysts

PubMed Central

Clarke, Richard; Suresh, Priya; Thomas, Rose

2016-01-01

Aim The aim of the study was to evaluate whether the twinkle artefact is a valuable feature in the sonographic diagnosis of superficial epidermoid cysts. Materials and methods A retrospective search was undertaken of our institution’s Radiology Information System and pathology database to identify cases of superficial masses showing the twinkle artefact that proceeded to surgical excision. Results Eighteen superficial masses demonstrating the twinkle artefact were identified that were submitted for pathological analysis. Of these, 17 were confirmed to represent epidermoid cysts and only 1 case had an alternative diagnosis (proliferating trichilemmal cyst). Conclusion The presence of the twinkle artefact appears to be a specific and valuable ancillary sonographic feature for the diagnosis of superficial epidermoid cysts. PMID:27867407

Pathology as the enabler of human research.

PubMed

Crawford, James M; Tykocinski, Mark L

2005-09-01

Academic Pathology is a key player in human molecular science and in the powerful initiatives of the National Institutes of Health. Pathologists generate data crucial to virtually every molecular study of human tissue, and have the necessary skills and authority to oversee processing of human tissues for research analysis. We advocate that Academic Pathology is optimally positioned to drive the molecular revolution in study of human disease, through human tissue collection, analysis, and databasing. This can be achieved through playing a major role in human tissue procurement and management; establishing high-quality 'Pathology Resource Laboratories'; providing the scientific expertise for pathology data sharing; and recruiting and training physician scientists. Pathology should position itself to be the local institutional driver of technology implementation and development, by operating the resource laboratories, providing the expertise for technical and conceptual design of research projects, maintaining the databases that link molecular and morphological information on human tissues with the requisite clinical databases, providing education and mentorship of technology users, and nurturing new research through the development of preliminary data. We also consider that outstanding pathology journals are available for the publication of research emanating from such studies, to the benefit of the pathology profession as an academic enterprise. It is our earnest hope that Academic Pathology can play a leading role in the remarkable advances to be made as the 21st century unfolds.

The Geropathology Research Network: An Interdisciplinary Approach for Integrating Pathology Into Research on Aging.

PubMed

Ladiges, Warren; Ikeno, Yuji; Niedernhofer, Laura; McIndoe, Richard A; Ciol, Marcia A; Ritchey, Jerry; Liggitt, Denny

2016-04-01

Geropathology is the study of aging and age-related lesions and diseases in the form of whole necropsies/autopsies, surgical biopsies, histology, and molecular biomarkers. It encompasses multiple subspecialties of geriatrics, anatomic pathology, molecular pathology, clinical pathology, and gerontology. In order to increase the consistency and scope of communication in the histologic and molecular pathology assessment of tissues from preclinical and clinical aging studies, a Geropathology Research Network has been established consisting of pathologists and scientists with expertise in the comparative pathology of aging, the design of aging research studies, biostatistical methods for analysis of aging data, and bioinformatics for compiling and annotating large sets of data generated from aging studies. The network provides an environment to promote learning and exchange of scientific information and ideas for the aging research community through a series of symposia, the development of uniform ways of integrating pathology into aging studies, and the statistical analysis of pathology data. The efforts of the network are ultimately expected to lead to a refined set of sentinel biomarkers of molecular and anatomic pathology that could be incorporated into preclinical and clinical aging intervention studies to increase the relevance and productivity of these types of investigations. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Repair or Replacement for Isolated Tricuspid Valve Pathology? Insights from a Surgical Analysis on Long-Term Survival

PubMed Central

Farag, Mina; Arif, Rawa; Sabashnikov, Anton; Zeriouh, Mohamed; Popov, Aron-Frederik; Ruhparwar, Arjang; Schmack, Bastian; Dohmen, Pascal M.; Szabó, Gábor; Karck, Matthias; Weymann, Alexander

2017-01-01

Background Long-term follow-up data concerning isolated tricuspid valve pathology after replacement or reconstruction is limited. Current American Heart Association guidelines equally recommend repair and replacement when surgical intervention is indicated. Our aim was to investigate and compare operative mortality and long-term survival in patients undergoing isolated tricuspid valve repair surgery versus replacement. Material/Methods Between 1995 and 2011, 109 consecutive patients underwent surgical correction of tricuspid valve pathology at our institution for varying structural pathologies. A total of 41 (37.6%) patients underwent tricuspid annuloplasty/repair (TAP) with or without ring implantation, while 68 (62.3%) patients received tricuspid valve replacement (TVR) of whom 36 (53%) were mechanical and 32 (47%) were biological prostheses. Results Early survival at 30 days after surgery was 97.6% in the TAP group and 91.1% in the TVR group. After 6 months, 89.1% in the TAP group and 87.8% in the TVR group were alive. In terms of long-term survival, there was no further mortality observed after one year post surgery in both groups (Log Rank p=0.919, Breslow p=0.834, Tarone-Ware p=0.880) in the Kaplan-Meier Survival analysis. The 1-, 5-, and 8-year survival rates were 85.8% for TAP and 87.8% for TVR group. Conclusions Surgical repair of the tricuspid valve does not show survival benefit when compared to replacement. Hence valve replacement should be considered generously in patients with reasonable suspicion that regurgitation after repair will reoccur. PMID:28236633

Tyrosine Nitration within the Proline-Rich Region of Tau in Alzheimer's Disease

PubMed Central

Reyes, Juan F.; Fu, Yifan; Vana, Laurel; Kanaan, Nicholas M.; Binder, Lester I.

2011-01-01

A substantial body of evidence suggests that nitrative injury contributes to neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative disorders. Previously, we showed in vitro that within the tau protein the N-terminal tyrosine residues (Y18 and Y29) are more susceptible to nitrative modifications than other tyrosine sites (Y197 and Y394). Using site-specific antibodies to nitrated tau at Y18 and Y29, we identified tau nitrated in both glial (Y18) and neuronal (Y29) tau pathologies. In this study, we report the characterization of two novel monoclonal antibodies, Tau-nY197 and Tau-nY394, recognizing tau nitrated at Y197 and Y394, respectively. By Western blot analysis, Tau-nY197 labeled soluble tau and insoluble paired helical filament proteins (PHF-tau) nitrated at Y197 from control and AD brain samples. Tau-nY394 failed to label soluble tau isolated from control or severe AD samples, but labeled insoluble PHF-tau to a limited extent. Immunohistochemical analysis using Tau-nY197 revealed the hallmark tau pathology associated with AD; Tau-nY394 did not detect any pathological lesions characteristic of the disorder. These data suggest that a subset of the hallmark pathological inclusions of AD contain tau nitrated at Y197. However, nitration at Y197 was also identified in soluble tau from all control samples, including those at Braak stage 0, suggesting that nitration at this site in the proline-rich region of tau may have normal biological functions in the human brain. PMID:21514440

Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial.

PubMed

Ali, H R; Dariush, A; Thomas, J; Provenzano, E; Dunn, J; Hiller, L; Vallier, A-L; Abraham, J; Piper, T; Bartlett, J M S; Cameron, D A; Hayward, L; Brenton, J D; Pharoah, P D P; Irwin, M J; Walton, N A; Earl, H M; Caldas, C

2017-08-01

We have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown. The ARTemis trial randomly assigned 800 women with early stage breast cancer between May 2009 and January 2013 to three cycles of docetaxel, followed by three cycles of fluorouracil, epirubicin and cyclophosphamide once every 21 days with or without four cycles of bevacizumab. The primary endpoint was pCR (absence of invasive cancer in the breast and lymph nodes). We quantified lymphocyte density within haematoxylin and eosin (H&E) whole slide images using our previously described computational pathology approach: for every detected lymphocyte the average distance to the nearest 50 lymphocytes was calculated and the density derived from this statistic. We analyzed both pre-treatment biopsies and post-treatment surgical samples of the tumour bed. Of the 781 patients originally included in the primary endpoint analysis of the trial, 609 (78%) were included for baseline lymphocyte density analyses and a subset of 383 (49% of 781) for analyses of change in lymphocyte density. The main reason for loss of patients was the availability of digitized whole slide images. Pre-treatment lymphocyte density modelled as a continuous variable was associated with pCR on univariate analysis (odds ratio [OR], 2.92; 95% CI, 1.78-4.85; P < 0.001) and after adjustment for clinical covariates (OR, 2.13; 95% CI, 1.24-3.67; P = 0.006). Increased pre- to post-treatment lymphocyte density showed an independent inverse association with pCR (adjusted OR, 0.1; 95% CI, 0.033-0.31; P < 0.001). Lymphocyte density in pre-treatment biopsies was validated as an independent predictor of pCR in breast cancer. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients. NCT01093235. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Long-term outcomes of tissue-based ACTH-antibody assay-guided transsphenoidal resection of pituitary adenomas in Cushing disease.

PubMed

Erfe, J Mark; Perry, Avital; McClaskey, John; Inzucchi, Silvio E; James, Whitney Sheen; Eid, Tore; Bronen, Richard A; Mahajan, Amit; Huttner, Anita; Santos, Florecita; Spencer, Dennis

2017-10-13

OBJECTIVE Cushing disease is caused by a pituitary micro- or macroadenoma that hypersecretes adrenocorticotropic hormone (ACTH), resulting in hypercortisolemia. For decades, transsphenoidal resection (TSR) has been an efficacious treatment but with certain limitations, namely precise tumor localization and complete excision. The authors evaluated the novel use of a double-antibody sandwich assay for the real-time quantitation of ACTH in resected pituitary specimens with the goals of augmenting pathological diagnosis and ultimately improving long-term patient outcome. METHODS This study involved a retrospective review of records and an analysis of assay values, pathology slides, and MRI studies of patients with Cushing disease who had undergone TSR in the period from 2009 to 2014 and had at least 1 year of follow-up in coordination with an endocrinologist. In the operating room, biopsy specimens from the patients had been analyzed for tissue ACTH concentration. Additional samples were simultaneously sent for frozen-section pathological analysis. The ACTH assay performance was compared against pathology assessments of surgical tumor samples using receiver operating characteristic (ROC) analysis and against pre- and postoperative MRI studies. RESULTS Fourteen patients underwent TSR with guidance by ACTH-antibody assay and pathological assessment of 127 biopsy samples and were followed up for an average of 3 years. The ACTH threshold for discriminating adenomatous from normal tissue was 290,000 pg/mg of tissue, based on jointly maximized sensitivity (95.0%) and specificity (71.3%). Lateralization discordance between preoperative MRI studies and surgical visualization was noted in 3 patients, confirming the impression that MRI alone may not achieve optimal localization. A majority of the patients (85.7%) attained long-term disease remission based on urinary free cortisol levels, plasma cortisol levels, and long-term corticosteroid therapy. Comparisons of patient-months of remission and treatment failure showed that the remission rate in the study sample statistically exceeds the rate in historical controls (71.9%; p = 0.0007, Fisher's exact test). Long-term unexpected hormonal deficiencies were statistically similar between study patients (29%) and those in a meta-analysis (25%; p = 0.7596, Fisher's exact test). CONCLUSIONS These preliminary findings reflect the promising potential of tissue-based ACTH-antibody-guided assay for improving the cure rates of Cushing disease patients undergoing TSR. Further studies with larger sample sizes, further refinements of assay interpretation, and longer-term follow-ups are needed.

Alzheimer's disease pathological lesions activate the spleen tyrosine kinase.

PubMed

Schweig, Jonas Elias; Yao, Hailan; Beaulieu-Abdelahad, David; Ait-Ghezala, Ghania; Mouzon, Benoit; Crawford, Fiona; Mullan, Michael; Paris, Daniel

2017-09-06

The pathology of Alzheimer's disease (AD) is characterized by dystrophic neurites (DNs) surrounding extracellular Aβ-plaques, microgliosis, astrogliosis, intraneuronal tau hyperphosphorylation and aggregation. We have previously shown that inhibition of the spleen tyrosine kinase (Syk) lowers Aβ production and tau hyperphosphorylation in vitro and in vivo. Here, we demonstrate that Aβ-overexpressing Tg PS1/APPsw, Tg APPsw mice, and tau overexpressing Tg Tau P301S mice exhibit a pathological activation of Syk compared to wild-type littermates. Syk activation is occurring in a subset of microglia and is age-dependently increased in Aβ-plaque-associated dystrophic neurites of Tg PS1/APPsw and Tg APPsw mice. In Tg Tau P301S mice, a pure model of tauopathy, activated Syk occurs in neurons that show an accumulation of misfolded and hyperphosphorylated tau in the cortex and hippocampus. Interestingly, the tau pathology is exacerbated in neurons that display high levels of Syk activation supporting a role of Syk in the formation of tau pathological species in vivo. Importantly, human AD brain sections show both pathological Syk activation in DNs around Aβ deposits and in neurons immunopositive for pathological tau species recapitulating the data obtained in transgenic mouse models of AD. Additionally, we show that Syk overexpression leads to increased tau accumulation and promotes tau hyperphosphorylation at multiple epitopes in human neuron-like SH-SY5Y cells, further supporting a role of Syk in the formation of tau pathogenic species. Collectively, our data show that Syk activation occurs following Aβ deposition and the formation of tau pathological species. Given that we have previously shown that Syk activation also promotes Aβ formation and tau hyperphosphorylation, our data suggest that AD pathological lesions may be self-propagating via a Syk dependent mechanism highlighting Syk as an attractive therapeutic target for the treatment of AD.

Detection of Impaired Cerebral Autoregulation Using Selected Correlation Analysis: A Validation Study

PubMed Central

Brawanski, Alexander

2017-01-01

Multimodal brain monitoring has been utilized to optimize treatment of patients with critical neurological diseases. However, the amount of data requires an integrative tool set to unmask pathological events in a timely fashion. Recently we have introduced a mathematical model allowing the simulation of pathophysiological conditions such as reduced intracranial compliance and impaired autoregulation. Utilizing a mathematical tool set called selected correlation analysis (sca), correlation patterns, which indicate impaired autoregulation, can be detected in patient data sets (scp). In this study we compared the results of the sca with the pressure reactivity index (PRx), an established marker for impaired autoregulation. Mean PRx values were significantly higher in time segments identified as scp compared to segments showing no selected correlations (nsc). The sca based approach predicted cerebral autoregulation failure with a sensitivity of 78.8% and a specificity of 62.6%. Autoregulation failure, as detected by the results of both analysis methods, was significantly correlated with poor outcome. Sca of brain monitoring data detects impaired autoregulation with high sensitivity and sufficient specificity. Since the sca approach allows the simultaneous detection of both major pathological conditions, disturbed autoregulation and reduced compliance, it may become a useful analysis tool for brain multimodal monitoring data. PMID:28255331

Detection of Impaired Cerebral Autoregulation Using Selected Correlation Analysis: A Validation Study.

PubMed

Proescholdt, Martin A; Faltermeier, Rupert; Bele, Sylvia; Brawanski, Alexander

2017-01-01

Multimodal brain monitoring has been utilized to optimize treatment of patients with critical neurological diseases. However, the amount of data requires an integrative tool set to unmask pathological events in a timely fashion. Recently we have introduced a mathematical model allowing the simulation of pathophysiological conditions such as reduced intracranial compliance and impaired autoregulation. Utilizing a mathematical tool set called selected correlation analysis (sca), correlation patterns, which indicate impaired autoregulation, can be detected in patient data sets (scp). In this study we compared the results of the sca with the pressure reactivity index (PRx), an established marker for impaired autoregulation. Mean PRx values were significantly higher in time segments identified as scp compared to segments showing no selected correlations (nsc). The sca based approach predicted cerebral autoregulation failure with a sensitivity of 78.8% and a specificity of 62.6%. Autoregulation failure, as detected by the results of both analysis methods, was significantly correlated with poor outcome. Sca of brain monitoring data detects impaired autoregulation with high sensitivity and sufficient specificity. Since the sca approach allows the simultaneous detection of both major pathological conditions, disturbed autoregulation and reduced compliance, it may become a useful analysis tool for brain multimodal monitoring data.

Characterizing psychological dimensions in non-pathological subjects through autonomic nervous system dynamics

PubMed Central

Nardelli, Mimma; Valenza, Gaetano; Cristea, Ioana A.; Gentili, Claudio; Cotet, Carmen; David, Daniel; Lanata, Antonio; Scilingo, Enzo P.

2015-01-01

The objective assessment of psychological traits of healthy subjects and psychiatric patients has been growing interest in clinical and bioengineering research fields during the last decade. Several experimental evidences strongly suggest that a link between Autonomic Nervous System (ANS) dynamics and specific dimensions such as anxiety, social phobia, stress, and emotional regulation might exist. Nevertheless, an extensive investigation on a wide range of psycho-cognitive scales and ANS non-invasive markers gathered from standard and non-linear analysis still needs to be addressed. In this study, we analyzed the discerning and correlation capabilities of a comprehensive set of ANS features and psycho-cognitive scales in 29 non-pathological subjects monitored during resting conditions. In particular, the state of the art of standard and non-linear analysis was performed on Heart Rate Variability, InterBreath Interval series, and InterBeat Respiration series, which were considered as monovariate and multivariate measurements. Experimental results show that each ANS feature is linked to specific psychological traits. Moreover, non-linear analysis outperforms the psychological assessment with respect to standard analysis. Considering that the current clinical practice relies only on subjective scores from interviews and questionnaires, this study provides objective tools for the assessment of psychological dimensions. PMID:25859212

Favorable Prognosis in Patients With High-Grade Glioma With Radiation Necrosis: The University of Colorado Reoperation Series

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

Rusthoven, Kyle E.; Olsen, Christine; Franklin, Wilbur

Purpose: To analyze the pathology, outcomes, and prognostic factors in patients with high-grade glioma undergoing reoperation after radiotherapy (RT). Methods and Materials: Fifty-one patients with World Health Organization Grade 3-4 glioma underwent reoperation after prior RT. The median dose of prior RT was 60 Gy, and 84% received chemotherapy as part of their initial treatment. Estimation of the percentage of necrosis and recurrent tumor in each reoperation specimen was performed. Pathology was classified as RT necrosis if {>=}80% of the specimen was necrotic and as tumor recurrence if {>=}20% was tumor. Predictors of survival were analyzed using log-rank comparisons andmore » Cox proportional hazards regression. Results: The median interval between the completion of RT and reoperation was 6.7 months (range, 1-59 months). Pathologic analysis showed RT necrosis in 27% and recurrence in 73% of cases. Thirteen patients required a reoperation for uncontrolled symptoms. Among them, 1 patient (8%) had pathology showing RT necrosis, and 12 (92%) had tumor recurrence. Median survival after reoperation was longer for patients with RT necrosis (21.8 months vs. 7.0 months, p = 0.047). In 7 patients with Grade 4 tumors treated with temozolomide-based chemoradiation with RT necrosis, median survival from diagnosis and reoperation were 30.2 months and 21.8 months, respectively. Conclusions: Patients with RT necrosis at reoperation have improved survival compared with patients with tumor recurrence. Future efforts to intensify local therapy and increase local tumor control in patients with high-grade glioma seem warranted.« less

Outcome of Transsphenoidal Surgery for Cushing Disease: A Single-Center Experience Over 32 Years.

PubMed

Chandler, William F; Barkan, Ariel L; Hollon, Todd; Sakharova, Alla; Sack, Jayson; Brahma, Barunashish; Schteingart, David E

2016-02-01

Transsphenoidal surgery is the standard approach for treating Cushing disease. Evidence is needed to document effectiveness. To analyze results of transsphenoidal surgery in 276 consecutive patients, including 19 children. Medical records were reviewed for patients treated initially with surgery for Cushing disease from 1980 to 2012. Radiographic features, pathology, remissions, recurrences, and complications were recorded. Patients were categorized for statistical analysis based on tumor size (microadenomas, macroadenomas, and negative imaging) and remission type (type 1 = morning cortisol ≤3 μg/dL; type 2 = morning cortisol normal). Females comprised 78% of patients and were older than men. Imaging showed 50% microadenomas, 13% macroadenomas, and 37% negative for tumor. Remission rates for microadenomas, macroadenomas, and negative imaging were 89%, 66%, and 71%, respectively. Patients with microadenomas were more likely to have type 1 remission. Pathology showed adrenocorticotropic hormone-secreting adenomas in 82% of microadenomas, in 100% of macroadenomas, and in 43% of negative imaging. The incidence of hyperplasia was 8%. The finding of hyperplasia or no tumor on pathology predicted treatment failure. The recurrence rate was 17%, with an average time to recurrence of 4.0 years. Patients with type 1 remission had a lower rate of recurrence (13% type 1 vs 50% type 2) and a longer time to recurrence. Children had similar imaging findings, remission rates, and pathology. There were no operative deaths. Transsphenoidal surgery provides a safe and effective treatment for Cushing disease. For both adults and children, the best outcomes occurred in patients with microadenomas and/or those with type 1 remission.

Network Mechanisms Generating Abnormal and Normal Hippocampal High-Frequency Oscillations: A Computational Analysis1,2,3

PubMed Central

Catoni, Nicholas

2015-01-01

Abstract High-frequency oscillations (HFOs) are an intriguing potential biomarker for epilepsy, typically categorized according to peak frequency as either ripples (100–250 Hz) or fast ripples (>250 Hz). In the hippocampus, fast ripples were originally thought to be more specific to epileptic tissue, but it is still very difficult to distinguish which HFOs are caused by normal versus pathological brain activity. In this study, we use a computational model of hippocampus to investigate possible network mechanisms underpinning normal ripples, pathological ripples, and fast ripples. Our results unify several prior findings regarding HFO mechanisms, and also make several new predictions regarding abnormal HFOs. We show that HFOs are generic, emergent phenomena whose characteristics reflect a wide range of connectivity and network input. Although produced by different mechanisms, both normal and abnormal HFOs generate similar ripple frequencies, underscoring that peak frequency is unable to distinguish the two. Abnormal ripples are generic phenomena that arise when input to pyramidal cells overcomes network inhibition, resulting in high-frequency, uncoordinated firing. In addition, fast ripples transiently and sporadically arise from the precise conditions that produce abnormal ripples. Lastly, we show that such abnormal conditions do not require any specific network structure to produce coherent HFOs, as even completely asynchronous activity is capable of producing abnormal ripples and fast ripples in this manner. These results provide a generic, network-based explanation for the link between pathological ripples and fast ripples, and a unifying description for the entire spectrum from normal ripples to pathological fast ripples. PMID:26146658

The COST Action IC0604 "Telepathology Network in Europe" (EURO-TELEPATH).

PubMed

García-Rojo, Marcial; Gonçalves, Luís; Blobel, Bernd

2012-01-01

The COST Action IC0604 "Telepathology Network in Europe" (EURO-TELEPATH) is a European COST Action that has been running from 2007 to 2011. COST Actions are funded by the COST (European Cooperation in the field of Scientific and Technical Research) Agency, supported by the Seventh Framework Programme for Research and Technological Development (FP7), of the European Union. EURO-TELEPATH's main objectives were evaluating and validating the common technological framework and communication standards required to access, transmit and manage digital medical records by pathologists and other medical professionals in a networked environment. The project was organized in four working groups. orking Group 1 "Business modeling in pathology" has designed main pathology processes - Frozen Study, Formalin Fixed Specimen Study, Telepathology, Cytology, and Autopsy -using Business Process Modeling Notation (BPMN). orking Group 2 "Informatics standards in pathology" has been dedicated to promoting the development and application of informatics standards in pathology, collaborating with Integrating the Healthcare Enterprise (IHE), Digital Imaging and Communications in Medicine (DICOM), Health Level Seven (HL7), and other standardization bodies. Working Group 3 "Images: Analysis, Processing, Retrieval and Management" worked on the use of virtual or digital slides that are fostering the use of image processing and analysis in pathology not only for research purposes, but also in daily practice. Working Group 4 "Technology and Automation in Pathology" was focused on studying the adequacy of current existing technical solutions, including, e.g., the quality of images obtained by slide scanners, or the efficiency of image analysis applications. Major outcome of this action are the collaboration with international health informatics standardization bodies to foster the development of standards for digital pathology, offering a new approach for workflow analysis, based in business process modeling. Health terminology standardization research has become a topic of high interest. Future research work should focus on standardization of automatic image analysis and tissue microarrays imaging.

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.

Evaluation of the 8th AJCC staging system for pathologically versus clinically staged pancreatic adenocarcinoma: A time to revisit a dogma?

PubMed

Abdel-Rahman, Omar

2018-02-01

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic exocrine adenocarcinoma has been released. The current study seeks to assess the 7th and 8th editions among patients registered within the surveillance, epidemiology and end results (SEER) database. SEER database (2010-2013) has been accessed through SEER*Stat program and AJCC 8th edition stages were reconstructed utilizing the collaborative stage descriptions. Kaplan-Meier analysis of overall survival and pancreatic cancer-specific survival analyses (according to both 7th and 8th editions and according to whether pathological or clinical staging were conducted) has been performed. Multivariate analysis of factors affecting pancreatic cancer-specific survival was also conducted through a Cox proportional hazard model. A total of 18  948 patients with pancreatic adenocarcinoma were identified in the period from 2010-2013. Pancreatic cancer-specific survival among pathologically staged patients and according to the 8th edition showed significant differences for all pair wise comparisons among different stages (P < 0.0001) except for the comparison between stage IA and stage IB (P = 0.307) and the comparison between stage IB and stage IIA (P = 0.116). Moreover, P value for stage IA vs IIA was 0.014; while pancreatic cancer-specific survival according to the 7th edition among pathologically staged patients showed significant differences for all pair wise comparisons among different stages (P < 0.0001) except for the comparison between IA and IB (P = 0.072), the comparison between stage IIA and stage IIB (P = 0.065), the comparison between stage IIA and stage III (P = 0.059) and the comparison between IIB and III (P = 0.595). Among clinically staged patients (i.e. those who did not undergo initial radical surgery), the prognostic performance of both 7th and 8th stages for both overall survival and pancreatic cancer-specific survival was limited. There is clearly a need to have two staging systems for pancreatic adenocarcinoma: pathological and clinical staging systems. Copyright © 2018 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.

Clinical Features of Idiopathic Interstitial Pneumonia with Systemic Sclerosis-Related Autoantibody in Comparison with Interstitial Pneumonia with Systemic Sclerosis

PubMed Central

Yamakawa, Hideaki; Hagiwara, Eri; Kitamura, Hideya; Yamanaka, Yumie; Ikeda, Satoshi; Sekine, Akimasa; Baba, Tomohisa; Iso, Shinichiro; Okudela, Koji; Iwasawa, Tae; Takemura, Tamiko; Kuwano, Kazuyoshi; Ogura, Takashi

2016-01-01

Background Patients with idiopathic interstitial pneumonias sometimes have a few features of connective tissue disease (CTD) and yet do not fulfil the diagnostic criteria for any specific CTD. Objective This study was conducted to elucidate the characteristics, prognosis, and disease behavior in patients with interstitial lung disease (ILD) associated with systemic sclerosis (SSc)-related autoantibodies. Methods We retrospectively analyzed medical records of 72 ILD patients: 40 patients with SSc (SSc-ILD) and 32 patients with SSc-related autoantibody-positive ILD but not with CTD (ScAb-ILD), indicating lung-dominant CTD with SSc-related autoantibody. Results Patients with SSc-ILD were predominantly females and non-smokers, and most had nonspecific interstitial pneumonia confirmed by high-resolution computed tomography (HRCT) and pathological analysis. However, about half of the patients with ScAb-ILD were male and current or ex-smokers. On HRCT analysis, honeycombing was more predominant in patients with ScAb-ILD than with SSc-ILD. Pathological analysis showed the severity of vascular intimal or medial thickening in the SSc-ILD patients to be significantly higher than that in the ScAb-ILD patients. Survival curves showed that the patients with ScAb-ILD had a significantly poorer outcome than those with SSc-ILD. Conclusion Data from this study suggest that lung-dominant CTD with SSc-related autoantibody is a different disease entity from SSc-ILD. PMID:27564852

TOWARD QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: Visualizing Blood Flow Speeds in Ocular Pathology Using Variable Interscan Time Analysis.

PubMed

Ploner, Stefan B; Moult, Eric M; Choi, WooJhon; Waheed, Nadia K; Lee, ByungKun; Novais, Eduardo A; Cole, Emily D; Potsaid, Benjamin; Husvogt, Lennart; Schottenhamml, Julia; Maier, Andreas; Rosenfeld, Philip J; Duker, Jay S; Hornegger, Joachim; Fujimoto, James G

2016-12-01

Currently available optical coherence tomography angiography systems provide information about blood flux but only limited information about blood flow speed. The authors develop a method for mapping the previously proposed variable interscan time analysis (VISTA) algorithm into a color display that encodes relative blood flow speed. Optical coherence tomography angiography was performed with a 1,050 nm, 400 kHz A-scan rate, swept source optical coherence tomography system using a 5 repeated B-scan protocol. Variable interscan time analysis was used to compute the optical coherence tomography angiography signal from B-scan pairs having 1.5 millisecond and 3.0 milliseconds interscan times. The resulting VISTA data were then mapped to a color space for display. The authors evaluated the VISTA visualization algorithm in normal eyes (n = 2), nonproliferative diabetic retinopathy eyes (n = 6), proliferative diabetic retinopathy eyes (n = 3), geographic atrophy eyes (n = 4), and exudative age-related macular degeneration eyes (n = 2). All eyes showed blood flow speed variations, and all eyes with pathology showed abnormal blood flow speeds compared with controls. The authors developed a novel method for mapping VISTA into a color display, allowing visualization of relative blood flow speeds. The method was found useful, in a small case series, for visualizing blood flow speeds in a variety of ocular diseases and serves as a step toward quantitative optical coherence tomography angiography.

Systematic evaluation of RNA quality, microarray data reliability and pathway analysis in fresh, fresh frozen and formalin-fixed paraffin-embedded tissue samples.

PubMed

Wimmer, Isabella; Tröscher, Anna R; Brunner, Florian; Rubino, Stephen J; Bien, Christian G; Weiner, Howard L; Lassmann, Hans; Bauer, Jan

2018-04-20

Formalin-fixed paraffin-embedded (FFPE) tissues are valuable resources commonly used in pathology. However, formalin fixation modifies nucleic acids challenging the isolation of high-quality RNA for genetic profiling. Here, we assessed feasibility and reliability of microarray studies analysing transcriptome data from fresh, fresh-frozen (FF) and FFPE tissues. We show that reproducible microarray data can be generated from only 2 ng FFPE-derived RNA. For RNA quality assessment, fragment size distribution (DV200) and qPCR proved most suitable. During RNA isolation, extending tissue lysis time to 10 hours reduced high-molecular-weight species, while additional incubation at 70 °C markedly increased RNA yields. Since FF- and FFPE-derived microarrays constitute different data entities, we used indirect measures to investigate gene signal variation and relative gene expression. Whole-genome analyses revealed high concordance rates, while reviewing on single-genes basis showed higher data variation in FFPE than FF arrays. Using an experimental model, gene set enrichment analysis (GSEA) of FFPE-derived microarrays and fresh tissue-derived RNA-Seq datasets yielded similarly affected pathways confirming the applicability of FFPE tissue in global gene expression analysis. Our study provides a workflow comprising RNA isolation, quality assessment and microarray profiling using minimal RNA input, thus enabling hypothesis-generating pathway analyses from limited amounts of precious, pathologically significant FFPE tissues.

[Forensic Analysis for 54 Cases of Suxamethonium Chloride Poisoning].

PubMed

Zhao, Y F; Zhao, B Q; Ma, K J; Zhang, J; Chen, F Y

2017-08-01

To observe and analyze the performance of forensic science in the cases of suxa- methonium chloride poisoning, and to improve the identification of suxamethonium chloride poisoning. Fifty-four cases of suxamethonium chloride poisoning were collected. The rules of determination of suxamethonium chloride poisoning were observed by the retrospective analysis of pathological and toxicological changes as well as case features. The pathological features of suxamethonium chloride poisoning were similar to the general changes of sudden death, which mainly included acute pulmonary congestion and edema, and partly showed myocardial disarray and fracture. Suxamethonium chloride could be detected in the heart blood of all cases and in skin tissue of part cases. Suxa-methonium chloride poisoning has the characteristics with fast death and covert means, which are difficult to rescue and easily miss inspection. For the cases of sudden death or suspicious death, determination of suxamethonium chloride should be taken as a routine detection index to prevent missing inspection. Copyright© by the Editorial Department of Journal of Forensic Medicine

Fusion of 4D echocardiography and cine cardiac magnetic resonance volumes using a salient spatio-temporal analysis

NASA Astrophysics Data System (ADS)

Atehortúa, Angélica; Garreau, Mireille; Romero, Eduardo

2017-11-01

An accurate left (LV) and right ventricular (RV) function quantification is important to support evaluation, diagnosis and prognosis of cardiac pathologies such as the cardiomyopathies. Currently, diagnosis by ultrasound is the most cost-effective examination. However, this modality is highly noisy and operator dependent, hence prone to errors. Therefore, fusion with other cardiac modalities may provide complementary information and improve the analysis of the specific pathologies like cardiomyopathies. This paper proposes an automatic registration between two complementary modalities, 4D echocardiography and Magnetic resonance images, by mapping both modalities to a common space of salience where an optimal registration between them is estimated. The obtained matrix transformation is then applied to the MRI volume which is superimposed to the 4D echocardiography. Manually selected marks in both modalities are used to evaluate the precision of the superimposition. Preliminary results, in three evaluation cases, show the distance between these marked points and the estimated with the transformation is about 2 mm.

[Topographic mapping of retinal function with a scanning laser ophthalmoscope and multifocal electroretinography using short M-sequences].

PubMed

Rudolph, G; Bechmann, M; Berninger, T; Kutschbach, E; Held, U; Tornow, R P; Kalpadakis, P; Zol'nikova, I V; Shamshinova, A M

2001-01-01

A new method of multifocal electroretinography making use of scanning laser ophthalmoscope with a wavelength of 630 nm (SLO-m-ERG), evoking short spatial visual stimuli on the retina, is proposed. Algorithm of presenting the visual stimuli and analysis of distribution of local electroretinograms on the surface of the retina is based on short m-sequences. Mathematical cross correlation analysis shows a three-dimensional distribution of bioelectrical activity of the retina in the central visual field. In normal subjects the cone bioelectrical activity is the maximum in the macular area (corresponding to the density of cone distribution) and absent in the blind spot. The method detects the slightest pathological changes in the retina under control of the site of stimulation and ophthalmoscopic picture of the fundus oculi. The site of the pathological process correlates with the topography of changes in bioelectrical activity of the examined retinal area in diseases of the macular area and pigmented retinitis detectable by ophthalmoscopy.

[Health status of immigrants arrived to Italian coast].

PubMed

Firenze, Alberto; Restivo, Vincenzo; Bonanno, Valentina; Aleo, Nicola; Pace, Stella; Marsala, Maria Grazia Laura; Palermo, Mario

2014-01-01

To analyze the factors involved in access to Emergency Department (ED) of undocumented immigrants in Lampedusa according to the country of origin. This is a retrospective observational study, carried out on newly arrived undocumented immigrants transferred to ED. Data were collected from medical records of Lampedusa ED between January 2012 and May 2013 on 326 undocumented immigrants. The outcomes evaluated are demographics characteristics and health condition of undocumented immigrants. In multivariate analysis associated factors to ED visits are: other pathologies rather than traumatic diseases (OR 0.22; p <0.001), younger age (OR 0.9; p <0.001) and female sex (OR 12.49; p=0.017) for Somalis; gastroenterological diseases (OR 2.55; p=0.026) and older age (OR 1.6; p=0.004) for Eritrean; neurological disease (OR 5.33; p=0.048) and male sex (OR 5.45; p=0.032) for Tunisian. This analysis shows that undocumented immigrants cannot be considered as a single population, because they generate a diversified set of pathological conditions.

MOVING BEYOND COLOR: THE CASE FOR MULTISPECTRAL IMAGING IN BRIGHTFIELD PATHOLOGY

PubMed Central

Cukierski, William J.; Qi, Xin; Foran, David J.

2009-01-01

A multispectral camera is capable of imaging a histologic slide at narrow bandwidths over the range of the visible spectrum. While several uses for multispectral imaging (MSI) have been demonstrated in pathology [1, 2], there is no unified consensus over when and how MSI might benefit automated analysis [3, 4]. In this work, we use a linear-algebra framework to investigate the relationship between the spectral image and its standard-image counterpart. The multispectral “cube” is treated as an extension of a traditional image in a high-dimensional color space. The concept of metamers is introduced and used to derive regions of the visible spectrum where MSI may provide an advantage. Furthermore, histological stains which are amenable to analysis by MSI are reported. We show the Commission internationale de l’éclairage (CIE) 1931 transformation from spectrum to color is non-neighborhood preserving. Empirical results are demonstrated on multispectral images of peripheral blood smears. PMID:19997528

Progression of Parkinson's Disease Pathology Is Reproduced by Intragastric Administration of Rotenone in Mice

PubMed Central

Pan-Montojo, Francisco; Anichtchik, Oleg; Dening, Yanina; Knels, Lilla; Pursche, Stefan; Jung, Roland; Jackson, Sandra; Gille, Gabriele; Spillantini, Maria Grazia; Reichmann, Heinz; Funk, Richard H. W.

2010-01-01

In patients with Parkinson's disease (PD), the associated pathology follows a characteristic pattern involving inter alia the enteric nervous system (ENS), the dorsal motor nucleus of the vagus (DMV), the intermediolateral nucleus of the spinal cord and the substantia nigra, providing the basis for the neuropathological staging of the disease. Here we report that intragastrically administered rotenone, a commonly used pesticide that inhibits Complex I of the mitochondrial respiratory chain, is able to reproduce PD pathological staging as found in patients. Our results show that low doses of chronically and intragastrically administered rotenone induce alpha-synuclein accumulation in all the above-mentioned nervous system structures of wild-type mice. Moreover, we also observed inflammation and alpha-synuclein phosphorylation in the ENS and DMV. HPLC analysis showed no rotenone levels in the systemic blood or the central nervous system (detection limit [rotenone]<20 nM) and mitochondrial Complex I measurements showed no systemic Complex I inhibition after 1.5 months of treatment. These alterations are sequential, appearing only in synaptically connected nervous structures, treatment time-dependent and accompanied by inflammatory signs and motor dysfunctions. These results strongly suggest that the local effect of pesticides on the ENS might be sufficient to induce PD-like progression and to reproduce the neuroanatomical and neurochemical features of PD staging. It provides new insight into how environmental factors could trigger PD and suggests a transsynaptic mechanism by which PD might spread throughout the central nervous system. PMID:20098733

[Diagnosis of temporo-mandibular joint dysfunction caused by occlusion pathology and treatment of such patients].

PubMed

Semkin, V A; Rabukhina, N A; Kravchenko, D V

2007-01-01

Patients with temporo-mandibular joint (TMJ) dysfunction need complex treatment that includes prosthetic treatment in intrajoint relation stabilization. In cases of TMJ pathology it is necessary to examine patients and make axiography, function analysis, MPI-analysis, magnetic resonance tomography and zonography of TMJ, electromyography of the masticatory muscles. The authors examined 47 patients with TMJ dysfunction, 43 of them had occlusion pathology. We managed to eliminate the dysfunction symptoms and to receive stable result of the treatment in all the patients.

Phosphorus poisoning in waterfowl

USGS Publications Warehouse

Coburn, D.R.; DeWitt, J.B.; Derby, J.V.; Ediger, E.

1950-01-01

Black ducks and mallards were found to be highly susceptible to phosphorus poisoning. 3 mg. of white phosphorus per kg. of body weight given in a single dose resulted in death of a black duck in 6 hours. Pathologic changes in both acute and chronic poisoning were studied. Data are presented showing that diagnosis can be made accurately by chemical analysis of stored tissues in cases of phosphorus poisoning.

Fluorescence and reflectance properties of hemoglobin-pigmented skin disorders

NASA Astrophysics Data System (ADS)

Troyanova, P.; Borisova, E.; Avramov, L.

2007-06-01

There has been growing interest in clinical application of laser-induced autofluorescence (LIAF) and reflectance spectroscopy (RS) to differentiate disease from normal surrounding tissue, including skin pathologies. Pigmented cutaneous lesions diagnosis plays important role in clinical practice, as malignant melanoma, which is characterized with greatest mortality from all skin cancer types, must be carefully discriminated form other colorized pathologies. The goals of this work were investigation of cutaneous hemoglobin-pigmented lesions (heamangioma, angiokeratoma, and fibroma) by the methods of LIAFS and RS. Spectra from healthy skin areas near to the lesion were detected to be used posteriori in analysis. Fluorescence and reflectance of cutaneous hemoglobin-pigmented lesions are used to develop criterion for differentiation from other pigmented pathologies. Origins of the spectral features obtained are discussed and determination of lesion types is achieved using selected spectral features. The spectral results, obtained were used to develop multispectral diagnostic algorithms based on the most prominent spectral features from the fluorescence and reflectance spectra of the lesions investigated. In comparison between normal skin and different cutaneous lesion types and between lesion types themselves sensitivities and specificities higher than 90 % were achieved. These results show a perspective possibility to differentiate hemoglobin-pigmented lesions from other pigmented pathologies using non-invasive and real time discrimination procedure.

Lacrimal fossa lesions: a review of 146 cases in Egypt

PubMed Central

Eldesouky, Mohammed A; Elbakary, Molham A; Sabik, Saly; Shareef, Mohamed M

2014-01-01

Purpose The incidence and clinical and imaging criteria of different pathological forms of lacrimal fossa lesions in the Delta region of Egypt were studied. Methods A retrospective study of patients with lacrimal fossa lesions for the past 10 years was conducted. A total of 146 cases were identified. Their medical records were reviewed for clinical and imaging data (computed tomography scan, magnetic resonance imaging scan, or both). A definitive diagnosis based on pathological examination of biopsies was also reviewed. Results Among the patients reviewed, 43.15% had inflammatory lacrimal gland lesions, 26.71% had lymphoproliferative lesions, and 21.92% had epithelial lesions; 8.22% had rare lesions (5.48% were dacryops and 2.74% had hemangioma). The study included 71.92% benign lesions and 28.08% malignant lesions, which were distributed between 19.18% malignant lymphoma and 8.9% malignant epithelial tumors. According to the pathological origin of the lesions, they may be classified into 78.08% nonepithelial lesions and 21.92% epithelial lesions (16.44% epithelial tumors, and 5.48% dermoid cysts). Conclusion Lacrimal fossa lesions show a wide pathological range. Inflammatory lesions are most frequent, followed by lymphoproliferative and epithelial lesions. Analysis of clinical and radiological criteria is helpful in the differential diagnosis of lacrimal gland lesions. PMID:25210428

Clinicopathologic Characteristics and Treatment Outcomes of Penile Cancer

PubMed Central

Nam, Jong Kil; Lee, Dong Hoon; Park, Sung Woo; Kam, Sung Chul; Lee, Ki Soo; Kim, Tae Hyo; Kim, Taek Sang; Oh, Cheol Kyu; Park, Hyun Jun

2017-01-01

Purpose The aim of this study was to assess the clinicopathologic characteristics of penile cancer, including patterns of therapy, oncologic results, and survival. Materials and Methods Between January 2005 and July 2015, 71 patients at 6 institutions who had undergone penectomy or penile biopsy were enrolled. Their medical records were reviewed to identify the mode of therapy, pathology reports, and cancer-specific survival (CSS) rate. Results Clinicopathologic and outcome information was available for 52 male patients (mean age, 64.3 years; mean follow-up, 61.4 months). At presentation, 17 patients were node-positive, and 4 had metastatic disease. Management was partial penectomy in 34 patients, total penectomy in 12 patients, and chemotherapy or radiotherapy in 6 patients. The pathology reports were squamous cell carcinoma in 50 patients and other types of carcinoma in the remaining 2 patients. Kaplan-Meier survival analysis showed a 5-year CSS rate of 84.0%. In univariate and multivariate analyses, the American Joint Committee on Cancer (AJCC) stage and pathologic grade were associated with survival. Conclusions Partial penectomy was the most common treatment of penile lesions. The oncologic outcomes were good, with a 5-year CSS of 84.0%. The AJCC stage and pathologic grade were independent prognostic factors for survival. PMID:28459145

Tau pathology does not affect experience-driven single-neuron and network-wide Arc/Arg3.1 responses.

PubMed

Rudinskiy, Nikita; Hawkes, Jonathan M; Wegmann, Susanne; Kuchibhotla, Kishore V; Muzikansky, Alona; Betensky, Rebecca A; Spires-Jones, Tara L; Hyman, Bradley T

2014-06-10

Intraneuronal neurofibrillary tangles (NFTs) - a characteristic pathological feature of Alzheimer's and several other neurodegenerative diseases - are considered a major target for drug development. Tangle load correlates well with the severity of cognitive symptoms and mouse models of tauopathy are behaviorally impaired. However, there is little evidence that NFTs directly impact physiological properties of host neurons. Here we used a transgenic mouse model of tauopathy to study how advanced tau pathology in different brain regions affects activity-driven expression of immediate-early gene Arc required for experience-dependent consolidation of long-term memories. We demonstrate in vivo that visual cortex neurons with tangles are as likely to express comparable amounts of Arc in response to structured visual stimulation as their neighbors without tangles. Probability of experience-dependent Arc response was not affected by tau tangles in both visual cortex and hippocampal pyramidal neurons as determined postmortem. Moreover, whole brain analysis showed that network-wide activity-driven Arc expression was not affected by tau pathology in any of the brain regions, including brain areas with the highest tangle load. Our findings suggest that intraneuronal NFTs do not affect signaling cascades leading to experience-dependent gene expression required for long-term synaptic plasticity.

Diagnostic value of the 2011 International Federation for Cervical Pathology and Colposcopy Terminology in predicting cervical lesions.

PubMed

Fan, Aiping; Wang, Chen; Zhang, Liqin; Yan, Ye; Han, Cha; Xue, Fengxia

2018-02-06

To evaluate the diagnostic accuracy of the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) colposcopic terminology. The clinicopathological data of 2262 patients who underwent colposcopy from September 2012 to September 2016 were reviewed. The colposcopic findings, colposcopic impression, and cervical histopathology of the patients were analyzed. Correlations between variables were evaluated using cervical histopathology as the gold standard. Colposcopic diagnosis matched biopsy histopathology in 1482 patients (65.5%), and the weighted kappa strength of agreement was 0.480 (P<0.01). Colposcopic diagnoses more often underestimated (22.1%) than overestimated (12.3%) cervical pathology. There was no significant difference between the colposcopic diagnosis and cervical pathology agreement among the various grades of lesions (P=0.282). The sensitivity, specificity for detecting high-grade lesions/carcinoma was 71.6% and 98.0%, respectively. Multivariate analysis showed that major changes were independent factors in predicting high-grade lesion/carcinoma, whereas transformation zone, lesion size, and non-stained were not statistically related to high-grade lesion/carcinoma. The 2011 IFCPC terminology can improve the diagnostic accuracy for all lesion severities. The categorization of major changes and minor changes is appropriate. However, colposcopic diagnosis remains unsatisfactory. Poor reproducibility of type 2 transformation zone and the significance of leukoplakia require further study.

Dose-volume effects in pathologic lymph nodes in locally advanced cervical cancer.

PubMed

Bacorro, Warren; Dumas, Isabelle; Escande, Alexandre; Gouy, Sebastien; Bentivegna, Enrica; Morice, Philippe; Haie-Meder, Christine; Chargari, Cyrus

2018-03-01

In cervical cancer patients, dose-volume relationships have been demonstrated for tumor and organs-at-risk, but not for pathologic nodes. The nodal control probability (NCP) according to dose/volume parameters was investigated. Patients with node-positive cervical cancer treated curatively with external beam radiotherapy (EBRT) and image-guided brachytherapy (IGABT) were identified. Nodal doses during EBRT, IGABT and boost were converted to 2-Gy equivalent (α/β = 10 Gy) and summed. Pathologic nodes were followed individually from diagnosis to relapse. Statistical analyses comprised log-rank tests (univariate analyses), Cox proportional model (factors with p ≤ 0.1 in univariate) and Probit analyses. A total of 108 patients with 254 unresected pathological nodes were identified. The mean nodal volume at diagnosis was 3.4 ± 5.8 cm 3 . The mean total nodal EQD2 doses were 55.3 ± 5.6 Gy. Concurrent chemotherapy was given in 96%. With a median follow-up of 33.5 months, 20 patients (18.5%) experienced relapse in nodes considered pathologic at diagnosis. Overall nodal recurrence rate was 9.1% (23/254). On univariate analyses, nodal volume (threshold: 3 cm 3 , p < .0001) and lymph node dose (≥57.5 Gy α/β10 , p = .039) were significant for nodal control. The use of simultaneous boost was borderline for significance (p = .07). On multivariate analysis, volume (HR = 8.2, 4.0-16.6, p < .0001) and dose (HR = 2, 1.05-3.9, p = .034) remained independent factors. Probit analysis combining dose and volume showed significant relationships with NCP, with increasing gap between the curves with higher nodal volumes. A nodal dose-volume effect on NCP is demonstrated for the first time, with increasing NCP benefit of additional doses to higher-volume nodes. Copyright © 2018 Elsevier Inc. All rights reserved.

Functional Visual Improvement After Cataract Surgery in Eyes With Age-Related Macular Degeneration: Results of the Ophthalmic Surgical Outcomes Data Project.

PubMed

Stock, Michael V; Vollman, David E; Baze, Elizabeth F; Chomsky, Amy S; Daly, Mary K; Lawrence, Mary G

2015-04-01

To determine if cataract surgery on eyes with AMD confers as much functional visual improvement as surgery on eyes without retinal pathology. This is a retrospective analysis of 4924 cataract surgeries from the Veterans Healthcare Administration Ophthalmic Surgical Outcomes Data Project (OSOD). We included cases of eyes with AMD that had both preoperative and postoperative NEI-VFQ-25 questionnaires submitted and compared their outcomes with controls without retinal pathology. We excluded patients with other retinal pathologies (740 patients). The analyses compared changes in visual acuity and overall functional visual improvement and its subscales using t-tests, multivariate logistic regressions, and linear regression modeling. Preoperative and postoperative questionnaires were submitted by 58.3% of AMD and 63.8% of no retinal pathology cases (controls). Analysis of overall score showed that cataract surgery on eyes with AMD led to increased visual function (13.8 ± 2.4 NEI-VFQ units, P < 0.0001); however, increases were significantly less when compared with controls (-6.4 ± 2.9 NEI-VFQ units, P < 0.0001). Preoperative best-corrected visual acuity (preBCVA) in AMD was predictive of postoperative visual function (r = -0.38, P < 0.0001). In controls, postoperative visual function was only weakly associated with preBCVA (r = -0.075, P = 0.0002). Patients with AMD with vision of 20/40 or better had overall outcomes similar to controls (-2.2 ± 4.7 NEI-VFQ units, P = 0.37). Cataract surgery on eyes with AMD offers an increase in functional visual improvement; however, the amount of benefit is associated with the eye's preBCVA. For eyes with preBCVA of 20/40 or greater, the improvement is similar to that of patients without retinal pathology. However, if preBCVA is less than 20/40, the amount of improvement was shown to be significantly less and decreased with decreasing preBCVA.

Integration of Traditional and E-Learning Methods to Improve Learning Outcomes for Dental Students in Histopathology.

PubMed

Ariana, Armin; Amin, Moein; Pakneshan, Sahar; Dolan-Evans, Elliot; Lam, Alfred K

2016-09-01

Dental students require a basic ability to explain and apply general principles of pathology to systemic, dental, and oral pathology. Although there have been recent advances in electronic and online resources, the academic effectiveness of using self-directed e-learning tools in pathology courses for dental students is unclear. The aim of this study was to determine if blended learning combining e-learning with traditional learning methods of lectures and tutorials would improve students' scores and satisfaction over those who experienced traditional learning alone. Two consecutive cohorts of Bachelor of Dentistry and Oral Health students taking the general pathology course at Griffith University in Australia were compared. The control cohort experienced traditional methods only, while members of the study cohort were also offered self-directed learning materials including online resources and online microscopy classes. Final assessments for the course were used to compare the differences in effectiveness of the intervention, and students' satisfaction with the teaching format was evaluated using questionnaires. On the final course assessments, students in the study cohort had significantly higher scores than students in the control cohort (p<0.01). Analysis of questionnaire results showed improved student satisfaction with the course in the study cohort. These findings suggest that the use of e-learning tools such as virtual microscopy and interactive online resources for delivering pathology instruction can be an effective supplement for developing dental students' competence, confidence, and satisfaction.

Standardized synoptic cancer pathology reports - so what and who cares? A population-based satisfaction survey of 970 pathologists, surgeons, and oncologists.

PubMed

Lankshear, Sara; Srigley, John; McGowan, Thomas; Yurcan, Marta; Sawka, Carol

2013-11-01

Cancer Care Ontario implemented synoptic pathology reporting across Ontario, impacting the practice of pathologists, surgeons, and medical and radiation oncologists. The benefits of standardized synoptic pathology reporting include enhanced completeness and improved consistency in comparison with narrative reports, with reported challenges including increased workload and report turnaround time. To determine the impact of synoptic pathology reporting on physician satisfaction specific to practice and process. A descriptive, cross-sectional design was utilized involving 970 clinicians across 27 hospitals. An 11-item survey was developed to obtain information regarding timeliness, completeness, clarity, and usability. Open-ended questions were also employed to obtain qualitative comments. A 51% response rate was obtained, with descriptive statistics reporting that physicians perceive synoptic reports as significantly better than narrative reports. Correlation analysis revealed a moderately strong, positive relationship between respondents' perceptions of overall satisfaction with the level of information provided and perceptions of completeness for clinical decision making (r = 0.750, P < .001) and ease of finding information for clinical decision making (r = 0.663, P < .001). Dependent t tests showed a statistically significant difference in the satisfaction scores of pathologists and oncologists (t169 = 3.044, P = .003). Qualitative comments revealed technology-related issues as the most frequently cited factor impacting timeliness of report completion. This study provides evidence of strong physician satisfaction with synoptic cancer pathology reporting as a clinical decision support tool in the diagnosis, prognosis, and treatment of cancer patients.

