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Sample records for adverse pathologic features

  1. Feature Importance in Nonlinear Embeddings (FINE): Applications in Digital Pathology.

    PubMed

    Ginsburg, Shoshana B; Lee, George; Ali, Sahirzeeshan; Madabhushi, Anant

    2016-01-01

    Quantitative histomorphometry (QH) refers to the process of computationally modeling disease appearance on digital pathology images by extracting hundreds of image features and using them to predict disease presence or outcome. Since constructing a robust and interpretable classifier is challenging in a high dimensional feature space, dimensionality reduction (DR) is often implemented prior to classifier construction. However, when DR is performed it can be challenging to quantify the contribution of each of the original features to the final classification result. We have previously presented a method for scoring features based on their importance for classification on an embedding derived via principal components analysis (PCA). However, nonlinear DR involves the eigen-decomposition of a kernel matrix rather than the data itself, compounding the issue of classifier interpretability. In this paper we present feature importance in nonlinear embeddings (FINE), an extension of our PCA-based feature scoring method to kernel PCA (KPCA), as well as several NLDR algorithms that can be cast as variants of KPCA. FINE is applied to four digital pathology datasets to identify key QH features for predicting the risk of breast and prostate cancer recurrence. Measures of nuclear and glandular architecture and clusteredness were found to play an important role in predicting the likelihood of recurrence of both breast and prostate cancers. Compared to the t-test, Fisher score, and Gini index, FINE was able to identify a stable set of features that provide good classification accuracy on four publicly available datasets from the NIPS 2003 Feature Selection Challenge.

  2. Functional Feature Selection by Weighted Projections in Pathological Voice Detection

    NASA Astrophysics Data System (ADS)

    Sánchez Giraldo, Luis; Martínez Tabares, Fernando; Castellanos Domínguez, Germán

    In this paper, we introduce an adaptation of a multivariate feature selection method to deal with functional features. In our case, observations are described by a set of functions defined over a common domain (e.g. a time interval). The feature selection method consists on combining variable weighting with a feature extraction projection. Although the employed method was primarily intended for observations described by vectors in ℝ n , we propose a simple extension that allows us to select a set of functional features, which is well suited for classification. This study is complemented by the incorporation of Functional Principal Component Analysis (FPCA) that project functions into a finite dimensional space were we can perform classification easily. Another remarkable property of FPCA is that it can provide insight about the nature of the functional features. The proposed algorithms are tested on a pathological voice detection task. Two databases are considered: Massachusetts Eye and Ear Infirmary Voice Laboratory voice disorders database and Universidad Politécnica de Madrid voice database. As a result, we obtain a canonical function whose time average is enough to reach similar performances to the ones reported in the literature.

  3. Pathological and molecular features of adrenocortical carcinoma: an update.

    PubMed

    Volante, M; Buttigliero, C; Greco, E; Berruti, A; Papotti, M

    2008-07-01

    The pathological diagnosis of adrenocortical carcinoma (ACC), which is based on gross and microscopic criteria, is subjective. None of the features are absolutely indicative of malignancy, although their combination in a scoring system may correctly identify ACC. The Weiss system, which is currently the most popular, combines nine morphological parameters, of which three are structural ("dark" cytoplasm, diffuse architecture, necrosis), three are cytological (atypia, mitotic count, atypical mitotic figures) and three are related to invasion (of sinusoids, veins and tumour capsule). Although there are strictly defined criteria for each feature, some are straightforward and objective, while others are potentially more problematic (diffuse architecture, necrosis, sinusoidal, venous and capsular invasions). The classification of oncocytic and paediatric adrenocortical tumours is even more challenging, as not all of the above morphological parameters are predictors of malignancy in these tumour types. As an alternative to the morphological approach, a wide array of chromosomal, genetic, molecular and immunohistochemical markers have been tested in ACC to identify reliable diagnostic and prognostic factors. Genetic and epigenetic alterations of p53, IGF-2 and molecules involved in cancer cell invasive properties seem the most promising. These molecular markers may not only play a role in the biology of these tumours and have prognostic implications, but may also be used as potential targets for treatment. However, these markers are not sufficiently sensitive and specific to replace conventional morphological criteria. PMID:18430754

  4. HPV vaccines: their pathology-based discovery, benefits, and adverse effects.

    PubMed

    Nicol, Alcina F; de Andrade, Cecilia V; Russomano, Fabio B; Rodrigues, Luana S L; Oliveira, Nathalia S; Provance, David William; Nuovo, Gerard J

    2015-12-01

    The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings.

  5. HPV vaccines: their pathology-based discovery, benefits, and adverse effects.

    PubMed

    Nicol, Alcina F; de Andrade, Cecilia V; Russomano, Fabio B; Rodrigues, Luana S L; Oliveira, Nathalia S; Provance, David William; Nuovo, Gerard J

    2015-12-01

    The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings. PMID:26321154

  6. Pathological Role of Serum- and Glucocorticoid-Regulated Kinase 1 in Adverse Ventricular Remodeling

    PubMed Central

    Das, Saumya; Aiba, Takeshi; Rosenberg, Michael; Hessler, Katherine; Xiao, Chunyang; Quintero, Pablo A.; Ottaviano, Filomena G.; Knight, Ashley C.; Graham, Evan L.; Boström, Pontus; Morissette, Michael R.; del Monte, Federica; Begley, Michael J.; Cantley, Lewis C.; Ellinor, Patrick T.; Tomaselli, Gordon F.; Rosenzweig, Anthony