Loss of Bin1 Promotes the Propagation of Tau Pathology.

PubMed

Calafate, Sara; Flavin, William; Verstreken, Patrik; Moechars, Diederik

2016-10-18

Tau pathology propagates within synaptically connected neuronal circuits, but the underlying mechanisms are unclear. BIN1-amphiphysin2 is the second most prevalent genetic risk factor for late-onset Alzheimer's disease. In diseased brains, the BIN1-amphiphysin2 neuronal isoform is downregulated. Here, we show that lowering BIN1-amphiphysin2 levels in neurons promotes Tau pathology propagation whereas overexpression of neuronal BIN1-amphiphysin2 inhibits the process in two in vitro models. Increased Tau propagation is caused by increased endocytosis, given our finding that BIN1-amphiphysin2 negatively regulates endocytic flux. Furthermore, blocking endocytosis by inhibiting dynamin also reduces Tau pathology propagation. Using a galectin-3-binding assay, we show that internalized Tau aggregates damage the endosomal membrane, allowing internalized aggregates to leak into the cytoplasm to propagate pathology. Our work indicates that lower BIN1 levels promote the propagation of Tau pathology by efficiently increasing aggregate internalization by endocytosis and endosomal trafficking. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Diagnostic Efficiency in Digital Pathology: A Comparison of Optical Versus Digital Assessment in 510 Surgical Pathology Cases.

PubMed

Mills, Anne M; Gradecki, Sarah E; Horton, Bethany J; Blackwell, Rebecca; Moskaluk, Christopher A; Mandell, James W; Mills, Stacey E; Cathro, Helen P

2018-01-01

Prior work has shown that digital images and microscopic slides can be interpreted with comparable diagnostic accuracy. Although accuracy has been well-validated, the interpretative time for digital images has scarcely been studied and concerns about efficiency remain a major barrier to adoption. We investigated the efficiency of digital pathology when compared with glass slide interpretation in the diagnosis of surgical pathology biopsy and resection specimens. Slides were pulled from 510 surgical pathology cases from 5 organ systems (gastrointestinal, gynecologic, liver, bladder, and brain). Original diagnoses were independently confirmed by 2 validating pathologists. Diagnostic slides were scanned using the Philips IntelliSite Pathology Solution. Each case was assessed independently on digital and optical by 3 reading pathologists, with a ≥6 week washout period between modalities. Reading pathologists recorded assessment times for each modality; digital times included time to load the case. Diagnostic accuracy was determined based on whether a rendered diagnosis differed significantly from the original diagnosis. Statistical analysis was performed to assess for differences in interpretative times across modalities. All 3 reading pathologists showed comparable diagnostic accuracy across optical and digital modalities (mean major discordance rates with original diagnosis: 4.8% vs. 4.4%, respectively). Mean assessment times ranged from 1.2 to 9.1 seconds slower on digital versus optical. The slowest reader showed a significant learning effect during the course of the study so that digital assessment times decreased over time and were comparable with optical times by the end of the series. Organ site and specimen type did not significantly influence differences in interpretative times. In summary, digital image reading times compare favorably relative to glass slides across a variety of organ systems and specimen types. Mean increase in assessment time is 4 seconds/case. This time can be minimized with experience and may be further balanced by the improved ease of electronic chart access allowed by digital slide viewing, as well as quantitative assessments which can be expedited on digital images.

TDP-43 pathology and memory impairment in elders without pathologic diagnoses of AD or FTLD

PubMed Central

Yu, Lei; Wilson, Robert S.; Chen, Er-Yun; Bennett, David A.; Schneider, Julie A.

2017-01-01

Objective: To investigate the association of TAR DNA-binding protein 43 (TDP-43) pathology with memory, other cognitive domains, and dementia in community-dwelling elders without pathologic diagnoses of Alzheimer disease (AD) or frontotemporal lobar degeneration (FTLD). Methods: Of 1,058 autopsied participants, 343 (32.4%) did not have pathologic diagnoses of AD or FTLD. Diagnosis of dementia was based on clinical evaluation and cognitive performance tests, which were used to create summary measures of global cognition and of 5 cognitive domains. TDP-43 pathology evaluated in 6 brain regions by immunohistochemistry was converted into a summary measure of TDP-43 severity. Results: Of 343 participants, 135 (39.4%) had TDP-43 pathology with a mean TDP-43 severity score of 0.394 (SD 0.490). TDP-43 inclusions were confined to the amygdala (stage 1) in 43.7% of participants, 40% showed additional involvement of the hippocampus or entorhinal cortex (stages 2), while fewer (16.3%) showed additional TDP-43 pathology in the temporal and frontal cortices (stage 3). Severity of TDP-43 pathology was independently related to lower function in global cognition and episodic and semantic memory while increased odds of dementia was only a trend. When participants with hippocampal sclerosis (HS) were excluded from the models, TDP-43 pathology remained associated with lower episodic memory but relationships with global cognition, semantic memory, and dementia were attenuated. Conclusions: TDP-43 pathology in elders, without pathologic diagnoses of AD or FTLD, is common and independently associated with lower function in episodic memory, while its associations with global cognitive impairment and dementia are difficult to separate from HS. PMID:28087828

Heartbeat Complexity Modulation in Bipolar Disorder during Daytime and Nighttime.

PubMed

Nardelli, Mimma; Lanata, Antonio; Bertschy, Gilles; Scilingo, Enzo Pasquale; Valenza, Gaetano

2017-12-20

This study reports on the complexity modulation of heartbeat dynamics in patients affected by bipolar disorder. In particular, a multiscale entropy analysis was applied to the R-R interval series, that were derived from electrocardiographic (ECG) signals for a group of nineteen subjects comprised of eight patients and eleven healthy control subjects. They were monitored using a textile-based sensorized t-shirt during the day and overnight for a total of 47 diurnal and 27 nocturnal recordings. Patients showed three different mood states: depression, hypomania and euthymia. Results show a clear loss of complexity during depressive and hypomanic states as compared to euthymic and healthy control states. In addition, we observed that a more significant complexity modulation among healthy and pathological mood states occurs during the night. These findings suggest that bipolar disorder is associated with an enhanced sleep-related dysregulation of the Autonomic Nervous System (ANS) activity, and that heartbeat complex dynamics may serve as a viable marker of pathological conditions in mental health.

[Association of serum decoy receptor 3 protein level with the clinicopathologic features of bladder transitional cell carcinoma].

PubMed

Wang, Dong; Wang, Jian; Chen, Guojun

2013-12-01

To investigate the association of serum levels of decoy receptor 3(DcR3) protein and the clinicopathologic features of bladder transitional cell carcinoma. Enzyme-linked immunosorbent assay was used to examine the serum levels of DcR3 in patients with bladder transitional cell carcinoma for analysis of its association with the patients' age, gender, clinical stages and pathological classification. The patients with bladder transitional cell carcinoma showed a significantly elevated serum level of DcR3 (183.43 ∓78.45 pg/m1) compared with the normal level (116.65∓97.43 pg/m1, P<0.05). The serum level of DcR3 in the patients showed close correlations with the TNM stage and pathological classification of the tumor (P<0.05) but not with the patients' age or gender (P>0.05). In patients with bladder transitional cell carcinoma, a high serum level of DcR3 suggests a higher malignancy of the tumor.

A fetus with an X;1 balanced reciprocal translocation and eye disease.

PubMed Central

Seller, M J; Pal, K; Horsley, S; Davies, A F; Berry, A C; Meredith, R; McCartney, A C

1995-01-01

A 19 week female fetus is described with a de novo X;1 reciprocal balanced translocation, with the breakpoint on the X chromosome at Xp11.4, and eye pathology consistent with the early stages of Norrie disease. The fetus seems to be an example of a female manifesting an X linked recessive disease, and it was shown that the normal X chromosome was completely inactivated in all cells examined. Norrie disease has been mapped to Xp11.3, and fluorescence in situ hybridisation studies showed that the Norrie disease gene had not obviously been disrupted. Mutation screening by SSCP analysis showed no aberrant fragments of the coding region of the gene. Several eye disease genes map to the same region of the X chromosome, but are excluded on grounds of pathology. One possibility is that this fetus has a Norrie-like eye disease caused by the mutation of another gene located at Xp11.4. If this is so, there are implications for prenatal diagnosis. Images PMID:7562972

Computational analysis identifies putative prognostic biomarkers of pathological scarring in skin wounds.

PubMed

Nagaraja, Sridevi; Chen, Lin; DiPietro, Luisa A; Reifman, Jaques; Mitrophanov, Alexander Y

2018-02-20

Pathological scarring in wounds is a prevalent clinical outcome with limited prognostic options. The objective of this study was to investigate whether cellular signaling proteins could be used as prognostic biomarkers of pathological scarring in traumatic skin wounds. We used our previously developed and validated computational model of injury-initiated wound healing to simulate the time courses for platelets, 6 cell types, and 21 proteins involved in the inflammatory and proliferative phases of wound healing. Next, we analysed thousands of simulated wound-healing scenarios to identify those that resulted in pathological (i.e., excessive) scarring. Then, we identified candidate proteins that were elevated (or decreased) at the early stages of wound healing in those simulations and could therefore serve as predictive biomarkers of pathological scarring outcomes. Finally, we performed logistic regression analysis and calculated the area under the receiver operating characteristic curve to quantitatively assess the predictive accuracy of the model-identified putative biomarkers. We identified three proteins (interleukin-10, tissue inhibitor of matrix metalloproteinase-1, and fibronectin) whose levels were elevated in pathological scars as early as 2 weeks post-wounding and could predict a pathological scarring outcome occurring 40 days after wounding with 80% accuracy. Our method for predicting putative prognostic wound-outcome biomarkers may serve as an effective means to guide the identification of proteins predictive of pathological scarring.

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis

PubMed Central

Chen, Zhe; Zhang, Lingli; Zeng, Linan; Yang, Xiaoyan; Jiang, Lucan; Gui, Ge; Zhang, Zuojie

2017-01-01

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4–15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for pathological neonatal jaundice. Methods: Databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) were searched and the deadline is December 2016. Randomized controlled trials (RCTs) of probiotics supplementation for pathological neonatal jaundice in publications were extracted by two reviewers. The cochrane tool was applied to assessing the risk of bias of the trials. The extracted information of RCTs should include efficacy rate, serum total bilirubin level, time of jaundice fading, duration of phototherapy, duration of hospitalization, adverse reactions. The main outcomes of the trials were analyzed by Review Manager 5.3 software. The relative risks (RR) or mean difference (MD) with a 95% confidence interval (CI) was used to measure the effect. Results: 13 RCTs involving 1067 neonatal with jaundice were included in the meta-analysis. Probiotics supplementation treatment showed efficacy [RR: 1.19, 95% CI (1.12, 1.26), P < 0.00001] in neonatal jaundice. It not only decreased the total serum bilirubin level after 3day [MD: −18.05, 95% CI (−25.51, −10.58), P < 0.00001], 5day [MD: -23.49, 95% CI (−32.80, −14.18), P < 0.00001], 7day [MD: −33.01, 95% CI (−37.31, −28.70), P < 0.00001] treatment, but also decreased time of jaundice fading [MD: −1.91, 95% CI (−2.06, −1.75), P < 0.00001], as well as the duration of phototherapy [MD: −0.64, 95% CI (−0.84, −0.44), P < 0.00001] and hospitalization [MD: −2.68, 95% CI (−3.18, −2.17), P < 0.00001], when compared with the control group. Additionally, no serious adverse reaction was reported. Conclusion: This meta-analysis shows that probiotics supplementation therapy is an effective and safe treatment for pathological neonatal jaundice. PMID:28713275

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis.

PubMed

Chen, Zhe; Zhang, Lingli; Zeng, Linan; Yang, Xiaoyan; Jiang, Lucan; Gui, Ge; Zhang, Zuojie

2017-01-01

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4-15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for pathological neonatal jaundice. Methods: Databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) were searched and the deadline is December 2016. Randomized controlled trials (RCTs) of probiotics supplementation for pathological neonatal jaundice in publications were extracted by two reviewers. The cochrane tool was applied to assessing the risk of bias of the trials. The extracted information of RCTs should include efficacy rate, serum total bilirubin level, time of jaundice fading, duration of phototherapy, duration of hospitalization, adverse reactions. The main outcomes of the trials were analyzed by Review Manager 5.3 software. The relative risks (RR) or mean difference (MD) with a 95% confidence interval (CI) was used to measure the effect. Results: 13 RCTs involving 1067 neonatal with jaundice were included in the meta-analysis. Probiotics supplementation treatment showed efficacy [RR: 1.19, 95% CI (1.12, 1.26), P < 0.00001] in neonatal jaundice. It not only decreased the total serum bilirubin level after 3day [MD: -18.05, 95% CI (-25.51, -10.58), P < 0.00001], 5day [MD: -23.49, 95% CI (-32.80, -14.18), P < 0.00001], 7day [MD: -33.01, 95% CI (-37.31, -28.70), P < 0.00001] treatment, but also decreased time of jaundice fading [MD: -1.91, 95% CI (-2.06, -1.75), P < 0.00001], as well as the duration of phototherapy [MD: -0.64, 95% CI (-0.84, -0.44), P < 0.00001] and hospitalization [MD: -2.68, 95% CI (-3.18, -2.17), P < 0.00001], when compared with the control group. Additionally, no serious adverse reaction was reported. Conclusion: This meta-analysis shows that probiotics supplementation therapy is an effective and safe treatment for pathological neonatal jaundice.

[Computer technologies in teaching pathological anatomy].

PubMed

Ponomarev, A B; Fedorov, D N

2015-01-01

The paper gives experience with personal computers used at the Academician A.L. Strukov Department of Pathological Anatomy for more than 20 years. It shows the objective necessity of introducing computer technologies at all stages of acquiring skills in anatomical pathology, including lectures, students' free work, test check, etc.

Pathological response after neoadjuvant bevacizumab- or cetuximab-based chemotherapy in resected colorectal cancer liver metastases.

PubMed

Pietrantonio, Filippo; Mazzaferro, Vincenzo; Miceli, Rosalba; Cotsoglou, Christian; Melotti, Flavia; Fanetti, Giuseppe; Perrone, Federica; Biondani, Pamela; Muscarà, Cecilia; Di Bartolomeo, Maria; Coppa, Jorgelina; Maggi, Claudia; Milione, Massimo; Tamborini, Elena; de Braud, Filippo

2015-07-01

Neoadjuvant chemotherapy (NACT) prior to liver resection is advantageous for patients with colorectal cancer liver metastases (CLM). Bevacizumab- or cetuximab-based NACT may affect patient outcome and curative resection rate, but comparative studies on differential tumour regression grade (TRG) associated with distinct antibodies-associated regimens are lacking. Ninety-three consecutive patients received NACT plus bevacizumab (n = 46) or cetuximab (n = 47) followed by CLM resection. Pathological response was determined in each resected metastasis as TRG rated from 1 (complete) to 5 (no response). Except for KRAS mutations prevailing in bevacizumab versus cetuximab (57 vs. 21 %, p = 0.001), patients characteristics were well balanced. Median follow-up was 31 months (IQR 17-48). Bevacizumab induced significantly better pathological response rates (TRG1-3: 78 vs. 34 %, p < 0.001) as well as complete responses (TRG1: 13 vs. 0 %, p = 0.012) with respect to cetuximab. Three-year progression-free survival (PFS) and overall survival (OS) were not significantly different in the two cohorts. At multivariable analysis, significant association with pathological response was found for number of resected metastases (p = 0.015) and bevacizumab allocation (p < 0.001), while KRAS mutation showed only a trend. Significant association with poorer PFS and OS was found for low grades of pathological response (p = 0.009 and p < 0.001, respectively), R2 resection or presence of extrahepatic disease (both p < 0.001) and presence of KRAS mutation (p = 0.007 and p < 0.001, respectively). Bevacizumab-based regimens, although influenced by the number of metastases and KRAS status, improve significantly pathological response if compared to cetuximab-based NACT. Possible differential impact among regimens on patient outcome has still to be elucidated.

Continuous measurement of breast tumor hormone receptor expression: a comparison of two computational pathology platforms

PubMed Central

Ahern, Thomas P.; Beck, Andrew H.; Rosner, Bernard A.; Glass, Ben; Frieling, Gretchen; Collins, Laura C.; Tamimi, Rulla M.

2017-01-01

Background Computational pathology platforms incorporate digital microscopy with sophisticated image analysis to permit rapid, continuous measurement of protein expression. We compared two computational pathology platforms on their measurement of breast tumor estrogen receptor (ER) and progesterone receptor (PR) expression. Methods Breast tumor microarrays from the Nurses’ Health Study were stained for ER (n=592) and PR (n=187). One expert pathologist scored cases as positive if ≥1% of tumor nuclei exhibited stain. ER and PR were then measured with the Definiens Tissue Studio (automated) and Aperio Digital Pathology (user-supervised) platforms. Platform-specific measurements were compared using boxplots, scatter plots, and correlation statistics. Classification of ER and PR positivity by platform-specific measurements was evaluated with areas under receiver operating characteristic curves (AUC) from univariable logistic regression models, using expert pathologist classification as the standard. Results Both platforms showed considerable overlap in continuous measurements of ER and PR between positive and negative groups classified by expert pathologist. Platform-specific measurements were strongly and positively correlated with one another (rho≥0.77). The user-supervised Aperio workflow performed slightly better than the automated Definiens workflow at classifying ER positivity (AUCAperio=0.97; AUCDefiniens=0.90; difference=0.07, 95% CI: 0.05, 0.09) and PR positivity (AUCAperio=0.94; AUCDefiniens=0.87; difference=0.07, 95% CI: 0.03, 0.12). Conclusion Paired hormone receptor expression measurements from two different computational pathology platforms agreed well with one another. The user-supervised workflow yielded better classification accuracy than the automated workflow. Appropriately validated computational pathology algorithms enrich molecular epidemiology studies with continuous protein expression data and may accelerate tumor biomarker discovery. PMID:27729430

[Andrological status of adolescents and its connection to anthropometric and hormonal descriptions in the students of technical college group].

PubMed

Lutov, Iu V; Seliatitskaia, V G; Epanchintseva, E A; Riabichenko, T I

2014-01-01

The purpose of this investigation was to study the interrelation of andrological status with anthropometric and hormonal descriptions for age-specific features discovery of male sexual system pathological states at technical college students. 147 adolescents aged 15-17 years old were examined. Only 41 of them were found to have no abnormalities in their genital system development; in 35 adolescents sexual development was delayed; and 97 adolescents were found to have various andrological diseases (varicocele, phimosis, gynecomastia, testicular asymmetry, etc.) or clinical signs for development of these diseases. In 26 adolescences delayed sexual development was combined with the andrological pathology. The normal andrological status was usually accompanied with the highest frequency of low values of anthropometric indicators and indices that reflect the influence of various hormonal systems on the bodily constitution, as well as expressed anthropometricheterogeneity. In adolescents with andrological pathology or clinical signs for its development, in all anthropometric parameters the higher values were seen more frequently than low values against the background of highest group anthropometric homogeneity. Summative anthropometric characteristics of the adolescents group with delayed sexual development were between those of the adolescents groups with normal andrological status and andrological pathology The number of correlational relationships of anthropometric and hormonal indicators with the levels of cortisol and dehydroepiandrosteronesulphate was the lowest in the group of adolescents with normal andrological status as compared to their peers with delayed sexual development and andrological pathology. Only in the group of adolescents with normal andrological status the correlation analysis of data showed physiological influence of sexual hormones on anthropometric indicators. Thus, lower influence of sexual system hormones during this ontogenesis stage contributes to slowing down the process of sexual maturation both with the development of andrological pathology in adolescents.

Prevalence and pattern of glenohumeral injuries among acute high-grade acromioclavicular joint instabilities.

PubMed

Pauly, Stephan; Kraus, Natascha; Greiner, Stefan; Scheibel, Markus

2013-06-01

With increasing numbers of arthroscopically assisted acromioclavicular (AC) joint stabilization procedures has come an increase in reports of concomitant glenohumeral injuries among AC joint separations. The aim of the present study was to evaluate the prevalence, pattern, and cause of glenohumeral pathologies among a large patient population with acute high-grade AC joint instability. A total of 125 patients (13 women, 112 men) with high-grade AC joint dislocation (6 Rockwood II; 119 Rockwood V) underwent diagnostic glenohumeral arthroscopy before AC joint repair. Pathologic lesions were evaluated for acute or degenerative origin and, if considered relevant, treated all-arthroscopically. Concomitant glenohumeral pathologies were found in 38 of 125 patients (30.4%). Analysis of pathogenesis distinguished different patterns of accompanying injuries: acute intra-articular lesions, related to the recent shoulder trauma, were found in 9 patients (7.2%), degenerative lesions, considered to be unrelated to the recent trauma, were found in 18 (14.4%), and 11 (8.8%) had an unclear traumatic correlation (intermediate group). Within the acute and the degenerative group, affected structures were predominantly partial, articular-sided tears of the anterosuperior rotator cuff, including instabilities of the pulley complex, followed by pathologies of the long head of the biceps and superior labrum anteroposterior lesions. The intermediate group presented mainly with articular-sided partial tears of the subscapularis tendon. This prospective study showed a high prevalence (30%) of concomitant glenohumeral pathologies, of which some indicate additional surgical therapy and could be missed by an isolated open AC repair. Hence, the arthroscopic approach for AC joint stabilization allows for the diagnosis and treatment of associated intra-articular pathologies. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Does a uterine manipulator affect cervical cancer pathology or identification of lymphovascular space involvement?

PubMed

Rakowski, Joseph A; Tran, Tien Anh N; Ahmad, Sarfraz; James, Jeffrey A; Brudie, Lorna A; Pernicone, Peter J; Radi, Michael J; Holloway, Robert W

2012-10-01

Uterine manipulators are a useful adjunct for robotic-assisted radical hysterectomy (RARH), but some surgeons avoid their use for fear of altering pathology or interpretation of lymphovascular space involvement (LVSI). We retrospectively compared clinico-pathological data and tumor pathology from patients with cervical cancer operated by laparotomy vs. RARH. Charts from cervical cancer patients who underwent radical hysterectomy from January-1997 to June-2010 were reviewed for tumor histology, grade, FIGO stage, lymph node status, LVSI, depth of invasion, and tumor size. A ConMed V-Care® uterine manipulator was used in all robotic cases. H&E stained slides from 20 robotic and 24 open stage IB1 cases with LVSI reported in the original pathology were re-reviewed by a blinded pathologist for analysis of tissue artifacts and LVSI. Two-hundred-thirty-six cases (185 open, 51 robotic) with stages IA2, IB1 and IB2 cervical cancer were reviewed. No significant differences in histology (squamous cell carcinoma, 65% vs. 51%; p=0.1), IB1 lesion size (≤2 cm, 62% vs. 61%, p>0.1), LVSI (34% vs. 39%, p>0.1), and depth of stromal invasion (p>0.1) was found between open and robotic groups. Histologic examination of all IB1 cervical carcinomas revealed a higher degree of surface disruption [45% (9/20) vs. 12.6% (3/24), p=0.038] and artifactual "parametrial carryover" [65% (13/20) vs. 29% (7/24), p=0.037] in robotic vs. open groups, respectively, but no significant differences in the rate of LVSI. RARH cases that utilized a uterine manipulator did not show any clinico-pathological differences in depth of invasion, LVSI, or parametrial involvement compared to open cases. Copyright © 2012 Elsevier Inc. All rights reserved.

Barium enema and CT volumetry for predicting pathologic response to preoperative chemoradiotherapy in rectal cancer patients.

PubMed

Murono, Koji; Kawai, Kazushige; Tsuno, Nelson H; Ishihara, Soichiro; Yamaguchi, Hironori; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

2014-06-01

Preoperative chemoradiotherapy has been widely used for the prevention of local recurrence of locally advanced rectal cancer, and the effect of chemoradiotherapy is known to be associated with overall survival. We aimed to evaluate the association of the pathologic response grade with tumor recurrence rate after chemoradiotherapy, using radiographic analysis and the Response Evaluation Criteria in Solid Tumors as the parameters. This study was conducted at a single tertiary care institution in Japan. This was a retrospective cohort study of patients undergoing preoperative chemoradiotherapy. A total of 101 low rectal cancer patients receiving preoperative chemoradiotherapy from July 2004 to August 2012 were enrolled. The tumor reduction rate was measured with the use of traditional Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry, and the correlation between the reduction rate and the pathologic response grade was examined. The tumor reduction rate assessed according to Response Evaluation Criteria in Solid Tumors showed no association with the pathologic response grade (p =0.61). In contrast, the radiographic response rate by both barium enema and CT volumetry strongly correlated with the pathologic response grade (p < 0.0001 and p = 0.001).In terms of local tumor recurrence, those diagnosed as high responders by the pathologic response grade, Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry had a lower recurrence rate (p =0.03, p =0.03, p =0.0002, and p =0.001). The difference between high responders and low responders was especially prominent by barium enema and CT volumetry. The study is limited by its retrospective nature. Double-contrast barium enema and CT volumetry were superior to Response Evaluation Criteria in Solid Tumors in evaluating the effect of chemoradiotherapy and predicting the likelihood of tumor recurrence.

Analysis of Radiation Effects in Digital Subtraction Angiography of Intracranial Artery Stenosis.

PubMed

Guo, Chaoqun; Shi, Xiaolei; Ding, Xianhui; Zhou, Zhiming

2018-04-21

Intracranial artery stenosis (IAS) is the most common cause for acute cerebral accidents. Digital subtraction angiography (DSA) is the gold standard to detect IAS and usually brings excess radiation exposure to examinees and examiners. The artery pathology might influence the interventional procedure, causing prolonged radiation effects. However, no studies on the association between IAS pathology and operational parameters are available. A retrospective analysis was conducted on 93 patients with first-ever stroke/transient ischemic attack, who received DSA examination within 3 months from onset in this single center. Comparison of baseline characteristics was determined by 2-tailed Student's t-test or the chi-square test between subjects with and without IAS. A binary logistic regression analysis was performed to determine the association between IAS pathology and the items with a P value <0.05 in Student's t-test or chi-square test. There were 93 candidates (42 with IAS and 51 without IAS) in this study. The 2 groups shared no significance of the baseline characteristics (P > 0.05). We found a significantly higher total time, higher kerma area product, greater total dose, and greater DSA dose in the IAS group than in those without IAS (P < 0.05). A binary logistic regression analysis indicated the significant association between total time and IAS pathology (P < 0.05) but no significance in kerma area product, radiation dose, and DSA dose (P > 0.05). IAS pathology would indicate a prolonged total time of DSA procedure in clinical practice. However, the radiation effects would not change with pathologic changes. Copyright © 2018 Elsevier Inc. All rights reserved.

High-grade poorly differentiated neuroendocrine carcinoma of the breast with low oncotype Dx recurrence score: A case report.

PubMed

Munoz-Zuluaga, Carlos A; Kotiah, Sandy; Studeman, Kimberley D

2017-01-01

Primary neuroendocrine carcinoma of the breast (NECB) is a rare malignant tumor with controversial biological behavior and a lack of data guiding treatment decisions due to its scarcity. Cancer gene-expression profiling tests provide a better indication of clinical prognosis and help determine the best clinical management versus the traditional clinical and pathological parameters. This is a report of a NECB with a genetic assay that showed a low-risk tumor despite high-grade and poorly differentiated histopathological features. Patient outcomes correlate with the low risk classification without the need for adjuvant chemotherapy despite the standard clinical-pathologic approach. Analysis of cancer related genes expression and outcomes in historical NECB may elucidate new insight of this rare disease.

[Refractive errors in patients with cerebral palsy].

PubMed

Mrugacz, Małgorzata; Bandzul, Krzysztof; Kułak, Wojciech; Poppe, Ewa; Jurowski, Piotr

2013-04-01

Ocular changes are common in patients with cerebral palsy (CP) and they exist in about 50% of cases. The most common are refractive errors and strabismus disease. The aim of the paper was to estimate the relativeness between refractive errors and neurological pathologies in patients with selected types of CP. MATERIAL AND METHODS. The subject of the analysis was showing refractive errors in patients within two groups of CP: diplegia spastica and tetraparesis, with nervous system pathologies taken into account. Results. This study was proven some correlations between refractive errors and type of CP and severity of the CP classified in GMFCS scale. Refractive errors were more common in patients with tetraparesis than with diplegia spastica. In the group with diplegia spastica more common were myopia and astigmatism, however in tetraparesis - hyperopia.

Amyloid and Tau PET Demonstrate Region-Specific Associations in Normal Older People

PubMed Central

Lockhart, Samuel N.; Schöll, Michael; Baker, Suzanne L.; Ayakta, Nagehan; Swinnerton, Kaitlin N.; Bell, Rachel K.; Mellinger, Taylor J.; Shah, Vyoma D.; O’Neil, James P.; Janabi, Mustafa; Jagust, William J.

2017-01-01

β-amyloid (Aβ) and tau pathology become increasingly prevalent with age, however, the spatial relationship between the two pathologies remains unknown. We examined local (same region) and non-local (different region) associations between these 2 aggregated proteins in 46 normal older adults using [18F]AV-1451 (for tau) and [11C]PiB (for Aβ) positron emission tomography (PET) and 1.5T magnetic resonance imaging (MRI) images. While local voxelwise analyses showed associations between PiB and AV-1451 tracer largely in the temporal lobes, k-means clustering revealed that some of these associations were driven by regions with low tracer retention. We followed this up with a whole-brain region-by-region (local and non-local) partial correlational analysis. We calculated each participant’s mean AV-1451 and PiB uptake values within 87 regions of interest (ROI). Pairwise ROI analysis demonstrated many positive PiB—AV-1451 associations. Importantly, strong positive partial correlations (controlling for age, sex, and global gray matter fraction, p < .01) were identified between PiB in multiple regions of association cortex and AV-1451 in temporal cortical ROIs. There were also less frequent and weaker positive associations of regional PiB with frontoparietal AV-1451 uptake. Particularly in temporal lobe ROIs, AV-1451 uptake was strongly predicted by PiB across multiple ROI locations. These data indicate that Aβ and tau pathology show significant local and non-local regional associations among cognitively normal elderly, with increased PiB uptake throughout the cortex correlating with increased temporal lobe AV-1451 uptake. The spatial relationship between Aβ and tau accumulation does not appear to be specific to Aβ location, suggesting a regional vulnerability of temporal brain regions to tau accumulation regardless of where Aβ accumulates. PMID:28232190

Parameters indicative of persistence of valvular pathology at initial diagnosis in acute rheumatic carditis: the role of albumin and CD19 expression.

PubMed

Oner, Taliha; Ozdemir, Rahmi; Genc, Dildar Bahar; Kucuk, Mehmet; Karadeniz, Cem; Demirpence, Savas; Yilmazer, Murat Muhtar; Mese, Timur; Tavli, Vedide; Genel, Ferah

The aim of this study is to define the predictors of chronic carditis in patients with acute rheumatic carditis (ARC). Patients diagnosed with ARC between May 2010 and May 2011 were included in the study. Echocardiography, electrocardiography, lymphocyte subset analysis, acute phase reactants, plasma albumin levels, and antistreptolysin-O (ASO) tests were performed at initial presentation. The echocardiographic assessments were repeated at the sixth month of follow-up. The patients were divided into two groups according to persistence of valvular pathology at 6th month as Group 1 and Group 2, and all clinical and laboratory parameters at admission were compared between two groups of valvular involvement. During the one-year study period, 22 patients had valvular disease. Seventeen (77.2%) patients showed regression in valvular pathology. An initial mild regurgitation disappeared in eight patients (36.3%). Among seven (31.8%) patients with moderate regurgitation initially, the regurgitation disappeared in three, and four patients improved to mild regurgitation. Two patients with a severe regurgitation initially improved to moderate regurgitation (9.1%). In five (22.8%) patients, the grade of regurgitation [moderate regurgitation in one (4.6%), and severe regurgitation in 4 (18.2%)] remained unchanged. The albumin level was significantly lower at diagnosis in Group 2 (2.6±0.48g/dL). Lymphocyte subset analysis showed a significant decrease in the CD8 percentage and a significant increase in CD19 percentage at diagnosis in Group 2 compared to Group 1. The blood albumin level and the percentage of CD8 and CD19 (+) lymphocytes at diagnosis may help to predict chronic valvular disease risk in patients with acute rheumatic carditis. Copyright © 2016. Published by Elsevier Editora Ltda.

Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function.

PubMed

Sunitha, Balaraju; Gayathri, Narayanappa; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Nalini, Atchayaram; Padmanabhan, Balasundaram; Srinivas Bharath, Muchukunte Mukunda

2016-07-01

Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from dysferlinopathy (Dysfy), polymyositis (PM), and distal myopathy with rimmed vacuoles (DMRV) displayed morphological and biochemical evidences of mitochondrial dysfunction. Proteomic analysis revealed down-regulation of electron transport chain (ETC) subunits, assembly factors, and tricarboxylic acid (TCA) cycle enzymes, with 80 proteins common among the three pathologies. Mitochondrial proteins from muscle pathologies also displayed higher Trp oxidation that could alter the local structure. Cover image for this issue: doi: 10.1111/jnc.13324. © 2016 International Society for Neurochemistry.

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.

Determination of the pathological state of skin samples by optical polarimetry parameters

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; Ortega-Quijano, N.; Buelta, L.; Arce-Diego, J. L.

2008-11-01

Polarimetry is widely known to involve a series of powerful optical techniques that characterize the polarization behaviour of a sample. In this work, we propose a method for applying polarimetric procedures to the characterization of biological tissues, in order to differentiate between healthy and pathologic tissues on a polarimetric basis. Usually, medical morphology diseases are diagnosed based on histological alterations of the tissue. The fact that these alterations will be reflected in polarization information highlights the suitability of polarimetric procedures for diagnostic purposes. The analysis is mainly focused on the depolarization properties of the media, as long as the internal structure strongly affects the polarization state of the light that interacts with the sample. Therefore, a method is developed in order to determine the correlation between pathological ultraestructural characteristics and the subsequent variations in the polarimetric parameters of the backscattered light. This study is applied to three samples of porcine skin corresponding to a healthy region, a mole, and a cancerous region. The results show that the method proposed is indeed an adequate technique in order to achieve an early, accurate and effective cancer detection.

Giant fibroadenomatoid hyperplasia of the breast: a case report.

PubMed

Zhang, Hao; Wang, Xin-Lu; Ren, Wei-Dong; Shi, Tie-Mei

2014-01-01

Fibroadenomatoid hyperplasia of the breast (FAHB) is a rare benign breast lesion and its clinical features are similar to fibroadenoma and fibrocystic changes. FAHB has been previously termed sclerosing lobular hyperplasia, fibroadenomatosis, fibroadenomatoid change, or fibroadenomatoid mastopathy. Typically, FAHB is derived from stroma and epithelia. The pathologic characteristics of FAHB are microfocal lobulocentric proliferation of stroma accompanied by epithelial and myoepithelial components resembling similar histological changes, as found in fibroadenoma, apocrine hyperplasia, intraductal hyperplasia, and lobular hyperplasia. FAHB could be present as a localized or diffused pattern in pathology. Most cases show no well-circumscribed mass lesions and no apparent capsules; it is usually identified as an incidental finding in other benign lesions or in random sampling in cancerous breast tissues. FAHB is categorized as a benign proliferative breast disease and it has previously been reported; however, the authors believe this study may be the first case with two giant masses reported. Fiber adenoma hyperplasia is a rare cystic hyperplasia of breast pathology and its ultrasonographic manifestations are easily confused with breast cancer. Comparative MRI ultrasound analysis will help make the differential diagnosis. © 2014 S. Karger AG, Basel.

Dynamic 3D echocardiography in virtual reality

PubMed Central

van den Bosch, Annemien E; Koning, Anton HJ; Meijboom, Folkert J; McGhie, Jackie S; Simoons, Maarten L; van der Spek, Peter J; Bogers, Ad JJC

2005-01-01

Background This pilot study was performed to evaluate whether virtual reality is applicable for three-dimensional echocardiography and if three-dimensional echocardiographic 'holograms' have the potential to become a clinically useful tool. Methods Three-dimensional echocardiographic data sets from 2 normal subjects and from 4 patients with a mitral valve pathological condition were included in the study. The three-dimensional data sets were acquired with the Philips Sonos 7500 echo-system and transferred to the BARCO (Barco N.V., Kortrijk, Belgium) I-space. Ten independent observers assessed the 6 three-dimensional data sets with and without mitral valve pathology. After 10 minutes' instruction in the I-Space, all of the observers could use the virtual pointer that is necessary to create cut planes in the hologram. Results The 10 independent observers correctly assessed the normal and pathological mitral valve in the holograms (analysis time approximately 10 minutes). Conclusion this report shows that dynamic holographic imaging of three-dimensional echocardiographic data is feasible. However, the applicability and use-fullness of this technology in clinical practice is still limited. PMID:16375768

Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer disease.

PubMed

Lurain, Nell S; Hanson, Barbara A; Martinson, Jeffrey; Leurgans, Sue E; Landay, Alan L; Bennett, David A; Schneider, Julie A

2013-08-15

Serum, cerebrospinal fluid (CSF), and cryopreserved lymphocytes from subjects in the Rush Alzheimer's Disease Center Religious Orders Study were analyzed for associations between cytomegalovirus (CMV) infection and clinical and pathological markers of Alzheimer disease. CMV antibody levels were associated with neurofibrillary tangles (NFTs). CSF interferon γ was only detected in seropositive subjects and was significantly associated with NFTs. The percentage of senescent T cells (CD4+ or CD8+CD28-CD57+) was significantly higher for CMV-seropositive as compared to CMV-seronegative subjects and was marginally associated with the pathologic diagnosis of Alzheimer disease (CD4+) or amyloid-β (CD8+). Immunocytochemical analysis showed induction of amyloid-β in human foreskin fibroblasts (HFFs) infected with each of 3 clinical CMV strains. In the same subjects, there was no association of herpes simplex virus type 1 (HSV-1) antibody levels with CMV antibody levels or clinical or pathological markers of Alzheimer disease. HSV-1 infection of HFFs did not induce amyloid-β. These data support an association between CMV and the development of Alzheimer disease.

Neuronal dystonin isoform 2 is a mediator of endoplasmic reticulum structure and function.

PubMed

Ryan, Scott D; Ferrier, Andrew; Sato, Tadasu; O'Meara, Ryan W; De Repentigny, Yves; Jiang, Susan X; Hou, Sheng T; Kothary, Rashmi

2012-02-01

Dystonin/Bpag1 is a cytoskeletal linker protein whose loss of function in dystonia musculorum (dt) mice results in hereditary sensory neuropathy. Although loss of expression of neuronal dystonin isoforms (dystonin-a1/dystonin-a2) is sufficient to cause dt pathogenesis, the diverging function of each isoform and what pathological mechanisms are activated upon their loss remains unclear. Here we show that dt(27) mice manifest ultrastructural defects at the endoplasmic reticulum (ER) in sensory neurons corresponding to in vivo induction of ER stress proteins. ER stress subsequently leads to sensory neurodegeneration through induction of a proapoptotic caspase cascade. dt sensory neurons display neurodegenerative pathologies, including Ca(2+) dyshomeostasis, unfolded protein response (UPR) induction, caspase activation, and apoptosis. Isoform-specific loss-of-function analysis attributes these neurodegenerative pathologies to specific loss of dystonin-a2. Inhibition of either UPR or caspase signaling promotes the viability of cells deficient in dystonin. This study provides insight into the mechanism of dt neuropathology and proposes a role for dystonin-a2 as a mediator of normal ER structure and function.

A Cluster-then-label Semi-supervised Learning Approach for Pathology Image Classification.

PubMed

Peikari, Mohammad; Salama, Sherine; Nofech-Mozes, Sharon; Martel, Anne L

2018-05-08

Completely labeled pathology datasets are often challenging and time-consuming to obtain. Semi-supervised learning (SSL) methods are able to learn from fewer labeled data points with the help of a large number of unlabeled data points. In this paper, we investigated the possibility of using clustering analysis to identify the underlying structure of the data space for SSL. A cluster-then-label method was proposed to identify high-density regions in the data space which were then used to help a supervised SVM in finding the decision boundary. We have compared our method with other supervised and semi-supervised state-of-the-art techniques using two different classification tasks applied to breast pathology datasets. We found that compared with other state-of-the-art supervised and semi-supervised methods, our SSL method is able to improve classification performance when a limited number of labeled data instances are made available. We also showed that it is important to examine the underlying distribution of the data space before applying SSL techniques to ensure semi-supervised learning assumptions are not violated by the data.

Virological and Immunological Characteristics of Human Cytomegalovirus Infection Associated With Alzheimer Disease

PubMed Central

Lurain, Nell S.; Hanson, Barbara A.; Martinson, Jeffrey; Leurgans, Sue E.; Landay, Alan L.; Bennett, David A.; Schneider, Julie A.

2013-01-01

Serum, cerebrospinal fluid (CSF), and cryopreserved lymphocytes from subjects in the Rush Alzheimer's Disease Center Religious Orders Study were analyzed for associations between cytomegalovirus (CMV) infection and clinical and pathological markers of Alzheimer disease. CMV antibody levels were associated with neurofibrillary tangles (NFTs). CSF interferon γ was only detected in seropositive subjects and was significantly associated with NFTs. The percentage of senescent T cells (CD4+ or CD8+CD28−CD57+) was significantly higher for CMV-seropositive as compared to CMV-seronegative subjects and was marginally associated with the pathologic diagnosis of Alzheimer disease (CD4+) or amyloid-β (CD8+). Immunocytochemical analysis showed induction of amyloid-β in human foreskin fibroblasts (HFFs) infected with each of 3 clinical CMV strains. In the same subjects, there was no association of herpes simplex virus type 1 (HSV-1) antibody levels with CMV antibody levels or clinical or pathological markers of Alzheimer disease. HSV-1 infection of HFFs did not induce amyloid-β. These data support an association between CMV and the development of Alzheimer disease. PMID:23661800

Robust lung identification in MSCT via controlled flooding and shape constraints: dealing with anatomical and pathological specificity

NASA Astrophysics Data System (ADS)

Fetita, Catalin; Tarando, Sebastian; Brillet, Pierre-Yves; Grenier, Philippe A.

2016-03-01

Correct segmentation and labeling of lungs in thorax MSCT is a requirement in pulmonary/respiratory disease analysis as a basis for further processing or direct quantitative measures: lung texture classification, respiratory functional simulations, intrapulmonary vascular remodeling evaluation, detection of pleural effusion or subpleural opacities, are only few clinical applications related to this requirement. Whereas lung segmentation appears trivial for normal anatomo-pathological conditions, the presence of disease may complicate this task for fully-automated algorithms. The challenges come either from regional changes of lung texture opacity or from complex anatomic configurations (e.g., thin septum between lungs making difficult proper lung separation). They make difficult or even impossible the use of classic algorithms based on adaptive thresholding, 3-D connected component analysis and shape regularization. The objective of this work is to provide a robust segmentation approach of the pulmonary field, with individualized labeling of the lungs, able to overcome the mentioned limitations. The proposed approach relies on 3-D mathematical morphology and exploits the concept of controlled relief flooding (to identify contrasted lung areas) together with patient-specific shape properties for peripheral dense tissue detection. Tested on a database of 40 MSCT of pathological lungs, the proposed approach showed correct identification of lung areas with high sensitivity and specificity in locating peripheral dense opacities.

Microarray expression analysis and identification of serum biomarkers for Niemann-Pick disease, type C1.

PubMed

Cluzeau, Celine V M; Watkins-Chow, Dawn E; Fu, Rao; Borate, Bhavesh; Yanjanin, Nicole; Dail, Michelle K; Davidson, Cristin D; Walkley, Steven U; Ory, Daniel S; Wassif, Christopher A; Pavan, William J; Porter, Forbes D

2012-08-15

Niemann-Pick disease type C (NPC) is a lysosomal storage disorder characterized by liver disease and progressive neurodegeneration. Deficiency of either NPC1 or NPC2 leads to the accumulation of cholesterol and glycosphingolipids in late endosomes and early lysosomes. In order to identify pathological mechanisms underlying NPC and uncover potential biomarkers, we characterized liver gene expression changes in an Npc1 mouse model at six ages spanning the pathological progression of the disease. We identified altered gene expression at all ages, including changes in asymptomatic, 1-week-old mice. Biological pathways showing early altered gene expression included: lipid metabolism, cytochrome P450 enzymes involved in arachidonic acid and drug metabolism, inflammation and immune responses, mitogen-activated protein kinase and G-protein signaling, cell cycle regulation, cell adhesion and cytoskeleton remodeling. In contrast, apoptosis and oxidative stress appeared to be late pathological processes. To identify potential biomarkers that could facilitate monitoring of disease progression, we focused on a subset of 103 differentially expressed genes that encode secreted proteins. Further analysis identified two secreted proteins with increased serum levels in NPC1 patients: galectin-3 (LGALS3), a pro-inflammatory molecule, and cathepsin D (CTSD), a lysosomal aspartic protease. Elevated serum levels of both proteins correlated with neurological disease severity and appeared to be specific for NPC1. Expression of Lgals3 and Ctsd was normalized following treatment with 2-hydroxypropyl-β-cyclodextrin, a therapy that reduces pathological findings and significantly increases Npc1(-/-) survival. Both LGALS3 and CTSD have the potential to aid in diagnosis and serve as biomarkers to monitor efficacy in therapeutic trials.

Clinicopathological analysis of biopsy-proven diabetic nephropathy based on the Japanese classification of diabetic nephropathy.

PubMed

Furuichi, Kengo; Shimizu, Miho; Yuzawa, Yukio; Hara, Akinori; Toyama, Tadashi; Kitamura, Hiroshi; Suzuki, Yoshiki; Sato, Hiroshi; Uesugi, Noriko; Ubara, Yoshifumi; Hohino, Junichi; Hisano, Satoshi; Ueda, Yoshihiko; Nishi, Shinichi; Yokoyama, Hitoshi; Nishino, Tomoya; Kohagura, Kentaro; Ogawa, Daisuke; Mise, Koki; Shibagaki, Yugo; Makino, Hirofumi; Matsuo, Seiichi; Wada, Takashi

2018-06-01

The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis. The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy. The median observation period was 70.4 (IQR 20.9-101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m 2 /year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%. This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.

Imaging correlates of pathology in corticobasal syndrome(Podcast)

PubMed Central

Whitwell, J.L.; Jack, C.R.; Boeve, B.F.; Parisi, J.E.; Ahlskog, J.E.; Drubach, D.A.; Senjem, M.L.; Knopman, D.S.; Petersen, R.C.; Dickson, D.W.; Josephs, K.A.

2010-01-01

Background: Corticobasal syndrome (CBS) can be associated with different underlying pathologies that are difficult to predict based on clinical presentation. The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS. Methods: This was a case-control study of 24 patients with CBS who had undergone MRI during life and came to autopsy. Pathologic diagnoses included frontotemporal lobar degeneration (FTLD) with TDP-43 immunoreactivity in 5 (CBS-TDP), Alzheimer disease (AD) in 6 (CBS-AD), corticobasal degeneration in 7 (CBS-CBD), and progressive supranuclear palsy in 6 (CBS-PSP). Voxel-based morphometry and atlas-based parcellation were used to assess atrophy across the CBS groups and compared to 24 age- and gender-matched controls. Results: All CBS pathologic groups showed gray matter loss in premotor cortices, supplemental motor area, and insula on imaging. However, CBS-TDP and CBS-AD showed more widespread patterns of loss, with frontotemporal loss observed in CBS-TDP and temporoparietal loss observed in CBS-AD. CBS-TDP showed significantly greater loss in prefrontal cortex than the other groups, whereas CBS-AD showed significantly greater loss in parietal lobe than the other groups. The focus of loss was similar in CBS-CBD and CBS-PSP, although more severe in CBS-CBD. Conclusions: Imaging patterns of atrophy in CBS vary according to pathologic diagnosis. Widespread atrophy points toward a pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD-TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy predominantly involving the premotor and supplemental motor area suggests CBD or PSP pathology. GLOSSARY AAL = automated anatomic labeling; AD = Alzheimer disease; CBD = corticobasal degeneration; CBS = corticobasal syndrome; CDR-SB = Clinical Dementia Rating sum of boxes; FDR = false discovery rate; FTLD = frontotemporal lobar degeneration; MMSE = Mini-Mental State Examination; PSP = progressive supranuclear palsy; ROI = region of interest; SMA = supplemental motor area; TDP = TDP-43 immunoreactivity; TIV = total intracranial volume; VBM = voxel-based morphometry. PMID:21098403

Altered neural reward representations in pathological gamblers revealed by delay and probability discounting.

PubMed

Miedl, Stephan F; Peters, Jan; Büchel, Christian

2012-02-01

The neural basis of excessive delay discounting and reduced risk sensitivity of pathological gamblers with a particular focus on subjective neural reward representations has not been previously examined. To examine how pathological gamblers represent subjective reward value at a neural level and how this is affected by gambling severity. Model-based functional magnetic resonance imaging study with patients and control subjects. Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf. Participants were recruited from the local community by advertisement and through self-help groups. A sample of 16 pathological gamblers (according to the DSM-IV definition) was matched by age, sex, smoking status, income, educational level, and handedness to 16 healthy controls. Pathological gamblers showed increased discounting of delayed rewards and a trend toward decreased discounting of probabilistic rewards compared with matched controls. At the neural level, a significant group × condition interaction indicated that reward representations in the gamblers were modulated in a condition-specific manner, such that they exhibited increased (delay discounting) and decreased (probability discounting) neural value correlations in the reward system. In addition, throughout the reward system, neuronal value signals for delayed rewards were negatively correlated with gambling severity. The results extend previous reports of a generally hypoactive reward system in pathological gamblers by showing that, even when subjective reward valuation is accounted for, gamblers still show altered reward representations. Furthermore, results point toward a gradual degradation of mesolimbic reward representations for delayed rewards during the course of pathological gambling.

Neuroinflammation is increased in the parietal cortex of atypical Alzheimer's disease.

PubMed

Boon, Baayla D C; Hoozemans, Jeroen J M; Lopuhaä, Boaz; Eigenhuis, Kristel N; Scheltens, Philip; Kamphorst, Wouter; Rozemuller, Annemieke J M; Bouwman, Femke H

2018-05-29

While most patients with Alzheimer's disease (AD) present with memory complaints, 30% of patients with early disease onset present with non-amnestic symptoms. This atypical presentation is thought to be caused by a different spreading of neurofibrillary tangles (NFT) than originally proposed by Braak and Braak. Recent studies suggest a prominent role for neuroinflammation in the spreading of tau pathology. We aimed to explore whether an atypical spreading of pathology in AD is associated with an atypical distribution of neuroinflammation. Typical and atypical AD cases were selected based on both NFT distribution and amnestic or non-amnestic clinical presentation. Immunohistochemistry was performed on the temporal pole and superior parietal lobe of 10 typical and 9 atypical AD cases. The presence of amyloid-beta (N-terminal; IC16), pTau (AT8), reactive astrocytes (GFAP), microglia (Iba1, CD68, and HLA-DP/DQ/DR), and complement factors (C1q, C3d, C4b, and C5b-9) was quantified by image analysis. Differences in lobar distribution patterns of immunoreactivity were statistically assessed using a linear mixed model. We found a temporal dominant distribution for amyloid-beta, GFAP, and Iba1 in both typical and atypical AD. Distribution of pTau, CD68, HLA-DP/DQ/DR, C3d, and C4b differed between AD variants. Typical AD cases showed a temporal dominant distribution of these markers, whereas atypical AD cases showed a parietal dominant distribution. Interestingly, when quantifying for the number of amyloid-beta plaques instead of stained surface area, atypical AD cases differed in distribution pattern from typical AD cases. Remarkably, plaque morphology and localization of neuroinflammation within the plaques was different between the two phenotypes. Our data show a different localization of neuroinflammatory markers and amyloid-beta plaques between AD phenotypes. In addition, these markers reflect the atypical distribution of tau pathology in atypical AD, suggesting that neuroinflammation might be a crucial link between amyloid-beta deposits, tau pathology, and clinical symptoms.

Fractal analysis of scatter imaging signatures to distinguish breast pathologies

NASA Astrophysics Data System (ADS)

Eguizabal, Alma; Laughney, Ashley M.; Krishnaswamy, Venkataramanan; Wells, Wendy A.; Paulsen, Keith D.; Pogue, Brian W.; López-Higuera, José M.; Conde, Olga M.