    2012-01-01

    Background Heart failure is a growing cause of morbidity and mortality. Cardiac PI3-kinase signaling promotes cardiomyocyte survival and function but is paradoxically activated in heart failure, suggesting chronic activation of this pathway may become maladaptive. Here we investigated the downstream PI3-kinase effector, SGK1 (serum- and glucocorticoid-regulated kinase-1), in heart failure and its complications. Methods and Results We found that cardiac SGK1 is activated in human and murine heart failure. We investigated the role of SGK1 in the heart using cardiac-specific expression of constitutively-active or dominant-negative SGK1. Cardiac-specific activation of SGK1 in mice increased mortality, cardiac dysfunction, and ventricular arrhythmias. The pro-arrhythmic effects of SGK1 were linked to biochemical and functional changes in the cardiac sodium channel and could be reversed by treatment with ranolazine, a blocker of the late sodium current. Conversely, cardiac-specific inhibition of SGK1 protected mice after hemodynamic stress from fibrosis, heart failure, and sodium channel alterations. Conclusions SGK1 appears both necessary and sufficient for key features of adverse ventricular remodeling and may provide a novel therapeutic target in cardiac disease. PMID:23019294

  7. Clinical and pathological features of patients with nemaline myopathy.

    PubMed

    Yin, Xi; Pu, Chuan Qiang; Wang, Qian; Liu, Jie Xiao; Mao, Yan Ling

    2014-07-01

    Nemaline myopathy (NM) is a rare congenital myopathy of great heterogeneity, characterized by the presence of rods in the cytoplasm of muscle fibers. This study aimed to summarize and analyze retrospectively the clinicopathological features of 28 patients with NM. Among the 28 patients, 15 were classified as of the typical congenital type, manifested as lower- or four-limb weakness as the first symptom and slowly progressive course. Six patients were classified as of childhood onset type, with lower-limb weakness and progressive course. Seven patients were classified as of the adult onset type, with rapidly progressive course and obvious muscle atrophy. Patient's 1, 16 and 23 had rapid clinical progression. On follow up, the three patients showed respiratory failure. Limb weakness in all patients was proximal‑dominant. Hypotonia was observed in most patients. High arched feet were also observed as dysmorfic features. In all patients, the creatine kinase (CK) level was normal or mildly elevated, and electromyography revealed myogenic changes. Nemaline bodies were observed under a light microscope in more than half of the patients' muscle fibers, and especially in type I fibers. All patients showed fiber type I predominance and atrophy. Modified Gömöri trichrome staining showed characteristic purple‑colored rods. Muscle electron microscopy revealed the presence of high electron‑dense nemaline bodies around the nucleus, and of a disorganized myofibrillar apparatus, with broken myofilaments and irregular myofibrils and Z lines. The 28 patients with NM shared a number of clinical features, such as proximal limb weakness, reduced deep tendon reflex and dysmorfic features. Differences were also observed between the three types of patients, with regards to course progression, disease severity and respiratory failure. In conclusion, patients with NM showed great clinical heterogeneity. The diagnosis of NM was mainly based on the muscle biopsy. PMID:24788569

  8. Acute Chorioamnionitis and Funisitis: Definition, Pathologic Features, and Clinical Significance

    PubMed Central

    Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee

    2015-01-01

    ; however, in fetuses, it is a risk factor for short- and long-term complications (i.e. neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental pathology. Illustrations of the lesions and diagrams of the mechanisms of disease are provided. PMID:26428501

  9. Pathological features of olfactory neuroblastoma in an axolotl (Ambystoma mexicanum).

    PubMed

    Shioda, Chieko; Uchida, Kazuyuki; Nakayama, Hiroyuki

    2011-08-01

    A one-year-old, female Mexican axolotl (Ambystoma mexicanum) had a rough-surfaced, polypoid, pink tumor mass of approximately 10 mm in diameter in the oral cavity. Histologically, the tumor extended from the ethmoturbinate region and into the oral cavity and had replaced some of the maxillary bone tissue. The tumor mass was composed of a lobular architecture of small round-shaped tumor cells with occasional Flexner-Wintersteiner-like rosette formation. There were no metastatic lesions in the other organs. Immunohistochemically, the tumor cells were partly positive for several neural markers (class III beta-tubulin, S-100 protein, and doublecortin) and intensely positive for an epithelial marker (cytokeratin AE1/AE3). These results suggest that the present tumor originated from neuroectodermal tissue. Considering the location and histological and immunohistochemical features of the tumor, a diagnosis of olfactory neuroblastoma was made.

  10. Pathogenesis, clinical features and pathology of chronic arsenicosis.

    PubMed

    Sengupta, Sujit Ranjan; Das, Nilay Kanti; Datta, Pijush Kanti

    2008-01-01

    Arsenicosis is a multisystem disorder, with virtually no system spared from its vicious claw; though its predominant manifestations are linked to cutaneous involvement. Cutaneous effects take the form of pigmentary changes, hyperkeratosis, and skin cancers (Bowen's disease, squamous cell carcinoma, and basal cell epithelioma). Peripheral vascular disease (blackfoot disease), hypertension, ischemic heart disease, noncirrhotic portal hypertension, hepatomegaly, peripheral neuropathy, respiratory and renal involvement, bad obstetrical outcome, hematological disturbances, and diabetes mellitus are among the other clinical features linked to arsenic toxicity. The effects are mediated principally by the trivalent form of arsenic (arsenite), which by its ability to bind with sulfhydryl groups present in various essential compounds leads to inactivation and derangement of body function. Though the toxicities are mostly linked to the trivalent state, arsenic is consumed mainly in its pentavalent form (arsenate), and reduction of arsenate to arsenite is mediated through glutathione. Body attempts to detoxify the agent via repeated oxidative methylation and reduction reaction, leading to the generation of methylated metabolites, which are excreted in the urine. Understandably the detoxification/bio-inactivation process is not a complete defense against the vicious metalloid, and it can cause chromosomal aberration, impairment of DNA repair process, alteration in the activity of tumor suppressor gene, etc., leading to genotoxicity and carcinogenicity. Arsenic causes apoptosis via free radical generation, and the cutaneous toxicity is linked to its effect on various cytokines (e.g., IL-8, TGF-beta, TNF-alpha, GM-CSF), growth factors, and transcription factors. Increased expression of cytokeratins, keratin-16 (marker for hyperproliferation) and keratin-8 and -18 (marker for less differentiated epithelial cells), can be related to the histopathological findings of hyperkeratosis

  11. CD117 expression in breast phyllodes tumors correlates with adverse pathologic parameters and reduced survival.

    PubMed

    Tan, Wai Jin; Thike, Aye Aye; Tan, Sie Yong; Tse, Gary M-K; Tan, Min-Han; Bay, Boon Huat; Tan, Puay Hoon

    2015-03-01

    CD117 (c-kit) is a type III receptor tyrosine kinase encoded by the KIT gene. Deregulation of expression and mutations in the gene are implicated in various tumors. Reports of CD117 expression in phyllodes tumors have been controversial. We aim to investigate the protein expression of CD117 and mutations in the KIT gene in phyllodes tumors, and correlate the findings with pathological parameters and clinical outcome. A total of 272 cases were included in this study. CD117 expression was investigated by immunohistochemistry on tissue microarray sections. Toluidine blue staining was performed to indicate mast cells. Overall, 28 (10%) cases were CD117 positive. CD117 expression was significantly associated with tumor grade (P<0.001), increased stromal hypercellularity (P=0.003), stromal atypia (P=0.01), and stromal mitotic activity (P<0.001), permeative microscopic margins (P=0.002), and presence of hemorrhage (P=0.001). Expression was also associated with poorer overall survival (P=0.003). Nineteen cases were further selected for mutation screening through the Affymetrix OncoScan platform. No mutation of the KIT gene was found. Despite a lack of mutations in the KIT gene, CD117 protein expression is associated with unfavorable pathological parameters and poorer prognosis, suggesting an underlying role in the biology of phyllodes tumors.

  12. Text mining for the Vaccine Adverse Event Reporting System: medical text classification using informative feature selection

    PubMed Central

    Nguyen, Michael D; Woo, Emily Jane; Markatou, Marianthi; Ball, Robert

    2011-01-01

    Objective The US Vaccine Adverse Event Reporting System (VAERS) collects spontaneous reports of adverse events following vaccination. Medical officers review the reports and often apply standardized case definitions, such as those developed by the Brighton Collaboration. Our objective was to demonstrate a multi-level text mining approach for automated text classification of VAERS reports that could potentially reduce human workload. Design We selected 6034 VAERS reports for H1N1 vaccine that were classified by medical officers as potentially positive (Npos=237) or negative for anaphylaxis. We created a categorized corpus of text files that included the class label and the symptom text field of each report. A validation set of 1100 labeled text files was also used. Text mining techniques were applied to extract three feature sets for important keywords, low- and high-level patterns. A rule-based classifier processed the high-level feature representation, while several machine learning classifiers were trained for the remaining two feature representations. Measurements Classifiers' performance was evaluated by macro-averaging recall, precision, and F-measure, and Friedman's test; misclassification error rate analysis was also performed. Results Rule-based classifier, boosted trees, and weighted support vector machines performed well in terms of macro-recall, however at the expense of a higher mean misclassification error rate. The rule-based classifier performed very well in terms of average sensitivity and specificity (79.05% and 94.80%, respectively). Conclusion Our validated results showed the possibility of developing effective medical text classifiers for VAERS reports by combining text mining with informative feature selection; this strategy has the potential to reduce reviewer workload considerably. PMID:21709163

  13. Uncommon non-Hodgkin lymphomas of childhood: pathological diagnosis, clinical features and treatment approaches.

    PubMed

    Sandlund, John T; Perkins, Sherrie L

    2015-06-01

    We provide a review of the pathological and clinical features for uncommon B-cell and T-cell lymphomas of childhood with a specific focus on advances in treatment approaches and outcomes. There is clearly a need for prospective investigation of both the clinical and biological features of the uncommon non-Hodgkin lymphoma subtypes in childhood. These results should lead to more uniform and more effective treatment approaches. PMID:25851546

  14. Distinct Clinic-Pathological Features of Early Differentiated-Type Gastric Cancers after Helicobacter pylori Eradication.

    PubMed

    Horiguchi, Noriyuki; Tahara, Tomomitsu; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Shibata, Tomoyuki; Ohmiya, Naoki

    2016-01-01

    Background. Gastric cancer is discovered even after successful eradication of H. pylori. We investigated clinic pathological features of early gastric cancers after H. pylori eradication. Methods. 51 early gastric cancers (EGCs) from 44 patients diagnosed after successful H. pylori eradication were included as eradication group. The clinic-pathological features were compared with that of 131 EGCs from 120 patients who did not have a history of H. pylori eradication (control group). Results. Compared with control group, clinic-pathological features of eradication group were characterized as depressed (p < 0.0001), reddish (p = 0.0001), and smaller (p = 0.0095) lesions, which was also confirmed in the comparison of six metachronous lesions diagnosed after initial ESD and subsequent successful H. pylori eradication. Prevalence of both SM2 (submucosal invasion greater than 500 μm) and unexpected SM2 cases tended to be higher in eradication group (p = 0.077, 0.0867, resp.). Prevalence of inconclusive diagnosis of gastric cancer during pretreatment biopsy was also higher in the same group (26.0% versus 1.6%, p < 0.0001). Conclusions. Informative clinic pathological features of EGC after H. pylori eradication are depressed, reddish appearances, which should be treated as a caution because histological diagnosis of cancerous tissue is sometimes difficult by endoscopic biopsy. PMID:27212944