2013-02-01

Fractal analysis combined with a label-free scattering technique is proposed for describing the pathological architecture of tumors. Clinicians and pathologists are conventionally trained to classify abnormal features such as structural irregularities or high indices of mitosis. The potential of fractal analysis lies in the fact of being a morphometric measure of the irregular structures providing a measure of the object's complexity and self-similarity. As cancer is characterized by disorder and irregularity in tissues, this measure could be related to tumor growth. Fractal analysis has been probed in the understanding of the tumor vasculature network. This work addresses the feasibility of applying fractal analysis to the scattering power map (as a physical modeling) and principal components (as a statistical modeling) provided by a localized reflectance spectroscopic system. Disorder, irregularity and cell size variation in tissue samples is translated into the scattering power and principal components magnitude and its fractal dimension is correlated with the pathologist assessment of the samples. The fractal dimension is computed applying the box-counting technique. Results show that fractal analysis of ex-vivo fresh tissue samples exhibits separated ranges of fractal dimension that could help classifier combining the fractal results with other morphological features. This contrast trend would help in the discrimination of tissues in the intraoperative context and may serve as a useful adjunct to surgeons.

Prevalence of alcohol-related pathologies at autopsy: Estonian Forensic Study of Alcohol and Premature Death

PubMed Central

Tuusov, Jana; Lang, Katrin; Väli, Marika; Pärna, Kersti; Tõnisson, Mailis; Ringmets, Inge; McKee, Martin; Helander, Anders; Leon, David A

2014-01-01

Aims Alcohol can induce diverse serious pathologies, yet this complexity may be obscured when alcohol-related deaths are classified according to a single underlying cause. We sought to quantify this issue and its implications for analysing mortality data. Design, Setting and Participants Cross-sectional study included 554 men aged 25–54 in Estonia undergoing forensic autopsy in 2008–09. Measurements Potentially alcohol-related pathologies were identified following macroscopic and histological examination. Alcohol biomarkers levels were determined. For a subset (26%), drinking behaviour was provided by next-of-kin. The Estonian Statistics Office provided underlying cause of death. Findings Most deaths (75%) showed evidence of potentially alcohol-related pathologies, and 32% had pathologies in two or more organs. The liver was most commonly affected [60.5%, 95% confidence interval (CI) = 56.3–64.6] followed by the lungs (18.6%, 95% CI = 15.4–22.1), stomach (17.5%, 95% CI = 14.4–20.9), pancreas (14.1%, 95% CI = 11.3–17.3), heart (4.9%, 95% CI = 3.2–7.0) and oesophagus (1.4%, 95% CI = 0.6–2.8). Only a minority with liver pathology had a second pathology. The number of pathologies correlated with alcohol biomarkers (phosphatidylethanol, gamma-glytamyl transpeptidase in blood, ethylglucuronide, ethylsulphate in urine). Despite the high prevalence of liver pathology, few deaths had alcoholic liver disease specified as the underlying cause. Conclusion The majority of 554 men aged 25–54 undergoing forensic autopsy in Estonia in 2008–09 showed evidence of alcohol-related pathology. However, the recording of deaths by underlying cause failed to capture the scale and nature of alcohol-induced pathologies found. PMID:25066373

Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer’s disease or corticobasal degeneration brains

PubMed Central

Boluda, Susana; Iba, Michiyo; Zhang, Bin; Raible, Kevin M.; Lee, Virginia M-Y.; Trojanowski, John Q.

2015-01-01

Filamentous tau pathologies are hallmark lesions of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and corticobasal degeneration (CBD) which show cell type-specific and topographically distinct tau inclusions. Growing evidence supports templated transmission of tauopathies through functionally interconnected neuroanatomical pathways suggesting that different self-propagating strains of pathological tau could account for the diverse manifestations of neurodegenerative tauopathies. Here, we describe the rapid and distinct cell type-specific spread of pathological tau following intracerebral injections of CBD or AD brain extracts enriched in pathological tau (designated CBD-Tau and AD-Tau, respectively) in young human mutant P301S tau transgenic (Tg) mice (line PS19) ~6–9 months before they show onset of mutant tau transgene-induced tau pathology. At 1 month post-injection of CBD-Tau, tau inclusions developed predominantly in oligodendrocytes of the fimbria and white matter near the injection sites with infrequent intraneuronal tau aggregates. In contrast, injections of AD-Tau in young PS19 mice induced tau pathology predominantly in neuronal perikarya with little or no oligodendrocyte involvement 1 month post-injection. With longer post-injection survival intervals of up to 6 months, CBD-Tau- and AD-Tau-induced tau pathology spread to different brain regions distant from the injection sites while maintaining the cell type-specific pattern noted above. Finally, CA3 neuron loss was detected 3 months post-injection of AD-Tau but not CBD-Tau. Thus, AD-Tau and CBD-Tau represent specific pathological tau strains that spread differentially and may underlie distinct clinical and pathological features of these two tauopathies. Hence, these strains could become targets to develop disease-modifying therapies for CBD and AD. PMID:25534024

Pathological jealousy and pathological love: Apples to apples or apples to oranges?

PubMed

Stravogiannis, Andrea Lorena da C; Kim, Hyoun S; Sophia, Eglacy C; Sanches, Cíntia; Zilberman, Monica L; Tavares, Hermano

2018-01-01

Pathological jealousy evokes emotions, thoughts, and behaviors that cause damage to social and interpersonal relationships. On the other hand, pathological love is the uncontrollable behavior of caring for a partner that results in neglecting the needs of the self. The aim of the present research was to assess the similarities and differences between the two psychopathologies of love. To this end, thirty-two individuals with pathological jealousy and 33 individuals with pathological love were compared on demographics, aspects of romantic relationship (jealousy, satisfaction, love style), psychiatric co-morbidities, personality and psychological characteristics (e.g., impulsivity). In a univariate analysis individuals with pathological jealousy were more likely to be in a current relationship and reported greater satisfaction. The avoidant attachment and the ludus love style were associated with pathological jealousy whereas the secure attachment and agape love style was associated with pathological love. Almost three-quarters (72.3%) of the sample met criteria for a current psychiatric disorder, however no differences emerged between the pathological jealousy and pathological love groups. In a binary logistic regression, relationship status and impairments in parenting significantly differentiated the groups. While both pathological jealousy and pathological love share similarities, they also present with unique differences, which may have important treatment implications. Copyright © 2017 Elsevier B.V. All rights reserved.

Time-course microarray analysis for identifying candidate genes involved in obesity-associated pathological changes in the mouse colon.

PubMed

Bae, Yun Jung; Kim, Sung-Eun; Hong, Seong Yeon; Park, Taesun; Lee, Sang Gyu; Choi, Myung-Sook; Sung, Mi-Kyung

2016-01-01

Obesity is known to increase the risk of colorectal cancer. However, mechanisms underlying the pathogenesis of obesity-induced colorectal cancer are not completely understood. The purposes of this study were to identify differentially expressed genes in the colon of mice with diet-induced obesity and to select candidate genes as early markers of obesity-associated abnormal cell growth in the colon. C57BL/6N mice were fed normal diet (11% fat energy) or high-fat diet (40% fat energy) and were euthanized at different time points. Genome-wide expression profiles of the colon were determined at 2, 4, 8, and 12 weeks. Cluster analysis was performed using expression data of genes showing log 2 fold change of ≥1 or ≤-1 (twofold change), based on time-dependent expression patterns, followed by virtual network analysis. High-fat diet-fed mice showed significant increase in body weight and total visceral fat weight over 12 weeks. Time-course microarray analysis showed that 50, 47, 36, and 411 genes were differentially expressed at 2, 4, 8, and 12 weeks, respectively. Ten cluster profiles representing distinguishable patterns of genes differentially expressed over time were determined. Cluster 4, which consisted of genes showing the most significant alterations in expression in response to high-fat diet over 12 weeks, included Apoa4 (apolipoprotein A-IV), Ppap2b (phosphatidic acid phosphatase type 2B), Cel (carboxyl ester lipase), and Clps (colipase, pancreatic), which interacted strongly with surrounding genes associated with colorectal cancer or obesity. Our data indicate that Apoa4 , Ppap2b , Cel , and Clps are candidate early marker genes associated with obesity-related pathological changes in the colon. Genome-wide analyses performed in the present study provide new insights on selecting novel genes that may be associated with the development of diseases of the colon.

The Investigation of Construct Validity of Diagnostic and Statistical Manual of Mental Disorder-5 Personality Traits on Iranian sample with Antisocial and Borderline Personality Disorders.

PubMed

Amini, Mehdi; Pourshahbaz, Abbas; Mohammadkhani, Parvaneh; Ardakani, Mohammad-Reza Khodaie; Lotfi, Mozhgan

2014-12-01

The goal of this study was to examine the construct validity of the diagnostic and statistical manual of mental disorder-5 (DSM-5) conceptual model of antisocial and borderline personality disorders (PDs). More specifically, the aim was to determine whether the DSM-5 five-factor structure of pathological personality trait domains replicated in an independently collected sample that differs culturally from the derivation sample. This study was on a sample of 346 individuals with antisocial (n = 122) and borderline PD (n = 130), and nonclinical subjects (n = 94). Participants randomly selected from prisoners, out-patient, and in-patient clients. Participants were recruited from Tehran prisoners, and clinical psychology and psychiatry clinics of Razi and Taleghani Hospital, Tehran, Iran. The SCID-II-PQ, SCID-II, DSM-5 Personality Trait Rating Form (Clinician's PTRF) were used to diagnosis of PD and to assessment of pathological traits. The data were analyzed by exploratory factor analysis. Factor analysis revealed a 5-factor solution for DSM-5 personality traits. Results showed that DSM-5 has adequate construct validity in Iranian sample with antisocial and borderline PDs. Factors similar in number with the other studies, but different in the content. Exploratory factor analysis revealed five homogeneous components of antisocial and borderline PDs. That may represent personality, behavioral, and affective features central to the disorder. Furthermore, the present study helps understand the adequacy of DSM-5 dimensional approach to evaluation of personality pathology, specifically on Iranian sample.

Pathological analysis, detection of antigens, FasL expression analysis and leucocytes survival analysis in tilapia (Oreochromis niloticus) after infection with green fluorescent protein labeled Streptococcus agalactiae.

PubMed

Wang, Jingyuan; Wu, Jinying; Yi, Liyuan; Hou, Zengxin; Li, Wensheng

2017-03-01

The pathogenesis of Streptococcus agalactiae infection in tilapia has not been fully described. To understand this, we investigated the clinic-pathological features of acute experimental septicemia in tilapia (Oreochromis niloticus) after receiving an intra-peritoneal injection with S. agalactiae THN-1901GFP. Immunohistochemistry and sections of pathological tissues were used to estimate the level of damage in the head-kidney, liver, spleen and trunk-kidney. The expression of FasL was analyzed by western blotting in these samples based on their damage levels. Leucocytes were isolated from the head-kidney and incubated with S. agalactiae THN-1901GFP. Then, phagocytosis, programmed cell death and the expression of FasL were analyzed. The infected tissues showed varying degrees of necrosis and histolysis. The serous membrane of the intestine was dissolved by S. agalactiae THN-1901GFP. Antigens of S. agalactiae THN-1901GFP accumulated in different parts of the infected organs. In the head-kidney and spleen, the expression of FasL was up-regulated in parallel with increased tissue damage. After being incubated with S. agalactiae THN-1901GFP, the phagocytic capacity and ability were both very high and the expression of FasL remained high in leucocytes. S. agalactiae THN-1901GFP was able to survive for a long period of time after being engulfed by phagocytic cells. These findings offer insight into the pathogenesis of S. agalactiae infection in tilapia. Copyright © 2017 Elsevier Ltd. All rights reserved.

MassImager: A software for interactive and in-depth analysis of mass spectrometry imaging data.

PubMed

He, Jiuming; Huang, Luojiao; Tian, Runtao; Li, Tiegang; Sun, Chenglong; Song, Xiaowei; Lv, Yiwei; Luo, Zhigang; Li, Xin; Abliz, Zeper

2018-07-26

Mass spectrometry imaging (MSI) has become a powerful tool to probe molecule events in biological tissue. However, it is a widely held viewpoint that one of the biggest challenges is an easy-to-use data processing software for discovering the underlying biological information from complicated and huge MSI dataset. Here, a user-friendly and full-featured MSI software including three subsystems, Solution, Visualization and Intelligence, named MassImager, is developed focusing on interactive visualization, in-situ biomarker discovery and artificial intelligent pathological diagnosis. Simplified data preprocessing and high-throughput MSI data exchange, serialization jointly guarantee the quick reconstruction of ion image and rapid analysis of dozens of gigabytes datasets. It also offers diverse self-defined operations for visual processing, including multiple ion visualization, multiple channel superposition, image normalization, visual resolution enhancement and image filter. Regions-of-interest analysis can be performed precisely through the interactive visualization between the ion images and mass spectra, also the overlaid optical image guide, to directly find out the region-specific biomarkers. Moreover, automatic pattern recognition can be achieved immediately upon the supervised or unsupervised multivariate statistical modeling. Clear discrimination between cancer tissue and adjacent tissue within a MSI dataset can be seen in the generated pattern image, which shows great potential in visually in-situ biomarker discovery and artificial intelligent pathological diagnosis of cancer. All the features are integrated together in MassImager to provide a deep MSI processing solution at the in-situ metabolomics level for biomarker discovery and future clinical pathological diagnosis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Parasitic infection by larval helminths in Antarctic fishes: pathological changes and impact on the host body condition index

USGS Publications Warehouse

Santoro, Mario; Mattiucci, Simonetta; Work, Thierry M.; Cimmaruta, Roberta; Nardi, Valentina; Cipriani, Paolo; Bellisario, Bruno; Nascetti, Giuseppe

2013-01-01

We examined pathological changes and relationship between body condition index (BCI) and parasitic infection in 5 species of fish, including 42 icefish Chionodraco hamatus (Channichtyidae), 2 dragonfish Cygnodraco mawsoni (Bathydraconidae), 30 emerald rock cod Trematomus bernacchii, 46 striped rock cod T. hansoni and 9 dusty rock cod T. newnesi (Nototheniidae) from the Ross Sea, Antarctica. All parasites were identified by a combination of morphology and mtDNA cytochrome-oxidase-2 sequence (mtDNA cox2) analysis, except Contracaecum osculatum s.l., for which only the latter was used. Five larval taxa were associated with pathological changes including 2 sibling species (D and E) of the C. osculatum species complex and 3 cestodes including plerocercoids of a diphyllobothridean, and 2 tetraphyllidean forms including cercoids with monolocular and bilocular bothridia. The most heavily infected hosts were C. hamatus and C. mawsoni, with C. hamatus most often infected by C. osculatum sp. D and sp. E and diphyllobothrideans, while C. mawsoni was most often infected with tetraphyllidean forms. Histologically, all fish showed varying severity of chronic inflammation associated with larval forms of helminths. Diphyllobothrideans and C. osculatum spp. were located in gastric muscularis or liver and were associated with necrosis and mild to marked fibrosis. Moderate multifocal rectal mucosal chronic inflammation was associated with attached tetraphyllidean scolices. C. hamatus showed a strong negative correlation between BCI and parasite burden.

Parkinson disease and progressive supranuclear palsy: protein expression in skin.

PubMed

Rodríguez-Leyva, Ildefonso; Chi-Ahumada, Erika G; Carrizales, Juan; Rodríguez-Violante, Mayela; Velázquez-Osuna, Salvador; Medina-Mier, Verónica; Martel-Gallegos, María G; Zarazúa, Sergio; Enríquez-Macías, Lourdes; Castro, Adriana; Calderón-Garcidueñas, Ana Laura; Jiménez-Capdeville, María E

2016-03-01

This study characterizes the expression of tau (p-tau) and α-synuclein (α-syn) by immunohistochemistry in the skin of three different populations: healthy control (HC), Parkinson disease (PD), and progressive supranuclear paralysis (PSP) subjects, with the purpose of finding a biomarker that could differentiate between subjects with PD and PSP. We evaluated the presence of p-tau and α-syn in a pilot study in the skin of three distinct groups of patients: 17 healthy subjects, 17 patients with PD, and 10 patients with PSP. Four millimeters punch biopsies were obtained from the occipital area and analyzed by immunohistochemistry using antibodies against α-syn and phosphorylated species of tau. PHF (paired helical filaments) antibody identifies p-tau in both normal and pathological conditions and AT8 recognizes p-tau characteristic of pathological conditions. Differences between the three groups were assessed by quantification of immunopositive areas in the epidermis. The immunopositivity pattern of p-tau and α-syn was significantly different among the three groups. Healthy subjects showed minimal staining using AT8 and α-syn. The PD group showed significantly higher α-syn and AT8 immunopositivity, while the PSP group only expressed higher AT8 immunopositivity than HCs. These data suggest that the skin reflects brain pathology. Therefore, immunohistochemical analysis of p-tau and α-syn in the skin can be useful for further characterization of PD and PSP.

The pathological features of idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas.

PubMed

Kojima, Yoko; Okudela, Koji; Matsumura, Mai; Omori, Takahiro; Baba, Tomohisa; Sekine, Akimasa; Woo, Tetsukan; Umeda, Shigeaki; Takemura, Tamiko; Mitsui, Hideaki; Suzuki, Takehisa; Tateishi, Yoko; Iwasawa, Tae; Arai, Hiromasa; Tajiri, Michihiko; Ogura, Takashi; Kameda, Yoichi; Masuda, Munetaka; Ohashi, Kenich

2017-03-01

To investigate the pathological features of idiopathic interstitial pneumonia (IIP)-associated pulmonary adenocarcinoma. Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected to analysis. Adenocarcinomas in the IIP group were subdivided into two groups: one group included tumours connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group), and the other included tumours unrelated to honeycomb lesions (the NH-IIP group). Histomorphological appearance and immunohistochemical expression were compared among the H-IIP group, the NH-IIP group, and the non-IIP group. Most of the tumour cells in the H-IIP group had a tall, columnar shape that showed similar features to proximal bronchial epithelium, whereas tumour cells in the NH-IIP group and the non-IIP group had a club-like shape that showed similar features to respiratory bronchiolar/alveolar epithelium. Adenocarcinomas in the H-IIP group tended to be negative for thyroid transcription factor-1 (TTF-1) and positive for hepatocyte nuclear factor-4α (HNF-4α). The frequency of EGFR mutations was significantly lower in adenocarcinomas in the H-IIP group, although the frequencies of KRAS and ALK mutations did not differ among the three groups. Idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas, especially those arising from honeycomb lesions, have distinct pathological features. © 2016 John Wiley & Sons Ltd.

Parasitic infection by larval helminths in Antarctic fishes: pathological changes and impact on the host body condition index.

PubMed

Santoro, Mario; Mattiucci, Simonetta; Work, Thierry; Cimmaruta, Roberta; Nardi, Valentina; Cipriani, Paolo; Bellisario, Bruno; Nascetti, Giuseppe

2013-07-22

We examined pathological changes and relationship between body condition index (BCI) and parasitic infection in 5 species of fish, including 42 icefish Chionodraco hamatus (Channichtyidae), 2 dragonfish Cygnodraco mawsoni (Bathydraconidae), 30 emerald rock cod Trematomus bernacchii, 46 striped rock cod T. hansoni and 9 dusty rock cod T. newnesi (Nototheniidae) from the Ross Sea, Antarctica. All parasites were identified by a combination of morphology and mtDNA cytochrome-oxidase-2 sequence (mtDNA cox2) analysis, except Contracaecum osculatum s.l., for which only the latter was used. Five larval taxa were associated with pathological changes including 2 sibling species (D and E) of the C. osculatum species complex and 3 cestodes including plerocercoids of a diphyllobothridean, and 2 tetraphyllidean forms including cercoids with monolocular and bilocular bothridia. The most heavily infected hosts were C. hamatus and C. mawsoni, with C. hamatus most often infected by C. osculatum sp. D and sp. E and diphyllobothrideans, while C. mawsoni was most often infected with tetraphyllidean forms. Histologically, all fish showed varying severity of chronic inflammation associated with larval forms of helminths. Diphyllobothrideans and C. osculatum spp. were located in gastric muscularis or liver and were associated with necrosis and mild to marked fibrosis. Moderate multifocal rectal mucosal chronic inflammation was associated with attached tetraphyllidean scolices. C. hamatus showed a strong negative correlation between BCI and parasite burden.

Development and Demonstration of a Networked Telepathology 3-D Imaging, Databasing, and Communication System

DTIC Science & Technology

1996-10-01

aligned using an octree search algorithm combined with cross correlation analysis . Successive 4x downsampling with optional and specifiable neighborhood...desired and the search engine embedded in the OODBMS will find the requested imagery and que it to the user for further analysis . This application was...obtained during Hoftmann-LaRoche production pathology imaging performed at UMICH. Versant works well and is easy to use; 3) Pathology Image Analysis

Clinical and pathological analysis of IgA nephropathy with chronic renal failure.

PubMed

Liu, Yuyuan; Hu, Qinfeng; Shen, Ping; Tang, Li; Yuan, Gang; Zhou, Yongmei; Chai, Huaqi

2016-10-01

To investigative clinical and pathological characteristics of IgA nephropathy with chronic renal failure. Clinical and pathological findings from 65 cases of IgA nephropathy with chronic renal failure were reviewed. Pathological characteristics of all the cases were analyzed according to WHO definition and Oxford Classification. Evaluating the severity of pathological lesions by the Katafuchi R semiquantitative scoring system, and analyzing their relationship with clinical indexes of renal function. Of all 65 cases the male and female ratio was 1.4, and the mean age was 37 ± 13 years old. Levels of systolic pressure, mean arterial pressure (MAP), blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), album (Alb), serum IgG and 24 h urinary protein were related with eGRF level (p < 0.05, respectively). The most common pathological type was proliferative sclerosis glomerulonephritis (PSGN) and M1S1E0T0 according to WHO definition and Oxford Classification, respectively, and most of the 65 cases had glomerulosclerosis. Simple IgA deposition was the most common immunopathologic type. Of all the cases, 44.6% accompanied with C3 while 4.6% with C1q. Further analysis revealed there were no relationships between severity of pathological lesion and levels of clinical indexes (Scr and eGRF) (p > 0.05). IgA nephropathy with chronic renal failure usually occurred in young adults, and it had severe clinical condition and pathological changes, while there was no significant relationship between them.

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.

Wheeze sound analysis using computer-based techniques: a systematic review.

PubMed

Ghulam Nabi, Fizza; Sundaraj, Kenneth; Chee Kiang, Lam; Palaniappan, Rajkumar; Sundaraj, Sebastian

2017-10-31

Wheezes are high pitched continuous respiratory acoustic sounds which are produced as a result of airway obstruction. Computer-based analyses of wheeze signals have been extensively used for parametric analysis, spectral analysis, identification of airway obstruction, feature extraction and diseases or pathology classification. While this area is currently an active field of research, the available literature has not yet been reviewed. This systematic review identified articles describing wheeze analyses using computer-based techniques on the SCOPUS, IEEE Xplore, ACM, PubMed and Springer and Elsevier electronic databases. After a set of selection criteria was applied, 41 articles were selected for detailed analysis. The findings reveal that 1) computerized wheeze analysis can be used for the identification of disease severity level or pathology, 2) further research is required to achieve acceptable rates of identification on the degree of airway obstruction with normal breathing, 3) analysis using combinations of features and on subgroups of the respiratory cycle has provided a pathway to classify various diseases or pathology that stem from airway obstruction.

Routine conventional karyotyping of lymphoma staging bone marrow samples does not contribute clinically relevant information.

PubMed

Nardi, Valentina; Pulluqi, Olja; Abramson, Jeremy S; Dal Cin, Paola; Hasserjian, Robert P

2015-06-01

Bone marrow (BM) evaluation is an important part of lymphoma staging, which guides patient management. Although positive staging marrow is defined as morphologically identifiable disease, such samples often also include flow cytometric analysis and conventional karyotyping. Cytogenetic analysis is a labor-intensive and costly procedure and its utility in this setting is uncertain. We retrospectively reviewed pathological reports of 526 staging marrow specimens in which conventional karyotyping had been performed. All samples originated from a single institution from patients with previously untreated Hodgkin and non-Hodgkin lymphomas presenting in an extramedullary site. Cytogenetic analysis revealed clonal abnormalities in only eight marrow samples (1.5%), all of which were positive for lymphoma by morphologic evaluation. Flow cytometry showed a small clonal lymphoid population in three of the 443 morphologically negative marrow samples (0.7%). Conventional karyotyping is rarely positive in lymphoma staging marrow samples and, in our cohort, the BM karyotype did not contribute clinically relevant information in the vast majority of cases. Our findings suggest that karyotyping should not be performed routinely on BM samples taken to stage previously diagnosed extramedullary lymphomas unless there is pathological evidence of BM involvement by lymphoma. © 2015 Wiley Periodicals, Inc.

Prognostic factors and genes associated with endometrial cancer based on gene expression profiling by bioinformatics analysis.

PubMed

Zhang, Ying; Zhang, Wei; Li, Xinglan; Li, Dapeng; Zhang, Xiaoling; Yin, Yajie; Deng, Xiangyun; Sheng, Xiugui

2016-06-01

Endometrial cancer (EC) is the most prevalent malignancy worldwide. Although several efforts had been made to explore the molecular mechanism responsible for EC progression, it is still not fully understood. To evaluate the clinical characteristics and prognostic factors of patients with EC, and further to search for novel genes associated with EC progression. We recruited 328 patients with EC and analyzed prognostic factors using Cox proportional hazard regression model. Further, a gene expression profile of EC was used to identify the differentially expressed genes (DEGs) between normal samples and tumor samples. Subsequently, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis ( http://www.genome.jp/kegg/ ) for DEGs were performed, and then protein-protein interaction (PPI) network of DEGs as well as the subnetwork of PPI were constructed with plug-in, MCODE by mapping DEGs into the Search Tool for the Retrieval of Interacting Genes database. Our results showed that body mass index (BMI), hypertension, myometrial invasion, pathological type, and Glut4 positive expression were prognostic factors in EC (P < 0.05). Bioinformatics analysis showed that upregulated DEGs were associated with cell cycle, and downregulated DEGs were related to MAPK pathway. Meanwhile, PPI network analysis revealed that upregulated CDK1 and CCNA2 as well as downregulated JUN and FOS were listed in top two nodes with high degrees. Patients with EC should be given more focused attentions in respect of pathological type, BMI, hypertension, and Glut4-positive expression. In addition, CDK1, CCNA2, JUN, and FOS might play important roles in EC development.

Objective Dysphonia Quantification in Vocal Fold Paralysis: Comparing Nonlinear with Classical Measures

PubMed Central

Little, Max A.; Costello, Declan A. E.; Harries, Meredydd L.

2010-01-01

Summary Clinical acoustic voice-recording analysis is usually performed using classical perturbation measures, including jitter, shimmer, and noise-to-harmonic ratios (NHRs). However, restrictive mathematical limitations of these measures prevent analysis for severely dysphonic voices. Previous studies of alternative nonlinear random measures addressed wide varieties of vocal pathologies. Here, we analyze a single vocal pathology cohort, testing the performance of these alternative measures alongside classical measures. We present voice analysis pre- and postoperatively in 17 patients with unilateral vocal fold paralysis (UVFP). The patients underwent standard medialization thyroplasty surgery, and the voices were analyzed using jitter, shimmer, NHR, nonlinear recurrence period density entropy (RPDE), detrended fluctuation analysis (DFA), and correlation dimension. In addition, we similarly analyzed 11 healthy controls. Systematizing the preanalysis editing of the recordings, we found that the novel measures were more stable and, hence, reliable than the classical measures on healthy controls. RPDE and jitter are sensitive to improvements pre- to postoperation. Shimmer, NHR, and DFA showed no significant change (P > 0.05). All measures detect statistically significant and clinically important differences between controls and patients, both treated and untreated (P < 0.001, area under curve [AUC] > 0.7). Pre- to postoperation grade, roughness, breathiness, asthenia, and strain (GRBAS) ratings show statistically significant and clinically important improvement in overall dysphonia grade (G) (AUC = 0.946, P < 0.001). Recalculating AUCs from other study data, we compare these results in terms of clinical importance. We conclude that, when preanalysis editing is systematized, nonlinear random measures may be useful for monitoring UVFP-treatment effectiveness, and there may be applications to other forms of dysphonia. PMID:19900790

p53 expression in patients with ulcerative colitis - associated with dysplasia and carcinoma: a systematic meta-analysis.

PubMed

Lu, Xiaohong; Yu, Yuanjie; Tan, Shiyun

2017-10-25

Tumor suppressor gene p53 expression has been reported in patients with ulcerative colitis (UC). However, the correlation between p53 expression and UC remains controversial. The aim of this meta-analysis was to investigate the association between p53 expression and different pathological types of UC. Publications were searched in the PubMed, Embase, EBSCO, Wangfang, and CNKI databases. The overall odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were summarized in this study. Final 19 papers were identified in this meta-analysis, including 1068 patients with UC and 130 normal tissue samples. Immunohistochemical p53 expression was significantly higher in UC without dysplasia and carcinoma (UC group) compared to normal tissue samples (OR = 3.14, P = 0.001), higher in UC with dysplasia than in UC group (OR = 10.76, P < 0.001), and higher in UC with colorectal cancer (CRC) than in UC with dysplasia (OR = 1.69, P = 0.035). Subgroup analysis of ethnicity (UC group vs. normal tissues) showed that p53 expression was correlated with UC in Asians, but not in Caucasians. When UC with dysplasia was compared to UC group, p53 expression was linked to UC with dysplasia among both Asians and Caucasians. When UC-CRC was compared to UC with dysplasia, p53 expression was not associated with UC-CRC in both Caucasians and Asians. p53 expression was closely associated with UC-CRC development. p53 expression showed different ethnic characteristics among different pathological types of UC.

Hippocampal α-Synuclein in Dementia with Lewy Bodies Contributes to Memory Impairment and Is Consistent with Spread of Pathology

PubMed Central

Roy, Subhojit; Galasko, Douglas R.; Hansen, Lawrence A.; Masliah, Eliezer

2017-01-01

Despite considerable research to uncover them, the anatomic and neuropathologic correlates of memory impairment in dementia with Lewy bodies (DLB) remain unclear. While some studies have implicated Lewy bodies in the neocortex, others have pointed to α-synuclein pathology in the hippocampus. We systematically examined hippocampal Lewy pathology and its distribution in hippocampal subfields in 95 clinically and neuropathologically characterized human cases of DLB, finding that α-synuclein pathology was highest in two hippocampal-related subregions: the CA2 subfield and the entorhinal cortex (EC). While the EC had numerous classic somatic Lewy bodies, CA2 contained mainly Lewy neurites in presumed axon terminals, suggesting the involvement of the EC → CA2 circuitry in the pathogenesis of DLB symptoms. Clinicopathological correlations with measures of verbal and visual memory supported a role for EC Lewy pathology, but not CA2, in causing these memory deficits. Lewy pathology in CA1—the main output region for CA2—correlated best with results from memory testing despite a milder pathology. This result indicates that CA1 may be more functionally relevant than CA2 in the context of memory impairment in DLB. These correlations remained significant after controlling for several factors, including concurrent Alzheimer's pathology (neuritic plaques and neurofibrillary tangles) and the interval between time of testing and time of death. Our data suggest that although hippocampal Lewy pathology in DLB is predominant in CA2 and EC, memory performance correlates most strongly with CA1 burden. SIGNIFICANCE STATEMENT This study provides a detailed neuropathologic analysis of hippocampal Lewy pathology in human patients with autopsy-confirmed dementia with Lewy bodies. The approach—informed by regional molecular markers, concurrent Alzheimer's pathology analysis, and relevant clinical data—helps tease out the relative contribution of Lewy pathology to memory dysfunction in the disease. Levels of Lewy pathology were found to be highest in the hippocampal CA2 subregion and entorhinal cortex, implicating a potentially overlooked circuit in disease pathogenesis. However, correlation with memory performance was strongest with CA1. This unexpected finding suggests that Lewy pathology must reach a critical burden across hippocampal circuitry to contribute to memory dysfunction beyond that related to other factors, notably coexisting Alzheimer's disease tau pathology. PMID:28039370

Analysis of pathological data of renal biopsy at one single center in China from 1987 to 2012.

PubMed

Zhang, Xueguang; Liu, Shuwen; Tang, Li; Wu, Jie; Chen, Pu; Yin, Zhong; Li, Minxia; Xie, Yuansheng; Cai, Guangyan; Wei, Ribao; Qiu, Qiang; Wang, Yuanda; Shi, Suozhu; Chen, Xiangmei

2014-01-01

In China, the prevalence of chronic kidney disease has increased significantly. Many studies shows that the spectrum of kidney disease had changed in recent years. We retrospectively analyzed the pathological types of renal biopsy and its spectrum change at the General Hospital of the Chinese People's Liberation Army from December 1987 to December 2012, in order to offer new supporting evidences for further specifying the distribution of renal pathological types in China. According to the "Revised Protocol for the Histological Typing of Glomerulopathy" (WHO, 1995), pathological diagnosis of renal biopsy was classified, detection rate of each pathological type was summarized (i.e., percentage of total renal biopsy cases), study period was divided at an interval of 5 years, and age-stratified distribution change of main pathological types was analyzed. The proportion of pathological types in 11 618 cases of renal biopsy was as follows: primary glomerulonephritis (PGN, 70.7%), secondary glomerulonephritis (SGN, 20.7%), tubular-interstitial nephropathy (4.0%), hereditary/rare nephropathy (0.3%), end-stage renal disease (0.9%), and unclassified renal disease (3.3%). Among PGN, there was IgA nephropathy (IgAN, 37.0%), membranous nephropathy (MN, 11.8%), mesangial proliferative glomerulonephritis (MsPGN, 8.9%), minimal change disease (MCD, 6.6%), and focal segmental glomerulosclerosis (3.9%). Among SGN there was lupus nephritis (LN, 5.5%), Henoch-Schönlein purpura glomerulonephritis (5.3%), hepatitis B virus-associated nephritis (HBVAN, 3.03%), diabetic nephropathy (2.2%), and hypertension/malignant hypertension-associated renal damage (1.9%). Pathological data were analyzed from 1987-1992 to 2008-2012 (after age adjustment). Detection rate of IgAN tended to rise (P < 0.001). Detection rates of MN and MCD rose significantly (P < 0.001), but detection rate of MsPGN dropped significantly (P < 0.001). Among SGN, detection rate of HBVAN tended to drop (P < 0.001). In China, PGN was the most common glomerulopathy (mostly IgAN), LN was the most common SGN, and detection rate of MN and MCD rose significantly.

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.

Targeted metabolomic profiling in rat tissues reveals sex differences.

PubMed

Ruoppolo, Margherita; Caterino, Marianna; Albano, Lucia; Pecce, Rita; Di Girolamo, Maria Grazia; Crisci, Daniela; Costanzo, Michele; Milella, Luigi; Franconi, Flavia; Campesi, Ilaria

2018-03-16

Sex differences affect several diseases and are organ-and parameter-specific. In humans and animals, sex differences also influence the metabolism and homeostasis of amino acids and fatty acids, which are linked to the onset of diseases. Thus, the use of targeted metabolite profiles in tissues represents a powerful approach to examine the intermediary metabolism and evidence for any sex differences. To clarify the sex-specific activities of liver, heart and kidney tissues, we used targeted metabolomics, linear discriminant analysis (LDA), principal component analysis (PCA), cluster analysis and linear correlation models to evaluate sex and organ-specific differences in amino acids, free carnitine and acylcarnitine levels in male and female Sprague-Dawley rats. Several intra-sex differences affect tissues, indicating that metabolite profiles in rat hearts, livers and kidneys are organ-dependent. Amino acids and carnitine levels in rat hearts, livers and kidneys are affected by sex: male and female hearts show the greatest sexual dimorphism, both qualitatively and quantitatively. Finally, multivariate analysis confirmed the influence of sex on the metabolomics profiling. Our data demonstrate that the metabolomics approach together with a multivariate approach can capture the dynamics of physiological and pathological states, which are essential for explaining the basis of the sex differences observed in physiological and pathological conditions.

Pathology during acute infections: contributions of intracellular pathogens and the CTL response.

PubMed

Ganusov, Vitaly V; Antia, Rustom

2005-06-22

Previous work has shown how, in the case of cytotoxic T-lymphocyte (CTL) responses to persistent viral infections, pathology may arise as a consequence of cell destruction directly by the virus or indirectly due to the CTL response, leading to maximum pathology at intermediate efficacy of the immune response. We expand these studies to consider pathology arising during acute infections with intracellular pathogens controlled by the CTL response. We show that, in contrast to persistent infections, pathology during acute infections is minimized with increasing efficacy of the immune response. The implications of these results for vaccination are discussed.

The use of magnetic resonance mammography in women at increased risk for developing breast cancer

PubMed Central

Popiela, Tadeusz J.; Herman-Sucharska, Izabela; Urbanik, Andrzej

2012-01-01

Introduction The use of conventional imaging techniques, namely mammography (MMG) and ultrasound (US), for breast cancer (BC) detection in women at high risk for the disease does not bring optimal results in many cases. Aim The present study evaluated the effectiveness of magnetic resonance (MR) mammography (MRM) in cases where US and MMG failed to detect suspected breast lesions. Material and methods The study group consisted of 379 women who had had no breast pathologies detected by US and MMG. This group was then divided into 4 groups according to the relative risk of breast cancer development. All the women underwent MRM, and any breast pathology detected by MRM was then verified by open surgical biopsy (OSB). Results Based on the MRM findings, 37 women with breast pathologies were identified. All detected pathologies were then classified into one of the BIRADS (Breast Imaging Reporting and Data System) categories. Of these, 33 patients underwent open surgical biopsy. There were a total of 17 benign and 16 malignant breast pathologies that were not visualized by US and MMG. The types of malignancies found, in order of their frequency, were as follows: invasive ductal carcinoma (11 cases), ductal carcinoma in situ (2 cases), invasive lobular carcinoma (2 cases), and lobular carcinoma in situ (1 case). An analysis of MRM effectiveness in detecting BC showed 93.7% sensitivity and 64.71% specificity. Conclusions All women with a 20% or greater lifetime risk of developing BC should undergo annual MRM as a diagnostic adjunct to US and MMG. PMID:23630555

Identification and quantitative evaluation of the fiber structure in the pathological tissue using Mueller matrix microscope

NASA Astrophysics Data System (ADS)

Zhou, Jialing; He, Honghui; Wang, Ye; Ma, Hui

2017-02-01

Fiber structure changes in the various pathological processes, such as the increase of fibrosis in liver diseases, the derangement of fiber in cervical cancer and so on. Currently, clinical pathologic diagnosis is regarded as the golden criterion, but different doctors with discrepancy in knowledge and experience may obtain different conclusions. Up to a point, quantitative evaluation of the fiber structure in the pathological tissue can be of great service to quantitative diagnosis. Mueller matrix measurement is capable of probing comprehensive microstructural information of samples and different wavelength of lights can provide more information. In this paper, we use a Mueller matrix microscope with light sources in six different wavelength. We use unstained, dewaxing liver tissue slices in four stages and the pathological biopsy of the filtration channels from rabbit eyes as samples. We apply the Mueller matrix polar decomposition (MMPD) parameter δ which corresponds to retardance to liver slices. The mean value of abnormal region get bigger when the level of fibrosis get higher and light in short wavelength is more sensitive to the microstructure of fiber. On the other hand, we use the Mueller matrix transformation (MMT) parameter Φ which is associated to the angel of fast axis in the analysis of the slices of the filtration channels from rabbit eyes. The value of kurtosis and the value of skewness shows big difference between new born region and normal region and can reveal the arrangement of fiber. These results indicate that the Mueller matrix microscope has great potential in auxiliary diagnosis.

[Sinonasal-type hemangiopericytoma: a clinicopathologic analysis of 6 cases].

PubMed

Wang, Shu-yi; Zhu, Xiong-zeng

2006-05-01

To study the clinicopathologic features, histologic diagnosis and differential diagnosis of sinonasal-type of hemangiopericytoma (SNTHPC). The clinical, radiographic and pathologic findings of 6 cases of SNTHPC were analyzed. Immunohistochemistry and electron microscopy were performed on selected examples. Amongst the 6 patients studied, 4 were males and 2 were females. The age of patients ranged from 56 to 71 years (mean = 60.5 years old). The commonest clinical presentation was nasal obstruction and/or epistaxis. Other symptoms could include increased nasal secretion, eyeball pain, decreased visual acuity, increased tear secretion and headache. The tumor involved nasal cavity and/or paranasal sinuses. Gross examination showed polypoid tumor masses, brownish fleshy tissue or whitish tumor tissue fragments. Histologically, the tumor showed a mixture of diffuse, fascicular, storiform, reticulated and whorled growth patterns. The tumor cells were spindle-shaped and possessed clear to eosinophilic cytoplasm. Mitotic figures were rarely seen. The intervening vasculature was characteristically thin-walled, with focal hyalinization changes and rarely the staghorn pattern. Immunohistochemical study showed that the tumor cells expressed vimentin (6/6), smooth muscle actin (5/6) and CD34 (3/6). Electron microscopy demonstrated the presence of intracytoplasmic myofilaments. The tumor cells were linked together by primitive cell junctions. In general, the histologic diagnosis of SNTHPC was difficult, and only 1 case had the correct initial pathologic diagnosis made. Follow-up data were available in 5 patients and 2 of them had local recurrences. SNTHPC is a low to intermediate grade soft tissue tumor with pericytes differentiation. Correct diagnosis relies on detailed pathologic assessment and application of ancillary investigations.

Experimental Design and Data Analysis Issues Contribute to Inconsistent Results of C-Bouton Changes in Amyotrophic Lateral Sclerosis.

PubMed

Dukkipati, S Shekar; Chihi, Aouatef; Wang, Yiwen; Elbasiouny, Sherif M

2017-01-01

The possible presence of pathological changes in cholinergic synaptic inputs [cholinergic boutons (C-boutons)] is a contentious topic within the ALS field. Conflicting data reported on this issue makes it difficult to assess the roles of these synaptic inputs in ALS. Our objective was to determine whether the reported changes are truly statistically and biologically significant and why replication is problematic. This is an urgent question, as C-boutons are an important regulator of spinal motoneuron excitability, and pathological changes in motoneuron excitability are present throughout disease progression. Using male mice of the SOD1-G93A high-expresser transgenic ( G93A ) mouse model of ALS, we examined C-boutons on spinal motoneurons. We performed histological analysis at high statistical power, which showed no difference in C-bouton size in G93A versus wild-type motoneurons throughout disease progression. In an attempt to examine the underlying reasons for our failure to replicate reported changes, we performed further histological analyses using several variations on experimental design and data analysis that were reported in the ALS literature. This analysis showed that factors related to experimental design, such as grouping unit, sampling strategy, and blinding status, potentially contribute to the discrepancy in published data on C-bouton size changes. Next, we systematically analyzed the impact of study design variability and potential bias on reported results from experimental and preclinical studies of ALS. Strikingly, we found that practices such as blinding and power analysis are not systematically reported in the ALS field. Protocols to standardize experimental design and minimize bias are thus critical to advancing the ALS field.

Qualitative content analysis in nursing research: concepts, procedures and measures to achieve trustworthiness.

PubMed

Graneheim, U H; Lundman, B

2004-02-01

Qualitative content analysis as described in published literature shows conflicting opinions and unsolved issues regarding meaning and use of concepts, procedures and interpretation. This paper provides an overview of important concepts (manifest and latent content, unit of analysis, meaning unit, condensation, abstraction, content area, code, category and theme) related to qualitative content analysis; illustrates the use of concepts related to the research procedure; and proposes measures to achieve trustworthiness (credibility, dependability and transferability) throughout the steps of the research procedure. Interpretation in qualitative content analysis is discussed in light of Watzlawick et al.'s [Pragmatics of Human Communication. A Study of Interactional Patterns, Pathologies and Paradoxes. W.W. Norton & Company, New York, London] theory of communication.

Imaging biomarkers in multiple Sclerosis: From image analysis to population imaging.

PubMed

Barillot, Christian; Edan, Gilles; Commowick, Olivier

2016-10-01

The production of imaging data in medicine increases more rapidly than the capacity of computing models to extract information from it. The grand challenges of better understanding the brain, offering better care for neurological disorders, and stimulating new drug design will not be achieved without significant advances in computational neuroscience. The road to success is to develop a new, generic, computational methodology and to confront and validate this methodology on relevant diseases with adapted computational infrastructures. This new concept sustains the need to build new research paradigms to better understand the natural history of the pathology at the early phase; to better aggregate data that will provide the most complete representation of the pathology in order to better correlate imaging with other relevant features such as clinical, biological or genetic data. In this context, one of the major challenges of neuroimaging in clinical neurosciences is to detect quantitative signs of pathological evolution as early as possible to prevent disease progression, evaluate therapeutic protocols or even better understand and model the natural history of a given neurological pathology. Many diseases encompass brain alterations often not visible on conventional MRI sequences, especially in normal appearing brain tissues (NABT). MRI has often a low specificity for differentiating between possible pathological changes which could help in discriminating between the different pathological stages or grades. The objective of medical image analysis procedures is to define new quantitative neuroimaging biomarkers to track the evolution of the pathology at different levels. This paper illustrates this issue in one acute neuro-inflammatory pathology: Multiple Sclerosis (MS). It exhibits the current medical image analysis approaches and explains how this field of research will evolve in the next decade to integrate larger scale of information at the temporal, cellular, structural and morphological levels. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Examining the influence of actual-ideal self-discrepancies, depression, and escapism, on pathological gaming among massively multiplayer online adolescent gamers.

PubMed

Li, Dongdong; Liau, Albert; Khoo, Angeline

2011-09-01

This study examined whether actual-ideal self-discrepancy (AISD) is related to pathological gaming through escapism as a means of reducing depression for adolescent massively multiplayer online gamers. A Discrepancy-reduction Motivation model of pathological video gaming was tested. A survey was conducted on 161 adolescent gamers from secondary schools. Two mediation effects were tested using path analysis: (a) depression would mediate the relationship between AISDs and escapism, and (b) escapism would mediate the relationship between depression and pathological gaming. Results support the hypotheses stated above. The indirect effects of both AISD and depression were significant on pathological gaming. AISD and escapism also had direct effects on pathological gaming. The present study suggests that pathological behaviors may be over-regulated coping strategies of approaching the ideal self and avoiding the actual self.

Spectral analysis of fundus autofluorescence pattern as a tool to detect early stages of degeneration in the retina and retinal pigment epithelium.

PubMed

Feldman, Tatiana B; Yakovleva, Marina A; Larichev, Andrey V; Arbukhanova, Patimat M; Radchenko, Alexandra Sh; Borzenok, Sergey A; Kuzmin, Vladimir A; Ostrovsky, Mikhail A

2018-05-22

The aim of this work is the determination of quantitative diagnostic criteria based on the spectral characteristics of fundus autofluorescence to detect early stages of degeneration in the retina and retinal pigment epithelium (RPE). RPE cell suspension samples were obtained from the cadaver eyes with and without signs of age-related macular degeneration (AMD). Fluorescence analysis at an excitation wavelength of 488 nm was performed. The fluorescence lifetimes of lipofuscin-granule fluorophores were measured by counting time-correlated photon method. Comparative analysis of fluorescence spectra of RPE cell suspensions from the cadaver eyes with and without signs of AMD showed a significant difference in fluorescence intensity at 530-580 nm in response to fluorescence excitation at 488 nm. It was notably higher in eyes with visual pathology than in normal eyes regardless of the age of the eye donor. Measurements of fluorescence lifetimes of lipofuscin fluorophores showed that the contribution of photooxidation and photodegradation products of bisretinoids to the total fluorescence at 530-580 nm of RPE cell suspensions was greater in eyes with visual pathology than in normal eyes. Because photooxidation and photodegradation products of bisretinoids are markers of photodestructive processes, which can cause RPE cell death and initiate degenerative processes in the retina, quantitative determination of increases in these bisretinoid products in lipofuscin granules may be used to establish quantitative diagnostic criteria for degenerative processes in the retina and RPE.

The association between expression of IFIT1 in podocytes of MRL/lpr mice and the renal pathological changes it causes: An animal study.

PubMed

Hu, Weiping; Niu, Guodong; Li, Hongbo; Gao, Hanyuan; Kang, Rudian; Chen, Xiaoqing; Lin, Ling

2016-11-22

Renal damage is the major cause of SLE associated mortality, and IFIT1expression was elevated in SLE cases in accordance of previous studies. Therefore, we conducted an animal study to identify the role of IFIT1 expression in renal pathological changes.18 female MRL/lpr mice and same number of female BALB/c mice were enrolled in present study. Quantitative analysis of urine protein, Complement C3 and C4, and anti-ds DNA antibody were conducted. HE and PAS staining and TEM analysis were employed to observe the pathological changes in renal tissue. Significant elevation on urine protein and anti-dsDNA and reduction on Complement C3 and C4 were observed in MRL/lpr mice when comparing the controls in same age. Staining and TEM analysis observed several pathological changes in glomerulus among MRL/lpr mice, including cellular enlargement, basement membrane thickening, and increased cellularcasts. The linear regression analysis found the optical density of IFIT1 was inversely associated with F-actin, Nephrin, and Podocin, but not Synatopodin. In summary, IFIT1 expression is associated with podocytes damage, and capable of suppressing some proteins essential to glomerular filtration.

Pre-treatment neutrophil to lymphocyte ratio as a predictive marker for pathological response to preoperative chemoradiotherapy in pancreatic cancer

PubMed Central

HASEGAWA, SHINICHIRO; EGUCHI, HIDETOSHI; TOMOKUNI, AKIRA; TOMIMARU, YOSHITO; ASAOKA, TADAFUMI; WADA, HIROSHI; HAMA, NAOKI; KAWAMOTO, KOICHI; KOBAYASHI, SHOGO; MARUBASHI, SHIGERU; KONNNO, MASAMITSU; ISHII, HIDESHI; MORI, MASAKI; DOKI, YUICHIRO; NAGANO, HIROAKI

2016-01-01

An elevated neutrophil to lymphocyte ratio (NLR) has been reported to be associated with the pathological response to neoadjuvant therapies in numerous types of cancer. The aim of the current study was to clarify the association between pre-treatment NLR and the pathological response to preoperative chemoradiotherapy in pancreatic cancer patients. This retrospective analysis included data from 56 consecutive patients whose tumors were completely surgically resected. All patients received preoperative therapy, consisting of gemcitabine-based chemotherapy (alone or in combination with S-1) combined with 40 or 50.4 Gy irradiation, prior to surgery. Predictive factors, including NLR, platelet to lymphocyte ratio (PLR), modified Glasgow prognostic score and prognostic nutrition index, were measured prior to treatment. A comparison was made between those who responded well pathologically (good response group, Evans classification IIb/III) and those with a poor response (Evans I/IIa). NLR was determined to be significantly higher in the poor response group. Multivariate analysis identified an elevated NLR as an independent risk factor for the poor pathological response [odds ratio (OR), 5.35; P=0.0257]. The pre-treatment NLR (≥2.2/<2.2) was found to be a statistically significant predictive indicator of pathological response (P=0.00699). The results demonstrate that pre-treatment NLR may be a useful predictive marker for the pathological response to preoperative therapy in pancreatic cancer patients. PMID:26893780

Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

PubMed

Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

The Pathology of Chronic Obstructive Pulmonary Disease: Progress in the 20th and 21st Centuries.

PubMed

Berg, Kyra; Wright, Joanne L

2016-12-01

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and is the fourth leading cause of death worldwide. There has been significant progress in the pathologic description and pathophysiologic analysis of COPD in the 20th and 21st centuries. We review the history, progression, and significance of pathologic alterations in COPD, including emphysematous changes, airway alterations, and vascular alterations. We also indicate what pathologic features of COPD the practicing pathologist should be describing in standard surgical and autopsy specimens.

[The clinicopathological features of acute fibrinous and organizing pneumonia].

PubMed

Qiu, Yu-ying; Miao, Li-yun; Cai, Hou-rong; Xiao, Yong-long; Ye, Qing; Meng, Fan-qing; Feng, An-ning

2013-06-01

To improve understanding of the clinical, radiological and pathological characteristics of acute fibrinous and organizing pneumonia (AFOP). The clinical data of 5 AFOP patients were retrospectively analyzed. AFOP was diagnosed via percutaneous lung biopsy guided by chest computerized tomography (CT) in the Affiliated Drum Tower Hospital of Nanjing University Medical School during March 2011 to June 2012. The clinical, radiological and pathological characteristics of those patients were summarized. Among the 5 patients, 2 were male and 3 were female, aging 43-61 years. They were all subacute onset. The main clinical manifestations were dyspnea, productive cough, fever and chest pain with hypoxemia via blood gas analysis. Bilateral infiltrates with diffuse and pathy distribution were the predominant features in chest HRCT. The pathological examination revealed slightly widened alveolar septa, 1ymphocyte and plasma cell infiltration and the presence of intra-alveolar fibrin in the form of fibrin "balls" (organization) within the alveolar spaces. No neutrophil, and eosinophil infiltration and hyaline membrane formation were detected, which was different from other well-recognized histologic patterns of acute lung injury, such as diffuse alveolar damage, cryptogenic organizing pneumonia and eosinophilic pneumonia. All patients were treated by corticosteroids and showed significant clinical and radiological improvement. AFOP has nospecific features, and its diagnosis depends on pathological examination. Treatment with corticosteroids is optimal. However, whether it is a unique interstitial disease needs to be further clinically investigated.