  15. Distinct Clinic-Pathological Features of Early Differentiated-Type Gastric Cancers after Helicobacter pylori Eradication

    PubMed Central

    Horiguchi, Noriyuki; Tahara, Tomomitsu; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Shibata, Tomoyuki; Ohmiya, Naoki

    2016-01-01

    Background. Gastric cancer is discovered even after successful eradication of H. pylori. We investigated clinic pathological features of early gastric cancers after H. pylori eradication. Methods. 51 early gastric cancers (EGCs) from 44 patients diagnosed after successful H. pylori eradication were included as eradication group. The clinic-pathological features were compared with that of 131 EGCs from 120 patients who did not have a history of H. pylori eradication (control group). Results. Compared with control group, clinic-pathological features of eradication group were characterized as depressed (p < 0.0001), reddish (p = 0.0001), and smaller (p = 0.0095) lesions, which was also confirmed in the comparison of six metachronous lesions diagnosed after initial ESD and subsequent successful H. pylori eradication. Prevalence of both SM2 (submucosal invasion greater than 500 μm) and unexpected SM2 cases tended to be higher in eradication group (p = 0.077, 0.0867, resp.). Prevalence of inconclusive diagnosis of gastric cancer during pretreatment biopsy was also higher in the same group (26.0% versus 1.6%, p < 0.0001). Conclusions. Informative clinic pathological features of EGC after H. pylori eradication are depressed, reddish appearances, which should be treated as a caution because histological diagnosis of cancerous tissue is sometimes difficult by endoscopic biopsy. PMID:27212944

  16. Pathology

    SciTech Connect

    Rubin, E.; Farber, J.L. )

    1988-01-01

    This book contains 29 chapters. Some of the titles are: Genetic and Systemic Diseases; Cell Injury; Inflammation; The Gastrointestinal o Tract; The Pancreas; Environmental and Nutritional Pathology; Infectious and Parasitic Diseases; and Blood Vessels.

  17. Glioma grading using cell nuclei morphologic features in digital pathology images

    NASA Astrophysics Data System (ADS)

    Reza, Syed M. S.; Iftekharuddin, Khan M.

    2016-03-01

    This work proposes a computationally efficient cell nuclei morphologic feature analysis technique to characterize the brain gliomas in tissue slide images. In this work, our contributions are two-fold: 1) obtain an optimized cell nuclei segmentation method based on the pros and cons of the existing techniques in literature, 2) extract representative features by k-mean clustering of nuclei morphologic features to include area, perimeter, eccentricity, and major axis length. This clustering based representative feature extraction avoids shortcomings of extensive tile [1] [2] and nuclear score [3] based methods for brain glioma grading in pathology images. Multilayer perceptron (MLP) is used to classify extracted features into two tumor types: glioblastoma multiforme (GBM) and low grade glioma (LGG). Quantitative scores such as precision, recall, and accuracy are obtained using 66 clinical patients' images from The Cancer Genome Atlas (TCGA) [4] dataset. On an average ~94% accuracy from 10 fold crossvalidation confirms the efficacy of the proposed method.

  18. Nemaline bodies as unique pathological feature in the course of treated dermatomyositis.

    PubMed

    Letournel, F; Le Clec'h, C; Croué, A; Marcorelles, P; Lavigne, C; Pénisson-Besnier, I

    2010-01-01

    Dermatomyositis was diagnosed on clinical and muscle histological criteria in a 42-year-old woman. Despite treatment, the patient complained of deterioration of her muscle condition. Since her symptoms were discordant with the rest of the data, muscle biopsy was performed and disclosed rod-bearing non-atrophic fibers as the unique and predominant pathological feature. Their significance is examined in this paper. PMID:21073838

  19. Preventing eating disorder pathology: common and unique features of successful eating disorders prevention programs.

    PubMed

    Ciao, Anna C; Loth, Katie; Neumark-Sztainer, Dianne

    2014-07-01

    Over the past two decades, the field of eating disorders has made remarkable strides in identifying, evaluating, and disseminating successful prevention programs. The current review identifies and discusses nine distinct eating disorders prevention programs that reduce existing eating disorder pathology or prevent the onset of future pathology. Each program was evaluated in one or more controlled trial with a follow-up period of at least six months. We review the evidence base for these nine successful programs and discuss their common and unique features. Based on authors' descriptions of their programs in published trials, we found that all programs were theory-driven, targeted one or more eating disorder risk factor (e.g., body dissatisfaction), were delivered across multiple group sessions, and included at least some interactive content. Most programs included content related to healthy eating/nutrition, media literacy/sociocultural pressures, and body acceptance/body satisfaction. Notably, there was wide variation in some participant features (e.g., participant age, sex, risk status) and intervention features (e.g., setting and format, length and dose, providers), suggesting that a variety of programs are beneficial in impacting eating disorder pathology. Implications and directions for future research are discussed, including an increased focus on universal and indicated prevention programs, expanding programs to a wider age range and a broader spectrum of weight-related problems, and rigorous evaluation of programs through efficacy, effectiveness, and implementation research.

  20. Preventing Eating Disorder Pathology: Common and Unique Features of Successful Eating Disorders Prevention Programs

    PubMed Central

    Ciao, Anna C.; Loth, Katie; Neumark-Sztainer, Dianne

    2014-01-01

    Over the past two decades, the field of eating disorders has made remarkable strides in identifying, evaluating, and disseminating successful prevention programs. The current review identifies and discusses nine distinct eating disorders prevention programs that reduce existing eating disorder pathology or prevent the onset of future pathology. Each program was evaluated in one or more controlled trial with a follow-up period of at least six months. We review the evidence base for these nine successful programs and discuss their common and unique features. Based on authors’ descriptions of their programs in published trials, we found that all programs were theory-driven, targeted one or more eating disorder risk factor (e.g., body dissatisfaction), were delivered across multiple group sessions, and included at least some interactive content. Most programs included content related to healthy eating/nutrition, media literacy/sociocultural pressures, and body acceptance/body satisfaction. Notably, there was wide variation in some participant features (e.g., participant age, sex, risk status) and intervention features (e.g., setting and format, length and dose, providers), suggesting that a variety of programs are beneficial in impacting eating disorder pathology. Implications and directions for future research are discussed, including an increased focus on universal and indicated prevention programs, expanding programs to a wider age range and a broader spectrum of weight-related problems, and rigorous evaluation of programs through efficacy, effectiveness, and implementation research. PMID:24821099

  1. Effect of Preoperative Risk Group Stratification on Oncologic Outcomes of Patients with Adverse Pathologic Findings at Radical Prostatectomy

    PubMed Central

    Jang, Won Sik; Kim, Lawrence H. C.; Yoon, Cheol Yong; Rha, Koon Ho; Choi, Young Deuk; Hong, Sung Joon; Ham, Won Sik

    2016-01-01

    Background Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy based only on adverse pathologic findings (APFs), irrespective of preoperative risk group. We assessed whether a model incorporating both the preoperative risk group and APFs could predict long-term oncologic outcomes better than a model based on APFs alone. Methods We retrospectively reviewed 4,404 men who underwent radical prostatectomy (RP) at our institution between 1992 and 2014. After excluding patients receiving neoadjuvant therapy or with incomplete pathological or follow-up data, 3,092 men were included in the final analysis. APFs were defined as extraprostatic extension (EPE), seminal vesicle invasion (SVI), or a positive surgical margin (PSM). The adequacy of model fit to the data was compared using the likelihood-ratio test between the models with and without risk groups, and model discrimination was compared with the concordance index (c-index) for predicting biochemical recurrence (BCR) and prostate cancer-specific mortality (PCSM). We performed multivariate Cox proportional hazard model and competing risk regression analyses to identify predictors of BCR and PCSM in the total patient group and each of the risk groups. Results Adding risk groups to the model containing only APFs significantly improved the fit to the data (likelihood-ratio test, p <0.001) and the c-index increased from 0.693 to 0.732 for BCR and from 0.707 to 0.747 for PCSM. A RP Gleason score (GS) ≥8 and a PSM were independently associated with BCR in the total patient group and also each risk group. However, only a GS ≥8 and SVI were associated with PCSM in the total patient group (GS ≥8: hazard ratio [HR] 5.39 and SVI: HR 3.36) and the high-risk group (GS ≥8: HR 6.31 and SVI: HR 4.05). Conclusion The postoperative estimation of oncologic outcomes in men with APFs at RP was improved by considering preoperative risk group stratification. Although a PSM was an

  2. A Joint Time-Frequency and Matrix Decomposition Feature Extraction Methodology for Pathological Voice Classification

    NASA Astrophysics Data System (ADS)

    Ghoraani, Behnaz; Krishnan, Sridhar

    2009-12-01

    The number of people affected by speech problems is increasing as the modern world places increasing demands on the human voice via mobile telephones, voice recognition software, and interpersonal verbal communications. In this paper, we propose a novel methodology for automatic pattern classification of pathological voices. The main contribution of this paper is extraction of meaningful and unique features using Adaptive time-frequency distribution (TFD) and nonnegative matrix factorization (NMF). We construct Adaptive TFD as an effective signal analysis domain to dynamically track the nonstationarity in the speech and utilize NMF as a matrix decomposition (MD) technique to quantify the constructed TFD. The proposed method extracts meaningful and unique features from the joint TFD of the speech, and automatically identifies and measures the abnormality of the signal. Depending on the abnormality measure of each signal, we classify the signal into normal or pathological. The proposed method is applied on the Massachusetts Eye and Ear Infirmary (MEEI) voice disorders database which consists of 161 pathological and 51 normal speakers, and an overall classification accuracy of 98.6% was achieved.

  3. Time trends in pathologic features of radical prostatectomy--impact of family history.

    PubMed

    Marotte, Jeffrey B; Ferrari, Michelle K; McNeal, John E; Brooks, James D; Presti, Joseph C

    2004-01-01

    We investigated whether the clinical or pathological features of patients with a family history of prostate cancer treated by radical prostatectomy differ from patients without a family history. A retrospective analysis of patients treated by radical prostatectomy between 1989 through 2000 was performed. The clinical and pathologic features of patients with a family history (defined as at least one first-degree relative with prostate cancer, N = 103) were compared with those with no family history (N = 456). In addition, the patients were stratified into two groups, those treated from 1989 through 1992 and those treated after 1992. In the entire cohort from 1989 through 2000, patients with a family history had a greater proportion of well-differentiated tumors than the NFH group (26.2% vs. 17.8%; P = 0.05). From 1989 to 1992 there was no statistical difference between patients with a family history (FH) and those without a family history (NFH) with respect to age, prostate specific antigen (PSA), PSA density, clinical or pathologic stage, Gleason grade, or total tumor volume. However, after 1992 the FH group tended to be younger than the NFH group (61.1 vs. 63.4; P = 0.02) and have a lower PSA (6.8 vs. 7.9; P = 0.01) at the time of diagnosis. We believe these differences are predominantly driven by more aggressive screening in patients with a family history of prostate cancer rather than any true genetic differences.