Diagnostic value of the 2011 International Federation for Cervical Pathology and Colposcopy Terminology in predicting cervical lesions

PubMed Central

Zhang, Liqin; Yan, Ye; Han, Cha; Xue, Fengxia

2018-01-01

Objective To evaluate the diagnostic accuracy of the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) colposcopic terminology. Methods The clinicopathological data of 2262 patients who underwent colposcopy from September 2012 to September 2016 were reviewed. The colposcopic findings, colposcopic impression, and cervical histopathology of the patients were analyzed. Correlations between variables were evaluated using cervical histopathology as the gold standard. Results Colposcopic diagnosis matched biopsy histopathology in 1482 patients (65.5%), and the weighted kappa strength of agreement was 0.480 (P<0.01). Colposcopic diagnoses more often underestimated (22.1%) than overestimated (12.3%) cervical pathology. There was no significant difference between the colposcopic diagnosis and cervical pathology agreement among the various grades of lesions (P=0.282). The sensitivity, specificity for detecting high-grade lesions/carcinoma was 71.6% and 98.0%, respectively. Multivariate analysis showed that major changes were independent factors in predicting high-grade lesion/carcinoma, whereas transformation zone, lesion size, and non-stained were not statistically related to high-grade lesion/carcinoma. Conclusions The 2011 IFCPC terminology can improve the diagnostic accuracy for all lesion severities. The categorization of major changes and minor changes is appropriate. However, colposcopic diagnosis remains unsatisfactory. Poor reproducibility of type 2 transformation zone and the significance of leukoplakia require further study. PMID:29507681

Characterizing Deep Brain Stimulation effects in computationally efficient neural network models.

PubMed

Latteri, Alberta; Arena, Paolo; Mazzone, Paolo

2011-04-15

Recent studies on the medical treatment of Parkinson's disease (PD) led to the introduction of the so called Deep Brain Stimulation (DBS) technique. This particular therapy allows to contrast actively the pathological activity of various Deep Brain structures, responsible for the well known PD symptoms. This technique, frequently joined to dopaminergic drugs administration, replaces the surgical interventions implemented to contrast the activity of specific brain nuclei, called Basal Ganglia (BG). This clinical protocol gave the possibility to analyse and inspect signals measured from the electrodes implanted into the deep brain regions. The analysis of these signals led to the possibility to study the PD as a specific case of dynamical synchronization in biological neural networks, with the advantage to apply the theoretical analysis developed in such scientific field to find efficient treatments to face with this important disease. Experimental results in fact show that the PD neurological diseases are characterized by a pathological signal synchronization in BG. Parkinsonian tremor, for example, is ascribed to be caused by neuron populations of the Thalamic and Striatal structures that undergo an abnormal synchronization. On the contrary, in normal conditions, the activity of the same neuron populations do not appear to be correlated and synchronized. To study in details the effect of the stimulation signal on a pathological neural medium, efficient models of these neural structures were built, which are able to show, without any external input, the intrinsic properties of a pathological neural tissue, mimicking the BG synchronized dynamics.We start considering a model already introduced in the literature to investigate the effects of electrical stimulation on pathologically synchronized clusters of neurons. This model used Morris Lecar type neurons. This neuron model, although having a high level of biological plausibility, requires a large computational effort to simulate large scale networks. For this reason we considered a reduced order model, the Izhikevich one, which is computationally much lighter. The comparison between neural lattices built using both neuron models provided comparable results, both without traditional stimulation and in presence of all the stimulation protocols. This was a first result toward the study and simulation of the large scale neural networks involved in pathological dynamics.Using the reduced order model an inspection on the activity of two neural lattices was also carried out at the aim to analyze how the stimulation in one area could affect the dynamics in another area, like the usual medical treatment protocols require.The study of population dynamics that was carried out allowed us to investigate, through simulations, the positive effects of the stimulation signals in terms of desynchronization of the neural dynamics. The results obtained constitute a significant added value to the analysis of synchronization and desynchronization effects due to neural stimulation. This work gives the opportunity to more efficiently study the effect of stimulation in large scale yet computationally efficient neural networks. Results were compared both with the other mathematical models, using Morris Lecar and Izhikevich neurons, and with simulated Local Field Potentials (LFP).

Texture Analysis of Recurrence Plots Based on Wavelets and PSO for Laryngeal Pathologies Detection.

PubMed

Souza, Taciana A; Vieira, Vinícius J D; Correia, Suzete E N; Costa, Silvana L N C; de A Costa, Washington C; Souza, Micael A

2015-01-01

This paper deals with the discrimination between healthy and pathological speech signals using recurrence plots and wavelet transform with texture features. Approximation and detail coefficients are obtained from the recurrence plots using Haar wavelet transform, considering one decomposition level. The considered laryngeal pathologies are: paralysis, Reinke's edema and nodules. Accuracy rates above 86% were obtained by means of the employed method.

Effects of mood state on impulsivity in pathological buying.

PubMed

Nicolai, Jennifer; Darancó, Stefaniá; Moshagen, Morten

2016-10-30

Pathological buying is characterized by irrepressible buying behaviour and its negative consequences. A possible mechanism contributing to its development and maintenance is that buying episodes act as a maladaptive strategy to cope with negative emotions. Accordingly, pathological buying has been repeatedly associated with impulsivity, in particular with the tendency to experience strong reactions under negative affect. Relying on an experimental mood induction procedure, the present study tested in a sample of 100 individuals (a) whether individuals with pathological buying symptoms respond more impulsively in the Go/No-Go Task (as a measure of the behavioural inhibition aspect of impulsivity) and (b) whether this association is more pronounced in a negative mood. While controlling for comorbidities, the results show that pathological buying is associated with faster responses and a larger number of commission errors. Moreover, a significant interaction indicated that the association between pathological buying and performance the Go/No-Go Task was stronger in the negative mood condition. The present study thus shows that pathological buying is associated with deficits in the behavioural inhibition component of impulsivity. These deficits are most pronounced when mood is negative; in turn, this provides an explanation for the occurrence of excessive buying episodes following negative affect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Presence of tau pathology within foetal neural allografts in patients with Huntington's and Parkinson's disease.

PubMed

Cisbani, Giulia; Maxan, Alexander; Kordower, Jeffrey H; Planel, Emmanuel; Freeman, Thomas B; Cicchetti, Francesca

2017-11-01

Cell replacement has been explored as a therapeutic strategy to repair the brain in patients with Huntington's and Parkinson's disease. Post-mortem evaluations of healthy grafted tissue in such cases have revealed the development of Huntington- or Parkinson-like pathology including mutant huntingtin aggregates and Lewy bodies. An outstanding question remains if tau pathology can also be seen in patients with Huntington's and Parkinson's disease who had received foetal neural allografts. This was addressed by immunohistochemical/immunofluorescent stainings performed on grafted tissue of two Huntington's disease patients, who came to autopsy 9 and 12 years post-transplantation, and two patients with Parkinson's disease who came to autopsy 18 months and 16 years post-transplantation. We show that grafts also contain tau pathology in both types of transplanted patients. In two patients with Huntington's disease, the grafted tissue showed the presence of hyperphosphorylated tau [both AT8 (phospho-tau Ser202 and Thr205) and CP13 (pSer202) immunohistochemical stainings] pathological inclusions, neurofibrillary tangles and neuropil threads. In patients with Parkinson's disease, the grafted tissue was characterized by hyperphosphorylated tau (AT8; immunofluorescent staining) pathological inclusions, neurofibrillary tangles and neuropil threads but only in the patient who came to autopsy 16 years post-transplantation. Abundant tau-related pathology was observed in the cortex and striatum of all cases studied. While the striatum of the grafted Huntington's disease patient revealed an equal amount of 3-repeat and 4-repeat isoforms of tau, the grafted tissue showed elevated 4-repeat isoforms by western blot. This suggests that transplants may have acquired tau pathology from the host brain, although another possibility is that this was due to acceleration of ageing. This finding not only adds to the recent reports that tau pathology is a feature of these neurodegenerative diseases, but also that tau pathology can manifest in healthy neural tissue transplanted into the brains of patients with two distinct neurodegenerative disorders. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Image analysis and machine learning in digital pathology: Challenges and opportunities.

PubMed

Madabhushi, Anant; Lee, George

2016-10-01

With the rise in whole slide scanner technology, large numbers of tissue slides are being scanned and represented and archived digitally. While digital pathology has substantial implications for telepathology, second opinions, and education there are also huge research opportunities in image computing with this new source of "big data". It is well known that there is fundamental prognostic data embedded in pathology images. The ability to mine "sub-visual" image features from digital pathology slide images, features that may not be visually discernible by a pathologist, offers the opportunity for better quantitative modeling of disease appearance and hence possibly improved prediction of disease aggressiveness and patient outcome. However the compelling opportunities in precision medicine offered by big digital pathology data come with their own set of computational challenges. Image analysis and computer assisted detection and diagnosis tools previously developed in the context of radiographic images are woefully inadequate to deal with the data density in high resolution digitized whole slide images. Additionally there has been recent substantial interest in combining and fusing radiologic imaging and proteomics and genomics based measurements with features extracted from digital pathology images for better prognostic prediction of disease aggressiveness and patient outcome. Again there is a paucity of powerful tools for combining disease specific features that manifest across multiple different length scales. The purpose of this review is to discuss developments in computational image analysis tools for predictive modeling of digital pathology images from a detection, segmentation, feature extraction, and tissue classification perspective. We discuss the emergence of new handcrafted feature approaches for improved predictive modeling of tissue appearance and also review the emergence of deep learning schemes for both object detection and tissue classification. We also briefly review some of the state of the art in fusion of radiology and pathology images and also combining digital pathology derived image measurements with molecular "omics" features for better predictive modeling. The review ends with a brief discussion of some of the technical and computational challenges to be overcome and reflects on future opportunities for the quantitation of histopathology. Copyright © 2016 Elsevier B.V. All rights reserved.

The current state of resident training in genomic pathology: a comprehensive analysis utilizing the Resident In-Service Exam (RISE)

PubMed Central

Haspel, Richard L.; Rinder, Henry M.; Frank, Karen M.; Wagner, Jay; Ali, Asma M.; Fisher, Patrick B.; Parks, Eric R.

2014-01-01

Objectives To determine the current state of pathology resident training in genomic and molecular pathology. Methods The Training Residents in Genomics (TRIG) Working Group developed survey and knowledge questions for the 2013 Pathology Resident In-Service Examination (RISE). Sixteen demographic questions related to amount of training, current and predicted future use, and perceived ability in molecular pathology vs. genomic medicine were included along with five genomic pathology and 19 molecular pathology knowledge questions. Results A total of 2,506 pathology residents took the 2013 RISE with approximately 600 individuals per post-graduate year (PGY). For genomic medicine, 42% of PGY-4 respondents stated they had no training compared to 7% for molecular pathology (p<0.001). PGY-4 resident perceived ability in genomic medicine, comfort in discussing results, and predicted future use as a practicing pathologist were less than reported for molecular pathology (p<0.001). There was a greater increase by PGY in knowledge question scores for molecular than for genomic pathology. Conclusions The RISE is a powerful tool in assessing the state of resident training in genomic pathology and current results suggest a significant deficit. The results also provide a baseline to assess future initiatives to improve genomics education for pathology residents such as those developed by the TRIG Working Group. PMID:25239410

Metabolomic Changes in Rat Model of Cauda Equina Injury.

PubMed

Liu, Yang; Yang, Rui; Kong, Qingjie; Wang, Yuan; Zhang, Bin; Sun, Jingchuan; Yang, Yong; Zheng, Bing; Yuan, Hongbin; Shi, Jiangang

2017-06-01

To show the differences of metabolomic changes in a rat model of cauda equina injury (CEI) and find potent metabolic biomarkers of CEI. A total of 28 Sprague-Dawley rats were used in this study. After the rats were given anesthesia and fixed in a prone position, a piece of silicone block was placed into the epidural space below the lamina. Behavior tests including the Basso, Beattie, and Bresnahan open field locomotor scale and an inclined plane test were conducted 1 day and 2 days after surgery. The cauda equina tissue was collected 12 hours, 1 day, and 2 days after surgery. Ultraperformance liquid chromatography coupled with quadruple time-of-flight mass spectrometry was used for a quantitative analysis of cauda equine metabolic changes in rats from different groups. The differences between the metabolic profiles of the rats in 4 groups were analyzed using partial least squares discriminant analysis. In behavior tests and histologic analyses given 2 days after surgery, the animals showed remarkable organ dysfunction and pathologic damage. Metabolic profiles showed remarkable differences between the control and model groups. Thirty-four potential CEI metabolite biomarkers were identified between the control group and different time-point model groups. These potential biomarkers appeared in 15 metabolic pathways. Our results may improve the cause of CEI and provide a basis for clinical diagnosis and locating biomarkers in the early stages of the pathologic process of CEI. Copyright © 2017 Elsevier Inc. All rights reserved.

Creating normograms of dural sinuses in healthy persons using computer-assisted detection for analysis and comparison of cross-section dural sinuses in the brain.

PubMed

Anconina, Reut; Zur, Dinah; Kesler, Anat; Lublinsky, Svetlana; Toledano, Ronen; Novack, Victor; Benkobich, Elya; Novoa, Rosa; Novic, Evelyne Farkash; Shelef, Ilan

2017-06-01

Dural sinuses vary in size and shape in many pathological conditions with abnormal intracranial pressure. Size and shape normograms of dural brain sinuses are not available. The creation of such normograms may enable computer-assisted comparison to pathologic exams and facilitate diagnoses. The purpose of this study was to quantitatively evaluate normal magnetic resonance venography (MRV) studies in order to create normograms of dural sinuses using a computerized algorithm for vessel cross-sectional analysis. This was a retrospective analysis of MRV studies of 30 healthy persons. Data were analyzed using a specially developed Matlab algorithm for vessel cross-sectional analysis. The cross-sectional area and shape measurements were evaluated to create normograms. Mean cross-sectional size was 53.27±13.31 for the right transverse sinus (TS), 46.87+12.57 for the left TS (p=0.089) and 36.65+12.38 for the superior sagittal sinus. Normograms were created. The distribution of cross-sectional areas along the vessels showed distinct patterns and a parallel course for the median, 25th, 50th and 75th percentiles. In conclusion, using a novel computerized method for vessel cross-sectional analysis we were able to quantitatively characterize dural sinuses of healthy persons and create normograms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quorum sensing signal molecules produced by Pseudomonas aeruginosa cause inflammation and escape host factors in murine model of urinary tract infection.

PubMed

Gupta, Parul; Gupta, Ravi Kumar; Harjai, Kusum

2013-10-01

Quorum sensing (QS) is well established for its role in pathogenesis of various infections of Pseudomonas aeruginosa. However, its role in local tissue damage during urinary tract infection (UTI) is not yet fully established. To have insight in this, the present study was planned. UTI was established in mice using standard strain PAO1 and its isogenic QS mutant JP2. One group was challenged only with QS signals. Damage was assessed in terms of histopathology and pathology markers, malondialdehyde (MDA) and reactive nitrogen intermediates (RNI). Effect on pathogen motility, uroepithelial adhesion, and host serum sensitivity was also ascertained. PAO1-infected mice showed severe inflammation and tissue destruction, while mice infected with JP2 showed no significant destruction. JP2 was also unable to mount any tissue pathology markers, MDA and RNI, whereas PAO1 showed significantly higher levels of these two. Presence of only QS signals also showed considerable renal pathology. Strain JP2 also showed less motility, reduced uroepithelial cell adhesion, and increased serum sensitivity. Result highlights that QS signals induce local tissue pathology along with interference of host protective mechanisms during UTI.

Iatrogenic Creutzfeldt-Jakob disease with Amyloid-β pathology: an international study.

PubMed

Cali, Ignazio; Cohen, Mark L; Haїk, Stéphane; Parchi, Piero; Giaccone, Giorgio; Collins, Steven J; Kofskey, Diane; Wang, Han; McLean, Catriona A; Brandel, Jean-Philippe; Privat, Nicolas; Sazdovitch, Véronique; Duyckaerts, Charles; Kitamoto, Tetsuyuki; Belay, Ermias D; Maddox, Ryan A; Tagliavini, Fabrizio; Pocchiari, Maurizio; Leschek, Ellen; Appleby, Brian S; Safar, Jiri G; Schonberger, Lawrence B; Gambetti, Pierluigi

2018-01-08

The presence of pathology related to the deposition of amyloid-β (Aβ) has been recently reported in iatrogenic Creutzfeldt-Jakob disease (iCJD) acquired from inoculation of growth hormone (GH) extracted from human cadaveric pituitary gland or use of cadaveric dura mater (DM) grafts.To investigate this phenomenon further, a cohort of 27 iCJD cases - 21 with adequate number of histopathological sections - originating from Australia, France, Italy, and the Unites States, were examined by immunohistochemistry, amyloid staining, and Western blot analysis of the scrapie prion protein (PrP Sc ), and compared with age-group matched cases of sporadic CJD (sCJD), Alzheimer disease (AD) or free of neurodegenerative diseases (non-ND).Cases of iCJD and sCJD shared similar profiles of proteinase K-resistant PrP Sc with the exception of iCJD harboring the "MMi" phenotype. Cerebral amyloid angiopathy (CAA), either associated with, or free of, Thioflavin S-positive amyloid core plaques (CP), was observed in 52% of 21 cases of iCJD, which comprised 37.5% and 61.5% of the cases of GH- and DM-iCJD, respectively. If only cases younger than 54 years were considered, Aβ pathology affected 41%, 2% and 0% of iCJD, sCJD and non-ND, respectively. Despite the patients' younger age CAA was more severe in iCJD than sCJD, while Aβ diffuse plaques, in absence of Aβ CP, populated one third of sCJD. Aβ pathology was by far most severe in AD. Tau pathology was scanty in iCJD and sCJD.In conclusion, (i) despite the divergences in the use of cadaveric GH and DM products, our cases combined with previous studies showed remarkably similar iCJD and Aβ phenotypes indicating that the occurrence of Aβ pathology in iCJD is a widespread phenomenon, (ii) CAA emerges as the hallmark of the Aβ phenotype in iCJD since it is observed in nearly 90% of all iCJD with Aβ pathology reported to date including ours, and it is shared by GH- and DM-iCJD, (iii) although the contributions to Aβ pathology of other factors, including GH deficiency, cannot be discounted, our findings increase the mounting evidence that this pathology is acquired by a mechanism resembling that of prion diseases.

The Preoperative Composite Physiologic Index May Predict Mortality in Lung Cancer Patients with Combined Pulmonary Fibrosis and Emphysema.

PubMed

Ueno, Fumika; Kitaguchi, Yoshiaki; Shiina, Takayuki; Asaka, Shiho; Miura, Kentaro; Yasuo, Masanori; Wada, Yosuke; Yoshizawa, Akihiko; Hanaoka, Masayuki

2017-01-01

It remains unclear whether the preoperative pulmonary function parameters and prognostic indices that are indicative of nutritional and immunological status are associated with prognosis in lung cancer patients with combined pulmonary fibrosis and emphysema (CPFE) who have undergone surgery. The aim of this study is to identify prognostic determinants in these patients. The medical records of all patients with lung cancer associated with CPFE who had undergone surgery at Shinshu University Hospital were retrospectively reviewed to obtain clinical data, including the results of preoperative pulmonary function tests and laboratory examinations, chest high-resolution computed tomography (HRCT), and survival. Univariate Cox proportional hazards regression analysis showed that a high pathological stage of the lung cancer, a higher preoperative serum carcinoembryonic antigen level, and a higher preoperative composite physiologic index (CPI) were associated with a high risk of death. Multivariate analysis showed that a high pathological stage of the lung cancer (HR: 1.579; p = 0.0305) and a higher preoperative CPI (HR: 1.034; p = 0.0174) were independently associated with a high risk of death. In contrast, the severity of fibrosis or emphysema on chest HRCT, the individual pulmonary function parameters, the prognostic nutritional index, the neutrophil-to-lymphocyte ratio, and the platelet-to-lymphocyte ratio were not associated with prognosis. In the Kaplan-Meier analysis, the log-rank test showed significant differences in survival between the high-CPI and the low-CPI group (p = 0.0234). The preoperative CPI may predict mortality and provide more powerful prognostic information than individual pulmonary function parameters in lung cancer patients with CPFE who have undergone surgery. © 2017 S. Karger AG, Basel.

Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma.

PubMed

Chang, Wei-Chin; Lin, Chun-Shu; Yang, Cheng-Yu; Lin, Chih-Kung; Chen, Yuan-Wu

2018-04-01

Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals. We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002-2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004). Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis. LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

In depth analysis of the in vivo toxicity of venom from the jellyfish Stomolophus meleagris.

PubMed

Li, Rongfeng; Yu, Huahua; Yue, Yang; Liu, Song; Xing, Ronge; Chen, Xiaolin; Wang, Xueqin; Li, Pengcheng

2014-12-15

Jellyfish Stomolophus meleagris, a synonym of Nemopilema nomurai, which has often bloomed in the China Sea in recent years, is becoming an increasing threat to human health and life as a result of its strong toxicity. Each year, hundreds of thousands of people were stung, especially in the high season, and the victims suffered itch, edema, myalgia, dyspnea, hypotension, shock and even death. Here, we present the in-depth analysis of the in vivo toxicity of the venom from the jellyfish S. meleagris by using both an acute toxicological approach and pathological analyses. The venom showed an LD50 of approximately 2.92 μg/g body weight in mice following an intravenous injection and caused renal glomerular swelling, renal vesicle stricture, renal tubules dilatation, hepatic blood sinusoid dilatation, pulmonary edema and malignant pleural effusion. The pathological sections analysis showed that the kidney and liver were significantly damaged, but the heart, spleen and stomach had no observed changes. Additionally, the hemanalysis showed an increase of white blood cells (WBC), middle cells (Mid), alanine aminotransferase (ALT), blood urine nitrogen (BUN) and uric acid (UA) in the blood. Moreover, the mice also displayed convulsions, mouth bleeding, piloerection, dyspnea and death after the injection of the venom. In conclusion, this venom has a strong toxicity to the kidney of the mice and the acute renal failure might be one of the most important factors for the death after a severe sting. Hopefully, the present study will provide a significant reference for the treatment of stings by the jellyfish S. meleagris in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of difference of association between polymorphisms in the XRCC5, RPA3 and RTEL1 genes and glioma, astrocytoma and glioblastoma

PubMed Central

Jin, Tianbo; Wang, Yuan; Li, Gang; Du, Shuli; Yang, Hua; Geng, Tingting; Hou, Peng; Gong, Yongkuan

2015-01-01

Background: Gliomas are the most common aggressive brain tumors and have many complex pathological types. Previous reports have discovered that genetic mutations are associated with the risk of glioma. However, it is unclear whether uniform genetic mutations exist difference between glioma and its two pathological types in the Han Chinese population. Materials and methods: We evaluated 20 SNPs of 703 glioma cases (338 astrocytoma cases, 122 glioblastoma cases) and 635 controls in a Han Chinese population using χ2 test and genetic model analysis. Results: In three case-control studies, we found rs9288516 in XRCC5 gene showed a decreased risk of glioma (OR, 0.85; 95% CI, 0.73-0.99; P = 0.042) and glioblastoma (OR, 0.70; 95% CI, 0.52-0.92; P = 0.001) in the allele model. We identified rs414805 in RPA3 gene showed an increased risk of glioblastoma in allele model (OR, 1.38; 95% CI, 1.00-1.89; P = 0.047) and dominant model (OR, 1.57; 95% CI, 1.05-2.35; P = 0.027), analysis respectively. Meanwhile, rs2297440 in RTEL1 gene showed an increased risk of glioma (OR, 1.30; 95% CI, 1.10-1.54; P = 0.002) and astrocytoma (OR, 1.26; 95% CI, 1.02-1.54; P = 0.029) in the allele model. In addition, we also observed a haplotype of “GCT” in the RTEL1 gene with an increased risk of astrocytoma (P = 0.005). Conclusions: Polymorphisms in the XRCC5, RPA3 and RTEL1 genes, combinating with previous reaserches, are associated with glioma developing. However, those genes mutations may play different roles in the glioma, astrocytoma and glioblastoma, respectively. PMID:26328260

Analysis of difference of association between polymorphisms in the XRCC5, RPA3 and RTEL1 genes and glioma, astrocytoma and glioblastoma.

PubMed

Jin, Tianbo; Wang, Yuan; Li, Gang; Du, Shuli; Yang, Hua; Geng, Tingting; Hou, Peng; Gong, Yongkuan

2015-01-01

Gliomas are the most common aggressive brain tumors and have many complex pathological types. Previous reports have discovered that genetic mutations are associated with the risk of glioma. However, it is unclear whether uniform genetic mutations exist difference between glioma and its two pathological types in the Han Chinese population. We evaluated 20 SNPs of 703 glioma cases (338 astrocytoma cases, 122 glioblastoma cases) and 635 controls in a Han Chinese population using χ(2) test and genetic model analysis. In three case-control studies, we found rs9288516 in XRCC5 gene showed a decreased risk of glioma (OR, 0.85; 95% CI, 0.73-0.99; P = 0.042) and glioblastoma (OR, 0.70; 95% CI, 0.52-0.92; P = 0.001) in the allele model. We identified rs414805 in RPA3 gene showed an increased risk of glioblastoma in allele model (OR, 1.38; 95% CI, 1.00-1.89; P = 0.047) and dominant model (OR, 1.57; 95% CI, 1.05-2.35; P = 0.027), analysis respectively. Meanwhile, rs2297440 in RTEL1 gene showed an increased risk of glioma (OR, 1.30; 95% CI, 1.10-1.54; P = 0.002) and astrocytoma (OR, 1.26; 95% CI, 1.02-1.54; P = 0.029) in the allele model. In addition, we also observed a haplotype of "GCT" in the RTEL1 gene with an increased risk of astrocytoma (P = 0.005). Polymorphisms in the XRCC5, RPA3 and RTEL1 genes, combinating with previous reaserches, are associated with glioma developing. However, those genes mutations may play different roles in the glioma, astrocytoma and glioblastoma, respectively.

Prognostic impact of the integration of volumetric quantification of the solid part of the tumor on 3DCT and FDG-PET imaging in clinical stage IA adenocarcinoma of the lung.

PubMed

Furumoto, Hideyuki; Shimada, Yoshihisa; Imai, Kentaro; Maehara, Sachio; Maeda, Junichi; Hagiwara, Masaru; Okano, Tetsuya; Masuno, Ryuhei; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2018-07-01

The aim of this study was to conduct comparative analyses of the biological malignant potential of clinical stage IA adenocarcinoma using positron emission tomography/computed tomography (PET/CT), high-resolution CT (HRCT), and three-dimensional CT (3DCT). The predictive performance of these parameters was evaluated in terms of clinical outcomes and pathological invasiveness (positive lymphatic permeation, blood-vessel invasion, pleural invasion, and lymph-node metastasis). We enrolled 170 patients with c-IA adenocarcinoma who underwent PET/CT, HRCT, and 3D reconstruction of lung structures using the Synapse Vincent system (Fujifilm Corporation, Tokyo, Japan) followed by complete resection. Maximum standardized uptake values (SUV max ) of F 18 -fluorodeoxyglucose and the size and volume of the solid part of the tumor were quantified and analyzed in relation to surgical outcomes. Univariate analysis demonstrated that all the three parameters and whole-tumor volume were associated with unfavorable disease-free survival (DFS), while the volume of the solid part was the independent predictor on multivariate analysis (p < .001). The receiver operating characteristic curves for pathological invasiveness, determined using the variables dichotomized at each cut-off level (SUV max 2.4; solid-part size 1.23 cm; solid-part volume 779 mm 3 ), showed that all were significantly correlated with pathological invasiveness and prognosis, whereas the combination of SUV max and the solid-part volume was the most powerful predictor of survival and pathological invasiveness compared to any other parameters: the 4-year DFS and proportion of pathological invasiveness in patients with SUV max  > 2.4 and solid-part volume > 779 mm 3 versus those with SUV max  ≤ 2.4 or solid-part volume ≤779 mm 3 were 81.2% versus 98.3% (p < .001) and 84.3% versus 15.1% (p < .001), respectively. In c-IA adenocarcinoma, the volume of the solid part of the tumor was the independent predictor for unfavorable DFS, and the integration of the volume of the solid part and SUV max was highly beneficial for the prediction of survival and pathological invasiveness. Copyright © 2018 Elsevier B.V. All rights reserved.

Career Paths of Pathology Informatics Fellowship Alumni.

PubMed

Rudolf, Joseph W; Garcia, Christopher A; Hanna, Matthew G; Williams, Christopher L; Balis, Ulysses G; Pantanowitz, Liron; Tuthill, J Mark; Gilbertson, John R

2018-01-01

The alumni of today's Pathology Informatics and Clinical Informatics fellowships fill diverse roles in academia, large health systems, and industry. The evolving training tracks and curriculum of Pathology Informatics fellowships have been well documented. However, less attention has been given to the posttraining experiences of graduates from informatics training programs. Here, we examine the career paths of subspecialty fellowship-trained pathology informaticians. Alumni from four Pathology Informatics fellowship training programs were contacted for their voluntary participation in the study. We analyzed various components of training, and the subsequent career paths of Pathology Informatics fellowship alumni using data extracted from alumni provided curriculum vitae. Twenty-three out of twenty-seven alumni contacted contributed to the study. A majority had completed undergraduate study in science, technology, engineering, and math fields and combined track training in anatomic and clinical pathology. Approximately 30% (7/23) completed residency in a program with an in-house Pathology Informatics fellowship. Most completed additional fellowships (15/23) and many also completed advanced degrees (10/23). Common primary posttraining appointments included chief medical informatics officer (3/23), director of Pathology Informatics (10/23), informatics program director (2/23), and various roles in industry (3/23). Many alumni also provide clinical care in addition to their informatics roles (14/23). Pathology Informatics alumni serve on a variety of institutional committees, participate in national informatics organizations, contribute widely to scientific literature, and more than half (13/23) have obtained subspecialty certification in Clinical Informatics to date. Our analysis highlights several interesting phenomena related to the training and career trajectory of Pathology Informatics fellowship alumni. We note the long training track alumni complete in preparation for their careers. We believe flexible training pathways combining informatics and clinical training may help to alleviate the burden. We highlight the importance of in-house Pathology Informatics fellowships in promoting interest in informatics among residents. We also observe the many important leadership roles in academia, large community health systems, and industry available to early career alumni and believe this reflects a strong market for formally trained informaticians. We hope this analysis will be useful as we continue to develop the informatics fellowships to meet the future needs of our trainees and discipline.

Digital pathology: A systematic evaluation of the patent landscape.

PubMed

Cucoranu, Ioan C; Parwani, Anil V; Vepa, Suryanarayana; Weinstein, Ronald S; Pantanowitz, Liron

2014-01-01

Digital pathology is a relatively new field. Inventors of technology in this field typically file for patents to protect their intellectual property. An understanding of the patent landscape is crucial for companies wishing to secure patent protection and market dominance for their products. To our knowledge, there has been no prior systematic review of patents related to digital pathology. Therefore, the aim of this study was to systematically identify and evaluate United States patents and patent applications related to digital pathology. Issued patents and patent applications related to digital pathology published in the United States Patent and Trademark Office (USPTO) database (www.uspto.gov) (through January 2014) were searched using the Google Patents search engine (Google Inc., Mountain View, California, USA). Keywords and phrases related to digital pathology, whole-slide imaging (WSI), image analysis, and telepathology were used to query the USPTO database. Data were downloaded and analyzed using the Papers application (Mekentosj BV, Aalsmeer, Netherlands). A total of 588 United States patents that pertain to digital pathology were identified. In addition, 228 patent applications were identified, including 155 that were pending, 65 abandoned, and eight rejected. Of the 588 patents granted, 348 (59.18%) were specific to pathology, while 240 (40.82%) included more general patents also usable outside of pathology. There were 70 (21.12%) patents specific to pathology and 57 (23.75%) more general patents that had expired. Over 120 unique entities (individual inventors, academic institutions, and private companies) applied for pathology specific patents. Patents dealt largely with telepathology and image analysis. WSI related patents addressed image acquisition (scanning and focus), quality (z-stacks), management (storage, retrieval, and transmission of WSI files), and viewing (graphical user interface (GUI), workflow, slide navigation and remote control). An increasing number of recent patents focused on computer-aided diagnosis (CAD) and digital consultation networks. In the last 2 decades, there have been an increasing number of patents granted and patent applications filed related to digital pathology. The number of these patents quadrupled during the last decade, and this trend is predicted to intensify based on the number of patent applications already published by the USPTO.

Digital pathology: A systematic evaluation of the patent landscape

PubMed Central

Cucoranu, Ioan C.; Parwani, Anil V.; Vepa, Suryanarayana; Weinstein, Ronald S.; Pantanowitz, Liron

2014-01-01

Introduction: Digital pathology is a relatively new field. Inventors of technology in this field typically file for patents to protect their intellectual property. An understanding of the patent landscape is crucial for companies wishing to secure patent protection and market dominance for their products. To our knowledge, there has been no prior systematic review of patents related to digital pathology. Therefore, the aim of this study was to systematically identify and evaluate United States patents and patent applications related to digital pathology. Materials and Methods: Issued patents and patent applications related to digital pathology published in the United States Patent and Trademark Office (USPTO) database (www.uspto.gov) (through January 2014) were searched using the Google Patents search engine (Google Inc., Mountain View, California, USA). Keywords and phrases related to digital pathology, whole-slide imaging (WSI), image analysis, and telepathology were used to query the USPTO database. Data were downloaded and analyzed using the Papers application (Mekentosj BV, Aalsmeer, Netherlands). Results: A total of 588 United States patents that pertain to digital pathology were identified. In addition, 228 patent applications were identified, including 155 that were pending, 65 abandoned, and eight rejected. Of the 588 patents granted, 348 (59.18%) were specific to pathology, while 240 (40.82%) included more general patents also usable outside of pathology. There were 70 (21.12%) patents specific to pathology and 57 (23.75%) more general patents that had expired. Over 120 unique entities (individual inventors, academic institutions, and private companies) applied for pathology specific patents. Patents dealt largely with telepathology and image analysis. WSI related patents addressed image acquisition (scanning and focus), quality (z-stacks), management (storage, retrieval, and transmission of WSI files), and viewing (graphical user interface (GUI), workflow, slide navigation and remote control). An increasing number of recent patents focused on computer-aided diagnosis (CAD) and digital consultation networks. Conclusion: In the last 2 decades, there have been an increasing number of patents granted and patent applications filed related to digital pathology. The number of these patents quadrupled during the last decade, and this trend is predicted to intensify based on the number of patent applications already published by the USPTO. PMID:25057430

Flow and dissociation: examination of mean levels, cross-links, and links to emotional well-being across sports and recreational and pathological gambling.

PubMed

Wanner, Brigitte; Ladouceur, Robert; Auclair, Amélie V; Vitaro, Frank

2006-01-01

To examine whether flow (Csikszentmihalyi (1990). Flow: The psychology of optimal experience. NY: Harper & Row) and dissociation (Jacobs (1986). Journal of Gambling Behavior, 2, 15-31) are experienced across sports and recreational and pathological gambling, we assessed a sample of 511 college students (256 females and 255 males, M age = 19.54) that was comprised of 14 pathological gamblers, 21 non-addicted gamblers, and 476 athletes. The findings showed that both flow and dissociation lay on a continuum of subjective experiences across activity groups. Specifically, pathological gamblers experienced lower levels of flow than athletes, whereas recreational gamblers lay in between the previous groups in this regard. In contrast, pathological gamblers experienced higher mean levels of dissociation than athletes and recreational gamblers who, in turn, were similar in this regard. A LISREL model showed that flow was positively associated with general emotional well-being, whereas dissociation was negatively associated with well-being.

A pilot controlled trial of a cognitive dissonance-based body dissatisfaction intervention with young British men.

PubMed

Jankowski, Glen S; Diedrichs, Phillippa C; Atkinson, Melissa J; Fawkner, Helen; Gough, Brendan; Halliwell, Emma

2017-12-01

This pilot study evaluated a body image intervention for men, Body Project M. Seventy-four British undergraduate men took part in two 90-min intervention sessions, and completed standardised assessments of body image, bulimic pathology, and related outcomes at baseline, post-intervention, and 3-month follow-up. Fifty-three other men completed the questionnaires as an assessment-only control group. Per-protocol analysis showed that Body Project M improved men's dissatisfaction with body fat and muscularity, body appreciation, muscularity enhancing behaviours, appearance comparisons, and internalization (ds=0.46-0.80) at post-intervention. All except dissatisfaction with muscularity and internalization were sustained at 3-month follow-up. No effects were found for bulimic pathology. Post-intervention effects for dissatisfaction with muscularity and internalization only were retained under intention-to-treat analysis. Participants were favourable towards the intervention. This study provides preliminary evidence for the acceptability and post-intervention efficacy of Body Project M. Further development of the intervention is required to improve and sustain effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

A spectral approach for the quantitative description of cardiac collagen network from nonlinear optical imaging.

PubMed

Masè, Michela; Cristoforetti, Alessandro; Avogaro, Laura; Tessarolo, Francesco; Piccoli, Federico; Caola, Iole; Pederzolli, Carlo; Graffigna, Angelo; Ravelli, Flavia

2015-01-01

The assessment of collagen structure in cardiac pathology, such as atrial fibrillation (AF), is essential for a complete understanding of the disease. This paper introduces a novel methodology for the quantitative description of collagen network properties, based on the combination of nonlinear optical microscopy with a spectral approach of image processing and analysis. Second-harmonic generation (SHG) microscopy was applied to atrial tissue samples from cardiac surgery patients, providing label-free, selective visualization of the collagen structure. The spectral analysis framework, based on 2D-FFT, was applied to the SHG images, yielding a multiparametric description of collagen fiber orientation (angle and anisotropy indexes) and texture scale (dominant wavelength and peak dispersion indexes). The proof-of-concept application of the methodology showed the capability of our approach to detect and quantify differences in the structural properties of the collagen network in AF versus sinus rhythm patients. These results suggest the potential of our approach in the assessment of collagen properties in cardiac pathologies related to a fibrotic structural component.

Quantification of Vocal Fold Vibration in Various Laryngeal Disorders Using High-Speed Digital Imaging.

PubMed

Yamauchi, Akihito; Yokonishi, Hisayuki; Imagawa, Hiroshi; Sakakibara, Ken-Ichi; Nito, Takaharu; Tayama, Niro; Yamasoba, Tatsuya

2016-03-01

To quantify vibratory characteristics of various laryngeal disorders seen by high-speed digital imaging (HSDI). HSDI was performed on 78 patients with various laryngeal disorders (20 with polyp, 16 with carcinoma, 13 with leukoplakia, 6 with vocal fold nodule, and 33 with others) and 29 vocally healthy subjects. Obtained data were quantitatively evaluated by frame-by-frame analysis, laryngotopography, digital kymography, and glottal area waveform. Overall, patients with laryngeal pathologies showed greater asymmetry in amplitude, mucosal wave and phase, smaller mucosal wave, and poorer glottal closure than vocally healthy subjects. Furthermore, disease-specific vibratory disturbances that generally agreed with the findings in the literature were quantified: comparing polyp with nodule, differences were noted in longitudinal phase difference, amplitude, and mucosal wave. In comparison with leukoplakia and cancer, nonvibrating area was more frequently noted in cancer. The HSDI analysis of various voice disorders using multiple methods can help phonosurgeons to properly diagnose various laryngeal pathologies and to estimate the degree of their vocal disturbances. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Variable pathogenicity of exon 43del (FAA) in four Fanconi anaemia patients within a consanguineous family.

PubMed

Koc, A; Pronk, J C; Alikasifoglu, M; Joenje, H; Altay, C

1999-01-01

Four Fanconi anaemia group A (FAA) patients within two related consanguineous families are presented: the propositus (male, 13 years, transplanted at age 10), and his three cousins (one male, 8 years, and two female newborns). Assignment of the patients to FAA was based on the functional complementation analysis by somatic cell hybridization and confirmed by mutation screening showing a homozygous deletion of exon 43 (4267-4404del) in the FAA gene to be present in all four patients. The newborn patients had been diagnosed prenatally by DNA analysis. In spite of identical molecular pathology and close familial relationship the clinical phenotypes of the four patients were not concordant. Discordant symptoms included birthweight, pigmentation abnormalities, skeletal, renal and genital abnormalities, whereas microcephaly and possibly the haematological course were concordant. Differences in environmental conditions and/or genetic make-up along with chance effects during development may explain discordant phenotypes despite identical molecular pathology in these patients. However, our results do not rule out the possibility that the exon 43del mutation may have prognostic value for the haematological course of the disease.

Saliva Proteomics Analysis Offers Insights on Type 1 Diabetes Pathology in a Pediatric Population

PubMed Central

Pappa, Eftychia; Vastardis, Heleni; Mermelekas, George; Gerasimidi-Vazeou, Andriani; Zoidakis, Jerome; Vougas, Konstantinos

2018-01-01

The composition of the salivary proteome is affected by pathological conditions. We analyzed by high resolution mass spectrometry approaches saliva samples collected from children and adolescents with type 1 diabetes and healthy controls. The list of more than 2000 high confidence protein identifications constitutes a comprehensive characterization of the salivary proteome. Patients with good glycemic regulation and healthy individuals have comparable proteomic profiles. In contrast, a significant number of differentially expressed proteins were identified in the saliva of patients with poor glycemic regulation compared to patients with good glycemic control and healthy children. These proteins are involved in biological processes relevant to diabetic pathology such as endothelial damage and inflammation. Moreover, a putative preventive therapeutic approach was identified based on bioinformatic analysis of the deregulated salivary proteins. Thus, thorough characterization of saliva proteins in diabetic pediatric patients established a connection between molecular changes and disease pathology. This proteomic and bioinformatic approach highlights the potential of salivary diagnostics in diabetes pathology and opens the way for preventive treatment of the disease. PMID:29755368

A Meta-Analysis Examining the Influence of Pro-Eating Disorder Websites on Body Image and Eating Pathology.

PubMed

Rodgers, Rachel F; Lowy, Alice S; Halperin, Daniella M; Franko, Debra L

2016-01-01

Previous research has indicated that exposure to pro-eating disorder websites might increase eating pathology; however, the magnitude of this effect is unknown. This study aimed to conduct a systematic review and meta-analysis to examine the effect of exposure to pro-eating disorder websites on body image and eating pathology. Studies examining the relationship between exposure to pro-eating disorder websites and eating pathology-related outcomes were included. The systematic review identified nine studies. Findings revealed significant effect sizes of exposure to pro-eating disorder websites on body image dissatisfaction (five studies), d = .41, p = .003; dieting (six studies), d = .68, p < .001, and negative affect (three studies), d = 1.00, p < .001. No effect emerged for bulimic symptoms (four studies), d = .22, p = .73. Findings confirmed the effect of pro-eating disorder websites on body image and eating pathology, highlighting the need for enforceable regulation of these websites. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Consensus Guidelines for Practical Competencies in Anatomic Pathology and Laboratory Medicine for the Undifferentiated Graduating Medical Student

PubMed Central

Shah, Darshana T.; Cambor, Carolyn L.; Conran, Richard M.; Lin, Amy Y.; Peerschke, Ellinor I.B.; Pessin, Melissa S.; Harris, Ilene B.

2015-01-01

The practice of pathology is not generally addressed in the undergraduate medical school curriculum. It is desirable to develop practical pathology competencies in the fields of anatomic pathology and laboratory medicine for every graduating medical student to facilitate (1) instruction in effective utilization of these services for optimal patient care, (2) recognition of the role of pathologists and laboratory scientists as consultants, and (3) exposure to the field of pathology as a possible career choice. A national committee was formed, including experts in anatomic pathology and/or laboratory medicine and in medical education. Suggested practical pathology competencies were developed in 9 subspecialty domains based on literature review and committee deliberations. The competencies were distributed in the form of a survey in late 2012 through the first half of 2013 to the medical education community for feedback, which was subjected to quantitative and qualitative analysis. An approval rate of ≥80% constituted consensus for adoption of a competency, with additional inclusions/modifications considered following committee review of comments. The survey included 79 proposed competencies. There were 265 respondents, the majority being pathologists. Seventy-two percent (57 of 79) of the competencies were approved by ≥80% of respondents. Numerous comments (N = 503) provided a robust resource for qualitative analysis. Following committee review, 71 competencies (including 27 modified and 3 new competencies) were considered to be essential for undifferentiated graduating medical students. Guidelines for practical pathology competencies have been developed, with the hope that they will be implemented in undergraduate medical school curricula. PMID:28725750

Consensus Guidelines for Practical Competencies in Anatomic Pathology and Laboratory Medicine for the Undifferentiated Graduating Medical Student.

PubMed

Magid, Margret S; Shah, Darshana T; Cambor, Carolyn L; Conran, Richard M; Lin, Amy Y; Peerschke, Ellinor I B; Pessin, Melissa S; Harris, Ilene B

2015-01-01

The practice of pathology is not generally addressed in the undergraduate medical school curriculum. It is desirable to develop practical pathology competencies in the fields of anatomic pathology and laboratory medicine for every graduating medical student to facilitate (1) instruction in effective utilization of these services for optimal patient care, (2) recognition of the role of pathologists and laboratory scientists as consultants, and (3) exposure to the field of pathology as a possible career choice. A national committee was formed, including experts in anatomic pathology and/or laboratory medicine and in medical education. Suggested practical pathology competencies were developed in 9 subspecialty domains based on literature review and committee deliberations. The competencies were distributed in the form of a survey in late 2012 through the first half of 2013 to the medical education community for feedback, which was subjected to quantitative and qualitative analysis. An approval rate of ≥80% constituted consensus for adoption of a competency, with additional inclusions/modifications considered following committee review of comments. The survey included 79 proposed competencies. There were 265 respondents, the majority being pathologists. Seventy-two percent (57 of 79) of the competencies were approved by ≥80% of respondents. Numerous comments (N = 503) provided a robust resource for qualitative analysis. Following committee review, 71 competencies (including 27 modified and 3 new competencies) were considered to be essential for undifferentiated graduating medical students. Guidelines for practical pathology competencies have been developed, with the hope that they will be implemented in undergraduate medical school curricula.

Varicella zoster virus in the temporal artery of a patient with giant cell arteritis.

PubMed

Nagel, Maria A; Khmeleva, Nelly; Boyer, Philip J; Choe, Alexander; Bert, Robert; Gilden, Don

2013-12-15

We recently detected varicella zoster virus (VZV) in the temporal arteries (TA) of 5/24 patients with clinically suspect giant cell arteritis (GCA) whose TAs were GCA-negative pathologically; in those GCA-negative, VZV+TAs, virus antigen predominated in the arterial adventitia, but without medial necrosis and multinucleated giant cells. During our continuing search for VZV antigen in GCA-negative TAs, in the TA of one subject, we found abundant VZV antigen, as well as VZV DNA, in multiple regions (skip areas) of the TA spanning 350 μm, as well as in skeletal muscle adjacent to the infected TA. Additional pathological analysis of sections adjacent to those containing viral antigen revealed inflammation involving the arterial media and abundant multinucleated giant cells characteristic of GCA. Detection of VZV in areas of the TA with pathological features of GCA warrants further correlative pathological-virological analysis of VZV in GCA. © 2013.

Dissonance and Healthy Weight Eating Disorder Prevention Programs: Long-Term Effects from a Randomized Efficacy Trial

PubMed Central

Stice, Eric; Marti, C. Nathan; Spoor, Sonja; Presnell, Katherine; Shaw, Heather

2009-01-01

Adolescent girls with body dissatisfaction (N=481; SD=1.4) were randomized to a dissonance-based thin-ideal internalization reduction program, healthy weight control program, expressive-writing control condition, or assessment-only control condition. Dissonance participants showed significantly greater decreases in thin-ideal internalization, body dissatisfaction, negative affect, eating disorder symptoms, and psychosocial impairment, and lower risk for eating pathology onset through 2–3 year follow-up than assessment-only controls. Dissonance participants showed greater decreases in thin-ideal internalization, body dissatisfaction, and psychosocial impairment than expressive-writing controls. Healthy weight participants showed greater decreases in thin-ideal internalization, body dissatisfaction, negative affect, eating disorder symptoms, and psychosocial impairment, less increases in weight, and lower risk for eating pathology and obesity onset through 2–3 year follow-up than assessment-only controls. Healthy weight participants showed greater decreases in thin-ideal internalization and weight than expressive writing controls. Dissonance participants showed a 60% reduction in risk for eating pathology onset and healthy weight participants showed a 61% reduction in risk for eating pathology onset and a 55% reduction in risk for obesity onset relative to assessment-only controls through 3-year follow-up, implying that the effects are clinically important and enduring. PMID:18377128

[Correlation between iridology and general pathology].

PubMed

Demea, Sorina

2002-01-01

The research proposal is to evaluate the association between certain irian signs and general pathology of studied patients. There were studied 57 hospitalized patients; there was taken over all their iris images, which were analyzed through iridological protocols; in the same time the pathology of these patients was noted from their records in the hospital, concordant with the clinical diagnosis; all these information were included in a database for a computerised processing. The correlations resulted from, shows a high connection between the irian constitution establish through iridological criteria and the existent pathology. Iris examination can be very useful for diagnosis of a certain general pathology, in a holistic approach of the patient.

Wavelet analysis in two-dimensional tomography

NASA Astrophysics Data System (ADS)

Burkovets, Dimitry N.

2002-02-01

The diagnostic possibilities of wavelet-analysis of coherent images of connective tissue in its pathological changes diagnostics. The effectiveness of polarization selection in obtaining wavelet-coefficients' images is also shown. The wavelet structures, characterizing the process of skin psoriasis, bone-tissue osteoporosis have been analyzed. The histological sections of physiological normal and pathologically changed samples of connective tissue of human skin and spongy bone tissue have been analyzed.

TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease

PubMed Central

Mishra, Manjari; Hatanpaa, Kimmo J.; White, Charles L.; Johnson, Nancy; Rademaker, Alfred; Weitner, Bing Bing; Deng, Han-Xiang; Dubner, Steven D.; Weintraub, Sandra; Mesulam, Marsel

2010-01-01

The clinical syndrome of primary progressive aphasia (PPA) can be associated with a variety of neuropathologic diagnoses at autopsy. Thirty percent of cases have Alzheimer disease (AD) pathology, most often in the usual distribution, which defies principles of brain–behavior organization, in that aphasia is not symptomatic of limbic disease. The present study investigated whether concomitant TDP-43 pathology could resolve the lack of clinicoanatomic concordance. In this paper, 16 cases of clinical PPA and 10 cases of primarily non-aphasic frontotemporal dementia (FTD), all with AD pathology, were investigated to determine whether their atypical clinical phenotypes reflected the presence of additional TDP-43 pathology. A comparison group consisted of 27 cases of pathologic AD with the typical amnestic clinical phenotype of probable AD. Concomitant TDP-43 pathology was discovered in only three of the FTD and PPA but in more than half of the typical amnestic clinical phenotypes. Hippocampal sclerosis (HS) was closely associated with TDP-43 pathology when all groups were combined for analysis. Therefore, the clinical phenotypes of PPA and FTD in cases with pathologic AD are only rarely associated with TDP-43 proteinopathy. Furthermore, medial temporal TDP-43 pathology is more tightly linked to HS than to clinical phenotype. These findings challenge the current notions about clinicopathologic correlation, especially about the role of multiple pathologies. PMID:20361198

European and US publications in the 50 highest ranking pathology journals from 2000 to 2006.

PubMed

Fritzsche, F R; Oelrich, B; Dietel, M; Jung, K; Kristiansen, G

2008-04-01

To analyse the contributions of the 15 primary member states of the European Union and selected non-European countries to pathological research between 2000 and 2006. Pathological journals were screened using ISI Web of Knowledge database. The number of publications and related impact factors were determined for each country. Relevant socioeconomic indicators were related to the scientific output. Subsequently, results were compared to publications in 10 of the leading biomedical journals. The research output remained generally stable. In Europe, the UK, Germany, France, Italy and Spain ranked top concerning contributions to publications and impact factors in the pathological and leading general biomedical journals. With regard to socioeconomic data, smaller, mainly northern European countries showed a relatively higher efficiency. Of the lager countries, the UK is the most efficient in that respect. The rising economic powers of China and India were consistently in the rear. Results mirror the leading role of the USA in pathology research but also show the relevance of European scientists. The scientometric approach in this study provides a new fundamental and comparative overview of pathology research in the European Union and the USA which could help to benchmark scientific output among countries.

[Adolescent pathological gambling].

PubMed

Petit, A; Karila, L; Lejoyeux, M

2015-05-01

Although experts have long thought that the problems of gambling involved only adults, recent studies tend to show that teenagers are also affected. The objective of this paper is to show the characteristics of pathological gambling in adolescents. This review focuses on the clinical features, prevalence, psychopathology, prevention and treatment of this disorder. A review of the medical literature was conducted, using PubMed, using the following keywords alone or combined: pathological gambling, dependence, addiction and adolescents. We selected 12 English articles from 1997 to 2014. Recent work estimate that between 4 and 8% of adolescents suffer from problem gambling, and the prevalence of pathological gambling is 2-4 times higher in adolescents than in adults. The term adolescent pathological gambler starts early around the age of 10-12 years, with a quick change of status from casual to that of problem gambler and player. Complications appear quickly and comorbidities are common. There is no curative pharmacological treatment approved by health authorities. Pathological gambling among adolescents has grown significantly in recent years and should be promptly taken care of. Further studies must be performed to improve our understanding of this problem among adolescents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Applications of pathology-assisted image analysis of immunohistochemistry-based biomarkers in oncology.