  4. Clinical features and outcomes of focal segmental glomerulosclerosis pathologic variants in Korean adult patients

    PubMed Central

    2014-01-01

    Background Many studies have shown that clinical characteristics and outcomes differ depending on pathologic variants of focal segmental glomerulosclerosis (FSGS). However, these are not well defined in Asian populations. Methods This retrospective study evaluated clinical features and outcomes of pathologic FSGS variants in 111 adult patients between January 2004 and December 2012. Primary outcome was the composite of doubling of baseline serum creatinine concentrations (D-SCr) or onset of end-stage renal disease (ESRD). Secondary outcome included complete (CR) or partial remission (PR). Results There were 70 (63.1%), 20 (18.0%), 17 (15.3%), 3 (2.7%), and 1 (0.9%) patients with not-otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants, respectively. At presentation, nephrotic-range proteinuria occurred more commonly in tip lesion than in other variants. The overall 5-year renal survival rate was 76.8%. During a median follow-up of 34.5 months, only 1 (5.0%) patient with a tip lesion reached the composite end point compared to 2 (11.8%) and 12 (17.1%) patients in perihilar and NOS variants, but this difference was not statistically significant in an adjusted Cox model. However, tip lesion was associated with a significantly increased probability of achieving CR (P = 0.044). Conclusion Similar to other populations, Korean adult patients with FSGS have distinct clinical features with the exception of a rare frequency of cellular and collapsing variants. Although pathologic variants were not associated with overall outcome, the tip variant exhibited favorable outcome in terms of achieving remission. Further studies are required to delineate long-term outcome and response to treatment of the pathologic variants. PMID:24666814

  5. MRI features of Binswanger’s disease predict prognosis and associated pathology

    PubMed Central

    Akiguchi, Ichiro; Budka, Herbert; Shirakashi, Yoshitomo; Woehrer, Adelheid; Watanabe, Toshiyuki; Shiino, Akihiko; Yamamoto, Yasumasa; Kawamoto, Yasuhiro; Krampla, Wolfgang; Jungwirth, Susanne; Fischer, Peter

    2014-01-01

    Objective To identify the prevalence of MRI features of Binswanger’s disease (BD), specifically MRI with diffuse white matter lesions and scattered multiple lacunes (BD-MRI), and to describe neurological features and pathological outcomes of a community-based cohort study. Methods Of 697 participants (all 75 years old), 503 completed neurological examinations at baseline and were followed-up every 30 months thereafter with MRIs, the mini-mental state examination (MMSE) and the Unified Parkinson Disease Rating Scale-Motor Section (UPDRSM). Data from participants with BD-MRI were compared with those from participants with predominant white matter lesions (WML-MRI), scattered multiple lacunes (ML-MRI), or normal MRIs. Results Fourteen BD-MRI patients (2.8%) were detected at baseline. The mean MMSE scores in the BD-MRI, WML-MRI, ML-MRI, and normal MRIs groups were 26.4, 28.2, 28.4, and 28.5, respectively, and the mean UPDRSM scores were 9.1, 1.3, 3.1, and 1.7, respectively. At the 30-month follow-up, mortality rates in the normal MRIs, WML-MRI and ML-MRI were 4%, 9.1%, and 22.2%, respectively, and follow-up MRIs were available for 80%, 82%, and 61% of the participants, respectively. In the BD-MRI, however, five patients were deceased, and only five follow-up individual MRIs were available (33.3%). Autopsies were performed on six of eight BD-MRI brains, and these brains fulfilled the pathological criteria for BD independent of Alzheimer disease pathology. All these six individuals also showed systemic atherosclerosis and renal arterio-arteriolosclerosis. Interpretation The BD-MRI participants had poor prognoses and showed pure BD pathology with advanced systemic vascular disease. BD-MRI appears to be a predictor of vascular neurocognitive impairment. PMID:25493272

  6. The characteristic ultrasound features of specific types of ovarian pathology (review).

    PubMed

    Sayasneh, Ahmad; Ekechi, Christine; Ferrara, Laura; Kaijser, Jeroen; Stalder, Catriona; Sur, Shyamaly; Timmerman, Dirk; Bourne, Tom

    2015-02-01

    Characterizing ovarian masses enables patients with malignancy to be appropriately triaged for treatment by subspecialist gynecological oncologists, which has been shown to optimize care and improve survival. Furthermore, correctly classifying benign masses facilitates the selection of patients with ovarian pathology that may either not require intervention, or be suitable for minimal access surgery if intervention is required. However, predicting whether a mass is benign or malignant is not the only clinically relevant information that we need to know before deciding on appropriate treatment. Knowing the specific histology of a mass is becoming of increasing importance as management options become more tailored to the individual patient. For example predicting a mucinous borderline tumor gives the opportunity for fertility sparing surgery, and will highlight the need for further gastrointestinal assessment. For benign disease, predicting the presence of an endometrioma and possible deeply infiltrating endometriosis is important when considering both who should perform and the extent of surgery. An examiner's subjective assessment of the morphological and vascular features of a mass using ultrasonography has been shown to be highly effective for predicting whether a mass is benign or malignant. Many masses also have features that enable a reliable diagnosis of the specific pathology of a particular mass to be made. In this narrative review we aim to describe the typical morphological features seen on ultrasound of different adnexal masses and illustrate these by showing representative ultrasound images.

  7. Clinical and Pathological Features of Lipoleiomyoma of the Uterine Corpus: A Review of 76 Cases

    PubMed Central

    Akbulut, Metin; Gündoğan, Mehmet; Yörükoğlu, Aygün

    2014-01-01

    Background: Uterine lipoleiomyoma is a rare and specific type of leiomyoma with a considerable amount of adipocytes. Aims: The aim of the study was to investigate the clinical, pathological and immunohistochemical features of lipoleiomyoma of the uterine corpus, and review its histogenesis and differential diagnosis from other neoplastic and non-neoplastic lesions in order to obtain a detailed profile of this somewhat uncommon lesion. Study Design: Descriptive study. Methods: This study is a retrospective analysis of 70 consecutive women with 76 lipoleiomyomas, who underwent surgery mainly for uterine leiomyoma and gynecological carcinomas between January 2000 and April 2013. Clinical and pathological information was obtained from medical records. Immunohistochemistry was applied in selected cases. Parametric methods were used to compare clinical and pathologic features. Results: The patients ranged in age from 34 to 77 years (mean 55.49 years). Lipoleiomyomas ranged from 0.5 to 55 cm in diameter (mean 5.50 cm). Typical macroscopic and microscopic features were noted. Sixty-nine (90.7%) tumors were in the uterine corpus and five (6.5%) were in the cervix. One broad ligament tumor and one retroperitoneal tumor were also studied. No tumors displayed cytologic atypia, mitosis, necrosis, calcification, or other degenerative changes. Immunohistochemically, the adipose tissue element was positive for vimentin, desmin, S100 protein, estrogen (ER), progesterone (PR), and Ki-67. Among patients with lipoleiomyomas, 53 cases (75.7%) had different types of lesions associated with hyperestrogenic status, such as adenomyosis, endometriosis, endometrial hyperplasia, and polyps, complex atypical endometrial hyperplasia, and gynecologic carcinomas. The follow-up period ranged from one to eight years (mean 4.6 years). There were no recurrences or tumor-related fatalities. Conclusion: In the present study, the lipoleiomyomas were seen more frequently in patients with adenomyosis

  8. Interobserver Agreement on Pathologic Features of Liver Biopsy Tissue in Patients with Nonalcoholic Fatty Liver Disease

    PubMed Central

    Jung, Eun Sun; Lee, Kyoungbun; Yu, Eunsil; Kang, Yun Kyung; Cho, Mee-Yon; Kim, Joon Mee; Moon, Woo Sung; Jeong, Jin Sook; Park, Cheol Keun; Park, Jae-Bok; Kang, Dae Young; Sohn, Jin Hee; Jin, So-Young

    2016-01-01

    Background: The histomorphologic criteria for the pathological features of liver tissue from patients with non-alcoholic fatty liver disease (NAFLD) remain subjective, causing confusion among pathologists and clinicians. In this report, we studied interobserver agreement of NAFLD pathologic features and analyzed causes of disagreement. Methods: Thirty-one cases of clinicopathologically diagnosed NAFLD from 10 hospitals were selected. One hematoxylin and eosin and one Masson’s trichrome-stained virtual slide from each case were blindly reviewed with regard to 12 histological parameters by 13 pathologists in a gastrointestinal study group of the Korean Society of Pathologists. After the first review, we analyzed the causes of disagreement and defined detailed morphological criteria. The glass slides from each case were reviewed a second time after a consensus meeting. The degree of interobserver agreement was determined by multi-rater kappa statistics. Results: Kappa values of the first review ranged from 0.0091–0.7618. Acidophilic bodies (k = 0.7618) and portal inflammation (k = 0.5914) showed high levels of agreement, whereas microgranuloma (k = 0.0984) and microvesicular fatty change (k = 0.0091) showed low levels of agreement. After the second review, the kappa values of the four major pathological features increased from 0.3830 to 0.5638 for steatosis grade, from 0.1398 to 0.2815 for lobular inflammation, from 0.1923 to 0.3362 for ballooning degeneration, and from 0.3303 to 0.4664 for fibrosis. Conclusions: More detailed histomorphological criteria must be defined for correct diagnosis and high interobserver agreement of NAFLD. PMID:27086596

  9. Pathology Features in Bethesda Guidelines Predict Colorectal Cancer Microsatellite Instability: A Population-Based Study

    PubMed Central

    Jenkins, Mark A.; Hayashi, Shinichi; O’shea, Anne-Marie; Burgart, Lawrence J.; Smyrk, Tom C.; Shimizu, David; Waring, Paul M.; Ruszkiewicz, Andrew R.; Pollett, Aaron F.; Redston, Mark; Barker, Melissa A.; Baron, John A.; Casey, Graham R.; Dowty, James G.; Giles, Graham G.; Limburg, Paul; Newcomb, Polly; Young, Joanne P.; Walsh, Michael D.; Thibodeau, Stephen N.; Lindor, Noralane M.; Lemarchand, Loïc; Gallinger, Steven; Haile, Robert W.; Potter, John D.; Hopper, John L.; Jass, Jeremy R.