PubMed

Shinde, V; Burke, K E; Chakravarty, A; Fleming, M; McDonald, A A; Berger, A; Ecsedy, J; Blakemore, S J; Tirrell, S M; Bowman, D

2014-01-01

Immunohistochemistry-based biomarkers are commonly used to understand target inhibition in key cancer pathways in preclinical models and clinical studies. Automated slide-scanning and advanced high-throughput image analysis software technologies have evolved into a routine methodology for quantitative analysis of immunohistochemistry-based biomarkers. Alongside the traditional pathology H-score based on physical slides, the pathology world is welcoming digital pathology and advanced quantitative image analysis, which have enabled tissue- and cellular-level analysis. An automated workflow was implemented that includes automated staining, slide-scanning, and image analysis methodologies to explore biomarkers involved in 2 cancer targets: Aurora A and NEDD8-activating enzyme (NAE). The 2 workflows highlight the evolution of our immunohistochemistry laboratory and the different needs and requirements of each biological assay. Skin biopsies obtained from MLN8237 (Aurora A inhibitor) phase 1 clinical trials were evaluated for mitotic and apoptotic index, while mitotic index and defects in chromosome alignment and spindles were assessed in tumor biopsies to demonstrate Aurora A inhibition. Additionally, in both preclinical xenograft models and an acute myeloid leukemia phase 1 trial of the NAE inhibitor MLN4924, development of a novel image algorithm enabled measurement of downstream pathway modulation upon NAE inhibition. In the highlighted studies, developing a biomarker strategy based on automated image analysis solutions enabled project teams to confirm target and pathway inhibition and understand downstream outcomes of target inhibition with increased throughput and quantitative accuracy. These case studies demonstrate a strategy that combines a pathologist's expertise with automated image analysis to support oncology drug discovery and development programs.

Correlation between MRI evidence of degenerative condylar surface changes, induction of articular disc displacement and pathological joint sounds in the temporomandibular joint.

PubMed

Honda, Kosuke; Natsumi, Yoshiko; Urade, Masahiro

2008-12-01

The relationship of bony changes in the condylar surfaces in articular disc displacement without reduction in temporomandibular joint (TMJ) was investigated using diagnostic imaging. The study also evaluated whether the bony changes in the condylar surfaces limit disc and condyle motion, and produce pathological joint sounds. Thirty-seven joints in 28 patients diagnosed with degenerative bony changes in the condylar surfaces radiographically and anterior disc displacement without reduction using magnetic resonance imaging (MRI) were studied. The bony changes were assessed by radiographic examination and classified into two types: pathological bone changes (PBCs) including erosion, osteophyte formation and deformity, and adaptive bone changes (ABCs) including flattening and concavity. MRI was performed on the TMJ to examine the configuration and position of the discs. Joint sounds in the TMJ were determined using electrovibratograghy with a joint vibration analysis. The articular disc motion to the condyle in the PBC group was smaller than in the ABC group irrespective of the configuration of the disc, even though there were no significant differences between the two types of bony changes in the disc position during jaw closing. The joint vibration analysis of the TMJ showed that joint sounds with a higher frequency were observed in the PBC group than in the ABC group. High energy levels needed to produce the higher frequencies (over 300 Hz) were observed only in the PBC group.

Influence of Fasciola hepatica on Serum Biochemical Parameters and Vascular and Biliary System of Sheep Liver

PubMed Central

Hodžić, A; Zuko, A; Avdić, R; Alić, A; Omeragić, J; Jažić, A

2013-01-01

Background The aim of this study was to evaluate the functional capacity of the liver based on the activity of specific enzymes and bilirubin in serum and also to investigate the influence of mechanical and toxic effects of Fasciola hepatica on the structures of the blood vessels and biliary tract in the sheep liver. Methods Blood samples and liver of 63 indigenous sheep of Pramenka breed, slaughtered in the period from March to December 2009 were used. Based on parasitological findings in the liver, all animals were divided into two groups: control (n = 34) and infected group (n = 29). For investigation and description of pathological changes in sheep liver, naturally infected with F. hepatica, corrosion cast technique was used. Results Biochemical analysis of tested parameters showed a significant elevation (P≤0.05) of serum gamma-glutamyl transferase (GGT), total bilirubin (TBIL) and direct bilirubin (DBIL) in infected sheep group comparing with the control group. No significant differences were observed for activity of aspartate aminotranferase (AST) between groups. Vascular and biliary systems of the liver were found to be affected. Conclusion Results of biochemical analysis are consistent with pathological findings and measuring of tested parameters could be used in early diagnosis of sheep fasciolosis and to test the effectiveness of anthelmintic therapy. Corrosion cast technique is very useful for investigation of pathological changes and neoangiogenesis of vascular and biliary system in sheep liver, caused by mechanical and toxic effects of F. hepatica. PMID:23682266

Definition of a putative pathological region in PARK2 associated with autism spectrum disorder through in silico analysis of its functional structure.

PubMed

Conceição, Inês C; Rama, Maria M; Oliveira, Bárbara; Café, Cátia; Almeida, Joana; Mouga, Susana; Duque, Frederico; Oliveira, Guiomar; Vicente, Astrid M

2017-04-01

The PARK2 gene encodes Parkin, a component of a multiprotein E3 ubiquitin ligase complex that targets substrate proteins for proteasomal degradation. PARK2 mutations are frequently associated with Parkinson's disease, but structural alterations have also been described in patients with neurodevelopmental disorders (NDD), suggesting a pathological effect ubiquitous to neurodevelopmental and neurodegenerative brain processes. The present study aimed to define the critical regions for NDD within PARK2. To clarify PARK2 involvement in NDDs, we examined the frequency and location of copy number variants (CNVs) identified in patients from our sample and reported in the literature and relevant databases, and compared with control populations. Overall, the frequency of PARK2 CNVs was higher in controls than in NDD cases. However, closer inspection of the CNV location in PARK2 showed that the frequency of CNVs targeting the Parkin C-terminal, corresponding to the ring-between-ring (RBR) domain responsible for Parkin activity, is significantly higher in NDD cases than in controls. In contrast, CNVs targeting the N-terminal of Parkin, including domains that regulate ubiquitination activity, are very common both in cases and in controls. Although PARK2 may be a pathological factor for NDDs, likely not all variants are pathogenic, and a conclusive assessment of PARK2 variant pathogenicity requires an accurate analysis of their location within the coding region and encoded functional domains.

Characterization of in vitro healthy and pathological human liver tissue periodicity using backscattered ultrasound signals.

PubMed

Machado, Christiano Bittencourt; Pereira, Wagner Coelho de Albuquerque; Meziri, Mahmoud; Laugier, Pascal

2006-05-01

This work studied the periodicity of in vitro healthy and pathologic liver tissue, using backscattered ultrasound (US) signals. It utilized the mean scatterer spacing (MSS) as a parameter of tissue characterization, estimated by three methods: the spectral autocorrelation (SAC), the singular spectrum analysis (SSA) and the quadratic transformation method (SIMON). The liver samples were classified in terms of tissue status using the METAVIR scoring system. Twenty tissue samples were classified in four groups: F0, F1, F3 and F4 (five samples for each). The Kolmogorov-Smirnov test (applied on group pairs) resulted as nonsignificant (p > 0.05) for two pairs only: F1/F3 (for SSA) and F3/F4 (for SAC). A discriminant analysis was applied using as parameters the MSS mean (MSS) and standard deviation (sigmaMSS), the estimates histogram mode (mMSS), and the speed of US (mc(foie)) in the medium, to evaluate the degree of discrimination among healthy and pathologic tissues. The better accuracy (Ac) with SAC (80%) was with parameter group (MSS, sigmaMSS, mc(foie)), achieving a sensitivity (Ss) of 92.3% and a specificity (Sp) of 57.1%. For SSA, the group with all four parameters showed an Ac of 75%, an Ss of 78.6% and an Sp of 66.70%. SIMON obtained the best Ac of all (85%) with group (MSS, mMSS, mc(foie)), an Ss of 100%, but with an Sp of 50%.

Postural analysis in time and frequency domains in patients with Ehlers-Danlos syndrome.

PubMed

Galli, Manuela; Rigoldi, Chiara; Celletti, Claudia; Mainardi, Luca; Tenore, Nunzio; Albertini, Giorgio; Camerota, Filippo

2011-01-01

The goal of this work is to analyze postural control in Ehlers-Danlos syndrome (EDS) participants in time and frequency domain. This study considered a pathological group composed by 22 EDS participants performing a postural test consisting in maintaining standing position over a force platform for 30s in two conditions: open eyes (OE) and closed eyes (CE). In order to compare pathological group we acquired in the same conditions a control group composed by 20 healthy participants. The obtained center of pressure (COP) signal was analyzed in time and frequency domain using an AR model. Results revealed differences between pathological and control group: EDS participants pointed out difficulties in controlling COP displacements trying to keep it inside the BOS in AP direction and for this reason increased the use of ML mechanism in order to avoid the risk of fall. Also in CE conditions they demonstrated more difficulties in maintaining posture revealing the proprioceptive system is impaired, due to ligament laxity that characterized EDS participants. Frequency domain analysis showed no differences between the two groups, affirming that the changes in time domain reflected really the impairment to the postural control mechanism and not a different strategy assumed by EDS participants. These data could help in decision-making process to establish a correct rehabilitation approach, based on the reinforcing of muscle tone to supply the ligament laxity in order to prevent risks of falls and its consequences. Copyright © 2010 Elsevier Ltd. All rights reserved.

ADP/ATP mitochondrial carrier MD simulations to shed light on the structural-dynamical events that, after an additional mutation, restore the function in a pathological single mutant.

PubMed

Di Marino, Daniele; Oteri, Francesco; Morozzo Della Rocca, Blasco; Chillemi, Giovanni; Falconi, Mattia

2010-12-01

Molecular dynamics simulations of the wild type bovine ADP/ATP mitochondrial carrier, and of the single Ala113Pro and double Ala113Pro/Val180Met mutants, embedded in a lipid bilayer, have been carried out for 30ns to shed light on the structural-dynamical changes induced by the Val180Met mutation restoring the carrier function in the Ala113Pro pathologic mutant. Principal component analysis indicates that, for the three systems, the protein dynamics is mainly characterized by the motion of the matrix loops and of the odd-numbered helices having a conserved proline in their central region. Analysis of the motions shows a different behaviour of single pathological mutant with respect of the other two systems. The single mutation induces a regularization and rigidity of the H3 helix, lost upon the introduction of the second mutation. This is directly correlated to the salt bridge distribution involving residues Arg79, Asp134 and Arg234, hypothesized to interact with the substrate. In fact, in the wild type simulation two stable inter-helices salt bridges, crucial for substrate binding, are present almost over all the simulation time. In line with the impaired ADP transport, one salt interaction is lost in the single mutant trajectory but reappears in the double mutant simulation, where a salt bridge network matching the wild type is restored. Other important structural-dynamical properties, such as the trans-membrane helices mobility, analyzed via the principal component analysis, are similar for the wild type and double mutant while are different for the single mutant, providing a mechanistic explanation for their different functional properties. Copyright © 2010 Elsevier Inc. All rights reserved.

The histogram analysis of diffusion-weighted intravoxel incoherent motion (IVIM) imaging for differentiating the gleason grade of prostate cancer.

PubMed

Zhang, Yu-Dong; Wang, Qing; Wu, Chen-Jiang; Wang, Xiao-Ning; Zhang, Jing; Liu, Hui; Liu, Xi-Sheng; Shi, Hai-Bin

2015-04-01

To evaluate histogram analysis of intravoxel incoherent motion (IVIM) for discriminating the Gleason grade of prostate cancer (PCa). A total of 48 patients pathologically confirmed as having clinically significant PCa (size > 0.5 cm) underwent preoperative DW-MRI (b of 0-900 s/mm(2)). Data was post-processed by monoexponential and IVIM model for quantitation of apparent diffusion coefficients (ADCs), perfusion fraction f, diffusivity D and pseudo-diffusivity D*. Histogram analysis was performed by outlining entire-tumour regions of interest (ROIs) from histological-radiological correlation. The ability of imaging indices to differentiate low-grade (LG, Gleason score (GS) ≤6) from intermediate/high-grade (HG, GS > 6) PCa was analysed by ROC regression. Eleven patients had LG tumours (18 foci) and 37 patients had HG tumours (42 foci) on pathology examination. HG tumours had significantly lower ADCs and D in terms of mean, median, 10th and 75th percentiles, combined with higher histogram kurtosis and skewness for ADCs, D and f, than LG PCa (p < 0.05). Histogram D showed relatively higher correlations (ñ = 0.641-0.668 vs. ADCs: 0.544-0.574) with ordinal GS of PCa; and its mean, median and 10th percentile performed better than ADCs did in distinguishing LG from HG PCa. It is feasible to stratify the pathological grade of PCa by IVIM with histogram metrics. D performed better in distinguishing LG from HG tumour than conventional ADCs. • GS had relatively higher correlation with tumour D than ADCs. • Difference of histogram D among two-grade tumours was statistically significant. • D yielded better individual features in demonstrating tumour grade than ADC. • D* and f failed to determine tumour grade of PCa.

Transcriptome Pathway Analysis of Pathological and Physiological Aldosterone-Producing Human Tissues.

PubMed

Zhou, Junhua; Lam, Brian; Neogi, Sudeshna G; Yeo, Giles S H; Azizan, Elena A B; Brown, Morris J

2016-12-01

Primary aldosteronism is present in ≈10% of hypertensives. We previously performed a microarray assay on aldosterone-producing adenomas and their paired zona glomerulosa and fasciculata. Confirmation of top genes validated the study design and functional experiments of zona glomerulosa selective genes established the role of the encoded proteins in aldosterone regulation. In this study, we further analyzed our microarray data using AmiGO 2 for gene ontology enrichment and Ingenuity Pathway Analysis to identify potential biological processes and canonical pathways involved in pathological and physiological aldosterone regulation. Genes differentially regulated in aldosterone-producing adenoma and zona glomerulosa were associated with steroid metabolic processes gene ontology terms. Terms related to the Wnt signaling pathway were enriched in zona glomerulosa only. Ingenuity Pathway Analysis showed "NRF2-mediated oxidative stress response pathway" and "LPS (lipopolysaccharide)/IL-1 (interleukin-1)-mediated inhibition of RXR (retinoid X receptor) function" were affected in both aldosterone-producing adenoma and zona glomerulosa with associated genes having up to 21- and 8-fold differences, respectively. Comparing KCNJ5-mutant aldosterone-producing adenoma, zona glomerulosa, and zona fasciculata samples with wild-type samples, 138, 56, and 59 genes were differentially expressed, respectively (fold-change >2; P<0.05). ACSS3, encoding the enzyme that synthesizes acetyl-CoA, was the top gene upregulated in KCNJ5-mutant aldosterone-producing adenoma compared with wild-type. NEFM, a gene highly upregulated in zona glomerulosa, was upregulated in KCNJ5 wild-type aldosterone-producing adenomas. NR4A2, the transcription factor for aldosterone synthase, was highly expressed in zona fasciculata adjacent to a KCNJ5-mutant aldosterone-producing adenoma. Further interrogation of these genes and pathways could potentially provide further insights into the pathology of primary aldosteronism. © 2016 The Authors.

[Multivariate analysis of the association between consumption of fried food and gastric cancer and precancerous lesions].

PubMed

Guo, L W; Liu, S Z; Zhang, M; Chen, Q; Zhang, S K; Sun, X B

2018-02-06

Objective: To investigate the effect of fried food intake on the pathogenesis of gastric cancer and precancerous lesions. Methods: From 2005 to 2013, the residents aged 40-69 years from 11 counties/cities where cancer screening of upper gastrointestinal cancer were conducted in rural areas of Henan province as the subjects (82 367 cases). The information such as demography and lifestyle was collected. The residents were screened with endoscopic examination. The biopsy sampleswere diagnosed pathologically, according to pathological diagnosis criteria, the subjects with high risk were divided into the groups with different pathological degrees. The multivariate ordinal logistic regression analysis was used to analyze the relationship between the frequency of fried food intake and gastric cancer and precancerous lesions. Results: The study coverd 46 425 males and 35 942 females, with a age of (53.46±8.07)years. The study collected 6 707 cases of normal stomach, 2 325 cases of low grade intraepithelial neoplasia, 226 cases of high grade intraepithelial neoplasia and 331 cases of gastric cancer. Multivariate logistic regression analysis showed that, compared with those whoeat fried food less than one time per week, fried foods intake (<2 times/week: OR= 1.89, 95 %CI: 1.57-2.28; ≥ 2 times/week: OR= 1.91, 95 %CI: 1.66-2.20) were a risk factor for gastric cancer and precancerous lesions after adjustment for age, sex, marital status, educational level, body mass index (BMI), smoking and drinking status. Conclusion: The intake of fried food is a risk factor for gastric cancer and precancerous lesions. Therefore, reducing the intake of fried food can prevent the occurrence of gastric carcinoma and precancerous lesions.

The Oral Pathology Related Articles Published in Iranian Journal of Pathology from 2006 to 2015.

PubMed

Shamim, Thorakkal

2016-01-01

There is a paucity of information about the oral pathology related articles published in a pathology journal. This study aimed to audit the oral pathology related articles published in Iranian Journal of Pathology (Iran J Pathol) from 2006 to 2015. Bibliometric analysis of issues of Iran J Pathol from 2006 to 2015 was performed using web-based search. The articles published were analyzed for type of article and individual topic of oral pathology. The articles published were also checked for authorship trends. Out of the total 49 published articles related to oral pathology, case reports (21) and original articles (18) contributed the major share. The highest number of oral pathology related articles was published in 2011, 2014 and 2015 with 8 articles each and the least published year was 2012 with 1 article. Among the oral pathology related articles published, spindle cell neoplasms (7) followed by salivary gland tumors (5), jaw tumors (4), oral granulomatous conditions (4), lymphomas (4), oral cancer (3) and odontogenic cysts (3) form the major attraction of the contributors. The largest numbers of published articles related to oral pathology were received from Tehran University of Medical Sciences; Tehran (7) followed by Mashhad University of Medical Sciences, Mashhad (6) and Shahid Beheshti University of Medical Sciences, Tehran (5). This paper may be considered as a baseline study for the bibliometric information regarding oral pathology related articles published in a pathology journal.

The Oral Pathology Related Articles Published in Iranian Journal of Pathology from 2006 to 2015

PubMed Central

Shamim, Thorakkal

2016-01-01

Background: There is a paucity of information about the oral pathology related articles published in a pathology journal. This study aimed to audit the oral pathology related articles published in Iranian Journal of Pathology (Iran J Pathol) from 2006 to 2015. Methods: Bibliometric analysis of issues of Iran J Pathol from 2006 to 2015 was performed using web-based search. The articles published were analyzed for type of article and individual topic of oral pathology. The articles published were also checked for authorship trends. Results: Out of the total 49 published articles related to oral pathology, case reports (21) and original articles (18) contributed the major share. The highest number of oral pathology related articles was published in 2011, 2014 and 2015 with 8 articles each and the least published year was 2012 with 1 article. Among the oral pathology related articles published, spindle cell neoplasms (7) followed by salivary gland tumors (5), jaw tumors (4), oral granulomatous conditions (4), lymphomas (4), oral cancer (3) and odontogenic cysts (3) form the major attraction of the contributors. The largest numbers of published articles related to oral pathology were received from Tehran University of Medical Sciences; Tehran (7) followed by Mashhad University of Medical Sciences, Mashhad (6) and Shahid Beheshti University of Medical Sciences, Tehran (5). Conclusion: This paper may be considered as a baseline study for the bibliometric information regarding oral pathology related articles published in a pathology journal. PMID:27799973

Myofibroblastoma of the male breast: a rare entity with radiologic-pathologic correlation

PubMed Central

Comer, John D.; Cui, Xiaoyan; Eisen, Carolyn Sharyn; Abbey, Genevieve; Arleo, Elizabeth Kagan

2016-01-01

A 73-year old man with a history of multiple genitourinary malignancies was found to have a left retroareolar soft tissue mass on CT assessment of disease, and dedicated breast imaging was recommended. Diagnostic mammography and ultrasonography confirmed a solid mass, for which biopsy was recommended. Pathologic analysis demonstrated a spindle cell neoplasm with an immunoreactivity pattern consistent with myofibroblastoma. While this entity is benign, nonspecific imaging features necessitate tissue sampling for pathologic diagnosis, and, given pathologic rarity, open communication between the radiologist and pathologist is important to establish the correct diagnosis and to recommend appropriate management. PMID:27936420

A Comparison of Raman Spectral Features of Frozen and Deparaffinized Tissues in Neuroblastoma and Ganglioneuroma

NASA Astrophysics Data System (ADS)

Devpura, Suneetha; Thakur, Jagdish S.; Poulik, Janet M.; Rabah, Raja; Naik, Vaman M.; Naik, Ratna

2012-02-01

We have investigated the cellular regions in neuroblastoma and ganglioneuroma using Raman spectroscopy and compared their spectral characteristics with those of normal adrenal gland. Thin sections from both frozen and deparaffinized tissues, obtained from the same tissue specimen, were studied in conjunction with the pathological examination of the tissues. We found a significant difference in the spectral features of frozen sections of normal adrenal gland, neuroblastoma, and ganglioneuroma when compared to deparaffinized tissues. The quantitative analysis of the Raman data using chemometric methods of principal component analysis and discriminant function analysis obtained from the frozen tissues show a sensitivity and specificity of 100% each. The biochemical identification based on the spectral differences shows that the normal adrenal gland tissues have higher levels of carotenoids, lipids, and cholesterol compared to the neuroblastoma and ganglioneuroma frozen tissues. However, deparaffinized tissues show complete removal of these biochemicals in adrenal tissues. This study demonstrates that Raman spectroscopy combined with chemometric methods can successfully distinguish neuroblastoma and ganglioneuroma at cellular level.

Bacterial meningitic deafness: historical development of epidemiology and cellular pathology.

PubMed

Ruben, Robert

2008-04-01

Meningitis resulting in labyrinthitis and its associated hearing loss was first described by several authors during 1864 and 1865 but it was not integrated into the otological cannon until H. Knapp's publications of 1871. These reports were incorporated by St John Rossa in his textbook of 1873. Politzer, in 1882, included a fuller description of the clinical symptoms. Analysis of records of the etiologies of students in 90 schools for the deaf in North America from 1817 to 1893 showed that before the mid-1870s meningitis was rarely identified as an etiology (<1%) but by the 1880s it accounted for 10-20% of all etiologies, with male preponderance. Cellular pathology of meningitic labyrinthitis from the 1860s to the 1990s examined the ways in which bacteria invaded the inner ear. Human temporal bone studies were a major source of understanding of the pathological processes. Honda, in 1927, injected guinea pigs intracranially with live bacteria, and observed the effects on the membranous labyrinth. In 1988 Lebel's observation of the effectiveness of dexamethasone in preventing much deafness from meningitis stimulated the examination of the labyrinthine immune response. Immunological mechanisms can account for some of the variable morbidity of unilateral, progressive, less-than-severe deafness.

Exploring the development of cultural awareness amongst post-graduate speech-language pathology students.

PubMed

Howells, Simone; Barton, Georgina; Westerveld, Marleen

2016-06-01

Speech-language pathology programs globally need to prepare graduates to work with culturally and linguistically diverse populations. This study explored the knowledge, perceptions and experiences related to development of cultural awareness of graduate-entry Master of Speech Pathology students at an Australian university. Sixty students across both year-levels completed a cultural awareness survey at the beginning of the semester. To explore how clinical placement influenced students' knowledge and perceptions, year-2 students completed written reflections pre- and post-placement (n = 7) and participated in focus groups post-placement (n = 6). Survey results showed student interest in working with culturally and linguistically diverse populations was high (over 80%) and confidence was moderate (over 50%). More than 80% of students reported awareness of their own cultural identities, stereotypes and prejudices. Content analysis of focus group and written reflection data identified key concepts comprising of: (1) context-university, and clinical placement site; (2) competencies-professional and individual; and (3) cultural implications-clients' and students' cultural backgrounds. Findings suggest clinical placement may positively influence cultural awareness development and students' own cultural backgrounds may influence this more. Further exploration of how students move along a continuum of cultural development is warranted.

Mathematical methods in medicine: neuroscience, cardiology and pathology.

PubMed

Amigó, José M; Small, Michael

2017-06-28

The application of mathematics, natural sciences and engineering to medicine is gaining momentum as the mutual benefits of this collaboration become increasingly obvious. This theme issue is intended to highlight the trend in the case of mathematics. Specifically, the scope of this theme issue is to give a general view of the current research in the application of mathematical methods to medicine, as well as to show how mathematics can help in such important aspects as understanding, prediction, treatment and data processing. To this end, three representative specialties have been selected: neuroscience, cardiology and pathology. Concerning the topics, the 12 research papers and one review included in this issue cover biofluids, cardiac and virus dynamics, computational neuroscience, functional magnetic resonance imaging data processing, neural networks, optimization of treatment strategies, time-series analysis and tumour growth. In conclusion, this theme issue contains a collection of fine contributions at the intersection of mathematics and medicine, not as an exercise in applied mathematics but as a multidisciplinary research effort that interests both communities and our society in general.This article is part of the themed issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'. © 2017 The Author(s).

Ocular growth in the fetus. 1. Comparative study of axial length and biometric parameters in the fetus.

PubMed

Denis, D; Righini, M; Scheiner, C; Volot, F; Boubli, L; Dezard, X; Vola, J; Saracco, J B

1993-01-01

The knowledge of ocular growth during fetal life, when compared with other fetal biometric parameters, could not only provide a better definition of malformation syndromes but could also give a better understanding of certain pathological processes in premature babies and in newborns. As the literature concerning prenatal ocular dimensions contains few data, the aim of this study was to measure the axial length of the globe (AL) in fetuses and compare this measurement with their gestational age, weight, height, head circumference (HC) and thoracic circumference (TC) in order to compile a reference table. In the present study, 76 globes from 38 fetuses (18-41 weeks gestational age) from the Department of Pathology (Timone University Hospital, Marseille) were examined. Ultrasonography A and B were used to measure the AL, and a pathological examination determined fetal weight, HC, TC and height. We were interested to find out which of the parameters studied would give the best correlation with ocular growth. Statistical analysis showed that HC remained the most discriminant factor and correlated best with ocular growth. We thus obtained an equation for ocular size according to HC that could serve as a basis for detecting pre- or postnatal ocular defects.

[A contribution to the history of medicine in Poland: skeletal remains from a church hospital cemetery of the 14th 18th century in Łeczyca (Province of Łódź)].

PubMed

Lorkiewicz, Wiesław; Teul, Iwona; Zasadzka, Patrycja; Borucki, Andrzej

2011-01-01

We present the results of an anthropological and paleopathological analysis of 7 graves discovered at the site of a church-hospital complex existing in the 14th-18th century in Łeczyca (province of Łódź). The aim was to determine whether the skeletons revealed features typical for the function of the complex. The graves contained the remains of 8 persons: 4 men (2 of them aged 20-40 years and 2 aged 40-60 years), 2 women (aged 40-60 years), and 2 children (one aged 2-4 years and a 10-month-old fetus or neonate buried together with one of the women). Four skeletons of adults (out of 5 skeletons in a condition adequate for the study) showed pathological (degenerative) and traumatic lesions. Pathologies of the masticatory organ (mainly intravital loss of teeth and recession of the alveolar process) were seen in all preserved adult skulls. The high incidence of pathologies indicates that we were dealing with the remains of patients of a hospital.

Testing the Predictive Validity and Construct of Pathological Video Game Use

PubMed Central

Groves, Christopher L.; Gentile, Douglas; Tapscott, Ryan L.; Lynch, Paul J.

2015-01-01

Three studies assessed the construct of pathological video game use and tested its predictive validity. Replicating previous research, Study 1 produced evidence of convergent validity in 8th and 9th graders (N = 607) classified as pathological gamers. Study 2 replicated and extended the findings of Study 1 with college undergraduates (N = 504). Predictive validity was established in Study 3 by measuring cue reactivity to video games in college undergraduates (N = 254), such that pathological gamers were more emotionally reactive to and provided higher subjective appraisals of video games than non-pathological gamers and non-gamers. The three studies converged to show that pathological video game use seems similar to other addictions in its patterns of correlations with other constructs. Conceptual and definitional aspects of Internet Gaming Disorder are discussed. PMID:26694472

Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain

PubMed Central

Maphis, Nicole; Xu, Guixiang; Kokiko-Cochran, Olga N.; Jiang, Shanya; Cardona, Astrid; Ransohoff, Richard M.; Lamb, Bruce T.

2015-01-01

Pathological aggregation of tau is a hallmark of Alzheimer’s disease and related tauopathies. We have previously shown that the deficiency of the microglial fractalkine receptor (CX3CR1) led to the acceleration of tau pathology and memory impairment in an hTau mouse model of tauopathy. Here, we show that microglia drive tau pathology in a cell-autonomous manner. First, tau hyperphosphorylation and aggregation occur as early as 2 months of age in hTauCx3cr1−/− mice. Second, CD45+ microglial activation correlates with the spatial memory deficit and spread of tau pathology in the anatomically connected regions of the hippocampus. Third, adoptive transfer of purified microglia derived from hTauCx3cr1−/− mice induces tau hyperphosphorylation within the brains of non-transgenic recipient mice. Finally, inclusion of interleukin 1 receptor antagonist (Kineret®) in the adoptive transfer inoculum significantly reduces microglia-induced tau pathology. Together, our results suggest that reactive microglia are sufficient to drive tau pathology and correlate with the spread of pathological tau in the brain. PMID:25833819

The Molecular Pathology of Cushing Disease: Are We Nearly There?

PubMed

Grossman, Ashley B

2017-02-01

The molecular pathology of corticotroph tumors is surveyed in the light of recent work showing the induction of aggressive corticotroph tumors by the transgenic expression of epidermal growth factor receptors.

Heterogeneous data fusion for brain tumor classification.

PubMed

Metsis, Vangelis; Huang, Heng; Andronesi, Ovidiu C; Makedon, Fillia; Tzika, Aria

2012-10-01

Current research in biomedical informatics involves analysis of multiple heterogeneous data sets. This includes patient demographics, clinical and pathology data, treatment history, patient outcomes as well as gene expression, DNA sequences and other information sources such as gene ontology. Analysis of these data sets could lead to better disease diagnosis, prognosis, treatment and drug discovery. In this report, we present a novel machine learning framework for brain tumor classification based on heterogeneous data fusion of metabolic and molecular datasets, including state-of-the-art high-resolution magic angle spinning (HRMAS) proton (1H) magnetic resonance spectroscopy and gene transcriptome profiling, obtained from intact brain tumor biopsies. Our experimental results show that our novel framework outperforms any analysis using individual dataset.

Clinical image and pathology of hypertrophic cranial pachymeningitis.

PubMed

Shi, C H; Niu, S T; Zhang, Z Q

2014-12-12

The objective of this study was to examine the clinical findings, magnetic resonance imaging (MRI), pathological features, and treatment experiments of patients with hypertrophic cranial pachymeningitis (HCP). The clinical findings, MRI, and pathological appearances of 9 patients with HCP were analyzed retrospectively. The thickened dura mater was markedly enhanced after contrast media injection. The lesion near the brain hemisphere presented long regions of T1- and T2-weighted abnormal signal intensities. The abnormal signal intensities of the brain tissue were decreased significantly. Pathological examination demonstrated chronic inflammation changes, with cerebral dura mater fibrous tissue showing obvious hyperplasia, and the periphery of the blood vessel showing a great quantity of infiltrating phlegmonosis cells. HCP mainly presents headache and paralysis of multiple cranial nerves. The distinctive signs on brain MRIs involve strengthening the signal in the cerebral dura.

Performance of wavelet analysis and neural networks for pathological voices identification

NASA Astrophysics Data System (ADS)

Salhi, Lotfi; Talbi, Mourad; Abid, Sabeur; Cherif, Adnane

2011-09-01

Within the medical environment, diverse techniques exist to assess the state of the voice of the patient. The inspection technique is inconvenient for a number of reasons, such as its high cost, the duration of the inspection, and above all, the fact that it is an invasive technique. This study focuses on a robust, rapid and accurate system for automatic identification of pathological voices. This system employs non-invasive, non-expensive and fully automated method based on hybrid approach: wavelet transform analysis and neural network classifier. First, we present the results obtained in our previous study while using classic feature parameters. These results allow visual identification of pathological voices. Second, quantified parameters drifting from the wavelet analysis are proposed to characterise the speech sample. On the other hand, a system of multilayer neural networks (MNNs) has been developed which carries out the automatic detection of pathological voices. The developed method was evaluated using voice database composed of recorded voice samples (continuous speech) from normophonic or dysphonic speakers. The dysphonic speakers were patients of a National Hospital 'RABTA' of Tunis Tunisia and a University Hospital in Brussels, Belgium. Experimental results indicate a success rate ranging between 75% and 98.61% for discrimination of normal and pathological voices using the proposed parameters and neural network classifier. We also compared the average classification rate based on the MNN, Gaussian mixture model and support vector machines.

Changes in pathology test ordering by early career general practitioners: a longitudinal study.

PubMed

Magin, Parker J; Tapley, Amanda; Morgan, Simon; Henderson, Kim; Holliday, Elizabeth G; Davey, Andrew R; Ball, Jean; Catzikiris, Nigel F; Mulquiney, Katie J; van Driel, Mieke L

2017-07-17

To assess the number of pathology tests ordered by general practice registrars during their first 18-24 months of clinical general practice. Longitudinal analysis of ten rounds of data collection (2010-2014) for the Registrar Clinical Encounters in Training (ReCEnT) study, an ongoing, multicentre, cohort study of general practice registrars in Australia. The principal analysis employed negative binomial regression in a generalised estimating equations framework (to account for repeated measures on registrars).Setting, participants: General practice registrars in training posts with five of 17 general practice regional training providers in five Australian states. The registrar participation rate was 96.4%. Number of pathology tests requested per consultation. The time unit for analysis was the registrar training term (the 6-month full-time equivalent component of clinical training); registrars contributed data for up to four training terms. 876 registrars contributed data for 114 584 consultations. The number of pathology tests requested increased by 11% (95% CI, 8-15%; P < 0.001) per training term. Contrary to expectations, pathology test ordering by general practice registrars increased significantly during their first 2 years of clinical practice. This causes concerns about overtesting. As established general practitioners order fewer tests than registrars, test ordering may peak during late vocational training and early career practice. Registrars need support during this difficult period in the development of their clinical practice patterns.

HISTOPATHOLOGICAL ANALYSIS OF THE F344 RAT LUNG UPON EXPOSURE TO RETENOIC ACID, OVALBUMIN, MOLD SPORES AND CITRAL.

PubMed

Farah, Ibrahim O; Holt-Gray, Carlene; Cameron, Joseph A; Tucci, Michelle; Benghuzzi, Hamed

2017-01-01

The paradoxical role of retinoic acid (All Trans Retinoic Acid; ATRA) in the development of allergic and/or inflammatory complications in contrast to a therapeutic modality for lung pathology is not well understood or established in the literature. As well, the role of Citral (inhibitor of retinoid function; a non-toxic chemical that exists in two forms (diethyl; C1 or cis-trans dimethyl; C2), in the reversal of retinoic acid, ovalbumin and allergic mold spore pathophysiology is also not well ascertained under an in vivo setting. Therefore, it is hypothesized that exposure of F344 lung tissues to supra-physiologic levels of retinoic acid, ovalbumin and mold spores individually or in combination with each other will lead to inflammatory tissue pathology and that Citral 1 and 2 will reverse or ameliorate the related pathological damage to lung tissues. Even though ovalbumin and retinoic acid have been previously applied through intra-tracheal route in cancer prevention and immunological research, the objective of this study was to evaluate the histopathological implications of such exposure in vivo. This IACUC approved in vivo study used Fischer 344 rats ( n = 80 ; 229 to 273g), which were randomly assigned to controls as well as ovalbumin and mold-sensitized treatment groups (0.80 mg/kg and 1×10 9 mold spores combined from 4 strains/100 μl intra-tracheal; all others were dosed by intra-peritoneal injection at days 1 and 7 with 80 mg/kg each of ATRA as well as 20 and 50 mg/kg each of Citrals 1 or 2 individually or in combination to represent all four chemicals and mold spores treatments. Positive and negative controls for each treatment were also included in the study. Animals were housed in rat cages at the JSU Research Animal Core Facilities and were placed on a 12:12 light-dark cycle. A standard rodent diet and water access were provided ad libidum. All animals were sacrificed on day 21 and lung tissues were processed for histopathology. Slides were prepared and were digitized for comparison of tissues pathology. Results showed that exposure of the F344 rats to ovalbumin and ATRA showed various levels of lung tissue damage that was ameliorated by Citral 2 in combination. Mold and ATRA exposure caused various levels of lung tissue damage that was reversed by C1 in combination with each other. Taken together, the study showed that there are variable pathologic inflammatory responses from the interaction of ovalbumin, Citrals, mold spores and retinoic acid, and that the addition of Citrals have reversed lung tissue pathologies. These findings warrants further investigation as to the actual role of these interactions in relation to acute/chronic lung disease and the possibility of reversing retinoid-mediated pathologies in the Fisher rat model.

Summary of 2nd Nordic symposium on digital pathology

PubMed Central

Lundström, Claes; Thorstenson, Sten; Waltersson, Marie; Persson, Anders; Treanor, Darren

2015-01-01

Techniques for digital pathology are envisioned to provide great benefits in clinical practice, but experiences also show that solutions must be carefully crafted. The Nordic countries are far along the path toward the use of whole-slide imaging in clinical routine. The Nordic Symposium on Digital Pathology (NDP) was created to promote knowledge exchange in this area, between stakeholders in health care, industry, and academia. This article is a summary of the NDP 2014 symposium, including conclusions from a workshop on clinical adoption of digital pathology among the 144 attendees. PMID:25774316

Summary of 2(nd) Nordic symposium on digital pathology.

PubMed

Lundström, Claes; Thorstenson, Sten; Waltersson, Marie; Persson, Anders; Treanor, Darren

2015-01-01

Techniques for digital pathology are envisioned to provide great benefits in clinical practice, but experiences also show that solutions must be carefully crafted. The Nordic countries are far along the path toward the use of whole-slide imaging in clinical routine. The Nordic Symposium on Digital Pathology (NDP) was created to promote knowledge exchange in this area, between stakeholders in health care, industry, and academia. This article is a summary of the NDP 2014 symposium, including conclusions from a workshop on clinical adoption of digital pathology among the 144 attendees.

Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology.

PubMed

Bhargava, Rohit; Madabhushi, Anant

2016-07-11

Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area.

Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology

PubMed Central

Bhargava, Rohit; Madabhushi, Anant

2017-01-01

Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area. PMID:27420575

Perfusion alterations converge with patterns of pathological spread in transactive response DNA-binding protein 43 proteinopathies.

PubMed

Ferraro, Pilar M; Jester, Charles; Olm, Christopher A; Placek, Katerina; Agosta, Federica; Elman, Lauren; McCluskey, Leo; Irwin, David J; Detre, John A; Filippi, Massimo; Grossman, Murray; McMillan, Corey T

2018-04-17

Amyotrophic lateral sclerosis (ALS) and the behavioral variant of frontotemporal dementia (bvFTD) commonly share the presence of transactive response DNA-binding protein 43 (TDP-43) inclusions. Structural magnetic resonance imaging studies demonstrated evidence for TDP-43 pathology spread, but while structural imaging usually reveals overt neuronal loss, perfusion imaging may detect more subtle neural activity alterations. We evaluated perfusion as an early marker for incipient pathology-associated brain alterations in TDP-43 proteinopathies. Cortical thickness (CT) and perfusion measurements were obtained in ALS (N = 18), pathologically and/or genetically confirmed bvFTD-TDP (N = 12), and healthy controls (N = 33). bvFTD showed reduced frontotemporal CT, hypoperfusion encompassing orbitofrontal and temporal cortices, and hyperperfusion in motor and occipital regions. ALS did not show reduced CT, but exhibited hypoperfusion in motor and temporal regions, and hyperperfusion in frontal and occipital cortices. Frontotemporal hypoperfusion and reduced CT correlated with cognitive and behavioral impairments as investigated using Mini-Mental State Examination and Philadelphia Brief Assessment of Cognition in bvFTD, and hypoperfusion in motor regions correlated with motor disability as measured by the ALS Functional Rating Scale-Revised in ALS. Hypoperfusion marked early pathologically involved regions, while hyperperfusion characterized regions of late pathological involvement. Distinct perfusion patterns may provide early markers of pathology distribution in TDP-43 proteinopathies. Copyright © 2018 Elsevier Inc. All rights reserved.

Clinical and pathological features of myeloid leukemia cutis*

PubMed Central

Li, Li; Wang, Yanan; Lian, Christine Guo; Hu, Nina; Jin, Hongzhong; Liu, Yuehua

2018-01-01

Background Myeloid leukemia cutis is the terminology used for cutaneous manifestations of myeloid leukemia. Objective The purpose of this study was to study the clinical, histopathological and immunohistochemical features of myeloid leukemia cutis. Methods This was a retrospective study of clinical and pathological features of 10 patients with myeloid leukemia cutis. Results One patient developed skin lesions before the onset of leukemia, seven patients developed skin infiltration within 4-72 months after the onset of leukemia, and two patients developed skin lesions and systemic leukemia simultaneously. Of these patients, five presented with generalized papules or nodules, and five with localized masses. The biopsy of skin lesions showed a large number of tumor cells within the dermis and subcutaneous fat layer. Immunohistochemical analysis showed strong reactivity to myeloperoxidase (MPO), CD15, CD43 and CD45 (LCA) in most cases. NPM1 (nucleophosmin I) and FLT3-ITD (Fms-like tyrosine kinase 3-internal tandem duplication) mutations were identified in one case. Five patients with acute myelogenous leukemia and one patient with chronic myelomonocytic leukemia died within two months to one year after the onset of skin lesions. Study limitations This was a retrospective and small sample study. Conclusions In patients with myelogenous leukemia, skin infiltration usually occurs after, but occasionally before, the appearance of hemogram and myelogram abnormalities, and the presence of skin infiltration is often associated with a poor prognosis and short survival time. myeloid leukemia cutis often presents as generalized or localized nodules or masses with characteristic pathological and histochemical findings. PMID:29723350

Computer-aided prognosis on breast cancer with hematoxylin and eosin histopathology images: A review.

PubMed

Chen, Jia-Mei; Li, Yan; Xu, Jun; Gong, Lei; Wang, Lin-Wei; Liu, Wen-Lou; Liu, Juan

2017-03-01

With the advance of digital pathology, image analysis has begun to show its advantages in information analysis of hematoxylin and eosin histopathology images. Generally, histological features in hematoxylin and eosin images are measured to evaluate tumor grade and prognosis for breast cancer. This review summarized recent works in image analysis of hematoxylin and eosin histopathology images for breast cancer prognosis. First, prognostic factors for breast cancer based on hematoxylin and eosin histopathology images were summarized. Then, usual procedures of image analysis for breast cancer prognosis were systematically reviewed, including image acquisition, image preprocessing, image detection and segmentation, and feature extraction. Finally, the prognostic value of image features and image feature-based prognostic models was evaluated. Moreover, we discussed the issues of current analysis, and some directions for future research.

MR enterography in nonresponsive adult celiac disease: Correlation with endoscopic, pathologic, serologic, and genetic features.

PubMed

Radmard, Amir Reza; Hashemi Taheri, Amir Pejman; Salehian Nik, Elham; Kooraki, Soheil; Kolahdoozan, Shadi; Mirminachi, Babak; Sotoudeh, Masoud; Ekhlasi, Golnaz; Malekzadeh, Reza; Shahbazkhani, Bijan

2017-10-01

To assess small bowel abnormalities on magnetic resonance enterography (MRE) in adult patients with nonresponsive celiac disease (CD) and investigate their associations with endoscopic, histopathologic, serologic, and genetic features. This prospective study was carried out between September 2012 and August 2013. After approval by the Ethics Committee of our institution, informed consent was acquired from all participants. Forty consecutive patients with nonresponsive CD, aged 17-76 years, underwent MRE using a 1.5T unit. Sequences included T 2 -HASTE, True-FISP, pre- and postcontrast VIBE to assess the quantitative (number of ileal and jejunal folds) and qualitative (fold pattern abnormalities, mural thickening, increased enhancement, bowel dilatation, or intussusception) measures. Endoscopic manifestations were categorized as normal/mild vs. severe. Histopathological results were divided into mild and severe. Genotyping of HLA-DQ2 and DQ8 was performed. Serum levels of tissue-transglutaminase, endomysial, and gliadin antibodies were also determined. Logistic regression analysis and receiver operating characteristic (ROC) curve were used. Twenty-nine (72.5%) cases showed abnormal MRE. Reversed jejunoileal fold pattern had significant association with severe endoscopic (odds ratio [OR] = 8.38, 95% confidence interval [CI] 1.73-40.5) and pathologic features (OR = 7.36, 95% CI 1.33-40.54). An increased number of ileal folds/inch was significantly associated with severe MARSH score and positive HLA-DQ8. (P < 0.001 and P = 0.026, respectively). Ileal fold number had the highest areas under the curve for prediction of severe endoscopic (AUC: 0.75, P = 0.009) and pathologic (AUC: 0.84, P < 0.001) findings and positive anti-transglutaminase antibody (AUC: 0.85, P = 0.027). Fold pattern reversal on MRE is highly associated with endoscopic and pathologic features of refractory celiac disease (RCD). Increased ileal folds showed higher correlation with endoscopic-pathologic features, HLA-DQ8, and anti-transglutaminase level. MRE might be more sensitive for detection of increased ileal folds in CD rather than reduction of duodenal and jejunal folds due to better distension of ileal loops. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1096-1106. © 2017 International Society for Magnetic Resonance in Medicine.

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.

Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer

PubMed Central

Hergueta-Redondo, Marta; Sarrio, David; Molina-Crespo, Ángela; Vicario, Rocío; Bernadó-Morales, Cristina; Martínez, Lidia; Rojo-Sebastián, Alejandro; Serra-Musach, Jordi; Mota, Alba; Martínez-Ramírez, Ángel; Castilla, Maria Ángeles; González-Martin, Antonio; Pernas, Sonia; Cano, Amparo; Cortes, Javier; Nuciforo, Paolo G.; Peg, Vicente; Palacios, José; Pujana, Miguel Ángel; Arribas, Joaquín; Moreno-Bueno, Gema

2016-01-01

Around, 30–40% of HER2-positive breast cancers do not show substantial clinical benefit from the targeted therapy and, thus, the mechanisms underlying resistance remain partially unknown. Interestingly, ERBB2 is frequently co-amplified and co-expressed with neighbour genes that may play a relevant role in this cancer subtype. Here, using an in silico analysis of data from 2,096 breast tumours, we reveal a significant correlation between Gasdermin B (GSDMB) gene (located 175 kilo bases distal from ERBB2) expression and the pathological and clinical parameters of poor prognosis in HER2-positive breast cancer. Next, the analysis of three independent cohorts (totalizing 286 tumours) showed that approximately 65% of the HER2-positive cases have GSDMB gene amplification and protein over-expression. Moreover, GSDMB expression was also linked to poor therapeutic responses in terms of lower relapse free survival and pathologic complete response as well as positive lymph node status and the development of distant metastasis under neoadjuvant and adjuvant treatment settings, respectively. Importantly, GSDMB expression promotes survival to trastuzumab in different HER2-positive breast carcinoma cells, and is associated with trastuzumab resistance phenotype in vivo in Patient Derived Xenografts. In summary, our data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer. PMID:27462779

Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer.

PubMed

Hergueta-Redondo, Marta; Sarrio, David; Molina-Crespo, Ángela; Vicario, Rocío; Bernadó-Morales, Cristina; Martínez, Lidia; Rojo-Sebastián, Alejandro; Serra-Musach, Jordi; Mota, Alba; Martínez-Ramírez, Ángel; Castilla, Mª Ángeles; González-Martin, Antonio; Pernas, Sonia; Cano, Amparo; Cortes, Javier; Nuciforo, Paolo G; Peg, Vicente; Palacios, José; Pujana, Miguel Ángel; Arribas, Joaquín; Moreno-Bueno, Gema

2016-08-30

Around, 30-40% of HER2-positive breast cancers do not show substantial clinical benefit from the targeted therapy and, thus, the mechanisms underlying resistance remain partially unknown. Interestingly, ERBB2 is frequently co-amplified and co-expressed with neighbour genes that may play a relevant role in this cancer subtype. Here, using an in silico analysis of data from 2,096 breast tumours, we reveal a significant correlation between Gasdermin B (GSDMB) gene (located 175 kilo bases distal from ERBB2) expression and the pathological and clinical parameters of poor prognosis in HER2-positive breast cancer. Next, the analysis of three independent cohorts (totalizing 286 tumours) showed that approximately 65% of the HER2-positive cases have GSDMB gene amplification and protein over-expression. Moreover, GSDMB expression was also linked to poor therapeutic responses in terms of lower relapse free survival and pathologic complete response as well as positive lymph node status and the development of distant metastasis under neoadjuvant and adjuvant treatment settings, respectively. Importantly, GSDMB expression promotes survival to trastuzumab in different HER2-positive breast carcinoma cells, and is associated with trastuzumab resistance phenotype in vivo in Patient Derived Xenografts. In summary, our data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer.

Pathological and non-pathological variants of restrictive eating behaviors in middle childhood: A latent class analysis.

PubMed

Schmidt, Ricarda; Vogel, Mandy; Hiemisch, Andreas; Kiess, Wieland; Hilbert, Anja

2018-08-01

Although restrictive eating behaviors are very common during early childhood, their precise nature and clinical correlates remain unclear. Especially, there is little evidence on restrictive eating behaviors in older children and their associations with children's shape concern. The present population-based study sought to delineate subgroups of restrictive eating patterns in N = 799 7-14 year old children. Using Latent Class Analysis, children were classified based on six restrictive eating behaviors (for example, picky eating, food neophobia, and eating-related anxiety) and shape concern, separately in three age groups. For cluster validation, sociodemographic and objective anthropometric data, parental feeding practices, and general and eating disorder psychopathology were used. The results showed a 3-cluster solution across all age groups: an asymptomatic class (Cluster 1), a class with restrictive eating behaviors without shape concern (Cluster 2), and a class showing restrictive eating behaviors with prominent shape concern (Cluster 3). The clusters differed in all variables used for validation. Particularly, the proportion of children with symptoms of avoidant/restrictive food intake disorder was greater in Cluster 2 than Clusters 1 and 3. The study underlined the importance of considering shape concern to distinguish between different phenotypes of children's restrictive eating patterns. Longitudinal data are needed to evaluate the clusters' predictive effects on children's growth and development of clinical eating disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

The overall pathological status of the left hippocampus determines preoperative verbal memory performance in left mesial temporal lobe epilepsy.

PubMed

Witt, Juri-Alexander; Coras, Roland; Schramm, Johannes; Becker, Albert J; Elger, Christian E; Blümcke, Ingmar; Helmstaedter, Christoph

2014-04-01

Studies on hippocampal cell loss in epilepsy have produced diverging evidence as to which subfields are specifically related to memory. This may be due to rather small and often heterogeneous samples, or to different memory measures. Therefore, the current study examined hippocampal cell densities and memory in a large sample of patients with solely mesial temporal lobe epilepsy (mTLE), employing measures with proven sensitivity to mesiotemporal pathology. In 104 patients who had undergone epilepsy surgery for mTLE, we evaluated the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical verbal and figural memory while controlling for side-of-surgery and hemispheric dominance. First of all, patients showed material-specific memory impairment concordant with the lateralization of epilepsy. Factor analysis of segmental cell loss revealed a single factor reflecting the overall integrity of the hippocampus. The overall pathological status of the left hippocampus correlated with verbal memory parameters (r = 0.33-0.34, P < 0.05), especially when controlling for atypical hemispheric dominance (r = 0.50-0.57, P < 0.01), and explained up to 33% of the observed variance. Further analyses revealed no superior role of a single subfield or cell loss pattern for memory performance. No systematic relations between neuronal cell densities of the right hippocampus and memory function were found, nor did left or right hippocampal pathology explain figural memory parameters. The results suggest that the overall pathological status of the left hippocampus - rather than a specific subfield pathology - is predictive for verbal memory in mTLE. The finding that figural memory parameters, although sensitive to right mTLE, were not related to neuronal cell densities of the right hippocampus, puts the left/right hippocampus verbal/nonverbal memory dichotomy into perspective. Copyright © 2013 Wiley Periodicals, Inc.

Continuous measurement of breast tumour hormone receptor expression: a comparison of two computational pathology platforms.

PubMed

Ahern, Thomas P; Beck, Andrew H; Rosner, Bernard A; Glass, Ben; Frieling, Gretchen; Collins, Laura C; Tamimi, Rulla M

2017-05-01

Computational pathology platforms incorporate digital microscopy with sophisticated image analysis to permit rapid, continuous measurement of protein expression. We compared two computational pathology platforms on their measurement of breast tumour oestrogen receptor (ER) and progesterone receptor (PR) expression. Breast tumour microarrays from the Nurses' Health Study were stained for ER (n=592) and PR (n=187). One expert pathologist scored cases as positive if ≥1% of tumour nuclei exhibited stain. ER and PR were then measured with the Definiens Tissue Studio (automated) and Aperio Digital Pathology (user-supervised) platforms. Platform-specific measurements were compared using boxplots, scatter plots and correlation statistics. Classification of ER and PR positivity by platform-specific measurements was evaluated with areas under receiver operating characteristic curves (AUC) from univariable logistic regression models, using expert pathologist classification as the standard. Both platforms showed considerable overlap in continuous measurements of ER and PR between positive and negative groups classified by expert pathologist. Platform-specific measurements were strongly and positively correlated with one another (r≥0.77). The user-supervised Aperio workflow performed slightly better than the automated Definiens workflow at classifying ER positivity (AUC Aperio =0.97; AUC Definiens =0.90; difference=0.07, 95% CI 0.05 to 0.09) and PR positivity (AUC Aperio =0.94; AUC Definiens =0.87; difference=0.07, 95% CI 0.03 to 0.12). Paired hormone receptor expression measurements from two different computational pathology platforms agreed well with one another. The user-supervised workflow yielded better classification accuracy than the automated workflow. Appropriately validated computational pathology algorithms enrich molecular epidemiology studies with continuous protein expression data and may accelerate tumour biomarker discovery. 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/.

The Number of Pathologically Positive Lymph Nodes and Pathological Tumor Depth Predicts Prognosis in Patients With Poorly Differentiated Squamous Cell Carcinoma of the Oral Cavity

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

Kang, Chung-Jan; Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Lin, Chien-Yu

2011-11-15

Purpose: The objective of this retrospective study was twofold: (1) to investigate prognostic factors for clinical outcomes in patients with poorly differentiated oral cavity squamous cell carcinoma and (2) to identify specific prognostic subgroups that may help to guide treatment decisions. Methods and Materials: We examined 102 patients with poorly differentiated oral cavity squamous cell carcinoma. All patients were followed for at least 24 months after surgery or until death. The 5-year rates of local control, neck control, distant metastasis, disease-free, disease-specific, and overall survival served as main outcome measures. Results: The 5-year rates were as follows: local control (79%),more » neck control (64%), distant metastases (27%), disease-free survival (48%), disease-specific survival (52%), and overall survival (42%). Multivariable analysis showed that the number of pathologically positive nodes ({>=}4 vs. {<=}3) was a significant predictor of neck control, distant metastasis, and disease-free, disease-specific, and overall survival rates. In addition, the presence of tumor depth of {>=}11 mm (vs. <11 mm) was a significant predictor of distant metastasis, disease-specific survival, and overall survival rates. The combination of the two predictors (26.5%, 27/102) was independently associated with poorer neck control (p = 0.0319), distant metastasis (p < 0.0001), and disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p < 0.0001) rates. Conclusions: In patients with poorly differentiated oral cavity squamous cell carcinoma, the presence of at least 4 pathologically positive lymph nodes and of a pathological tumor depth {>=}11 mm identifies a subset of subjects with poor clinical outcomes. Patients carrying both risk factors are suitable candidates for the development of novel therapeutic approaches.« less

[Cervical Pap smear in an epidemiologically exposed population: ideas, facts and arguments].

PubMed

Doris, B; Boyer, L; Lavoué, V; Riou, F; Henno, S; Tas, P; Sévène, L; Levêque, J

2014-01-01

To analyse the prevalence of abnormal papsmears in a primary care center and the screening practices. Single-center retrospective study on 1,430 FCU performed in 1,251 patients between January 2009 and December 2011 with analysis of demographic, clinical and epidemiological chararacteristics of the women, and the monitoring of the patients with pathological papsmears. The study population was predominantly young (under 25), unmarried, nulliparous, and using contraception. Among the 1,244 FCU, nearly 90% of them were interpretable with the junction area interested. Nine percent were pathological with mainly ASC-US and L-SIL (3.5% and 4.5%) with no difference between more and less than 25years. Two factors were significantly associated with the presence of pathological papsmear: first intercourse before age 14 and smoking more than 10 cigarettes per day. Monitoring of patients with a pathological papsmear showed that 33% of patients had not an appropriate follow-up especially younger patients. To perform papsmear before 25 years because the patient has associated high risk HPV co-factors does not appear justified by the severity or frequency of cytological lesions, especially as it increases the financial cost and is responsible of potential deleterious actions such as conizations probably excessive among the youngest patients. Personalized monitoring of these patients with a pathological papsmear is required. The French practice recommendations on cervical cancer screening (first screening at age 25, 26 years cytological control then every 3 years up to 65 years in patients who have or have had sex) deserve to be applied in young and disadvantaged patients. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Processing of fallopian tube, ovary, and endometrial surgical pathology specimens: A survey of U.S. laboratory practices.

PubMed

Samimi, Goli; Trabert, Britton; Duggan, Máire A; Robinson, Jennifer L; Coa, Kisha I; Waibel, Elizabeth; Garcia, Edna; Minasian, Lori M; Sherman, Mark E

2018-03-01

Many high-grade serous carcinomas initiate in fallopian tubes as serous tubal intraepithelial carcinoma (STIC), a microscopic lesion identified with specimen processing according to the Sectioning and Extensive Examination of the Fimbria protocol (SEE-Fim). Given that the tubal origin of these cancers was recently recognized, we conducted a survey of pathology practices to assess processing protocols that are applied to gynecologic surgical pathology specimens in clinical contexts in which finding STIC might have different implications. We distributed a survey electronically to the American Society for Clinical Pathology list-serve to determine practice patterns and compared results between practice types by chi-square (χ2) tests for categorical variables. Free text comments were qualitatively reviewed. Survey responses were received from 159 laboratories (72 academic, 87 non-academic), which reported diverse specimen volumes and percentage of gynecologic samples. Overall, 74.1% of laboratories reported performing SEE-Fim for risk-reducing surgical specimens (82.5% academic versus 65.7% non-academic, p < 0.05). In specimens from surgery for benign indications in which initial microscopic sections showed an unanticipated suspicious finding, 75.9% of laboratories reported using SEE-Fim to process the remainder of the specimen (94.8% academic versus 76.4% non-academic, p < 0.01), and 84.6% submitted the entire fimbriae. Changes in the theories of pathogenesis of high-grade serous carcinoma have led to implementation of pathology specimen processing protocols that include detailed analysis of the fallopian tubes. These results have implications for interpreting trends in cancer incidence data and considering the feasibility of developing a bank of gynecologic tissues containing STIC or early cancer precursors. Published by Elsevier Inc.

Multi-channel MRI segmentation of eye structures and tumors using patient-specific features

PubMed Central

Ciller, Carlos; De Zanet, Sandro; Kamnitsas, Konstantinos; Maeder, Philippe; Glocker, Ben; Munier, Francis L.; Rueckert, Daniel; Thiran, Jean-Philippe

2017-01-01

Retinoblastoma and uveal melanoma are fast spreading eye tumors usually diagnosed by using 2D Fundus Image Photography (Fundus) and 2D Ultrasound (US). Diagnosis and treatment planning of such diseases often require additional complementary imaging to confirm the tumor extend via 3D Magnetic Resonance Imaging (MRI). In this context, having automatic segmentations to estimate the size and the distribution of the pathological tissue would be advantageous towards tumor characterization. Until now, the alternative has been the manual delineation of eye structures, a rather time consuming and error-prone task, to be conducted in multiple MRI sequences simultaneously. This situation, and the lack of tools for accurate eye MRI analysis, reduces the interest in MRI beyond the qualitative evaluation of the optic nerve invasion and the confirmation of recurrent malignancies below calcified tumors. In this manuscript, we propose a new framework for the automatic segmentation of eye structures and ocular tumors in multi-sequence MRI. Our key contribution is the introduction of a pathological eye model from which Eye Patient-Specific Features (EPSF) can be computed. These features combine intensity and shape information of pathological tissue while embedded in healthy structures of the eye. We assess our work on a dataset of pathological patient eyes by computing the Dice Similarity Coefficient (DSC) of the sclera, the cornea, the vitreous humor, the lens and the tumor. In addition, we quantitatively show the superior performance of our pathological eye model as compared to the segmentation obtained by using a healthy model (over 4% DSC) and demonstrate the relevance of our EPSF, which improve the final segmentation regardless of the classifier employed. PMID:28350816

Differentiation between malignant and benign thyroid nodules and stratification of papillary thyroid cancer with aggressive histological features: Whole-lesion diffusion-weighted imaging histogram analysis.

PubMed

Hao, Yonghong; Pan, Chu; Chen, WeiWei; Li, Tao; Zhu, WenZhen; Qi, JianPin

2016-12-01

To explore the usefulness of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) derived from reduced field-of-view (r-FOV) diffusion-weighted imaging (DWI) in differentiating malignant and benign thyroid nodules and stratifying papillary thyroid cancer (PTC) with aggressive histological features. This Institutional Review Board-approved, retrospective study included 93 patients with 101 pathologically proven thyroid nodules. All patients underwent preoperative r-FOV DWI at 3T. The whole-lesion ADC assessments were performed for each patient. Histogram-derived ADC parameters between different subgroups (pathologic type, extrathyroidal extension, lymph node metastasis) were compared. Receiver operating characteristic curve analysis was used to determine optimal histogram parameters in differentiating benign and malignant nodules and predicting aggressiveness of PTC. Mean ADC, median ADC, 5 th percentile ADC, 25 th percentile ADC, 75 th percentile ADC, 95 th percentile ADC (all P < 0.001), and kurtosis (P = 0.001) were significantly lower in malignant thyroid nodules, and mean ADC achieved the highest AUC (0.919) with a cutoff value of 1842.78 × 10 -6 mm 2 /s in differentiating malignant and benign nodules. Compared to the PTCs without extrathyroidal extension, PTCs with extrathyroidal extension showed significantly lower median ADC, 5 th percentile ADC, and 25 th percentile ADC. The 5 th percentile ADC achieved the highest AUC (0.757) with cutoff value of 911.5 × 10 -6 mm 2 /s for differentiating between PTCs with and without extrathyroidal extension. Whole-lesion ADC histogram analysis might help to differentiate malignant nodules from benign ones and show the PTCs with extrathyroidal extension. J. Magn. Reson. Imaging 2016;44:1546-1555. © 2016 International Society for Magnetic Resonance in Medicine.

MRI-based assessment of the pineal gland in a large population of children aged 0-5 years and comparison with pineoblastoma: part II, the cystic gland.

PubMed

Sirin, Selma; de Jong, Marcus C; Galluzzi, Paolo; Maeder, Philippe; Brisse, Hervé J; Castelijns, Jonas A; de Graaf, Pim; Goericke, Sophia L

2016-07-01

Pineal cysts are a common incidental finding on brain MRI with resulting difficulties in differentiation between normal glands and pineal pathologies. The aim of this study was to assess the size and morphology of the cystic pineal gland in children (0-5 years) and compare the findings with published pineoblastoma cases. In this retrospective multicenter study, 257 MR examinations (232 children, 0-5 years) were evaluated regarding pineal gland size (width, height, planimetric area, maximal cyst(s) size) and morphology. We performed linear regression analysis with 99 % prediction intervals of gland size versus age for the size parameters. Results were compared with a recent meta-analysis of pineoblastoma by de Jong et al. Follow-up was available in 25 children showing stable cystic findings in 48 %, cyst size increase in 36 %, and decrease in 16 %. Linear regression analysis gave 99 % upper prediction bounds of 10.8 mm, 10.9 mm, 7.7 mm and 66.9 mm(2), respectively, for cyst size, width, height, and area. The slopes (size increase per month) of each parameter were 0.030, 0.046, 0.021, and 0.25, respectively. Most of the pineoblastomas showed a size larger than the 99 % upper prediction margin, but with considerable overlap between the groups. We presented age-adapted normal values for size and morphology of the cystic pineal gland in children aged 0 to 5 years. Analysis of size is helpful in discriminating normal glands from cystic pineal pathologies such as pineoblastoma. We also presented guidelines for the approach of a solid or cystic pineal gland in hereditary retinoblastoma patients.

Boredom proneness in pathological gambling.

PubMed

Blaszczynski, A; McConaghy, N; Frankova, A

1990-08-01

To test the hypothesis that pathological gamblers seek stimulation as a means of reducing aversive under-aroused states of boredom and/or depression, the Beck Depression Inventory, Zuckerman's Sensation Seeking Scale and a Boredom Proneness Scale were administered to 48 diagnosed pathological gamblers and a control group of 40 family physician patients. Analyses of variance showed pathological gamblers obtained significantly higher boredom proneness and depression scores than those of controls. That the Boredom Proneness Scale failed to correlate with the Zuckerman Boredom Susceptibility subscale suggested the two measure differing dimensions. Results indicated the possible existence of three subtypes of pathological gamblers, one group characterized by boredom, another by depression, and a third by a mixture of both depression and boredom.

Relationship between Enterobius vermicularis and the incidence of acute appendicitis.

PubMed

Ramezani, Mohammad Arash; Dehghani, Mahmoud Reza

2007-01-01

The objective of this study was to evaluate the relationship between Enterobius vermicularis and the occurrence of acute appendicitis. Over a ten year period of time, all appendix specimens received by the department of pathology were reviewed for pathologic changes and the existence of E. vermicularis. Logistic regression was carried out to determine the odds ratio (OR) of the relationship between E. vermicularis and acute appendicitis. A total of 5048 specimens were reviewed. E. vermicularis was found in 144 (2.9%) cases. After separating by sex and adjusting for age logistic regression analysis showed the OR of E. vermicularis appendiceal infestation was 1.275 (95% CI = 0.42-3.9) for males and 1.678 (95% CI = 0.61-4.65) for females. Age was an independent risk factor for acute appendicitis in males (OR = 1.01, 95% CI = 1.003-1.017) and females (OR = 1.012, 95% CI = 1.005-1.02).

Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone

PubMed Central

Im, Hyungsoon; Castro, Cesar M.; Shao, Huilin; Liong, Monty; Song, Jun; Pathania, Divya; Fexon, Lioubov; Min, Changwook; Avila-Wallace, Maria; Zurkiya, Omar; Rho, Junsung; Magaoay, Brady; Tambouret, Rosemary H.; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho

2015-01-01

The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resource-limited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffraction-based approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts. PMID:25870273

PORTR: Pre-Operative and Post-Recurrence Brain Tumor Registration

PubMed Central

Niethammer, Marc; Akbari, Hamed; Bilello, Michel; Davatzikos, Christos; Pohl, Kilian M.

2014-01-01

We propose a new method for deformable registration of pre-operative and post-recurrence brain MR scans of glioma patients. Performing this type of intra-subject registration is challenging as tumor, resection, recurrence, and edema cause large deformations, missing correspondences, and inconsistent intensity profiles between the scans. To address this challenging task, our method, called PORTR, explicitly accounts for pathological information. It segments tumor, resection cavity, and recurrence based on models specific to each scan. PORTR then uses the resulting maps to exclude pathological regions from the image-based correspondence term while simultaneously measuring the overlap between the aligned tumor and resection cavity. Embedded into a symmetric registration framework, we determine the optimal solution by taking advantage of both discrete and continuous search methods. We apply our method to scans of 24 glioma patients. Both quantitative and qualitative analysis of the results clearly show that our method is superior to other state-of-the-art approaches. PMID:24595340

hCG - related molecules and their measurement.

PubMed

Szczerba, Anna; Białas, Piotr; Pięta, Paweł Piotr; Jankowska, Anna

2016-01-01

Measurements of human chorionic gonadotropin (hCG) synthesized by trophoblast cells is a powerful tool of pregnancy monitoring. It was showed that similarly to pregnancy also trophoblastic and nontrophoblastic malignancies produce variety of hCG molecules. In urine and serum of both pregnant women and tumors patients a fifteen various forms of hCG, such as: regular hCG, hyperglycosylated hCG and predominant hyperglycosylated hCG free β, were identified. These forms might be useful in order to recognize between physiological and pathological pregnancies as well as cancers. Even the presence of these different hormone variants is well documented the commercially available biochemical tests detecting hCG failed to identified and distinguish among these forms. Especially hard is to identify glycan chains linked to heterodimer. Thus, a detailed analysis of hCG-related molecules produced during physiological and pathological condition, together with a new tests development are needed.

Jung, Winnicott and the divided psyche.

PubMed

Saban, Mark

2016-06-01

In his review of Memories Dreams Reflections, Winnicott diagnosed Jung as suffering from a psychic split, and characterized the content and the structure of analytical psychology as primarily moulded and conditioned by Jung's own defensive quest for a 'self that he could call his own'. This pathologizing analysis continues to be endorsed by contemporary Jungian writers. In this paper I attempt to show that Winnicott's critique is fundamentally misguided because it derives from a psychoanalytic model of the psyche, a model that regards all dissociation as necessarily pathological. I argue that Jung's understanding of the psyche differs radically from this model, and further, that it conforms by and large to the kind of dissociative model that we find in the writings of Frederic Myers, William James and Theodor Flournoy. I conclude that a fruitful relationship between psychoanalysis and analytical psychology must depend upon an awareness of these important differences between the two psychic models. © 2016, The Society of Analytical Psychology.

Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone.

PubMed

Im, Hyungsoon; Castro, Cesar M; Shao, Huilin; Liong, Monty; Song, Jun; Pathania, Divya; Fexon, Lioubov; Min, Changwook; Avila-Wallace, Maria; Zurkiya, Omar; Rho, Junsung; Magaoay, Brady; Tambouret, Rosemary H; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho

2015-05-05

The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resource-limited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffraction-based approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts.

Feasibility of using negative ultrasonography results of axillary lymph nodes to predict sentinel lymph node metastasis in breast cancer patients.

PubMed

Chen, Xue; He, Yingjian; Wang, Jiwei; Huo, Ling; Fan, Zhaoqing; Li, Jinfeng; Xie, Yuntao; Wang, Tianfeng; Ouyang, Tao

2018-06-14

Knowledge of the pathology of axillary lymph nodes (ALN) in breast cancer patients is critical for determining their treatment. Ultrasound is the best noninvasive evaluation for the ALN status. However, the correlation between negative ultrasound results and the sentinel lymph nodes (SLN) pathology remains unknown. To test the hypothesis that negative ultrasound results of ALN predict the negative pathology results of SLN in breast cancer patients, we assessed the association between ALN ultrasonography-negative results and the SLN pathology in 3115 patients with breast cancer recruited between October 2010 and April 2016 from a single cancer center, prospective database. Of these patients who met the inclusion criteria, 2317 (74.4%) had no SLN pathological metastasis. In the univariate analysis, other 798 patient with positive SLN tended to be under age 40 and premenopausal, having large tumor sizes (>2 cm), higher histological grade of primary tumor, positive hormone receptors, and negative HER-2 status (P < .05 for all). In the multivariate analysis, menstrual status, tumor size, ER status and histological types of primary tumor remained to be independent predictors for SLN pathological metastasis. The area under curve (AUC) was 0.658 (95% CI = 0.637-0.679), P > .05. In conclusion, only a 74.4% consistency between ALN ultrasonography-negative results and negative pathological SLN results, although menstrual status, tumor size, histologic subtypes of primary tumor and ER status were found to be statistically independent predictors of positive SLN among patients negative for ALN ultrasonography. Therefore, the present study suggests that negative ultrasound results of ALN do not adequately predict the negative pathology results of SLN in breast cancer patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Measurement of the hyperelastic properties of 44 pathological ex vivo breast tissue samples

NASA Astrophysics Data System (ADS)

O'Hagan, Joseph J.; Samani, Abbas

2009-04-01

The elastic and hyperelastic properties of biological soft tissues have been of interest to the medical community. There are several biomedical applications where parameters characterizing such properties are critical for a reliable clinical outcome. These applications include surgery planning, needle biopsy and brachtherapy where tissue biomechanical modeling is involved. Another important application is interpreting nonlinear elastography images. While there has been considerable research on the measurement of the linear elastic modulus of small tissue samples, little research has been conducted for measuring parameters that characterize the nonlinear elasticity of tissues included in tissue slice specimens. This work presents hyperelastic measurement results of 44 pathological ex vivo breast tissue samples. For each sample, five hyperelastic models have been used, including the Yeoh, N = 2 polynomial, N = 1 Ogden, Arruda-Boyce, and Veronda-Westmann models. Results show that the Yeoh, polynomial and Ogden models are the most accurate in terms of fitting experimental data. The results indicate that almost all of the parameters corresponding to the pathological tissues are between two times to over two orders of magnitude larger than those of normal tissues, with C11 showing the most significant difference. Furthermore, statistical analysis indicates that C02 of the Yeoh model, and C11 and C20 of the polynomial model have very good potential for cancer classification as they show statistically significant differences for various cancer types, especially for invasive lobular carcinoma. In addition to the potential for use in cancer classification, the presented data are very important for applications such as surgery planning and virtual reality based clinician training systems where accurate nonlinear tissue response modeling is required.

Diffuse lung uptake (DLU) on Ga-67 scintigraph: Clinical, radiologic and pathologic correlation

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

Sy, W.M.; Seo, I.S.; Vieira, J.

1985-05-01

Review, analysis and correlation (clinical, radiologic and pathologic) of 29 consecutive adults (16 drug addicts and/or homosexuals) with DLU on Ga-67 scintigraph were made. Diffuse increased uptake of at least 75% of both lungs was considered as DLU. WFOF cameras were used to obtain 24 to 96 hr. scintigraphs after IV injection of 3-5 mCi of Ga-67 citrate. In 26, tissue diagnosis established: pneumocystis carinii (PC) 15, miliary tuberculosis (TB) 3, sarcoidosis (SR) 3, drug-induced toxicity 2, and toxoplasmosis (TX), primary hyperparathyroidism and nonspecific lymphocytic pneumonia-one each. In two with breast and one with esophageal carcinomas, no lung tissue diagnosismore » was sought. Concurrent chest x-rays were negative in 16, but in 7/16, lung infiltrate was later documented. An average of 31 days elapsed before x-rays became positive in four with PC, 7 days in two with TB, and 22 days in one with TX. In 13, concurrent x-rays showed lung infiltrate, but in 6, only subtle, localized rather than diffuse infiltrate was noted. Fourteen of 29 had at least two Ga-67 studies. In 12 (7 PC, 2 TB, 3 SR) of 14 whose repeat studies showed significant to total disappearance of DLU, all did well clinically. In two whose initial studies were negative or equivocal, they became clinically worse when the repeat study showed DLU. In three others (2 PC, 1 TX) who died, their single studies recorded intense DLU. DLU on gallium scintigraph indicated a variety of pathology. In 55.2%, gallium scintigraph predated x-ray findings by a few days to weeks. In 20.3%, x-ray findings were only subtle or localized. Scintigraphic changes correlated well with the clinical courses in various diseases.« less

Analysis of the research sample collections of Uppsala biobank.

PubMed

Engelmark, Malin T; Beskow, Anna H

2014-10-01

Uppsala Biobank is the joint and only biobank organization of the two principals, Uppsala University and Uppsala University Hospital. Biobanks are required to have updated registries on sample collection composition and management in order to fulfill legal regulations. We report here the results from the first comprehensive and overall analysis of the 131 research sample collections organized in the biobank. The results show that the median of the number of samples in the collections was 700 and that the number of samples varied from less than 500 to over one million. Blood samples, such as whole blood, serum, and plasma, were included in the vast majority, 84.0%, of the research sample collections. Also, as much as 95.5% of the newly collected samples within healthcare included blood samples, which further supports the concept that blood samples have fundamental importance for medical research. Tissue samples were also commonly used and occurred in 39.7% of the research sample collections, often combined with other types of samples. In total, 96.9% of the 131 sample collections included samples collected for healthcare, showing the importance of healthcare as a research infrastructure. Of the collections that had accessed existing samples from healthcare, as much as 96.3% included tissue samples from the Department of Pathology, which shows the importance of pathology samples as a resource for medical research. Analysis of different research areas shows that the most common of known public health diseases are covered. Collections that had generated the most publications, up to over 300, contained a large number of samples collected systematically and repeatedly over many years. More knowledge about existing biobank materials, together with public registries on sample collections, will support research collaborations, improve transparency, and bring us closer to the goals of biobanks, which is to save and prolong human lives and improve health and quality of life.

Brain extraction from normal and pathological images: A joint PCA/Image-Reconstruction approach.

PubMed

Han, Xu; Kwitt, Roland; Aylward, Stephen; Bakas, Spyridon; Menze, Bjoern; Asturias, Alexander; Vespa, Paul; Van Horn, John; Niethammer, Marc

2018-08-01

Brain extraction from 3D medical images is a common pre-processing step. A variety of approaches exist, but they are frequently only designed to perform brain extraction from images without strong pathologies. Extracting the brain from images exhibiting strong pathologies, for example, the presence of a brain tumor or of a traumatic brain injury (TBI), is challenging. In such cases, tissue appearance may substantially deviate from normal tissue appearance and hence violates algorithmic assumptions for standard approaches to brain extraction; consequently, the brain may not be correctly extracted. This paper proposes a brain extraction approach which can explicitly account for pathologies by jointly modeling normal tissue appearance and pathologies. Specifically, our model uses a three-part image decomposition: (1) normal tissue appearance is captured by principal component analysis (PCA), (2) pathologies are captured via a total variation term, and (3) the skull and surrounding tissue is captured by a sparsity term. Due to its convexity, the resulting decomposition model allows for efficient optimization. Decomposition and image registration steps are alternated to allow statistical modeling of normal tissue appearance in a fixed atlas coordinate system. As a beneficial side effect, the decomposition model allows for the identification of potentially pathological areas and the reconstruction of a quasi-normal image in atlas space. We demonstrate the effectiveness of our approach on four datasets: the publicly available IBSR and LPBA40 datasets which show normal image appearance, the BRATS dataset containing images with brain tumors, and a dataset containing clinical TBI images. We compare the performance with other popular brain extraction models: ROBEX, BEaST, MASS, BET, BSE and a recently proposed deep learning approach. Our model performs better than these competing approaches on all four datasets. Specifically, our model achieves the best median (97.11) and mean (96.88) Dice scores over all datasets. The two best performing competitors, ROBEX and MASS, achieve scores of 96.23/95.62 and 96.67/94.25 respectively. Hence, our approach is an effective method for high quality brain extraction for a wide variety of images. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of Macroscopic Pathology Measurements With Magnetic Resonance Imaging and Assessment of Microscopic Pathology Extension for Colorectal Liver Metastases

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

Mendez Romero, Alejandra, E-mail: a.mendezromero@erasmusmc.nl; Verheij, Joanne; Dwarkasing, Roy S.

2012-01-01

Purpose: To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases. Methods and Materials: In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapymore » treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests. Results: Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (r{sub s} = 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (r{sub s} = 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (r{sub s} = 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (r{sub s} = 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm. Conclusions: MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins.« less

Pathology crossword competition: an active and easy way of learning pathology in undergraduate medical education.

PubMed

Htwe, T T; Sabaridah, I; Rajyaguru, K M; Mazidah, A M

2012-02-01

In line with the trend to engage students in active learning, it is imperative to introduce new strategies that make learning more interesting, especially in undergraduate curricula. This study aimed to determine students' performance and perception in pathology crosswords as an active way of learning and to assess their ability to memorise difficult terms in pathology. A crossword competition in pathology was conducted for two batches (year 2009 and 2010) of Phase 2 medical students in Malaysia. Crossword puzzles were prepared using an online application. Two sets of puzzles were prepared, with 20 questions for the assessment of general pathology and 20 for systemic pathology. The purpose was to compare the students' recent and remote memorising abilities, as general pathology was taught a year before proceeding to systemic pathology teaching. There were 12 groups per batch, with 8-10 students in a group. Survey questionnaires were used to assess the students' perception of the competition. Descriptive analysis was performed for comparison of performance. The mean score of correctly answered questions in general pathology was 12.75 and 11.50 in batch 2009 and 2010, respectively. The mean score for systemic pathology was 14.50 in 2009 and 13.83 in 2010. Students in the 2009 batch performed better, but this was not statistically significant (p-value > 0.05). A positive response was observed from the questionnaires. Applying crossword puzzles as a new strategy is a useful and easy way for undergraduate medical students to learn pathology.

Backscattering analysis of high frequency ultrasonic imaging for ultrasound-guided breast biopsy

NASA Astrophysics Data System (ADS)

Cummins, Thomas; Akiyama, Takahiro; Lee, Changyang; Martin, Sue E.; Shung, K. Kirk

2017-03-01

A new ultrasound-guided breast biopsy technique is proposed. The technique utilizes conventional ultrasound guidance coupled with a high frequency embedded ultrasound array located within the biopsy needle to improve the accuracy in breast cancer diagnosis.1 The array within the needle is intended to be used to detect micro- calcifications indicative of early breast cancers such as ductal carcinoma in situ (DCIS). Backscattering analysis has the potential to characterize tissues to improve localization of lesions. This paper describes initial results of the application of backscattering analysis of breast biopsy tissue specimens and shows the usefulness of high frequency ultrasound for the new biopsy related technique. Ultrasound echoes of ex-vivo breast biopsy tissue specimens were acquired by using a single-element transducer with a bandwidth from 41 MHz to 88 MHz utilizing a UBM methodology, and the backscattering coefficients were calculated. These values as well as B-mode image data were mapped in 2D and matched with each pathology image for the identification of tissue type for the comparison to the pathology images corresponding to each plane. Microcalcifications were significantly distinguished from normal tissue. Adenocarcinoma was also successfully differentiated from adipose tissue. These results indicate that backscattering analysis is able to quantitatively distinguish tissues into normal and abnormal, which should help radiologists locate abnormal areas during the proposed ultrasound-guided breast biopsy with high frequency ultrasound.

A pathologist-designed imaging system for anatomic pathology signout, teaching, and research.

PubMed

Schubert, E; Gross, W; Siderits, R H; Deckenbaugh, L; He, F; Becich, M J

1994-11-01

Pathology images are derived from gross surgical specimens, light microscopy, immunofluorescence, electron microscopy, molecular diagnostic gels, flow cytometry, image analysis data, and clinical laboratory data in graphic form. We have implemented a network of desktop personal computers (PCs) that allow us to easily capture, store, and retrieve gross and microscopic, anatomic, and research pathology images. System architecture involves multiple image acquisition and retrieval sites and a central file server for storage. The digitized images are conveyed via a local area network to and from image capture or display stations. Acquisition sites consist of a high-resolution camera connected to a frame grabber card in a 486-type personal computer, equipped with 16 MB (Table 1) RAM, a 1.05-gigabyte hard drive, and a 32-bit ethernet card for access to our anatomic pathology reporting system. We have designed a push-button workstation for acquiring and indexing images that does not significantly interfere with surgical pathology sign-out. Advantages of the system include the following: (1) Improving patient care: the availability of gross images at time of microscopic sign-out, verification of recurrence of malignancy from archived images, monitoring of bone marrow engraftment and immunosuppressive intervention after bone marrow/solid organ transplantation on repeat biopsies, and ability to seek instantaneous consultation with any pathologist on the network; (2) enhancing the teaching environment: building a digital surgical pathology atlas, improving the availability of images for conference support, and sharing cases across the network; (3) enhancing research: case study compilation, metastudy analysis, and availability of digitized images for quantitative analysis and permanent/reusable image records for archival study; and (4) other practical and economic considerations: storing case requisition images and hand-drawn diagrams deters the spread of gross room contaminants and results in considerable cost savings in photographic media for conferences, improved quality assurance by porting control stains across the network, and a multiplicity of other advantages that enhance image and information management in pathology.

Modeling 4D Pathological Changes by Leveraging Normative Models

PubMed Central

Wang, Bo; Prastawa, Marcel; Irimia, Andrei; Saha, Avishek; Liu, Wei; Goh, S.Y. Matthew; Vespa, Paul M.; Van Horn, John D.; Gerig, Guido

2016-01-01

With the increasing use of efficient multimodal 3D imaging, clinicians are able to access longitudinal imaging to stage pathological diseases, to monitor the efficacy of therapeutic interventions, or to assess and quantify rehabilitation efforts. Analysis of such four-dimensional (4D) image data presenting pathologies, including disappearing and newly appearing lesions, represents a significant challenge due to the presence of complex spatio-temporal changes. Image analysis methods for such 4D image data have to include not only a concept for joint segmentation of 3D datasets to account for inherent correlations of subject-specific repeated scans but also a mechanism to account for large deformations and the destruction and formation of lesions (e.g., edema, bleeding) due to underlying physiological processes associated with damage, intervention, and recovery. In this paper, we propose a novel framework that provides a joint segmentation-registration framework to tackle the inherent problem of image registration in the presence of objects not present in all images of the time series. Our methodology models 4D changes in pathological anatomy across time and and also provides an explicit mapping of a healthy normative template to a subject’s image data with pathologies. Since atlas-moderated segmentation methods cannot explain appearance and locality pathological structures that are not represented in the template atlas, the new framework provides different options for initialization via a supervised learning approach, iterative semisupervised active learning, and also transfer learning, which results in a fully automatic 4D segmentation method. We demonstrate the effectiveness of our novel approach with synthetic experiments and a 4D multimodal MRI dataset of severe traumatic brain injury (TBI), including validation via comparison to expert segmentations. However, the proposed methodology is generic in regard to different clinical applications requiring quantitative analysis of 4D imaging representing spatio-temporal changes of pathologies. PMID:27818606

Chronic inflammatory disease and osteopathy: a systematic review.

PubMed

Cicchitti, Luca; Martelli, Marta; Cerritelli, Francesco

2015-01-01

Chronic inflammatory diseases (CID) are globally highly prevalent and characterized by severe pathological medical conditions. Several trials were conducted aiming at measuring the effects of manipulative therapies on patients affected by CID. The purpose of this review was to explore the extent to which osteopathic manipulative treatment (OMT) can be benefi-cial in medical conditions also classified as CID. This review included any type of experimental study which enrolled sub-jects with CID comparing OMT with any type of control procedure. The search was conducted on eight databases in January 2014 using a pragmatic literature search approach. Two independent re-viewers conducted study selection and data extraction for each study. The risk of bias was evaluated according to the Cochrane methods. Heterogeneity was assessed and meta-analysis performed where possible. 10 studies met the inclusion criteria for this review enrolling 386 subjects. The search identified six RCTs, one laboratory study, one cross-over pilot studies, one observation-al study and one case control pilot study. Results suggest a potential effect of osteopathic medicine on patients with medical pathologies associated with CID (in particular Chronic Obstructive Pul-monary Disease (COPD), Irritable Bowel Syndrome, Asthma and Peripheral Arterial Disease) com-pared to no treatment or sham therapy although data remain elusive. Moreover one study showed possible effects on arthritis rat model. Meta-analysis was performed for COPD studies only show-ing no effect of any type of OMT applied versus control. No major side effects were reported by those receiving OMT. The present systematic review showed inconsistent data on the effect of OMT in the treatment of medical conditions potentially associated with CID, however the OMT appears to be a safe approach. Further more robust trials are needed to determine the direction and magnitude of the effect of OMT and to generalize favorable results.

Infectious hematopoietic necrosis virus (IHNV) outbreak in farmed rainbow trout in Iran: Viral isolation, pathological findings, molecular confirmation, and genetic analysis.

PubMed

Ahmadivand, Sohrab; Soltani, Mehdi; Mardani, Karim; Shokrpoor, Sara; Hassanzadeh, Reza; Ahmadpoor, Mehran; Rahmati-Holasoo, Hooman; Meshkini, Saeid

2017-02-02

Infectious hematopoietic necrosis virus (IHNV) is the etiological agent of a contagious disease (IHN) mainly in salmonid fish. In the present study, we isolated and identified IHNV in trout fry from Iranian trout farms with unexplained high mortality in 2016. The affected fry showed cumulative mortality of 90% with the gross pathological signs including exophthalmia and hemorrhage of the eye, skin darkening, abdominal distension, ulceration of the snout, and the visceral pallor and yellowish fluid in the intestine. Histopathological examination revealed marked necrosis in the anterior kidney, liver and spleen with the intracytoplasmic inclusion bodies in the liver sections. Also, intranuclear inclusion body and marginated chromatin were observable in the hematopoietic cells of the kidney. The homogenates tissues of infected fry induced IHNV-positive cytopathic effects (CPE) in EPC cells and confirmed by RT-PCR reactions and sequencing. Phylogenetic analysis revealed the Iranian IHNV isolates belonged to the European (E) genogroup with 100% identity to some Italian isolates. This is the first report of IHNV infection in farmed trout fry in Iran describing the viral isolation, clinical symptoms, histopathological findings, molecular confirmation, and genetic analysis suggestion of the specific country of origin. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative analysis of perceptual evaluation, acoustic analysis and indirect laryngoscopy for vocal assessment of a population with vocal complaint.

PubMed

Nemr, Kátia; Amar, Ali; Abrahão, Marcio; Leite, Grazielle Capatto de Almeida; Köhle, Juliana; Santos, Alexandra de O; Correa, Luiz Artur Costa

2005-01-01

As a result of technology evolution and development, methods of voice evaluation have changed both in medical and speech and language pathology practice. To relate the results of perceptual evaluation, acoustic analysis and medical evaluation in the diagnosis of vocal and/or laryngeal affections of the population with vocal complaint. Clinical prospective. 29 people that attended vocal health protection campaign were evaluated. They were submitted to perceptual evaluation (AFPA), acoustic analysis (AA), indirect laryngoscopy (LI) and telelaryngoscopy (TL). Correlations between medical and speech language pathology evaluation methods were established, verifying possible statistical signification with the application of Fischer Exact Test. There were statistically significant results in the correlation between AFPA and LI, AFPA and TL, LI and TL. This research study conducted in a vocal health protection campaign presented correlations between speech language pathology evaluation and perceptual evaluation and clinical evaluation, as well as between vocal affection and/or laryngeal medical exams.

Studies on the alterations in haematological indices, micronuclei induction and pathological marker enzyme activities in Channa punctatus (spotted snakehead) perciformes, channidae exposed to thermal power plant effluent.

PubMed

Javed, Mehjbeen; Ahmad, Irshad; Ahmad, Ajaz; Usmani, Nazura; Ahmad, Masood

2016-01-01

The present study was conducted to assess the toxicity of thermal power plant effluent containing heavy metals (Fe > Cu > Zn > Mn > Ni > Co > Cr) on haematological indices, micronuclei, lobed nuclei and activity of pathological marker enzymes [alkaline phosphatase (ALP), aspartate transferase (AST), alanine transferase (ALT) and creatine kinase (CK)] in Channa punctatus. Total erythrocyte count (-54.52 %), hemoglobin (-36.98 %), packed cell volume (-36.25 %), mean corpuscular hemoglobin concentration (-1.41 %) and oxygen (O2) carrying capacity (-37.04 %) declined significantly over reference fish, however total leukocyte count (+25.43 %), mean corpuscular hemoglobin (+33.52 %) and mean corpuscular volume (+35.49 %) showed elevation. High frequency of micronuclei (1133.3 %) and lobed nuclei (150 %) were observed in exposed fish which may indicate mutagenesis. Activities of pathological marker enzymes ALP, AST, ALT and CK increased significantly in serum of exposed fish. The ratio of ALT: AST in exposed fish was beyond 1 which indicates manifestation of pathological processes. These biomarkers show that fish have macrocytic hypochromic anemia. Leukocytosis showed general defence response against heavy metal toxicity and marker enzymes showed tissue degeneration. In conclusion, thermal power plant effluent has strong potential to induce micronuclei, tissue pathology, making the fish anemic, weak, stressed and vulnerable to diseases.

Talk in Interaction in the Speech-Language Pathology Clinic: Bringing Theory to Practice through Discourse

ERIC Educational Resources Information Center

Leaby, Margaret M.; Walsh, Irene P.

2008-01-01

The importance of learning about and applying clinical discourse analysis to enhance the talk in interaction in the speech-language pathology clinic is discussed. The benefits of analyzing clinical discourse to explicate therapy dynamics are described.

Ivacaftor and sinonasal pathology in a cystic fibrosis patient with genotype deltaF508/S1215N.

PubMed

Vreede, C L; Berkhout, M C; Sprij, A J; Fokkens, W J; Heijerman, H G M

2015-05-01

In patients with Cystic Fibrosis and a type III mutation, ivacaftor (Kalydeco(®), Vertex) can increase the opening time of the CFTR channel and improve chloride transport. Research showed significant improvement of lung function and increase in weight following ivacaftor use. However, ivacaftor showed to have adverse events on the sinonasal system as well, such as upper respiratory tract infections, nasal congestion and headaches. This case report showed a positive effect of ivacaftor on the sinonasal pathology in a 17 year old patient with CF. After 5 months of ivacaftor use, the CT-sinus showed complete resolution of the opacification of the paranasal sinuses and a decrease in symptoms of sinonasal disease. This positive effect of ivacaftor on sinonasal pathology seems promising, therefore more research is needed to evaluate the effect of ivacaftor on the upper airways in CF. Copyright © 2014. Published by Elsevier B.V.

An improved high order texture features extraction method with application to pathological diagnosis of colon lesions for CT colonography

NASA Astrophysics Data System (ADS)

Song, Bowen; Zhang, Guopeng; Lu, Hongbing; Wang, Huafeng; Han, Fangfang; Zhu, Wei; Liang, Zhengrong

2014-03-01

Differentiation of colon lesions according to underlying pathology, e.g., neoplastic and non-neoplastic, is of fundamental importance for patient management. Image intensity based textural features have been recognized as a useful biomarker for the differentiation task. In this paper, we introduce high order texture features, beyond the intensity, such as gradient and curvature, for that task. Based on the Haralick texture analysis method, we introduce a virtual pathological method to explore the utility of texture features from high order differentiations, i.e., gradient and curvature, of the image intensity distribution. The texture features were validated on database consisting of 148 colon lesions, of which 35 are non-neoplastic lesions, using the random forest classifier and the merit of area under the curve (AUC) of the receiver operating characteristics. The results show that after applying the high order features, the AUC was improved from 0.8069 to 0.8544 in differentiating non-neoplastic lesion from neoplastic ones, e.g., hyperplastic polyps from tubular adenomas, tubulovillous adenomas and adenocarcinomas. The experimental results demonstrated that texture features from the higher order images can significantly improve the classification accuracy in pathological differentiation of colorectal lesions. The gain in differentiation capability shall increase the potential of computed tomography (CT) colonography for colorectal cancer screening by not only detecting polyps but also classifying them from optimal polyp management for the best outcome in personalized medicine.

Prognostic factors for keratocystic odontogenic tumor (odontogenic keratocyst): analysis of clinico-pathologic and immunohistochemical findings in cysts treated by enucleation.

PubMed

Kuroyanagi, Norio; Sakuma, Hidenori; Miyabe, Satoru; Machida, Junichiro; Kaetsu, Atsuo; Yokoi, Motoo; Maeda, Hatsuhiko; Warnakulasuriya, Saman; Nagao, Toru; Shimozato, Kazuo

2009-04-01

The purpose of this study was to determine prognostic factors for the recurrence of keratocystic odontogenic tumors (KCOTs) following simple enucleation by examining clinico-pathologic and immunohistochemical findings. Following enucleation, the frequency of recurrence among 32 subjects diagnosed with KCOT was analyzed for tumor site, radiographic and histologic features, and immunopositivity for Ki-67 and p53. Keratocystic odontogenic tumors in four out of 32 subjects (12.5%) recurred during the follow-up period (median: 33 months, range: 7-114 months). Three out of four subjects (75.0%) among recurrent group showed high expression of Ki-67 (LI >10%) in basal layer and four (4/28; 14.3%) among non-recurrence group (P = 0.025). Expression of p53 among non-recurrent group was observed in 11 subjects (11/28; 39.3%), and in three subjects (3/4; 75.0%) among the recurrent group (P = 0.295). Hazard risk for the recurrence of KCOT was 4.02 (95% CI 1.42-18.14) for high Ki-67 expression in the basal layer by the Cox proportional hazard model (P = 0.009). In our study, none of the other clinico-pathologic variables were associated with the recurrence of KCOT. The results suggested that the evaluation of Ki-67 expression in KCOT at the time of pathological diagnosis might be helpful for consideration of appropriate adjunctive surgical procedures to avoid a recurrence and may serve as a prognostic marker.

Aversive Startle Potentiation and Fear Pathology: Mediating Role of Threat Sensitivity and Moderating Impact of Depression

PubMed Central

Yancey, James R.; Vaidyanathan, Uma; Patrick, Christopher J.

2015-01-01

Enhanced startle during exposure to unpleasant cues (aversive startle potentiation; ASP) appears in the RDoC matrix as a physiological index of acute threat response. Increased ASP has been linked to focal fear disorders and to scale measures of dispositional fearfulness (i.e., threat sensitivity; THT+). However, some studies have reported reduced ASP for fear pathology accompanied by major depressive disorder (MDD) or pervasive distress. The current study evaluated whether (a) THT+ as indexed by reported dispositional fearfulness mediates the relationship between fear disorders (when unaccompanied by depression) and ASP, and (b) depression moderates relations of THT+ and fear disorders with ASP. Fear disorder participants without MDD showed enhanced ASP whereas those with MDD (or other distress conditions) showed evidence of reduced ASP. Continuous THT+ scores also predicted ASP, and this association: (a) was likewise moderated by depression/distress, and (b) accounted for the relationship between ASP and fear pathology without MDD. These findings point to a role for the RDoC construct of acute threat, operationalized dispositionally, in enhanced ASP shown by individuals with fear pathology unaccompanied by distress pathology. PMID:25448265

Computational pathology of pre-treatment biopsies identifies lymphocyte density as a predictor of response to neoadjuvant chemotherapy in breast cancer.

PubMed

Ali, H Raza; Dariush, Aliakbar; Provenzano, Elena; Bardwell, Helen; Abraham, Jean E; Iddawela, Mahesh; Vallier, Anne-Laure; Hiller, Louise; Dunn, Janet A; Bowden, Sarah J; Hickish, Tamas; McAdam, Karen; Houston, Stephen; Irwin, Mike J; Pharoah, Paul D P; Brenton, James D; Walton, Nicholas A; Earl, Helena M; Caldas, Carlos

2016-02-16

There is a need to improve prediction of response to chemotherapy in breast cancer in order to improve clinical management and this may be achieved by harnessing computational metrics of tissue pathology. We investigated the association between quantitative image metrics derived from computational analysis of digital pathology slides and response to chemotherapy in women with breast cancer who received neoadjuvant chemotherapy. We digitised tissue sections of both diagnostic and surgical samples of breast tumours from 768 patients enrolled in the Neo-tAnGo randomized controlled trial. We subjected digital images to systematic analysis optimised for detection of single cells. Machine-learning methods were used to classify cells as cancer, stromal or lymphocyte and we computed estimates of absolute numbers, relative fractions and cell densities using these data. Pathological complete response (pCR), a histological indicator of chemotherapy response, was the primary endpoint. Fifteen image metrics were tested for their association with pCR using univariate and multivariate logistic regression. Median lymphocyte density proved most strongly associated with pCR on univariate analysis (OR 4.46, 95 % CI 2.34-8.50, p < 0.0001; observations = 614) and on multivariate analysis (OR 2.42, 95 % CI 1.08-5.40, p = 0.03; observations = 406) after adjustment for clinical factors. Further exploratory analyses revealed that in approximately one quarter of cases there was an increase in lymphocyte density in the tumour removed at surgery compared to diagnostic biopsies. A reduction in lymphocyte density at surgery was strongly associated with pCR (OR 0.28, 95 % CI 0.17-0.47, p < 0.0001; observations = 553). A data-driven analysis of computational pathology reveals lymphocyte density as an independent predictor of pCR. Paradoxically an increase in lymphocyte density, following exposure to chemotherapy, is associated with a lack of pCR. Computational pathology can provide objective, quantitative and reproducible tissue metrics and represents a viable means of outcome prediction in breast cancer. ClinicalTrials.gov NCT00070278 ; 03/10/2003.

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.

Pathological speech signal analysis and classification using empirical mode decomposition.

PubMed

Kaleem, Muhammad; Ghoraani, Behnaz; Guergachi, Aziz; Krishnan, Sridhar

2013-07-01

Automated classification of normal and pathological speech signals can provide an objective and accurate mechanism for pathological speech diagnosis, and is an active area of research. A large part of this research is based on analysis of acoustic measures extracted from sustained vowels. However, sustained vowels do not reflect real-world attributes of voice as effectively as continuous speech, which can take into account important attributes of speech such as rapid voice onset and termination, changes in voice frequency and amplitude, and sudden discontinuities in speech. This paper presents a methodology based on empirical mode decomposition (EMD) for classification of continuous normal and pathological speech signals obtained from a well-known database. EMD is used to decompose randomly chosen portions of speech signals into intrinsic mode functions, which are then analyzed to extract meaningful temporal and spectral features, including true instantaneous features which can capture discriminative information in signals hidden at local time-scales. A total of six features are extracted, and a linear classifier is used with the feature vector to classify continuous speech portions obtained from a database consisting of 51 normal and 161 pathological speakers. A classification accuracy of 95.7 % is obtained, thus demonstrating the effectiveness of the methodology.

Microvessel prediction in H&E Stained Pathology Images using fully convolutional neural networks.

PubMed

Yi, Faliu; Yang, Lin; Wang, Shidan; Guo, Lei; Huang, Chenglong; Xie, Yang; Xiao, Guanghua

2018-02-27

Pathological angiogenesis has been identified in many malignancies as a potential prognostic factor and target for therapy. In most cases, angiogenic analysis is based on the measurement of microvessel density (MVD) detected by immunostaining of CD31 or CD34. However, most retrievable public data is generally composed of Hematoxylin and Eosin (H&E)-stained pathology images, for which is difficult to get the corresponding immunohistochemistry images. The role of microvessels in H&E stained images has not been widely studied due to their complexity and heterogeneity. Furthermore, identifying microvessels manually for study is a labor-intensive task for pathologists, with high inter- and intra-observer variation. Therefore, it is important to develop automated microvessel-detection algorithms in H&E stained pathology images for clinical association analysis. In this paper, we propose a microvessel prediction method using fully convolutional neural networks. The feasibility of our proposed algorithm is demonstrated through experimental results on H&E stained images. Furthermore, the identified microvessel features were significantly associated with the patient clinical outcomes. This is the first study to develop an algorithm for automated microvessel detection in H&E stained pathology images.

Visuoperception test predicts pathologic diagnosis of Alzheimer disease in corticobasal syndrome

PubMed Central

Tierney, Michael; Wassermann, Eric M.; Spina, Salvatore; Oblak, Adrian L.; Ghetti, Bernardino; Grafman, Jordan; Huey, Edward

2014-01-01

Objective: To use the Visual Object and Space Perception Battery (VOSP) to distinguish Alzheimer disease (AD) from non-AD pathology in corticobasal syndrome (CBS). Methods: This clinicopathologic study assessed 36 patients with CBS on the VOSP. All were autopsied. The primary dependent variable was a binary pathologic outcome: patients with CBS who had primary pathologic diagnosis of AD (CBS-AD, n = 10) vs patients with CBS without primary pathologic diagnosis of AD (CBS-nonAD, n = 26). We also determined sensitivity and specificity of individual VOSP subtests. Results: Patients with CBS-AD had younger onset (54.5 vs 63.6 years, p = 0.001) and lower memory scores on the Mattis Dementia Rating Scale–2 (16 vs 22 points, p = 0.003). Failure on the VOSP subtests Incomplete Letters (odds ratio [OR] 11.5, p = 0.006), Position Discrimination (OR 10.86, p = 0.008), Number Location (OR 12.27, p = 0.026), and Cube Analysis (OR 45.71 p = 0.0001) had significantly greater odds of CBS-AD than CBS-nonAD. These associations remained when adjusting for total Mattis Dementia Rating score, disease laterality, education, age, and sex. Receiver operating characteristic curves demonstrated significant accuracy for Incomplete Letters and all VOSP spatial subtests, with Cube Analysis performing best (area under the curve 0.91, p = 0.0004). Conclusions: In patients with CBS, failure on specific VOSP subtests is associated with greater odds of having underlying AD. There may be preferential involvement of the dorsal stream in CBS-AD. Classification of evidence: This study provides Class II evidence that some subtests of the VOSP accurately distinguish patients with CBS-AD from those without AD pathology (e.g., Cube Analysis sensitivity 100%, specificity 77%). PMID:24991033

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

PubMed

Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer's disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

PubMed Central

Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer’s disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing. PMID:24271328

[Analysis of heat transfer in the biological tissue layer with distributed system of blood vessels].

PubMed

Bogatov, N M; Pelipenko, O N

2005-09-01

Processes of heat transfer in the skin layer with blood vessels were investigated using mathematical modeling. Analysis of influence of a pathological state of blood vessels on heterogeneity of thermal field of the skin surface was carried out. For each site of body surface, there is a certain difference of temperature between normal and pathological sites, being specific for differential diagnosis of diseases of dermal and hypodermic vessels.

Unresolved mourning, supernatural beliefs and dissociation: a mediation analysis.

PubMed

Thomson, Paula; Jaque, S Victoria

2014-01-01

Unresolved mourning is marked by disorganized behavior and states of mind. In this study, we speculated that pathological dissociation would mediate the effects of unresolved mourning on supernatural beliefs. This hypothesis was determined based on findings that indicate an association between higher levels of dissociation, stronger beliefs in the supernatural and unresolved mourning. We examined two groups of participants, one classified as non-unresolved (non-U) (n = 56) and the other as unresolved (n = 26) (U) with respect to past loss/trauma as measured by the Adult Attachment Interview (AAI). Two self-report instruments were administered to measure supernatural beliefs and dissociation. As hypothesized, the multivariate analysis of variance indicated mean differences between the two groups. The unresolved group had greater belief in the supernatural and more pathological dissociative processes. The mediation analysis demonstrated that pathological dissociation fully mediated the effects of unresolved mourning on supernatural beliefs.

Gender differences in exercise dependence and eating disorders in young adults: a path analysis of a conceptual model.

PubMed

Meulemans, Shelli; Pribis, Peter; Grajales, Tevni; Krivak, Gretchen

2014-11-05

The purpose of our study was to study the prevalence of exercise dependence (EXD) among college students and to investigate the role of EXD and gender on exercise behavior and eating disorders. Excessive exercise can become an addiction known as exercise dependence. In our population of 517 college students, 3.3% were at risk for EXD and 8% were at risk for an eating disorder. We used Path analysis the simplest case of Structural Equation Modeling (SEM) to investigate the role of EXD and exercise behavior on eating disorders. We observed a small direct effect from gender to eating disorders. In females we observed significant direct effect between exercise behavior (r = -0.17, p = 0.009) and EXD (r = 0.34, p < 0.001) on eating pathology. We also observed an indirect effect of exercise behavior on eating pathology (r = 0.16) through EXD (r = 0.48, r2 = 0.23, p < 0.001). In females the total variance of eating pathology explained by the SEM model was 9%. In males we observed a direct effect between EXD (r = 0.23, p < 0.001) on eating pathology. We also observed indirect effect of exercise behavior on eating pathology (r = 0.11) through EXD (r = 0.49, r2 = 0.24, p < 0.001). In males the total variance of eating pathology explained by the SEM model was 5%.

Meeting Report: Tissue-based Image Analysis.

PubMed

Saravanan, Chandra; Schumacher, Vanessa; Brown, Danielle; Dunstan, Robert; Galarneau, Jean-Rene; Odin, Marielle; Mishra, Sasmita

2017-10-01

Quantitative image analysis (IA) is a rapidly evolving area of digital pathology. Although not a new concept, the quantification of histological features on photomicrographs used to be cumbersome, resource-intensive, and limited to specialists and specialized laboratories. Recent technological advances like highly efficient automated whole slide digitizer (scanner) systems, innovative IA platforms, and the emergence of pathologist-friendly image annotation and analysis systems mean that quantification of features on histological digital images will become increasingly prominent in pathologists' daily professional lives. The added value of quantitative IA in pathology includes confirmation of equivocal findings noted by a pathologist, increasing the sensitivity of feature detection, quantification of signal intensity, and improving efficiency. There is no denying that quantitative IA is part of the future of pathology; however, there are also several potential pitfalls when trying to estimate volumetric features from limited 2-dimensional sections. This continuing education session on quantitative IA offered a broad overview of the field; a hands-on toxicologic pathologist experience with IA principles, tools, and workflows; a discussion on how to apply basic stereology principles in order to minimize bias in IA; and finally, a reflection on the future of IA in the toxicologic pathology field.

Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial.

PubMed

Feng, Yan-Ru; Zhu, Yuan; Liu, Lu-Ying; Wang, Wei-Hu; Wang, Shu-Lian; Song, Yong-Wen; Wang, Xin; Tang, Yuan; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Zhang, Shi-Ping; Liu, Xin-Fan; Yu, Zi-Hao; Li, Ye-Xiong; Jin, Jing

2016-05-03

The aim of this study is to present an interim analysis of a phase III trial (NCT00714077) of postoperative concurrent capecitabine and radiotherapy with or without oxaliplatin for pathological stage II and III rectal cancer. Patients with pathologically confirmed stage II and III rectal cancer were randomized to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). The 3-year DFS rate was 73.9% in the Capox-RT group and 71.6% in the Cap-RT group (HR 0.92, p = 0.647), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence and distant metastasis between the two groups (p > 0.05). More grade 3-4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group (38.1% vs. 29.2%, p = 0.041). Inclusion of oxaliplatin in the capecitabine-based postoperative regimen did not improve DFS but increased toxicities for pathological stage II and III rectal cancer in this interim analysis.

Discordance in pathology report after central pathology review: Implications for breast cancer adjuvant treatment.

PubMed

Orlando, Laura; Viale, Giuseppe; Bria, Emilio; Lutrino, Eufemia Stefania; Sperduti, Isabella; Carbognin, Luisa; Schiavone, Paola; Quaranta, Annamaria; Fedele, Palma; Caliolo, Chiara; Calvani, Nicola; Criscuolo, Mario; Cinieri, Saverio

2016-12-01

Pathological predictive factors are the most important markers when selecting early breast cancer adjuvant therapy. In randomized clinical trials the variability in pathology report after central pathology review is noteworthy. We evaluated the discordance rate (DR) and inter-rater agreement between local and central histopathological report and the clinical implication on treatment decision. A retrospective analysis was conducted in a series of consecutive early breast cancer tumors diagnosed by local pathologists and subsequently reviewed at the Pathology Division of European Institute of Oncology. The inter-rater agreement (k) between local and central pathology was calculated for Ki-67, grading, hormone receptors (ER/PgR) and HER2/neu. The Bland-Altman plots were derived to determine discrepancies in Ki-67, ER and PgR. DR was calculated for ER/PgR and HER2. From 2007 to 2013, 187 pathology specimens from 10 Cancer Centers were reviewed. Substantial agreement was observed for ER (k0.612; 95% CI, 0538-0.686), PgR (k0.659; 95% CI, 0580-0.737), Ki-67 (k0.609; 95% CI, 0.534-0.684) and grading (k0.669; 95% CI, 0.569-0.769). Moderate agreement was found for HER2 (k0.546; 95% CI, 0444-0.649). DR was 9.5% (negativity to positivity) and 31.7% (positivity to negativity) for HER2 and 26.2% (negativity to positivity) and 12.5% (positivity to negativity) for ER/PgR. According to changes in Her2 and ER/PgR status, 23 (12.2%) and 33 (17.6%) systemic prescription were respectively modified. In our retrospective analysis, central pathological review has a significant impact in the decision-making process in early breast cancer, as shown in clinical trials. Further studies are warranted to confirm these provocative results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spontaneous correction of pathologic tooth migration and reduced infrabony pockets following nonsurgical periodontal therapy: a case report.

PubMed

Sato, Shuichi; Ujiie, Hisashi; Ito, Koichi

2004-10-01

This case report describes the spontaneous correction of pathologic tooth migration and reduced infrabony pockets after nonsurgical periodontal therapy. A 3-mm diastema between the maxillary incisors was closed completely, and the mandibular teeth, which had migrated pathologically, returned to the optimal position. Clinical evaluation showed a significant reduction in probing depth, with increased clinical attachment and bone deposition demonstrated radiologically.

Evaluation of an open source tool for indexing and searching enterprise radiology and pathology reports

NASA Astrophysics Data System (ADS)

Kim, Woojin; Boonn, William

2010-03-01

Data mining of existing radiology and pathology reports within an enterprise health system can be used for clinical decision support, research, education, as well as operational analyses. In our health system, the database of radiology and pathology reports exceeds 13 million entries combined. We are building a web-based tool to allow search and data analysis of these combined databases using freely available and open source tools. This presentation will compare performance of an open source full-text indexing tool to MySQL's full-text indexing and searching and describe implementation procedures to incorporate these capabilities into a radiology-pathology search engine.

[Study on the relationship between ultrasonographic features of papillary thyroid carcinoma and central cervical lymph node metastasis].

PubMed

Wang, X Q; Wei, W; Wei, X; Xu, Y; Wang, H L; Xing, X J; Zhang, S

2018-03-23

Objective: To investigate the correlation between ultrasonographic features of papillary thyroid carcinoma and central cervical lymph node metastasis. Methods: We retrospectively analyzed 486 patients with papillary thyroid carcinoma(PTC), pathologically confirmed after surgery in Tianjin Medical University Cancer Institute & Hospital. All patients were divided into central cervical lymph node metastasis group and non-metastasis group. No lateral cervical lymph node metastasis was found in preoperative ultrasonography and postoperative pathology. The characteristics of the ultrasound was observed and analyzed. Results: 297 out of 486 patients with papillary thyroid carcinomahad central metastasis, and the other 189 cases did not. Take pathology results as a standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of preoperative ultrasound diagnosis in PTC patients with central cervical lymph node metastasis were 35.3%, 88.6%, 83.2%, 47.4%, 56.6%, respectively. Univariate analysis showed that multi-focus, taller-than-wide, diameter>1 cm, located in the lower pole, ill-defined margin, hypoechogenicity, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma were significantly associated with central cervical lymph node metastasis (all P <0.05). Multivariate analysis showed that diameter>1 cm, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma became independent risk factors of central cervical neck lymph node metastasis (all P <0.05). Conclusions: Preoperative description of ultrasonographical features has important value to assess central cervical lymph node metastasis in patients with papillary thyroid carcinoma. More information could be provided for clinical treatment. When the papillary thyroid carcinoma presented as diameter>1 cm, micro-calcification, and capsule invasion more than 1/4 perimeter of, there will be a greater risk of central cervical lymph node metastasis, and we shall suggest prophylactic central lymph cervical node dissection.

Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy

PubMed Central

Panaite, Petrica-Adrian; Kuntzer, Thierry; Gourdon, Geneviève; Lobrinus, Johannes Alexander; Barakat-Walter, Ibtissam

2013-01-01

SUMMARY Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1). Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory problems. Using pressure plethysmography, we assessed the breathing function in control mice and DMSXL mice generated after large expansions of the CTG repeat in successive generations of DM1 transgenic mice. Statistical analysis of breathing function measurements revealed a significant decrease in the most relevant respiratory parameters in DMSXL mice, indicating impaired respiratory function. Histological and morphometric analysis showed pathological changes in diaphragmatic muscle of DMSXL mice, characterized by an increase in the percentage of type I muscle fibers, the presence of central nuclei, partial denervation of end-plates (EPs) and a significant reduction in their size, shape complexity and density of acetylcholine receptors, all of which reflect a possible breakdown in communication between the diaphragmatic muscles fibers and the nerve terminals. Diaphragm muscle abnormalities were accompanied by an accumulation of mutant DMPK RNA foci in muscle fiber nuclei. Moreover, in DMSXL mice, the unmyelinated phrenic afferents are significantly lower. Also in these mice, significant neuronopathy was not detected in either cervical phrenic motor neurons or brainstem respiratory neurons. Because EPs are involved in the transmission of action potentials and the unmyelinated phrenic afferents exert a modulating influence on the respiratory drive, the pathological alterations affecting these structures might underlie the respiratory impairment detected in DMSXL mice. Understanding mechanisms of respiratory deficiency should guide pharmaceutical and clinical research towards better therapy for the respiratory deficits associated with DM1. PMID:23180777

Analysis of peptidyl-propyl-cis/trans isomerase 1 (PIN1) gene -842(G > C) and -667(T > C) polymorphic variants in relation to breast cancer risk and clinico-pathological parameters.

PubMed

Naidu, Rakesh; Har, Yip C; Taib, Nur A M

2011-10-01

The purpose of this study was to investigate the association between the peptidyl-propyl-cis/trans isomerase 1 (PIN1) -842(G > C) and -667(T > C) polymorphic variants and breast cancer risk among Malaysian ethnic groups namely the Malays, Chinese and Indians, as well as clinico-pathological characteristics of the patients. The polymerase chain reaction-restriction fragment length polymorphism was used to genotype 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy. The distribution of -842(G > C) and -667(T > C) genotypes and alleles frequencies between breast cancer cases and normal individuals showed lack of statistical significance among the Malays (p > 0.05), Chinese (p > 0.05) and Indians (p > 0.05), respectively. Multivariate logistic regression analysis showed that the Malay, Chinese and Indian women who were -842CC homozygotes (p = 0.198, 0.089, 0.620), -842GC heterozygotes (p = 0.492, 0.176, 0.377) and -842C allele carriers (P = 0.226, 0.059, 0.669), respectively, were not associated with breast cancer risk. Furthermore Malay, Chinese and Indian women who were heterozygous (p = 0.777, 0.319, 0.710) and homozygous (p = 0.864, 0.986, 0.954) for -667C allele or carriers of -667C allele (p = 0.977, 0.915, 0.880), respectively, were not associated with an increased risk of breast cancer. None of the -842C and -667C allele genotypes were significantly associated with the clinico-pathological characteristics. Our findings suggest that the polymorphic variants of -842(G > C) and -667(T > C) genes may not appear to have an influence on breast cancer risk among Malaysian Malay, Chinese and Indian women.

IGF1R signalling in testicular germ cell tumour cells impacts on cell survival and acquired cisplatin resistance.

PubMed

Selfe, Joanna; Goddard, Neil C; McIntyre, Alan; Taylor, Kathryn R; Renshaw, Jane; Popov, Sergey D; Thway, Khin; Summersgill, Brenda; Huddart, Robert A; Gilbert, Duncan C; Shipley, Janet M

2018-02-01

Testicular germ cell tumours (TGCTs) are the most frequent malignancy and cause of death from solid tumours in the 20- to 40-year age group. Although most cases show sensitivity to cis-platinum-based chemotherapy, this is associated with long-term toxicities and chemo-resistance. Roles for receptor tyrosine kinases other than KIT are largely unknown in TGCT. We therefore conducted a phosphoproteomic screen and identified the insulin growth factor receptor-1 (IGF1R) as both highly expressed and activated in TGCT cell lines representing the nonseminomatous subtype. IGF1R was also frequently expressed in tumour samples from patients with nonseminomas. Functional analysis of cell line models showed that long-term shRNA-mediated IGF1R silencing leads to apoptosis and complete ablation of nonseminoma cells with active IGF1R signalling. Cell lines with high levels of IGF1R activity also showed reduced AKT signalling in response to decreased IGF1R expression as well as sensitivity to the small-molecule IGF1R inhibitor NVP-AEW541. These results were in contrast to those in the seminoma cell line TCAM2 that lacked IGF1R signalling via AKT and was one of the two cell lines least sensitive to the IGF1R inhibitor. The dependence on IGF1R activity in the majority of nonseminomas parallels the known role of IGF signalling in the proliferation, migration, and survival of primordial germ cells, the putative cell of origin for TGCT. Upregulation of IGF1R expression and signalling was also found to contribute to acquired cisplatin resistance in an in vitro nonseminoma model, providing a rationale for targeting IGF1R in cisplatin-resistant disease. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Automated Radiology-Pathology Module Correlation Using a Novel Report Matching Algorithm by Organ System.

PubMed

Dane, Bari; Doshi, Ankur; Gfytopoulos, Soterios; Bhattacharji, Priya; Recht, Michael; Moore, William

2018-05-01

Radiology-pathology correlation is time-consuming and is not feasible in most clinical settings, with the notable exception of breast imaging. The purpose of this study was to determine if an automated radiology-pathology report pairing system could accurately match radiology and pathology reports, thus creating a feedback loop allowing for more frequent and timely radiology-pathology correlation. An experienced radiologist created a matching matrix of radiology and pathology reports. These matching rules were then exported to a novel comprehensive radiology-pathology module. All distinct radiology-pathology pairings at our institution from January 1, 2016 to July 1, 2016 were included (n = 8999). The appropriateness of each radiology-pathology report pairing was scored as either "correlative" or "non-correlative." Pathology reports relating to anatomy imaged in the specific imaging study were deemed correlative, whereas pathology reports describing anatomy not imaged with the particular study were denoted non-correlative. Overall, there was 88.3% correlation (accuracy) of the radiology and pathology reports (n = 8999). Subset analysis demonstrated that computed tomography (CT) abdomen/pelvis, CT head/neck/face, CT chest, musculoskeletal CT (excluding spine), mammography, magnetic resonance imaging (MRI) abdomen/pelvis, MRI brain, musculoskeletal MRI (excluding spine), breast MRI, positron emission tomography (PET), breast ultrasound, and head/neck ultrasound all demonstrated greater than 91% correlation. When further stratified by imaging modality, CT, MRI, mammography, and PET demonstrated excellent correlation (greater than 96.3%). Ultrasound and non-PET nuclear medicine studies demonstrated poorer correlation (80%). There is excellent correlation of radiology imaging reports and appropriate pathology reports when matched by organ system. Rapid, appropriate radiology-pathology report pairings provide an excellent opportunity to close feedback loop to the interpreting radiologist. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

An early look at the Organ Procurement and Transplantation Network explant pathology form data.

PubMed

Harper, Ann M; Edwards, Erick; Washburn, W Kenneth; Heimbach, Julie

2016-06-01

In April 2012, the Organ Procurement and Transplantation Network (OPTN) implemented an online explant pathology form for recipients of liver transplantation who received additional wait-list priority for their diagnosis of hepatocellular carcinoma (HCC). The purpose of the form was to standardize the data being reported to the OPTN, which had been required since 2002 but were submitted to the OPTN in a variety of formats via facsimile. From April 2012 to December 2014, over 4500 explant forms were submitted, allowing for detailed analysis of the characteristics of the explanted livers. Data from the explant pathology forms were used to assess agreement with pretransplant imaging. Explant data were also used to assess the risk of recurrence. Of those with T2 priority, 55.7% were found to be stage T2 on explant. Extrahepatic spread (odds ratio [OR] = 6.8; P < 0.01), poor tumor differentiation (OR = 2.8; P < 0.01), microvascular invasion (OR = 2.6; P < 0.01), macrovascular invasion (OR = 3.2; P < 0.01), and whether the Milan stage based on the number and size of tumors on the explant form was T4 (OR = 2.4; P < 0.01) were the strongest predictors of recurrence. In conclusion, this analysis confirms earlier findings that showed an incomplete agreement between pretransplant imaging and posttransplant pathology in terms of HCC staging, though the number of patients with both no pretransplant treatment and no tumor in the explant was reduced from 20% to <1%. In addition, several factors were identified (eg, tumor burden, age, sex, region, ablative therapy, alpha-fetoprotein, Milan stage, vascular invasion, satellite lesions, etc.) that were predictive of HCC recurrence, allowing for more targeted surveillance of high-risk recipients. Continued evaluation of these data will help shape future guidelines or policy recommendations. Liver Transplantation 22 757-764 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

R.E.N.A.L. Nephrometry Score: A Preoperative Risk Factor Predicting the Fuhrman Grade of Clear-Cell Renal Carcinoma

PubMed Central

Chen, Shao-Hao; Wu, Yu-Peng; Li, Xiao-Dong; Lin, Tian; Guo, Qing-Yong; Chen, Ye-Hui; Huang, Jin-Bei; Wei, Yong; Xue, Xue-Yi; Zheng, Qing-Shui; Xu, Ning

2017-01-01

Objective: The purpose of this study was to evaluate the efficacy and feasibility of the R.E.N.A.L. Nephrometry Score to postoperatively predict high-grade clear-cell renal carcinoma (ccRCC). Methods: The study included 288 patients diagnosed with ccRCC who had complete CT/CTA data and R.E.N.A.L. Nephrometry Scores and underwent renal surgery at our center between January 2012 and December 2015. The relationship between the pathological grade of renal masses and R.E.N.A.L. Nephrometry Score was evaluated. Results: Univariate analysis indicated that diagnostic modality, cystic necrosis, enlargement of the regional lymph node, distant metastasis, clinical T stage, TNM stage, surgical modality, tumor size, nearness of the tumor to the collecting system or sinus, total Nephrometry Score and individual anatomic descriptor components were significantly associated with postoperative tumor grade (P < 0.05). Multivariate analysis showed that tumor size, the maximal diameter (R score), exophytic/endophytic properties (E score) and the location relative to the polar lines (L score) were independent prognostic factors to preoperatively predicting ccRCC pathological grade. The areas under the ROC curve with respect to the multi-parameter regression model (0.935, 95%CI: 0.904-0.966), tumor size (0.901, 95%CI: 0.866-0.937), R score (0.868, 95%CI: 0.825-0.911), E score (0.511, 95%CI: 0.442-0.581) and L score (0.842, 95%CI: 0.791-0.892) were calculated and compared. Conclusion: Tumor size, as well as R, E, and L scores were independent prognostic factors for high-grade pathology. Lager tumor sizes and higher R, E and L scores were more likely to be associated with high-grade pathological outcomes. Thus, the R.E.N.A.L. Score is of practical significance in facilitating urologists to make therapeutic decisions. PMID:29151960

IMPACT OF STAGE MIGRATION AND PRACTICE CHANGES ON HIGH RISK PROSTATE CANCER: RESULTS FROM PATIENTS TREATED WITH RADICAL PROSTATECTOMY OVER THE LAST TWO DECADES

PubMed Central

Fossati, N.; Passoni, N. M.; Moschini, M.; Gandaglia, G.; Larcher, A.; Freschi, M.; Guazzoni, G.; Sjoberg, D. D.; Vickers, A. J.; Montorsi, F.; Briganti, A.

2016-01-01

Background Phenotype of prostate cancer at diagnosis has changed through the years. We aim to evaluate the impact of year of surgery on clinical, pathologic and oncologic outcomes of high-risk prostate cancer patients. Patients and methods We evaluated 1,033 clinically high-risk patients, defined as the presence of at least one of the following risk factors: pre-operative prostate specific antigen (PSA) level >20 ng/ml, and/or clinical stage ≥T3, and/or biopsy Gleason score ≥8. Patients were treated between 1990 and 2013 at a single Institution. Year-per-year trends of clinical and pathologic characteristics were examined. Multivariable Cox regression analysis was used to test the relationship between year of surgery and oncologic outcomes. Results We observed a decrease over time in the proportion of high-risk patients with a pre-operative PSA level >20 ng/ml or clinical stage cT3. An opposite trend was seen for biopsy Gleason score ≥8. We observed a considerable increase in the median number of lymph nodes removed that was associated with an increased rate of LNI. At multivariable Cox regression analysis, year of surgery was associated with a reduced risk of biochemical recurrence (HR per 5-year: 0.90; 95% CI: 0.84–0.96; p=0.01) and distant metastasis (HR per 5-year: 0.91; 95% CI: 0.83–0.99; p=0.039), after adjusting for age, pre-operative PSA, pathologic stage, lymph node invasion, surgical margin status, and pathological Gleason score. Conclusions In this single center study, an increased diagnosis of localized and less extensive high-grade prostate cancer was observed over the last two decades. High-risk patients selected for radical prostatectomy showed better cancer control over time. Better definitions of what constitutes high-risk prostate cancer among contemporary patients are needed. PMID:25787671

Tissue Doppler Imaging can be useful to distinguish pathological from physiological left ventricular hypertrophy: a study in master athletes and mild hypertensive subjects

PubMed Central

Galanti, Giorgio; Toncelli, Loira; Del Furia, Francesca; Stefani, Laura; Cappelli, Brunello; De Luca, Alessio; Vono, Maria Concetta Roberta

2009-01-01

Background Transthoracic echocardiography left ventricular wall thickness is often increased in master athletes and it results by intense physical training. Left Ventricular Hypertrophy can also be due to a constant pressure overload. Conventional Pulsed Wave (PW) Doppler analysis of diastolic function sometimes fails to distinguish physiological from pathological LVH. The aim of this study is to evaluate the role of Pulsed Wave Tissue Doppler Imaging in differentiating pathological from physiological LVH in the middle-aged population. Methods we selected a group of 80 master athletes, a group of 80 sedentary subjects with essential hypertension and an apparent normal diastolic function at standard PW Doppler analysis. The two groups were comparable for increased left ventricular wall thickness and mass index (134.4 ± 19.7 vs 134.5 ± 22.1 gr/m2; p > .05). Diastolic function indexes using the PW technique were in the normal range for both. Results Pulsed Wave TDI study of diastolic function immediately distinguished the two groups. While in master athletes the diastolic TDI-derived parameters remained within normal range (E' 9.4 ± 3.1 cm/sec; E/E' 7.8 ± 2.1), in the hypertensive group these parameters were found to be constantly altered, with mean values and variation ranges always outside normal validated limits (E' 7.2 ± 2.4 cm/sec; E/E' 10.6 ± 3.2), and with E' and E/E' statistically different in the two groups (p < .001). Conclusion Our study showed that the TDI technique can be an easy and validated method to assess diastolic function in differentiating normal from pseudonormal diastolic patterns and it can distinguish physiological from pathological LVH emphasizing the eligibility certification required by legal medical legislation as in Italy. PMID:19845938

The Pathogenic Role of Low Range Repeats in SCA17.

PubMed

Shin, Jung Hwan; Park, Hyeyoung; Ehm, Gwan Hee; Lee, Woong Woo; Yun, Ji Young; Kim, Young Eun; Lee, Jee-Young; Kim, Han-Joon; Kim, Jong-Min; Jeon, Beom Seok; Park, Sung-Sup

2015-01-01

SCA17 is an autosomal dominant cerebellar ataxia with expansion of the CAG/CAA trinucleotide repeats in the TATA-binding protein (TBP) gene. SCA17 can have various clinical presentations including parkinsonism, ataxia, chorea and dystonia. SCA17 is diagnosed by detecting the expanded CAG repeats in the TBP gene; however, in the literature, pathologic repeat numbers as low as 41 overlap with normal repeat numbers. The subjects in this study included patients with involuntary movement disorders such as cerebellar ataxia, parkinsonism, chorea and dystonia who visited Seoul National University Hospital between Jan. 2006 and Apr. 2014 and were screened for SCA17. Those who were diagnosed with other genetic diseases or nondegenerative diseases were excluded. DNA from healthy subjects who did not have a family history of parkinsonism, ataxia, psychiatric symptoms, chorea or dystonia served as the control. In total, 5242 chromosomes from 2099 patients and 522 normal controls were analyzed. The total number of patients included in the analysis was 2099 (parkinsonism, 1706; ataxia, 345; chorea, 37; and dystonia, 11). In the normal control, up to 44 repeats were found. In the 44 repeat group, there were 7 (0.3%) patients and 1 (0.2%) normal control. In 43 repeat group, there were 8 (0.4%) patients and 2 (0.4%) normal controls. In the 42 repeat group, there were 16 (0.8%) patients and 3 (0.6%) normal controls. In 41 repeat group, there were 48 (2.3%) patients and 8 (1.5%) normal controls. Considering the overlaps and non-significant differences in allelic frequencies between the patients and the normal controls with low-expansions, we could not determine a definitive cutoff value for the pathologic CAG repeat number of SCA17. Because the statistical analysis between the normal controls and patients with low range expansions failed to show any differences so far, we must consider that clinical cases with low range expansions could be idiopathic movement disorders showing coincidental CAG/CAA expansions. Thus, we need to reconsider the pathologic role of low range expansions (41-42). Long term follow up and comprehensive investigations using autopsy and imaging studies in patients and controls with low range expansions are necessary to determine the cutoff value for the pathologic CAG repeat number of SCA17.

Authors' Reply.

PubMed

Li, Marilyn M; Datto, Michael; Duncavage, Eric J; Kulkarni, Shashikant; Lindeman, Neal I; Roy, Somak; Tsimberidou, Apostolia M; Vnencak-Jones, Cindy L; Wolff, Daynna J; Younes, Anas; Nikiforova, Marina N

2018-01-01

Authors' Reply to the Letter to the Editor by Montgomery et al (Identification of Germline Variants in Tumor Genomic Sequencing Analysis. J Mol Diagn 2017, 19:XXXX-XXXX). Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Micro-Raman spectroscopy of tissue samples for oral pathology follow-up monitoring

NASA Astrophysics Data System (ADS)

Delfino, I.; Camerlingo, C.; Zenone, F.; Perna, G.; Capozzi, V.; Cirillo, N.; Gaeta, G. M.; Lepore, M.

2010-04-01

An "in vitro" study of Raman spectra from oral human tissues is reported in order to the develop a diagnostic method suitable for "in vivo" oral pathology follow-up. The investigated pathology is Pemphigus Vulgaris (PV) for which new techniques for guiding and monitoring therapy would be particularly useful. Raman spectra were obtained in the wavenumber regions from 1000 to 1800 cm-1 and 2700 to 3200 cm-1 from tissues from patients at different stages of pathology (active PV, under therapy and in PV remission stage) as confirmed by histopathological and immunofluorescence analysis. Differences in the spectra depending on tissue illness stage arise in 1150-1250 cm-1 (amide III) and 1420-1450 cm-1 (CH3 deformation) regions and around 1650 cm-1 (amide I) and 2930 cm-1 (CH3 symmetric stretch). A wavelet deconvolution procedure was applied to the spectra for better discriminating among the three different stages of illness and a linear regression analysis was used to fully exploit the content of information of Raman spectra.

An optimal transportation approach for nuclear structure-based pathology.

PubMed

Wang, Wei; Ozolek, John A; Slepčev, Dejan; Lee, Ann B; Chen, Cheng; Rohde, Gustavo K

2011-03-01

Nuclear morphology and structure as visualized from histopathology microscopy images can yield important diagnostic clues in some benign and malignant tissue lesions. Precise quantitative information about nuclear structure and morphology, however, is currently not available for many diagnostic challenges. This is due, in part, to the lack of methods to quantify these differences from image data. We describe a method to characterize and contrast the distribution of nuclear structure in different tissue classes (normal, benign, cancer, etc.). The approach is based on quantifying chromatin morphology in different groups of cells using the optimal transportation (Kantorovich-Wasserstein) metric in combination with the Fisher discriminant analysis and multidimensional scaling techniques. We show that the optimal transportation metric is able to measure relevant biological information as it enables automatic determination of the class (e.g., normal versus cancer) of a set of nuclei. We show that the classification accuracies obtained using this metric are, on average, as good or better than those obtained utilizing a set of previously described numerical features. We apply our methods to two diagnostic challenges for surgical pathology: one in the liver and one in the thyroid. Results automatically computed using this technique show potentially biologically relevant differences in nuclear structure in liver and thyroid cancers.

An optimal transportation approach for nuclear structure-based pathology

PubMed Central

Wang, Wei; Ozolek, John A.; Slepčev, Dejan; Lee, Ann B.; Chen, Cheng; Rohde, Gustavo K.

2012-01-01

Nuclear morphology and structure as visualized from histopathology microscopy images can yield important diagnostic clues in some benign and malignant tissue lesions. Precise quantitative information about nuclear structure and morphology, however, is currently not available for many diagnostic challenges. This is due, in part, to the lack of methods to quantify these differences from image data. We describe a method to characterize and contrast the distribution of nuclear structure in different tissue classes (normal, benign, cancer, etc.). The approach is based on quantifying chromatin morphology in different groups of cells using the optimal transportation (Kantorovich-Wasserstein) metric in combination with the Fisher discriminant analysis and multidimensional scaling techniques. We show that the optimal transportation metric is able to measure relevant biological information as it enables automatic determination of the class (e.g. normal vs. cancer) of a set of nuclei. We show that the classification accuracies obtained using this metric are, on average, as good or better than those obtained utilizing a set of previously described numerical features. We apply our methods to two diagnostic challenges for surgical pathology: one in the liver and one in the thyroid. Results automatically computed using this technique show potentially biologically relevant differences in nuclear structure in liver and thyroid cancers. PMID:20977984

Comparative analysis of lentiviral vectors and modular protein nanovectors for traumatic brain injury gene therapy

PubMed Central

Negro-Demontel, María Luciana; Saccardo, Paolo; Giacomini, Cecilia; Yáñez-Muñoz, Rafael Joaquín; Ferrer-Miralles, Neus; Vazquez, Esther; Villaverde, Antonio; Peluffo, Hugo

2014-01-01

Traumatic brain injury (TBI) remains as one of the leading causes of mortality and morbidity worldwide and there are no effective treatments currently available. Gene therapy applications have emerged as important alternatives for the treatment of diverse nervous system injuries. New strategies are evolving with the notion that each particular pathological condition may require a specific vector. Moreover, the lack of detailed comparative studies between different vectors under similar conditions hampers the selection of an ideal vector for a given pathological condition. The potential use of lentiviral vectors versus several modular protein-based nanovectors was compared using a controlled cortical impact model of TBI under the same gene therapy conditions. We show that variables such as protein/DNA ratio, incubation volume, and presence of serum or chloroquine in the transfection medium impact on both nanovector formation and transfection efficiency in vitro. While lentiviral vectors showed GFP protein 1 day after TBI and increased expression at 14 days, nanovectors showed stable and lower GFP transgene expression from 1 to 14 days. No toxicity after TBI by any of the vectors was observed as determined by resulting levels of IL-1β or using neurological sticky tape test. In fact, both vector types induced functional improvement per se. PMID:26015985

Salivary flow rate and pH in patients with oral pathologies.

PubMed

Foglio-Bonda, P L; Brilli, K; Pattarino, F; Foglio-Bonda, A

2017-01-01

Determine salivary pH and flow rate (FR) in a sample of 164 patients who came to Oral Pathology ambulatory, 84 suffering from oral lesions and 80 without oral lesions. Another aim was to evaluate factors that influence salivary flow rate. Subjects underwent clinical examination and completed an anamnestic questionnaire in order to obtain useful information that was used to classify participants in different groups. Unstimulated whole saliva (UWS) was collected using the spitting method at 11:00 am. The FR was evaluated with the weighing technique and a portable pHmeter, equipped with a microelectrode, was used to measure pH. Both univariate and classification (single and Random Forest) analyses were performed. The data analysis showed that FR and pH showed significant differences (p < 0.001) between patients with oral lesions (FR = 0.336 mL/min, pH = 6.69) and the ones without oral lesions (FR = 0.492 mL/min, pH = 6.96). By Random Forest, oral lesions and antihypertensive drugs were ranked in the top two among the evaluated variables to discretize subjects with FR = 0.16 mL/min. Our study shows that there is a relationship between oral lesions, antihypertensive drugs and alteration of pH and FR.

Morphologically occult systemic mastocytosis in bone marrow: clinicopathologic features and an algorithmic approach to diagnosis.

PubMed

Reichard, Kaaren K; Chen, Dong; Pardanani, Animesh; McClure, Rebecca F; Howard, Matthew T; Kurtin, Paul J; Wood, Adam J; Ketterling, Rhett P; King, Rebecca L; He, Rong; Morice, William G; Hanson, Curtis A

2015-09-01

Bone marrow (BM) biopsy specimens involved by systemic mastocytosis (SM) typically show multifocal, compact, dense aggregates of spindled mast cells (MCs). However, some cases lack aggregate formation and fulfill the World Health Organization 2008 criteria for SM, based on minor criteria. We identified 26 BM cases of KIT D816V-mutated, morphologically occult SM in the BM. All patients had some combination of allergic/MC activating symptoms. Peripheral blood counts were generally normal. BM aspirates showed 5% or less MCs, which were only occasionally spindled. BM biopsy specimens showed no morphologic classic MC lesions. Tryptase immunohistochemistry (IHC) demonstrated interstitial, individually distributed MCs (up to 5%) with prominent spindling, lacking aggregate formation. MCs coexpressed CD25 by IHC and/or flow cytometry. Spindled MCs constituted more than 25% of total MCs in all cases and more than 50% in 20 of 26 cases. Morphologically occult involvement of normal-appearing BM by SM will be missed without appropriate clinical suspicion and pathologic evaluation by tryptase and CD25 IHC and KIT D816V mutation analysis. On the basis of these findings, we propose a cost-effective, data-driven, evidence-based algorithmic approach to the workup of these cases. Copyright© by the American Society for Clinical Pathology.

TET2 mutations in B cells of patients affected by angioimmunoblastic T-cell lymphoma.

PubMed

Schwartz, Friederike H; Cai, Qian; Fellmann, Eva; Hartmann, Sylvia; Mäyränpää, Mikko I; Karjalainen-Lindsberg, Marja-Liisa; Sundström, Christer; Scholtysik, René; Hansmann, Martin-Leo; Küppers, Ralf

2017-06-01

Angioimmunoblastic T-cell lymphomas (AITLs) frequently carry mutations in the TET2 and IDH2 genes. TET2 mutations represent early genetic lesions as they had already been detected in haematopoietic precursor cells of AITL patients. We show by analysis of whole-tissue sections and microdissected PD1 + cells that the frequency of TET2-mutated AITL is presumably even higher than reported (12/13 cases in our collection; 92%). In two-thirds of informative AITLs (6/9), a fraction of B cells was also TET2-mutated. Investigation of four AITLs by TET2 and IGHV gene sequencing of single microdissected B cells showed that between 10% and 60% of polyclonal B cells in AITL lymph nodes harboured the identical TET2 mutations of the respective T-cell lymphoma clone. Thus, TET2-mutated haematopoietic precursor cells in AITL patients not only give rise to the T-cell lymphoma but also generate a large population of mutated mature B cells. Future studies will show whether this is a reason why AITL patients frequently also develop B-cell lymphomas. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Usability of Immunohistochemistry in Forensic Samples With Varying Decomposition.

PubMed

Lesnikova, Iana; Schreckenbach, Marc Niclas; Kristensen, Maria Pihlmann; Papanikolaou, Liv Lindegaard; Hamilton-Dutoit, Stephen

2018-05-24

Immunohistochemistry (IHC) is an important diagnostic tool in anatomic and surgical pathology but is used less frequently in forensic pathology. Degradation of tissue because of postmortem decomposition is believed to be a major limiting factor, although it is unclear what impact such degradation actually has on IHC staining validity. This study included 120 forensic autopsy samples of liver, lung, and brain tissues obtained for diagnostic purposes. The time from death to autopsy ranged between 1 and more than 14 days. Samples were prepared using the tissue microarray technique. The antibodies chosen for the study included KL1 (for staining bile duct epithelium), S100 (for staining glial cells and myelin), vimentin (for endothelial cells in cerebral blood vessels), and CD45 (for pulmonary lymphocytes). Slides were evaluated by light microscopy. Immunohistochemistry reactions were scored according to a system based on the extent and intensity of the positive stain. An overall correlation between the postmortem interval and the IHC score for all tissue samples was found. Samples from decedents with a postmortem interval of 1 to 3 days showed positive staining with all antibodies, whereas samples from decedents with a longer postmortem interval showed decreased staining rates. Our results suggest that IHC analysis can be successfully used for postmortem diagnosis in a range of autopsy samples showing lesser degrees of decomposition.

Pathological video-game use among youth ages 8 to 18: a national study.

PubMed

Gentile, Douglas

2009-05-01

Researchers have studied whether some youth are "addicted" to video games, but previous studies have been based on regional convenience samples. Using a national sample, this study gathered information about video-gaming habits and parental involvement in gaming, to determine the percentage of youth who meet clinical-style criteria for pathological gaming. A Harris poll surveyed a randomly selected sample of 1,178 American youth ages 8 to 18. About 8% of video-game players in this sample exhibited pathological patterns of play. Several indicators documented convergent and divergent validity of the results: Pathological gamers spent twice as much time playing as nonpathological gamers and received poorer grades in school; pathological gaming also showed comorbidity with attention problems. Pathological status significantly predicted poorer school performance even after controlling for sex, age, and weekly amount of video-game play. These results confirm that pathological gaming can be measured reliably, that the construct demonstrates validity, and that it is not simply isomorphic with a high amount of play.

Virtual microscopy and digital pathology in training and education.

PubMed

Hamilton, Peter W; Wang, Yinhai; McCullough, Stephen J

2012-04-01

Traditionally, education and training in pathology has been delivered using textbooks, glass slides and conventional microscopy. Over the last two decades, the number of web-based pathology resources has expanded dramatically with centralized pathological resources being delivered to many students simultaneously. Recently, whole slide imaging technology allows glass slides to be scanned and viewed on a computer screen via dedicated software. This technology is referred to as virtual microscopy and has created enormous opportunities in pathological training and education. Students are able to learn key histopathological skills, e.g. to identify areas of diagnostic relevance from an entire slide, via a web-based computer environment. Students no longer need to be in the same room as the slides. New human-computer interfaces are also being developed using more natural touch technology to enhance the manipulation of digitized slides. Several major initiatives are also underway introducing online competency and diagnostic decision analysis using virtual microscopy and have important future roles in accreditation and recertification. Finally, researchers are investigating how pathological decision-making is achieved using virtual microscopy and modern eye-tracking devices. Virtual microscopy and digital pathology will continue to improve how pathology training and education is delivered. © 2012 The Authors APMIS © 2012 APMIS.

Interpersonal perception of pathological narcissism: a social relations analysis.

PubMed

Lukowitsky, Mark R; Pincus, Aaron L

2013-01-01

Impairments in self and interpersonal functioning are core features of personality pathology. Clinical theory and research indicate that compromised self-awareness and distorted interpersonal perceptions are particularly prominent in individuals exhibiting pathological narcissism and Narcissistic Personality Disorder. Therefore we conducted a study to gain a better understanding of interpersonal perception of pathological narcissism. A large sample (N=437) of moderately acquainted individuals assigned to 1 of 93 small mixed-sex groups completed self- and informant ratings on the Pathological Narcissism Inventory (PNI) in a round-robin design. The social relations model (SRM) was used to partition the variance in dyadic ratings to investigate several hypotheses about interpersonal perception of pathological narcissism. SRM analyses demonstrated evidence of assimilation (the tendency to perceive and rate others similarly) and consensus (the extent to which multiple observers form similar impressions of another person) in interpersonal perception of pathological narcissism. Results also indicated modest self-other agreement and assumed similarity (the tendency for people to perceive others as similar to themselves) for PNI higher order factors and subscale ratings. Finally, results suggested that individuals high in pathological narcissism had some awareness of how peers would rate them (metaperception) but believed that others would rate them similarly to how they rated themselves.

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

Histogram analysis of apparent diffusion coefficient at 3.0 T in urinary bladder lesions: correlation with pathologic findings.

PubMed

Suo, Shi-Teng; Chen, Xiao-Xi; Fan, Yu; Wu, Lian-Ming; Yao, Qiu-Ying; Cao, Meng-Qiu; Liu, Qiang; Xu, Jian-Rong

2014-08-01

To investigate the potential value of histogram analysis of apparent diffusion coefficient (ADC) obtained at standard (700 s/mm(2)) and high (1500 s/mm(2)) b values on a 3.0-T scanner in the differentiation of bladder cancer from benign lesions and in assessing bladder tumors of different pathologic T stages and to evaluate the diagnostic performance of ADC-based histogram parameters. In all, 52 patients with bladder lesions, including benign lesions (n = 7) and malignant tumors (n = 45; T1 stage or less, 23; T2 stage, 7; T3 stage, 8; and T4 stage, 7), were retrospectively evaluated. Magnetic resonance examination at 3.0 T and diffusion-weighted imaging were performed. ADC maps were obtained at two b values (b = 700 and 1500 s/mm(2); ie, ADC-700 and ADC-1500). Parameters of histogram analysis included mean, kurtosis, skewness, and entropy. The correlations between these parameters and pathologic results were revealed. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic value of histogram parameters. Significant differences were found in mean ADC-700, mean ADC-1500, skewness ADC-1500, and kurtosis ADC-1500 between bladder cancer and benign lesions (P = .002-.032). There were also significant differences in mean ADC-700, mean ADC-1500, and kurtosis ADC-1500 among bladder tumors of different pathologic T stages (P = .000-.046). No significant differences were observed in other parameters. Mean ADC-1500 and kurtosis ADC-1500 were significantly correlated with T stage, respectively (ρ = -0.614, P < .001; ρ = 0.374, P = .011). ROC analysis showed that the combination of mean ADC-1500 and kurtosis ADC-1500 has the maximal area under the ROC curve (AUC, 0.894; P < .001) in the differentiation of benign lesions and malignant tumors, with a sensitivity of 77.78% and specificity of 100%. AUCs for differentiating low- and high-stage tumors were 0.840 for mean ADC-1500 (P < .001) and 0.696 for kurtosis ADC-1500 (P = .015). Histogram analysis of ADC-1500 at 3.0 T can be useful in evaluation of bladder lesions. A combination of mean ADC-1500 and kurtosis ADC-1500 may be more beneficial in the differentiation of benign and malignant lesions. Mean ADC-1500 was the most promising parameter for differentiating low- from high-stage bladder cancer. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

A novel spinal kinematic analysis using X-ray imaging and vicon motion analysis: a case study.

PubMed

Noh, Dong K; Lee, Nam G; You, Joshua H

2014-01-01

This study highlights a novel spinal kinematic analysis method and the feasibility of X-ray imaging measurements to accurately assess thoracic spine motion. The advanced X-ray Nash-Moe method and analysis were used to compute the segmental range of motion in thoracic vertebra pedicles in vivo. This Nash-Moe X-ray imaging method was compared with a standardized method using the Vicon 3-dimensional motion capture system. Linear regression analysis showed an excellent and significant correlation between the two methods (R2 = 0.99, p < 0.05), suggesting that the analysis of spinal segmental range of motion using X-ray imaging measurements was accurate and comparable to the conventional 3-dimensional motion analysis system. Clinically, this novel finding is compelling evidence demonstrating that measurements with X-ray imaging are useful to accurately decipher pathological spinal alignment and movement impairments in idiopathic scoliosis (IS).

Regulatory T cell activity in immunosuppresive mice model of pseudomonas aeruginosa pneumonia.

PubMed

Li, Jun-Lu; Chen, Ting-Sang; Yuan, Cong-Cong; Zhao, Guo-Qiang; Xu, Min; Li, Xiao-Yan; Cao, Jie; Xing, Li-Hua

2017-08-01

Pseudomonas aeruginosa (PA) pneumonia is a refractory, even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process. We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells, i.e., Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10). Seventy-two BALB/c mice were divided into four groups randomly: control (A), PA pneumonia (B), immunosuppression (C) and immunosuppression with PA pneumonia (D). Mice were sacrificed at 4, 8 and 24 h after establishing experimental models. The pathological changes of lung tissue were graded, and the FOXP3 mRNA and serum IL-10 levels were detected. Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C, but significantly pathological changes were found in groups B and D, especially in group D at 8 h (P<0.05). The expression levels of FOXP3 mRNA in groups A and C showed no significant changes at the three time points, which were significantly lower than those in groups B and D (P<0.05). FOXP3 mRNA levels were lowest at 4 h, and there was significant difference between groups B and D (P<0.05). The serum levels of IL-10 in groups A and C were almost normal at the three time points, but decreased significantly in groups B and D (P<0.05). The serum levels of IL-10 decreased to the lowest at 8 h, especially in group D (P<0.05). The results indicate that PA pneumonia in immunosuppressive individuals worsens rapidly, which may be associated with Treg cells function disturbance. And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.

Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury.

PubMed

Tu, Tsang-Wei; Lescher, Jacob D; Williams, Rashida A; Jikaria, Neekita; Turtzo, L Christine; Frank, Joseph A

2017-01-01

Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate the interpretation of imaging and IHC observations.

Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury

PubMed Central

Lescher, Jacob D.; Williams, Rashida A.; Jikaria, Neekita; Turtzo, L. Christine; Frank, Joseph A.

2017-01-01

Abstract Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate the interpretation of imaging and IHC observations. PMID:26905805

Choroidal thinning in diabetes type 1 detected by 3-dimensional 1060 nm optical coherence tomography.

PubMed

Esmaeelpour, Marieh; Brunner, Simon; Ansari-Shahrezaei, Siamak; Shahrezaei, Siamak Ansari; Nemetz, Susanne; Povazay, Boris; Kajic, Vedran; Drexler, Wolfgang; Binder, Susanne

2012-10-03

To map choroidal (ChT) and retinal thickness (RT) in patients with diabetes type 1 with and without maculopathy and retinopathy in order to compare them with healthy subjects using high speed 3-dimensional (3D) 1060 nm optical coherence tomography (OCT). Thirty-three eyes from 33 diabetes type 1 subjects (23-57 years, 15 male) divided into groups of without pathology (NDR) and with pathology (DR; including microaneurysms, exudates, clinically significant macular-oedema and proliferative retinopathy) were compared with 20 healthy axial eye length and age-matched subjects (24-57 years, 9 male), imaged by high speed (60.000 A-scans/s) 3D 1060 nm OCT performed over 36° × 36° field of view. Ocular health status, disease duration, body mass index, haemoglobin-A1c, and blood pressure (bp) measurements were recorded. Subfoveal ChT, and 2D topographic maps between retinal pigment epithelium and the choroidal/scleral-interface, were automatically generated and statistically analyzed. Subfoveal ChT (mean ± SD, μm) for healthy eyes was 388 ± 109; significantly thicker than all diabetic groups, 291 ± 64 for NDR, and 303 ± 82 for DR (ANOVA P < 0.004, Tukey P = 0.01 for NDR and DR). Thinning did not relate to recorded factors (multi-regression analysis, P > 0.05). Compared with healthy eyes and the NDR, the averaged DR ChT-map demonstrated temporal thinning that extended superiorly and temporal-inferiorly (unpaired t-test, P < 0.05). Foveal RT and RT-maps showed no statistically significant difference between groups (mean SD, μm, healthy 212 ± 17, NDR 217 ± 15, DR 216 ± 27, ANOVA P > 0.05). ChT is decreased in diabetes type 1, independent of the absence of pathology and of diabetic disease duration. In eyes with pathology, 3D 1060 nm OCT averaged maps showed an extension of the thinning area matching retinal lesions and suggesting its involvement on onset or progression of disease.

State of the art in pathology business process analysis, modeling, design and optimization.

PubMed

Schrader, Thomas; Blobel, Bernd; García-Rojo, Marcial; Daniel, Christel; Słodkowska, Janina

2012-01-01

For analyzing current workflows and processes, for improving them, for quality management and quality assurance, for integrating hardware and software components, but also for education, training and communication between different domains' experts, modeling business process in a pathology department is inevitable. The authors highlight three main processes in pathology: general diagnostic, cytology diagnostic, and autopsy. In this chapter, those processes are formally modeled and described in detail. Finally, specialized processes such as immunohistochemistry and frozen section have been considered.

[Peracute mortality in common cranes (Grus grus)].

PubMed

Prange, H; Jonas, K; Gottschalk, C; Discher, U; Ribbeck, E; Mewes, W

2000-01-01

Out of a nonbreeding group of cranes, 10 birds died peracutely at the end of April 1998. The pathological investigation showed changes in the intestine, liver and kidneys caused probably by an intoxication; but corresponding analyses did not result in a specified poison. The proof of E. coli, Cl. perfringens and Campylobacter jejuni is to be interpreted as a subordinate result. 7 of 8 cranes had a low to high infestation with endoparasites (Porrocaeum spp., Eimeria pusilla, Echinostoma spp.). 5 of 8 birds showed leaness, possibly as a result of the migration exertion. Further on, the analysis results of a 9th crane found at another place are included in this paper.

Aerophagia induced by the nasal obstruction on experimental animals.

PubMed

Nakajima, K; Ohi, G

1977-04-01

The excessive accumulation of gas in the gastrointestinal tracts was invariably induced on experimental animals (mice, rats, guinea pigs, hamsters and rabbits) by simply obstructing nasal passages. The analysis of the gas showed the almost identical composition to the ambient air or flutus which was largely due to swallowed air. Also the numerous small foams were found on and underneath the epithelial lining of small intestine. The pathological evaluation was done both macroscopically and microscopically. Dying animals after nasal obstruction showed hemorrhagic and necrotic changes in the jejunum and ileum. This observation may cast some light to the pathogenesis of necrotizing enterocolitis in human neonatal.

A survey study on student preferences regarding pathology teaching in Germany: a call for curricular modernization.

PubMed

Herrmann, Florian E M; Lenski, Markus; Steffen, Julius; Kailuweit, Magdalena; Nikolaus, Marc; Koteeswaran, Rajasekaran; Sailer, Andreas; Hanszke, Anna; Wintergerst, Maximilian; Dittmer, Sissi; Mayr, Doris; Genzel-Boroviczény, Orsolya; Eley, Diann S; Fischer, Martin R

2015-06-02

Pathology is a discipline that provides the basis of the understanding of disease in medicine. The past decades have seen a decline in the emphasis laid on pathology teaching in medical schools and outdated pathology curricula have worsened the situation. Student opinions and thoughts are central to the questions of whether and how such curricula should be modernized. A survey was conducted among 1018 German medical students regarding their preferences in pathology teaching modalities and their satisfaction with lecture-based courses. A qualitative analysis was performed comparing a recently modernized pathology curriculum with a traditional lecture-based curriculum. The differences in modalities of teaching used were investigated. Student satisfaction with the lecture-based curriculum positively correlated with student grades (spearman's correlation coefficient 0.24). Additionally, students with lower grades supported changing the curriculum (spearman's correlation coefficient 0.47). The majority supported virtual microscopy, autopsies, seminars and podcasts as preferred didactic methods. The data supports the implementation of a pathology curriculum where tutorials, autopsies and supplementary computer-based learning tools play important roles.

Effect of age on the pathogenesis of duck tembusu virus in Cherry Valley ducks

PubMed Central

Li, Ning; Lv, Chuanwei; Yue, Ruichao; Shi, Ying; Wei, Liangmeng; Chai, Tongjie; Liu, Sidang

2015-01-01

The effect of host age on the outcome of duck tembusu virus (DTMUV) infection was studied in ducks. Three groups of Cherry Valley ducks at 1, 3, and 7 weeks of age were intramuscularly infected with DTMUV to systematically observe the clinical symptoms, pathological changes, tissue viral loads, and immune responses. Severe clinical symptoms and neurological dysfunction were observed in 1-week-old ducks as early as 2 days post infection (dpi) and some died at 5–7 dpi. Three weeks-old ducks showed similar but milder symptoms and no deaths. However, 7-weeks-old ducks showed only transient loss of appetite. Gross lesions gradually reduced in severity as ducks matured. One-week-old ducks showed endocardial hemorrhage, splenomegaly, swelling in the lymph follicles of the ileum, liver, and kidney swelling with degeneration, and meningeal hyperemia. Three-weeks-old ducks showed only mild pathological lesions. No visible lesions were observed in 7-weeks-old ducks. However, pathological histology analysis demonstrated all infected ducks displayed viral encephalitis. DTMUV could be detected in the brains of 1-week-old ducks as early as 1 dpi and virus titers of most organs in 1-week-old ducks were significantly higher than that of 3- and 7-weeks-old ducks at 3–5 dpi. The patterns of IFN-γ, IL-2, and serum neutralizing antibodies were similar, and there were significant difference between the youngest ducks and the older ducks at early infection stage (P < 0.05). More important is that although the antibody titers of all infected ducks were similar from 9 to 17 dpi, reduced clearance of virus was observed in the youngest groups comparing with the other two groups, indicating that immune system maturity was more important than the presence of neutralizing antibody. In summary, this study demonstrates that viral pathogenesis is strongest in 1-week-old ducks and the age-related immune response plays an important role in the pathogenesis of DTMUV in ducks. PMID:26106382

Effect of age on the pathogenesis of duck tembusu virus in Cherry Valley ducks.

PubMed

Li, Ning; Lv, Chuanwei; Yue, Ruichao; Shi, Ying; Wei, Liangmeng; Chai, Tongjie; Liu, Sidang

2015-01-01

The effect of host age on the outcome of duck tembusu virus (DTMUV) infection was studied in ducks. Three groups of Cherry Valley ducks at 1, 3, and 7 weeks of age were intramuscularly infected with DTMUV to systematically observe the clinical symptoms, pathological changes, tissue viral loads, and immune responses. Severe clinical symptoms and neurological dysfunction were observed in 1-week-old ducks as early as 2 days post infection (dpi) and some died at 5-7 dpi. Three weeks-old ducks showed similar but milder symptoms and no deaths. However, 7-weeks-old ducks showed only transient loss of appetite. Gross lesions gradually reduced in severity as ducks matured. One-week-old ducks showed endocardial hemorrhage, splenomegaly, swelling in the lymph follicles of the ileum, liver, and kidney swelling with degeneration, and meningeal hyperemia. Three-weeks-old ducks showed only mild pathological lesions. No visible lesions were observed in 7-weeks-old ducks. However, pathological histology analysis demonstrated all infected ducks displayed viral encephalitis. DTMUV could be detected in the brains of 1-week-old ducks as early as 1 dpi and virus titers of most organs in 1-week-old ducks were significantly higher than that of 3- and 7-weeks-old ducks at 3-5 dpi. The patterns of IFN-γ, IL-2, and serum neutralizing antibodies were similar, and there were significant difference between the youngest ducks and the older ducks at early infection stage (P < 0.05). More important is that although the antibody titers of all infected ducks were similar from 9 to 17 dpi, reduced clearance of virus was observed in the youngest groups comparing with the other two groups, indicating that immune system maturity was more important than the presence of neutralizing antibody. In summary, this study demonstrates that viral pathogenesis is strongest in 1-week-old ducks and the age-related immune response plays an important role in the pathogenesis of DTMUV in ducks.

[Clinical and pathological features of Alport syndrome in children].

PubMed

Zhu, Chun-Hua; Huang, Song-Ming; Wu, Hong-Mei; Bao, Hua-Ying; Chen, Ying; Han, Yuan; Zhao, Fei; Zhang, Ai-Hua; Zhang, Wei-Zhen

2010-03-01

To study the clinical and pathological features of Alport syndrome in children. The clinical and histopathological data of 10 hospitalized children with Alport syndrome from February 2007 to February 2009 were retrospectively reviewed. There were 7 males and 3 females, with the age ranging from 2 years to 6 years and 7 months (mean 3 years and 2 months). Five of 10 cases had positive family history. X-linked dominant inheritance Alport syndrome was diagnosed in 8 cases, and autosomal recessive inheritance Alport syndrome in 2 cases. Recurrent gross hematuria was found in 5 cases, hematuria and proteinuria in 3 cases, massive proteinuria in 1 case, and nephritic syndrome in 1 case. Under the light microscope, 8 cases presented with mesangial proliferation glomerulonephritis, and 2 cases with focal segmental glomerulosclerosis. Immunofluorescence assay showed that all cases had IgM deposition in glomerulus. Only 1 case showed typical glomerular basement membrane (GBM) pathological changes. All cases showed abnormal alpha-chain distribution in renal collagen IV. The children with Alport syndrome have diverse clinical manifestations. Characteristic histopathological presentations could not be found under a light microscope, mesangial proliferation glomerulonephritis is the dominant pathological change, and IgM deposition in glomerulus is common. The GBM pathological change in children is not common. Immunofluorescence assay of alpha-chain in collagen IV is needed for the diagnosis of Alport syndrome.

Low Reporting Quality of the Meta-Analyses in Diagnostic Pathology.

PubMed

Liu, Xulei; Kinzler, Michael; Yuan, Jiangfan; He, Guozhong; Zhang, Lanjing

2017-03-01

- Little is known regarding the reporting quality of meta-analyses in diagnostic pathology. - To compare reporting quality of meta-analyses in diagnostic pathology and medicine and to examine factors associated with reporting quality of diagnostic pathology meta-analyses. - Meta-analyses were identified in 12 major diagnostic pathology journals without specifying years and 4 major medicine journals in 2006 and 2011 using PubMed. Reporting quality of meta-analyses was evaluated using the 27-item checklist of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement published in 2009. A higher PRISMA score indicates higher reporting quality. - Forty-one diagnostic pathology meta-analyses and 118 medicine meta-analyses were included. Overall, reporting quality of meta-analyses in diagnostic pathology was lower than that in medicine (median [interquartile range] = 22 [15, 25] versus 27 [23, 28], P < .001). Compared with medicine meta-analyses, diagnostic pathology meta-analyses less likely reported 23 of the 27 items (85.2%) on the PRISMA checklist, but more likely reported the data items. Higher reporting quality of diagnostic pathology meta-analyses was associated with recent publication years (later than 2009 versus 2009 or earlier, P = .002) and non-North American first authors (versus North American, P = .001), but not journal publisher's location (P = .11). Interestingly, reporting quality was not associated with adjusted citation ratio for meta-analyses in either diagnostic pathology or medicine (P = .40 and P = .09, respectively). - Meta-analyses in diagnostic pathology had lower reporting quality than those in medicine. Reporting quality of diagnostic pathology meta-analyses is linked to publication year and first author's location, but not to journal publisher's location or article's adjusted citation ratios. More research and education on meta-analysis methodology may improve the reporting quality of diagnostic pathology meta-analyses.

Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla

PubMed Central

Hametner, Simon; Yao, Bing; van Gelderen, Peter; Merkle, Hellmut; Cantor, Fredric K.; Lassmann, Hans; Duyn, Jeff H.

2011-01-01

Previous authors have shown that the transverse relaxivity R2* and frequency shifts that characterize gradient echo signal decay in magnetic resonance imaging are closely associated with the distribution of iron and myelin in the brain's white matter. In multiple sclerosis, iron accumulation in brain tissue may reflect a multiplicity of pathological processes. Hence, iron may have the unique potential to serve as an in vivo magnetic resonance imaging tracer of disease pathology. To investigate the ability of iron in tracking multiple sclerosis-induced pathology by magnetic resonance imaging, we performed qualitative histopathological analysis of white matter lesions and normal-appearing white matter regions with variable appearance on gradient echo magnetic resonance imaging at 7 Tesla. The samples used for this study derive from two patients with multiple sclerosis and one non-multiple sclerosis donor. Magnetic resonance images were acquired using a whole body 7 Tesla magnetic resonance imaging scanner equipped with a 24-channel receive-only array designed for tissue imaging. A 3D multi-gradient echo sequence was obtained and quantitative R2* and phase maps were reconstructed. Immunohistochemical stainings for myelin and oligodendrocytes, microglia and macrophages, ferritin and ferritin light polypeptide were performed on 3- to 5-µm thick paraffin sections. Iron was detected with Perl's staining and 3,3′-diaminobenzidine-tetrahydrochloride enhanced Turnbull blue staining. In multiple sclerosis tissue, iron presence invariably matched with an increase in R2*. Conversely, R2* increase was not always associated with the presence of iron on histochemical staining. We interpret this finding as the effect of embedding, sectioning and staining procedures. These processes likely affected the histopathological analysis results but not the magnetic resonance imaging that was obtained before tissue manipulations. Several cellular sources of iron were identified. These sources included oligodendrocytes in normal-appearing white matter and activated macrophages/microglia at the edges of white matter lesions. Additionally, in white matter lesions, iron precipitation in aggregates typical of microbleeds was shown by the Perl's staining. Our combined imaging and pathological study shows that multi-gradient echo magnetic resonance imaging is a sensitive technique for the identification of iron in the brain tissue of patients with multiple sclerosis. However, magnetic resonance imaging-identified iron does not necessarily reflect pathology and may also be seen in apparently normal tissue. Iron identification by multi-gradient echo magnetic resonance imaging in diseased tissues can shed light on the pathological processes when coupled with topographical information and patient disease history. PMID:22171355

Factors that impact turnaround time of surgical pathology specimens in an academic institution.

PubMed

Patel, Samip; Smith, Jennifer B; Kurbatova, Ekaterina; Guarner, Jeannette

2012-09-01

Turnaround time of laboratory results is important for customer satisfaction. The College of American Pathologists' checklist requires an analytic turnaround time of 2 days or less for most routine cases and lets every hospital define what a routine specimen is. The objective of this study was to analyze which factors impact turnaround time of nonbiopsy surgical pathology specimens. We calculated the turnaround time from receipt to verification of results (adjusted for weekends and holidays) for all nonbiopsy surgical specimens during a 2-week period. Factors studied included tissue type, number of slides per case, decalcification, immunohistochemistry, consultations with other pathologists, and diagnosis. Univariate and multivariate analyses were performed. A total of 713 specimens were analyzed, 551 (77%) were verified within 2 days and 162 (23%) in 3 days or more. Lung, gastrointestinal, breast, and genitourinary specimens showed the highest percentage of cases being signed out in over 3 days. Diagnosis of malignancy (including staging of the neoplasia), consultation with other pathologists, having had a frozen section, and use of immunohistochemical stains were significantly associated with increased turnaround time in univariate analysis. Decalcification was not associated with increased turnaround time. In multivariate analysis, consultation with other pathologists, use of immunohistochemistry, diagnosis of malignancy, and the number of slides studied continued to be significantly associated with prolonged turnaround time. Our findings suggest that diagnosis of malignancy is central to significantly prolonging the turnaround time for surgical pathology specimens, thus institutions that serve cancer centers will have longer turnaround time than those that do not. Copyright © 2012 Elsevier Inc. All rights reserved.

Selective vulnerability of dentate granule cells prior to amyloid deposition in PDAPP mice: digital morphometric analyses.

PubMed

Wu, Chi-Cheng; Chawla, Faisal; Games, Dora; Rydel, Russell E; Freedman, Stephen; Schenk, Dale; Young, Warren G; Morrison, John H; Bloom, Floyd E

2004-05-04

Increasing evidence from mouse models of Alzheimer's disease shows that overexpression of a mutant form of the amyloid precursor protein (APP) and its product, beta-amyloid peptide, initiate pathological changes before amyloid deposition. To evaluate the cytological basis for one of these early changes, namely reduced volume of the dentate gyrus (DG), we have used high-throughput diOlistic cell loading and 3D neuronal reconstruction to investigate potential dendritic pathology of granule cells (GCs) in 90-day-old PDAPP mice. Labeled GCs from fixed hippocampal slices were selected randomly and imaged digitally by using confocal laser-scanning microscopy. The dendritic complexity of GCs was quantified according to subordinate morphological parameters, including soma position within the granule cell layer (superficial versus deep) and topographic location within the DG (dorsal versus ventral blade) along the anterior-posterior hippocampal axis. Initial analysis, which included all sampled GC types, revealed a 12% reduction of total dendritic length in PDAPP mice compared with littermate controls. Further analysis, performed with refined subgroups, found that superficially located GCs in the dorsal blade were profoundly altered, exhibiting a 23% loss in total dendritic length, whereas neurons in the ventral blade were unaffected. Superficial GCs were particularly vulnerable (a 32% reduction) in the posterior region of the DG. Furthermore, the dendritic reductions of this select group were uniformly localized within middle-to-outer portions of the dentate molecular layer. We conclude that substantial dendritic pathology is evident in 90-day-old PDAPP mice for a spatially defined subset of GCs well before amyloid accumulation occurs.

Selective vulnerability of dentate granule cells prior to amyloid deposition in PDAPP mice: Digital morphometric analyses

PubMed Central

Wu, Chi-Cheng; Chawla, Faisal; Games, Dora; Rydel, Russell E.; Freedman, Stephen; Schenk, Dale; Young, Warren G.; Morrison, John H.; Bloom, Floyd E.

2004-01-01

Increasing evidence from mouse models of Alzheimer's disease shows that overexpression of a mutant form of the amyloid precursor protein (APP) and its product, β-amyloid peptide, initiate pathological changes before amyloid deposition. To evaluate the cytological basis for one of these early changes, namely reduced volume of the dentate gyrus (DG), we have used high-throughput diOlistic cell loading and 3D neuronal reconstruction to investigate potential dendritic pathology of granule cells (GCs) in 90-day-old PDAPP mice. Labeled GCs from fixed hippocampal slices were selected randomly and imaged digitally by using confocal laser-scanning microscopy. The dendritic complexity of GCs was quantified according to subordinate morphological parameters, including soma position within the granule cell layer (superficial versus deep) and topographic location within the DG (dorsal versus ventral blade) along the anterior-posterior hippocampal axis. Initial analysis, which included all sampled GC types, revealed a 12% reduction of total dendritic length in PDAPP mice compared with littermate controls. Further analysis, performed with refined subgroups, found that superficially located GCs in the dorsal blade were profoundly altered, exhibiting a 23% loss in total dendritic length, whereas neurons in the ventral blade were unaffected. Superficial GCs were particularly vulnerable (a 32% reduction) in the posterior region of the DG. Furthermore, the dendritic reductions of this select group were uniformly localized within middle-to-outer portions of the dentate molecular layer. We conclude that substantial dendritic pathology is evident in 90-day-old PDAPP mice for a spatially defined subset of GCs well before amyloid accumulation occurs. PMID:15118092

Internet images of the speech pathology profession.

PubMed

Byrne, Nicole

2017-06-05

Objective The Internet provides the general public with information about speech pathology services, including client groups and service delivery models, as well as the professionals providing the services. Although this information assists the general public and other professionals to both access and understand speech pathology services, it also potentially provides information about speech pathology as a prospective career, including the types of people who are speech pathologists (i.e. demographics). The aim of the present study was to collect baseline data on how the speech pathology profession was presented via images on the Internet. Methods A pilot prospective observational study using content analysis methodology was conducted to analyse publicly available Internet images related to the speech pathology profession. The terms 'Speech Pathology' and 'speech pathologist' to represent both the profession and the professional were used, resulting in the identification of 200 images. These images were considered across a range of areas, including who was in the image (e.g. professional, client, significant other), the technology used and the types of intervention. Results The majority of images showed both a client and a professional (i.e. speech pathologist). While the professional was predominantly presented as female, the gender of the client was more evenly distributed. The clients were more likely to be preschool or school aged, however male speech pathologists were presented as providing therapy to selected age groups (i.e. school aged and younger adults). Images were predominantly of individual therapy and the few group images that were presented were all paediatric. Conclusion Current images of speech pathology continue to portray narrow professional demographics and client groups (e.g. paediatrics). Promoting images of wider scope to fully represent the depth and breadth of speech pathology professional practice may assist in attracting a more diverse group of people into the profession in the future. What is known about the topic? To date, research has not considered the promotional profile of allied health professionals on the Internet. There has been a lack of consideration of whether the way in which the professions are promoted may affect clients accessing allied health services or people entering careers. What does this paper add? This paper raises awareness of the lack of promotion of a diverse workforce in speech pathology and considers how this may affect changing the professional demographics in the future. It also provides a starting point for documentation in the form of a baseline for tracking future changes. It allows consideration of the fact that when designing health promotional and educational materials, it is crucial that diversity is displayed in the professional role, the client role and the setting in order to provide information and education to the general public about the health services provided. What are the implications for practitioners? The presentation of narrow demographics of both the professional and client may potentially affect people considering speech pathology as a future career. The appearance of narrow client demographics and diagnosis groups may also deter people from accessing services. For example, if the demonstrated images do not show older people accessing speech pathology services, then this may suggest that services are only for children. The results from the present case example are transferrable to other health professions with similar professional demographic profiles (e.g. occupational therapy). Consideration of the need to display a diverse client profile is relevant to all health and medical services, and demonstrates steps towards inclusiveness and increasing engagement of clients who may be currently less likely to access health services (including people who are Aboriginal or from a culturally and linguistically diverse background).

In vivo analysis of the iris thickness by spectral domain optical coherence tomography.

PubMed

Invernizzi, Alessandro; Cigada, Mario; Savoldi, Luisa; Cavuto, Silvio; Fontana, Luigi; Cimino, Luca

2014-09-01

To assess the effectiveness of spectral domain optical coherence tomography (SD-OCT) in providing in vivo measurements of iris thickness in healthy and pathological subjects. 14 healthy volunteers and 14 patients with unilateral Fuchs' uveitis were enrolled in the study. The two groups were comparable for age, gender and race. Each subject underwent complete clinical examination and anterior segment SD-OCT imaging in both eyes. SD-OCT scans of the iris were performed following a cross-sectional pattern. Iris thickness values were obtained using a purposely developed software-based analysis of OCT images. Measurements were carried out twice by two trained independent operators to assess intraobserver and interobserver repeatability. Analysis of iris thickness was conducted in four main quadrants: superior, inferior, nasal and temporal. Iris thickness values from normal subjects were compared with the ones measured in the affected and fellow eyes of patients with Fuchs' uveitis. Iris thickness measurements showed good intraobserver and interobserver repeatability (intraclass correlation coefficient >0.971). Superior and temporal iris sectors showed respectively thickest and thinnest values in all groups. In healthy eyes, iris thickness ranged from 327.92±37.29 μm temporally to 405.25±48.49 μm superiorly. Iris thickness measurements in the affected eyes of Fuchs' uveitis patients ranged from 285.48±56.02 μm temporally to 376.12±60.97 μm superiorly. Multiple comparison analysis showed iris thickness values to be significantly lower in eyes affected by Fuchs' uveitis than both in fellow eyes (p<0.001) of the same patients and in healthy eyes (p=0.0074). SD-OCT is a suitable technique for iris thickness assessment. Thickness analysis must be carried out using a sectorial approach, taking into consideration anatomical variations existing between different iris regions. SD-OCT is a potentially useful tool for detecting iris thickness variations induced by pathological conditions such as Fuchs' uveitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

High-dose interleukin2 - a 10-year single-site experience in the treatment of metastatic renal cell carcinoma: careful selection of patients gives an excellent outcome.

PubMed

Chow, S; Galvis, V; Pillai, M; Leach, R; Keene, E; Spencer-Shaw, A; Shablak, A; Shanks, J; Liptrot, T; Thistlethwaite, F; Hawkins, R E

2016-01-01

VEGF-targeted therapy has become the mainstay of treatment for majority of mRCC patients. For most patients, benefit is short-lived and therefore treatment remains palliative in intent. HD IL2 is an effective immunotherapy treatment capable of durable remission in some patients but its unselected use has been difficult due to its modest response rate and considerable adverse effects. Using set pathology criteria as a selection tool in clinical practice, we have been able to show improved outcomes in our previous report. Here, we present an updated and extended report of this treatment and seek to explore any pathological, clinical and treatment variables likely to predict better outcomes. This is an extension of a previously reported clinical audit, which includes mRCC cases treated with HD IL2 between 2003 and 2013. Since 2006, tumour specimens of potential candidates were routinely reviewed prospectively and stratified into Favourable or Other categories based on constitution of histological growth pattern, namely alveolar or solid versus papillary and/or sarcomatoid architecture; clear cell versus granular cell cytoplasmic morphology. HD IL2 was preferentially offered to patients with Favourable pathology. Outcome evaluation includes response rates, survival, and treatment tolerance. Multivariate analysis was performed to explore potential prognostic and predictive factors. Among prospectively selected patients with Favourable pathology ( n  = 106), overall response rate was 48.1 % (51/106) with CR rate of 21.6 % (23/106). Median OS was 58.1 months. Factors associated with significantly better response and/or survival includes favourable pathology pattern, higher cycle 1 tolerance and lower number of metastatic organ sites (<3). CAIX (Carbonic anhydrase 9) has prognostic value but is not predictive of response. Toxicities were those expected of IL2 but were manageable on general medical wards, with no treatment-related death. Importantly most complete responses were durable with 76 % (23/30) cases remained relapse-free (median 39 months follow up) and 2 of the seven who relapsed had had long-term disease free survival after resection of oligometastatic relapse. Our experience shows that HD IL2 remains an effective and safe treatment in well-selected cases of mRCC. The result in this single-institution patient series confirms similar outcomes to our previously reported retrospective series. Given the prospect of long-term remission, fit patients with Favourable histology and low disease burden should be considered for HD IL2 in an experienced centre. Better understanding has been gained from this in-depth analysis especially the examination of possible response predictors and strategies that can improve treatment outcome.

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

PubMed

Schrijver, Iris; Aziz, Nazneen; Farkas, Daniel H; Furtado, Manohar; Gonzalez, Andrea Ferreira; Greiner, Timothy C; Grody, Wayne W; Hambuch, Tina; Kalman, Lisa; Kant, Jeffrey A; Klein, Roger D; Leonard, Debra G B; Lubin, Ira M; Mao, Rong; Nagan, Narasimhan; Pratt, Victoria M; Sobel, Mark E; Voelkerding, Karl V; Gibson, Jane S

2012-11-01

This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Biliary cystadenoma associated with Opisthorchis viverrini infection in a domestic cat (Felis catus).

PubMed

Tiwananthagorn, Saruda; Srivorakul, Saralee; Khochakul, Varangpicha; Pringproa, Kidsadagon

2018-05-05

A 12-year-old, female, domestic cat (Felis catus) presented with dehydration, emaciation, anorexia, and lethargy. The cat was unresponsive to medical treatment and euthanized; the carcass was submitted for pathological diagnosis. Necropsy revealed icteric mucous membranes. The liver was enlarged, with multinodular, cystic, white masses, 0.5-4.0 cm in diameter, scattered throughout. Microscopically, the biliary epithelium presented with a proliferation of multifocal cystic masses, occasionally with periodic acid-Schiff-positive fluid within the cysts. Simple cuboidal epithelial cells showed small, round to oval, vesicular nuclei and rare mitotic figures. There were also multifocal trematode-like parasites situated within the biliary tracts. Immunohistochemistry of the cystic masses was positive for pan-cytokeratin and proliferating cell nuclear antigen, while negative for vimentin. Molecular analysis and gene sequencing of the parasite indicated that it was Opisthorchis viverrini. Based on the pathological findings and molecular analysis, the cat was diagnosed with biliary cystadenoma related to O. viverrini infection. This report described an unusual case of O. viverrini infection associated with biliary tumor in a cat, and raises the possibility of domestic cats as a reservoir host of the human liver fluke. Copyright © 2018 Elsevier B.V. All rights reserved.

In Silico Analysis of the Potential of the Active Compounds Fucoidan and Alginate Derived from Sargassum Sp. as Inhibitors of COX-1 and COX-2

PubMed Central

Dewi, Lestari

2016-01-01

Introduction: The enzyme cyclooxygenase (COX) is an enzyme that catalyzes the formation of one of the mediators of inflammation, the prostaglandins. Inhibition of COX allegedly can improve inflammation-induced pathological conditions. Aim: The purpose of the present study was to evaluate the potential of Sargassum sp. components, Fucoidan and alginate, as COX inhibitors. Material and methods: The study was conducted by means of a computational (in silico) method. It was performed in two main stages, the docking between COX-1 and COX-2 with Fucoidan, alginate and aspirin (for comparison) and the analysis of the amount of interactions formed and the residues directly involved in the process of interaction. Results: Our results showed that both Fucoidan and alginate had an excellent potential as inhibitors of COX-1 and COX-2. Fucoidan had a better potential as an inhibitor of COX than alginate. COX inhibition was expected to provide a more favorable effect on inflammation-related pathological conditions. Conclusion: The active compounds Fucoidan and alginate derived from Sargassum sp. were suspected to possess a good potential as inhibitors of COX-1 and COX-2. PMID:27594740

In Silico Analysis of the Potential of the Active Compounds Fucoidan and Alginate Derived from Sargassum Sp. as Inhibitors of COX-1 and COX-2.

PubMed

Dewi, Lestari

2016-06-01

The enzyme cyclooxygenase (COX) is an enzyme that catalyzes the formation of one of the mediators of inflammation, the prostaglandins. Inhibition of COX allegedly can improve inflammation-induced pathological conditions. The purpose of the present study was to evaluate the potential of Sargassum sp. components, Fucoidan and alginate, as COX inhibitors. The study was conducted by means of a computational (in silico) method. It was performed in two main stages, the docking between COX-1 and COX-2 with Fucoidan, alginate and aspirin (for comparison) and the analysis of the amount of interactions formed and the residues directly involved in the process of interaction. Our results showed that both Fucoidan and alginate had an excellent potential as inhibitors of COX-1 and COX-2. Fucoidan had a better potential as an inhibitor of COX than alginate. COX inhibition was expected to provide a more favorable effect on inflammation-related pathological conditions. The active compounds Fucoidan and alginate derived from Sargassum sp. were suspected to possess a good potential as inhibitors of COX-1 and COX-2.

Comparative peptidomic profile between human hypertrophic scar tissue and matched normal skin for identification of endogenous peptides involved in scar pathology.

PubMed

Li, Jingyun; Chen, Ling; Li, Qian; Cao, Jing; Gao, Yanli; Li, Jun

2018-08-01

Endogenous peptides recently attract increasing attention for their participation in various biological processes. Their roles in the pathogenesis of human hypertrophic scar remains poorly understood. In this study, we used liquid chromatography-tandem mass spectrometry to construct a comparative peptidomic profiling between human hypertrophic scar tissue and matched normal skin. A total of 179 peptides were significantly differentially expressed in human hypertrophic scar tissue, with 95 upregulated and 84 downregulated peptides between hypertrophic scar tissue and matched normal skin. Further bioinformatics analysis (Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis) indicated that precursor proteins of these differentially expressed peptides correlate with cellular process, biological regulation, cell part, binding and structural molecule activity ribosome, and PPAR signaling pathway occurring during pathological changes of hypertrophic scar. Based on prediction database, we found that 78 differentially expressed peptides shared homology with antimicrobial peptides and five matched known immunomodulatory peptides. In conclusion, our results show significantly altered expression profiles of peptides in human hypertrophic scar tissue. These peptides may participate in the etiology of hypertrophic scar and provide beneficial scheme for scar evaluation and treatments. © 2017 Wiley Periodicals, Inc.

Associations of Streptococcus suis Serotype 2 Ribotype Profiles with Clinical Disease and Antimicrobial Resistance

PubMed Central

Rasmussen, S. R.; Aarestrup, F. M.; Jensen, N. E.; Jorsal, S. E.

1999-01-01

A total of 122 Streptococcus suis serotype 2 strains were characterized thoroughly by comparing clinical and pathological observations, ribotype profiles, and antimicrobial resistance. Twenty-one different ribotype profiles were found and compared by cluster analysis, resulting in the identification of three ribotype clusters. A total of 58% of all strains investigated were of two ribotypes belonging to different ribotype clusters. A remarkable relationship existed between the observed ribotype profiles and the clinical-pathological observations because strains of one of the two dominant ribotypes were almost exclusively isolated from pigs with meningitis, while strains of the other dominant ribotype were never associated with meningitis. This second ribotype was isolated only from pigs with pneumonia, endocarditis, pericarditis, or septicemia. Cluster analysis revealed that strains belonging to the same ribotype cluster as one of the dominant ribotypes came from pigs that showed clinical signs similar to those of pigs infected with strains with the respective dominant ribotype profiles. Furthermore, strains belonging to different ribotype clusters had totally different patterns of resistance to antibiotics because strains isolated from pigs with meningitis were resistant to sulfamethazoxazole and strains isolated from pigs with pneumonia, endocarditis, pericarditis, or septicemia were resistant to tetracycline. PMID:9889228

In vivo growth of 60 non-screening detected lung cancers: a computed tomography study.

PubMed

Mets, Onno M; Chung, Kaman; Zanen, Pieter; Scholten, Ernst T; Veldhuis, Wouter B; van Ginneken, Bram; Prokop, Mathias; Schaefer-Prokop, Cornelia M; de Jong, Pim A

2018-04-01

Current pulmonary nodule management guidelines are based on nodule volume doubling time, which assumes exponential growth behaviour. However, this is a theory that has never been validated in vivo in the routine-care target population. This study evaluates growth patterns of untreated solid and subsolid lung cancers of various histologies in a non-screening setting.Growth behaviour of pathology-proven lung cancers from two academic centres that were imaged at least three times before diagnosis (n=60) was analysed using dedicated software. Random-intercept random-slope mixed-models analysis was applied to test which growth pattern most accurately described lung cancer growth. Individual growth curves were plotted per pathology subgroup and nodule type.We confirmed that growth in both subsolid and solid lung cancers is best explained by an exponential model. However, subsolid lesions generally progress slower than solid ones. Baseline lesion volume was not related to growth, indicating that smaller lesions do not grow slower compared to larger ones.By showing that lung cancer conforms to exponential growth we provide the first experimental basis in the routine-care setting for the assumption made in volume doubling time analysis. Copyright ©ERS 2018.

Fractal Analysis of Radiologists Visual Scanning Pattern in Screening Mammography

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

Alamudun, Folami T; Yoon, Hong-Jun; Hudson, Kathy

2015-01-01

Several investigators have investigated radiologists visual scanning patterns with respect to features such as total time examining a case, time to initially hit true lesions, number of hits, etc. The purpose of this study was to examine the complexity of the radiologists visual scanning pattern when viewing 4-view mammographic cases, as they typically do in clinical practice. Gaze data were collected from 10 readers (3 breast imaging experts and 7 radiology residents) while reviewing 100 screening mammograms (24 normal, 26 benign, 50 malignant). The radiologists scanpaths across the 4 mammographic views were mapped to a single 2-D image plane. Then,more » fractal analysis was applied on the derived scanpaths using the box counting method. For each case, the complexity of each radiologist s scanpath was estimated using fractal dimension. The association between gaze complexity, case pathology, case density, and radiologist experience was evaluated using 3 factor fixed effects ANOVA. ANOVA showed that case pathology, breast density, and experience level are all independent predictors of the visual scanning pattern complexity. Visual scanning patterns are significantly different for benign and malignant cases than for normal cases as well as when breast parenchyma density changes.« less

Retrospective study

PubMed Central

Lu, Chao; Lv, Xueyou; Lin, Yiming; Li, Dejian; Chen, Lihua; Ji, Feng; Li, Youming; Yu, Chaohui

2016-01-01

Abstract Conventional forceps biopsy (CFB) is the most popular way to screen for gastric epithelial neoplasia (GEN) and adenocarcinoma of gastric epithelium. The aim of this study was to compare the diagnostic accuracy between conventional forceps biopsy and endoscopic submucosal dissection (ESD). Four hundred forty-four patients who finally undertook ESD in our hospital were enrolled from Jan 1, 2009 to Sep 1, 2015. We retrospectively assessed the characteristics of pathological results of CFB and ESD. The concordance rate between CFB and ESD specimens was 68.92% (306/444). Men showed a lower concordance rate (63.61% vs 79.33%; P = 0.001) and concordance patients were younger (P = 0.048). In multivariate analysis, men significantly had a lower concordance rate (coefficient −0.730, P = 0.002) and a higher rate of pathological upgrade (coefficient −0.648, P = 0.015). Locations of CFB did not influence the concordance rate statistically. The concordance rate was relatively high in our hospital. According to our analysis, old men plus gastric fundus or antrum of CFB were strongly suggested to perform ESD if precancerous lesions were found. And young women with low-grade intraepithelial neoplasia could select regular follow-up. PMID:27472723

Brain Imaging and Behavioral Outcome in Traumatic Brain Injury.

ERIC Educational Resources Information Center

Bigler, Erin D.

1996-01-01

This review explores the cellular pathology associated with traumatic brain injury (TBI) and its relation to neurobehavioral outcomes, the relationship of brain imaging findings to underlying pathology, brain imaging techniques, various image analysis procedures and how they relate to neuropsychological testing, and the importance of brain imaging…

A National Program for Instructional Development in Veterinary Pathology.

ERIC Educational Resources Information Center

Ward, Billy, C.

1979-01-01

Results of a study by the American College of Veterinary Pathologists to investigate mechanisms to facilitate sharing of audiovisual programs include a content analysis in veterinary pathology, a guidebook for the preparation of instruction, 20 instructional programs, a lesson evaluation mechanism, and a proposal for sharing programs. (JMD)

The effect of pathological fractures on the prognosis of patients with osteosarcoma: a meta-analysis of 14 studies

PubMed Central

Zhou, Yifei; Lu, Qian; Xu, Jifeng; Yan, Ruijian; Zhu, Junkun; Xu, Juntao; Jiang, Xuesheng; Li, Jianyou; Wu, Fengfeng

2017-01-01

Osteosarcoma is a leading cause of malignant tumor related death. We conducted a meta-analysis to evaluate the association between pathological fractures and prognosis in patients with osteosarcoma. We searched PubMed, Web of Science, and Embase for studies published until May 15, 2017. Crude and adjusted relative risk (RR) with 95% confidence intervals were used to compare data between the case and control groups. Fourteen studies and 3910 patients were included in the final meta-analysis. No statistically significant difference was detected between the pathological fracture and non-pathological fracture groups in local recurrences analysis (RR = 1.102, 95% CI: 0.813–1.495, P = 0.531); however, a statistically significant difference was found between group in distant metastasis (RR = 1.424, 95% CI: 1.089–1.862, P = 0.01). For survival rates, the following RRs were calculated: 3-year overall survival (OS) (RR = 0.736, 95% CI: 0.593–0.912, P = 0.005); 5-year OS (RR = 0.889, 95% CI: 0.791–0.999, P = 0.049); 3-year event-free survival (EFS) (RR = 0.812, 95% CI: 0.682–0.966, P = 0.018); and 5-year EFS (RR = 0.876, 95% CI: 0.785–0.978, P = 0.019). The pooled estimate of RR was 0.673 (95% CI: 0.364–1.244, P = 0.206) for local recurrence in the amputation and limb salvage groups. In conclusion, our analysis indicated that there were no differences in local recurrence and local recurrence after limb salvage between patients with or without a fracture. Additionally, the patients with pathological fracture had a higher risk of distant metastasis and lower 3-year OS, 5-year OS, 3-year EFS, and 5-year EFS. Considering the limitations of this study, we believe that future large-scale studies should be performed to confirm our conclusions. PMID:29069847

Effects of bacterial infestation caused by human wastes on the skin structures of Mugil platanus Günther, 1880 (Mugilidae).

PubMed

Langer, S L; Vargas, V M F; Flores-Lopes, F; Malabarba, L R

2009-05-01

Manifestation of infectious pathologies in fishes usually increases in environments where organic wastes are disposed. Specimens of Mugil platanus Günther, 1880 and water samples collected at three points of the Tramandaí river were analyzed during a one year period. The macroscopic observation revealed ulcerations in the caudal peduncle area covered with a mass of amorphous and whitened tissues. Histopathologic analysis showed the presence of negative gram bacteria, probably responsible for alterations of the normal structure of the epidermic tissues. Non-parametric statistical analysis for ammonia concentration showed a significant variation among the three collected spots as well as in the multiple comparison between two spots. In this study, we describe cutaneous lesions observed in Mugil platanus specimens and tested their correlation with environmental ammonia concentration.

Problem-gambling severity, suicidality and DSM-IV Axis II personality disorders.

PubMed

Ronzitti, Silvia; Kraus, Shane W; Hoff, Rani A; Clerici, Massimo; Potenza, Marc N

2018-07-01

Despite the strong associations between personality disorders and problem/pathological gambling, few studies have investigated the relationships between personality disorders, problem-gambling severity and suicidal thoughts/behaviors. We examined the relationships between problem-gambling severity and personality disorders among individuals with differing levels of suicidality (none, thoughts alone, attempts). We analyzed data from 13,543 participants of the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC) study. First, differences in sociodemographic characteristics and prevalence of personality disorders were analyzed according to problem-gambling severity and suicidality status. Second, we performed a logistic regression to assess among the relationship between problem-gambling severity and DSM-IV Axis II psychopathology according to suicidality level. At-risk or problem/pathological gambling groups showed higher rates of a wide range of personality disorders compared to non-gamblers. Logistic regression showed that at-risk pathological gamblers had a higher odds ratio for any personality disorder in the group with no history of suicidality, particularly for cluster-B personality disorders. Odds ratio interaction analysis identified the relationship between problem-gambling severity and personality disorders, particularly those in cluster B, differ according to suicidality status. Our findings suggest a complex relationship between suicidality, problem-gambling severity and personality disorders. The stronger relationship between problem-gambling severity and personality disorders in people with no suicidality as compared to some suicidality suggests that some of the relationship between greater problem-gambling severity and Axis II psychopathology is accounted for by increased suicidality. The findings have implications for clinical interventions targeting suicidality in individuals with gambling disorders. Published by Elsevier Ltd.

Dura mater graft-associated Creutzfeldt-Jakob disease with 30-year incubation period.

PubMed

Shijo, Masahiro; Honda, Hiroyuki; Koyama, Sachiko; Ishitsuka, Koji; Maeda, Koichiro; Kuroda, Junya; Tanii, Mitsugu; Kitazono, Takanari; Iwaki, Toru

2017-06-01

Over 60% of all patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) have been diagnosed in Japan. The incubation period has ranged from 1 to 30 years and the age at onset from 15 to 80 years. Here, we report a 77-year-old male Japanese autopsied dCJD case with the longest incubation period so far in Japan. He received a cadaveric dural graft at the right cranial convexity following a craniotomy for meningioma at the age of 46. At 30 years post-dural graft placement, disorientation was observed as an initial symptom of dCJD. He rapidly began to present with inconsistent speech, cognitive impairment and tremor of the left upper extremity. Occasional myoclonic jerks were predominantly observed on the left side. Brain MRI presented hyperintense signals on diffusion-weighted and T2-weighted images, at the right cerebral cortex. The most hyperintense lesion was located at the right parietal lobe, where the dura mater graft had been transplanted. Single-photon emission CT scan showed markedly decreased cerebral blood flow at the right parietal lobe. EEG revealed diffuse and slow activities with periodic sharp-wave complex discharges seen in the right parietal, temporal and occipital lobes. He died of pneumonia 9 months after onset. Brain pathology revealed non-plaque-type dCJD. Laterality of neuropathological changes, including spongiform change, neuronal loss, gliosis or PrP deposits, was not evident. Western blot analysis showed type 1 PrP CJD . Alzheimer-type pathology and PSP-like pathology were also observed. © 2016 Japanese Society of Neuropathology.

Chromosome 17 and hereditary dementia: linkage studies in three non-Alzheimer families and kindreds with late-onset FAD.

PubMed

Bird, T D; Wijsman, E M; Nochlin, D; Leehey, M; Sumi, S M; Payami, H; Poorkaj, P; Nemens, E; Rafkind, M; Schellenberg, G D

1997-04-01

Several previous families with differing clinical and pathologic characteristics have demonstrated linkage to the 17q21-22 region. We have performed a linkage analysis with chromosome 17 markers on three families showing autosomal dominant inheritance of non-Alzheimer dementia and 60 kindreds with late-onset familial Alzheimer's disease (FAD). Family A shows unequivocal evidence of linkage with a maximum lod score of 5.0 for marker D17S934 (theta = 0.001). This family has an unusual syndrome of a schizophrenia-like psychosis beginning in the fifth or sixth decade followed by severe dementia with an average disease duration of 13.8 years. Neuropathology from five autopsies in this family has shown marked neurofibrillary tangle formation (NFT), degeneration of the amygdala, and no amyloid plaques. This confirms the presence of a gene associated with dementia on 17q and extends the related phenotype to include schizophrenia-like symptoms and classic NFT pathology. A second family with early aphasia progressing to dementia and cortical-basal ganglion-like degeneration also has suggestive evidence for linkage to 17q. A third family with very early-onset dementia (mean, 31 years) and nonspecific pathology can be excluded from the 17q region and emphasizes additional genetic heterogeneity in non-Alzheimer hereditary dementia. Finally, we also present evidence against linkage to D17S579 in the set of 60 families with late-onset FAD, providing further evidence that the chromosome 17 gene is unlikely to be involved in the pathogenesis of typical AD.

Transfer Technique Is Associated With Shoulder Pain and Pathology in People With Spinal Cord Injury: A Cross-Sectional Investigation.

PubMed

Hogaboom, Nathan S; Worobey, Lynn A; Boninger, Michael L

2016-10-01

To evaluate how transfer technique and subject characteristics relate to ultrasound measures of shoulder soft tissue pathology and self-reported shoulder pain during transfers in a sample of wheelchair users with spinal cord injury (SCI). Cross-sectional observational study. Research laboratory, national and local veterans' wheelchair sporting events. A convenience sample of wheelchair users (N=76) with nonprogressive SCI. Participants were aged >18 years, >1 year postinjury, and could complete repeated independent wheelchair transfers without the use of their leg muscles. Not applicable. Transfer pain items from the Wheelchair User's Shoulder Pain Index; transfer technique assessed using the Transfer Assessment Instrument (TAI); and shoulder pathology markers examined using the Ultrasound Shoulder Pathology Rating Scale (USPRS). Better transfer technique (higher TAI) correlated with less injury (lower USPRS) (partial η(2)=.062, P<.05) and less pain during transfers (partial η(2)=.049, P<.10). Greater age was the strongest predictor of greater pathology (USPRS total: partial η(2)=.225, supraspinatus grade: partial η(2)=.174, P<.01). An interaction between technique and weight was found (P<.10): participants with lower body weights showed a decrease in pathology markers with better transfer technique (low weight: R(2)=.422, P<.05; middle weight: R(2)=.200, P<.01), while those with higher weight showed little change with technique (R(2)=.018, P>.05). Participants with better transfer technique exhibited less shoulder pathology and reported less pain during transfers. The relationship between technique and pathology was strongest in lower-weight participants. While causation cannot be proven because of study design, it is possible that using a better transfer technique and optimizing body weight could reduce the incidence of shoulder pathology and pain. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

NARCISSISM AND CONCERN: THE RELATIONSHIP OF SELF-OBJECT NEEDS AND NARCISSISTIC SYMPTOMS WITH HEALTHY AND PATHOLOGICAL CONCERN.

PubMed

Friedemann, Yael; Tolmacz, Rami; Doron, Yonit

2016-03-01

While concern and narcissism seem to be contradictory in nature, clinical evidence and theoretical writings on pathological forms of concern--tracing their origin to deficiencies in early relationships with primary caretakers--suggest that the actual relationship between these two characteristics might be much more complicated. We respond to a study aimed to add empirical data to the clinical and theoretical knowledge examined the relationships between self-object functions, types of narcissism and pathological concern. The findings of the study showed that pathological concern was positively associated with self-object needs and that this association was mediated by covert narcissism. Our discussion focuses on the developmental and psychodynamic sources of pathological concern, as well as its significance in the intrapersonal and interpersonal domains.

18F-AV-1451 positron emission tomography in Alzheimer's disease and progressive supranuclear palsy.

PubMed

Passamonti, Luca; Vázquez Rodríguez, Patricia; Hong, Young T; Allinson, Kieren S J; Williamson, David; Borchert, Robin J; Sami, Saber; Cope, Thomas E; Bevan-Jones, W Richard; Jones, P Simon; Arnold, Robert; Surendranathan, Ajenthan; Mak, Elijah; Su, Li; Fryer, Tim D; Aigbirhio, Franklin I; O'Brien, John T; Rowe, James B

2017-03-01

The ability to assess the distribution and extent of tau pathology in Alzheimer's disease and progressive supranuclear palsy in vivo would help to develop biomarkers for these tauopathies and clinical trials of disease-modifying therapies. New radioligands for positron emission tomography have generated considerable interest, and controversy, in their potential as tau biomarkers. We assessed the radiotracer 18F-AV-1451 with positron emission tomography imaging to compare the distribution and intensity of tau pathology in 15 patients with Alzheimer's pathology (including amyloid-positive mild cognitive impairment), 19 patients with progressive supranuclear palsy, and 13 age- and sex-matched controls. Regional analysis of variance and a support vector machine were used to compare and discriminate the clinical groups, respectively. We also examined the 18F-AV-1451 autoradiographic binding in post-mortem tissue from patients with Alzheimer's disease, progressive supranuclear palsy, and a control case to assess the 18F-AV-1451 binding specificity to Alzheimer's and non-Alzheimer's tau pathology. There was increased 18F-AV-1451 binding in multiple regions in living patients with Alzheimer's disease and progressive supranuclear palsy relative to controls [main effect of group, F(2,41) = 17.5, P < 0.0001; region of interest × group interaction, F(2,68) = 7.5, P < 0.00001]. More specifically, 18F-AV-1451 binding was significantly increased in patients with Alzheimer's disease, relative to patients with progressive supranuclear palsy and with control subjects, in the hippocampus and in occipital, parietal, temporal, and frontal cortices (t's > 2.2, P's < 0.04). Conversely, in patients with progressive supranuclear palsy, relative to patients with Alzheimer's disease, 18F-AV-1451 binding was elevated in the midbrain (t = 2.1, P < 0.04); while patients with progressive supranuclear palsy showed, relative to controls, increased 18F-AV-1451 uptake in the putamen, pallidum, thalamus, midbrain, and in the dentate nucleus of the cerebellum (t's > 2.7, P's < 0.02). The support vector machine assigned patients' diagnoses with 94% accuracy. The post-mortem autoradiographic data showed that 18F-AV-1451 strongly bound to Alzheimer-related tau pathology, but less specifically in progressive supranuclear palsy. 18F-AV-1451 binding to the basal ganglia was strong in all groups in vivo. Postmortem histochemical staining showed absence of neuromelanin-containing cells in the basal ganglia, indicating that off-target binding to neuromelanin is an insufficient explanation of 18F-AV-1451 positron emission tomography data in vivo, at least in the basal ganglia. Overall, we confirm the potential of 18F-AV-1451 as a heuristic biomarker, but caution is indicated in the neuropathological interpretation of its binding. Off-target binding may contribute to disease profiles of 18F-AV-1451 positron emission tomography, especially in primary tauopathies such as progressive supranuclear palsy. We suggest that 18F-AV-1451 positron emission tomography is a useful biomarker to assess tau pathology in Alzheimer's disease and to distinguish it from other tauopathies with distinct clinical and pathological characteristics such as progressive supranuclear palsy. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia.

PubMed

Montironi, Rodolfo; Thompson, Deborah; Scarpelli, Marina; Mazzucchelli, Roberta; Peketi, Prasanthi; Hamilton, Peter W; Bostwick, David G; Bartels, Peter H

2004-08-01

This digital texture analysis-based study evaluates the chromatin organization state in flat and cribriform high-grade prostatic intraepithelial neoplasia (PIN), in the adjacent normal looking secretory epithelium and in the co-occurring adenocarcinoma. Digital texture analysis (karyometry) was carried out on hematoxylin and eosin-stained sections from 24 radical prostatectomy specimens with high-grade PIN (12 with flat and 12 with cribriform architectural pattern, respectively) and cancer. Quantification was also conducted on the normal looking secretory epithelium. Discriminant analysis and the nonsupervised learning algorithm P-index were used to identify suitable subsets of features useful for the discrimination and classification of pathological groups and to explore multivariate data structure in the pathological subgroups. The average nuclear abnormality increases monotonically from the histologically normal appearing secretory epithelium to high-grade PIN and to adenocarcinoma. The nuclei from the so-called perimeter compartment of the flat high-grade PIN lesions show a higher nuclear abnormality compared to the nuclei of the cribriform high-grade PINs. Discriminant analysis shows that flat and cribriform high-grade PINs fall into two populations. Processing by the nonsupervised learning algorithm P-index revealed the existence of three well-defined, distinct subpopulations of nuclei of different chromatin phenotype. In the flat high-grade PIN lesions the proportions of nuclei in the three subpopulations are 16.5% (low abnormality), 25.0% (mid abnormality) and 58.5% (high abnormality), respectively. In the cribriform high-grade PIN lesions, 100% of the nuclei are in the mid-abnormality subpopulation. These differences are also discernible in the co-occurring adenocarcinoma and the histologically normal appearing secretory epithelium. To conclude, karyometry and statistical analysis detect the existence of distinct cell subpopulations of different chromatin packaging and phenotype, with the nuclei from the flat high-grade PIN lesions, adjacent normal looking epithelium and co-occurring adenocarcinoma expressing a greater nuclear abnormality than in the specimens with cribriform high-grade PIN.

Gender Differences in Exercise Dependence and Eating Disorders in Young Adults: A Path Analysis of a Conceptual Model

PubMed Central

Meulemans, Shelli; Pribis, Peter; Grajales, Tevni; Krivak, Gretchen

2014-01-01

The purpose of our study was to study the prevalence of exercise dependence (EXD) among college students and to investigate the role of EXD and gender on exercise behavior and eating disorders. Excessive exercise can become an addiction known as exercise dependence. In our population of 517 college students, 3.3% were at risk for EXD and 8% were at risk for an eating disorder. We used Path analysis the simplest case of Structural Equation Modeling (SEM) to investigate the role of EXD and exercise behavior on eating disorders. We observed a small direct effect from gender to eating disorders. In females we observed significant direct effect between exercise behavior (r = −0.17, p = 0.009) and EXD (r = 0.34, p < 0.001) on eating pathology. We also observed an indirect effect of exercise behavior on eating pathology (r = 0.16) through EXD (r = 0.48, r2 = 0.23, p < 0.001). In females the total variance of eating pathology explained by the SEM model was 9%. In males we observed a direct effect between EXD (r = 0.23, p < 0.001) on eating pathology. We also observed indirect effect of exercise behavior on eating pathology (r = 0.11) through EXD (r = 0.49, r2 = 0.24, p < 0.001). In males the total variance of eating pathology explained by the SEM model was 5%. PMID:25379689

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

3D marker-controlled watershed for kidney segmentation in clinical CT exams.

PubMed

Wieclawek, Wojciech

2018-02-27

Image segmentation is an essential and non trivial task in computer vision and medical image analysis. Computed tomography (CT) is one of the most accessible medical examination techniques to visualize the interior of a patient's body. Among different computer-aided diagnostic systems, the applications dedicated to kidney segmentation represent a relatively small group. In addition, literature solutions are verified on relatively small databases. The goal of this research is to develop a novel algorithm for fully automated kidney segmentation. This approach is designed for large database analysis including both physiological and pathological cases. This study presents a 3D marker-controlled watershed transform developed and employed for fully automated CT kidney segmentation. The original and the most complex step in the current proposition is an automatic generation of 3D marker images. The final kidney segmentation step is an analysis of the labelled image obtained from marker-controlled watershed transform. It consists of morphological operations and shape analysis. The implementation is conducted in a MATLAB environment, Version 2017a, using i.a. Image Processing Toolbox. 170 clinical CT abdominal studies have been subjected to the analysis. The dataset includes normal as well as various pathological cases (agenesis, renal cysts, tumors, renal cell carcinoma, kidney cirrhosis, partial or radical nephrectomy, hematoma and nephrolithiasis). Manual and semi-automated delineations have been used as a gold standard. Wieclawek Among 67 delineated medical cases, 62 cases are 'Very good', whereas only 5 are 'Good' according to Cohen's Kappa interpretation. The segmentation results show that mean values of Sensitivity, Specificity, Dice, Jaccard, Cohen's Kappa and Accuracy are 90.29, 99.96, 91.68, 85.04, 91.62 and 99.89% respectively. All 170 medical cases (with and without outlines) have been classified by three independent medical experts as 'Very good' in 143-148 cases, as 'Good' in 15-21 cases and as 'Moderate' in 6-8 cases. An automatic kidney segmentation approach for CT studies to compete with commonly known solutions was developed. The algorithm gives promising results, that were confirmed during validation procedure done on a relatively large database, including 170 CTs with both physiological and pathological cases.

Ultrasound biomicroscopic imaging in paediatric ocular toxocariasis.

PubMed

Liu, Jinghua; Li, Songfeng; Deng, Guangda; Yang, Wenli; Chen, Wei; Lu, Hai

2017-11-01

To determine the potential and usefulness of ultrasound biomicroscopy (UBM) as a diagnostic procedure on a larger cohort of paediatric patients with ocular toxocariasis. UBM was performed on 41 eyes of 41 patients with ocular toxocariasis in order to determine configuration of peripheral retina, pars plana and vitreous. Location and range of peripheral pathology using ophthalmoscopy with scleral indentation, UBM and intraoperative confirmation were recorded and compared. Pathological structures such as vitreous condensations or membranes of various configuration and extent were identified by UBM. UBM revealed peripheral granuloma and pseudocystic changes in the peripheral vitreous in 15 of 41 eyes. Compared with indirect ophthalmoscope, statistical analysis showed significant differences in the number of clock-hours of peripheral pathology detected by UBM (p=0.015), while statistical differences were not found between UBM and intraoperative peripheral examinations using scleral indentation (p=0.432). UBM seems to be a valuable and reliable diagnostic technique for the evaluation of patients with ocular toxocariasis. Longitudinal studies will have to determine the relevance of UBM findings for the individual clinical course and their influence on therapeutic decisions. 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/.