    2010-01-01

    Background & Aims The revised Bethesda guidelines for Lynch syndrome recommend microsatellite instability (MSI) testing all colorectal cancers in patients diagnosed before age 50 years and colorectal cancers diagnosed in patients between ages 50 and 59 years with particular pathology features. Our aim was to identify pathology and other features that independently predict high MSI (MSI-H). Methods Archival tissue from 1098 population-based colorectal cancers diagnosed before age 60 years was tested for MSI. Pathology features, site, and age at diagnosis were obtained. Multiple logistic regression was performed to determine the predictive value of each feature, as measured by an odds ratio (OR), from which a scoring system (MsPath) was developed to estimate the probability a colorectal cancer is MSI-H. Results Fifteen percent of tumors (162) were MSI-H. Independent predictors were tumor-infiltrating lymphocytes (OR, 9.1; 95% confidence interval [CI], 5.9 –14.1), proximal subsite (OR, 4.7; 95% CI, 3.1–7.3), mucinous histology (OR, 2.8; 95% CI, 1.7– 4.8), poor differentiation (OR, 1.9; 95% CI, 1.2–3.1), Crohn’s-like reaction (OR, 1.9; 95% CI, 1.2–2.9), and diagnosis before age 50 years (OR, 1.9; 95% CI, 1.3–2.9). MsPath score ≥ 1.0 had a sensitivity of 93% and a specificity of 55% for MSI-H. Conclusions The probability an individual colorectal cancer is MSI-H is predicted well by the MsPath score. There is little value in testing for DNA mismatch repair loss in tumors, or for germline mismatch repair mutations, for colorectal cancers diagnosed in patients before age 60 years with an MSPath score <1 (approximately 50%). Pathology can identify almost all MSI-H colorectal cancers diagnosed before age 60 years. PMID:17631130

  10. A Case of Congenital Hepatic Fibrosis Associated With Medullary Sponge Kidney-Radiologic and Pathologic Features

    PubMed Central

    Zhu, Lei; Zhao, Gang; Jia, Chong-Fu; Li, Yan

    2012-01-01

    Congenital hepatic fibrosis is an exceedingly rare disease in China, where only very few cases with sufficient evidences and clinical data have been reported up to now. Here we reported a young patient, onset of hematemesis and melena, who had striking portal hypertension but without liver function damage. Computer tomography scans showed hepatosplenomegaly, intra-hepatic bile ducts dilation, thickening portal vein and tortuous spleen vein, and medullary sponge kidney. Liver biopsy found significant fibrosis in the portal area and ectasia of bile ductules. With sufficient radiologic and pathologic data, our case revealed the features of congenital hepatic fibrosis associated with medullary sponge kidney.

  11. Pathologic features of aggressive vulvar carcinoma are associated with epithelial-mesenchymal transition.

    PubMed

    Holthoff, Emily R; Spencer, Horace; Kelly, Thomas; Post, Steven R; Quick, Charles M

    2016-10-01

    Factors contributing to aggressive behavior in vulvar squamous cell carcinoma (vSCC) are poorly defined; however, a recent study has shown that vSCCs with an infiltrative pattern of invasion and fibromyxoid stroma are associated with worse outcomes than tumors with a pushing or nested pattern of invasion and lymphoplasmacytic stroma. Epithelial-mesenchymal transition (EMT) has been associated with tumor progression in a number of malignancies, and this study proposes that EMT contributes to tumor aggressiveness in this subset of vSCC. Immunohistochemistry was used to detect nuclear localization of β-catenin, loss of E-cadherin, and presence of vimentin in 58 cases of vSCC. The association of these phenotypic changes with pathologic features and clinical outcomes was tested using Fisher's exact and χ(2) analyses (significance at P≤.05). EMT-associated features were identified in 45 of 58 cases (78%) with 28 cases exhibiting more than one feature. Nuclear β-catenin and presence of vimentin were significantly more likely to occur in tumors with an infiltrative pattern of invasion or a fibromyxoid stromal response. Loss of E-cadherin was significantly associated with an infiltrative pattern, but not a fibromyxoid stroma. Risk for tumor recurrence was significantly increased in tumors with nuclear localization of β-catenin alone or in tumors displaying multiple EMT-associated features. These results suggest that the development of EMT may be a mechanism by which infiltrative vulvar tumors with a fibromyxoid stromal response behave more aggressively and convey worse outcomes than tumors that do not exhibit these pathologic features.

  12. Pathological features of FTLD-FUS in a Japanese population: analyses of nine cases.

    PubMed

    Kobayashi, Zen; Kawakami, Ito; Arai, Tetsuaki; Yokota, Osamu; Tsuchiya, Kuniaki; Kondo, Hiromi; Shimomura, Yoko; Haga, Chie; Aoki, Naoya; Hasegawa, Masato; Hosokawa, Masato; Oshima, Kenichi; Niizato, Kazuhiro; Ishizu, Hideki; Terada, Seishi; Onaya, Mitsumoto; Ikeda, Manabu; Oyanagi, Kiyomitsu; Nakano, Imaharu; Murayama, Shigeo; Akiyama, Haruhiko; Mizusawa, Hidehiro

    2013-12-15

    We investigated the pathological features of frontotemporal lobar degeneration (FTLD) with fused in sarcoma protein (FUS) accumulation (FTLD-FUS) in the Japanese population. Only one out of nine FTLD-FUS cases showed pathology that corresponds to atypical FTLD with ubiquitin-positive inclusions (aFTLD-U). Five were basophilic inclusion body disease (BIBD) and two were neuronal intermediate filament inclusion disease. The last case was unclassifiable and was associated with dystrophic neurites (DNs) as the predominant FUS pathology. The results of this study indicate an ethnic difference from western countries. In Japan, BIBD is the most common subtype of FTLD-FUS and aFTLD-U is rare, a finding which contrasts with aFTLD-U being the most common form in western countries. Immunohistochemical analyses of these FTLD-FUS cases reveal that FUS abnormally accumulated in neuronal cytoplasmic inclusions (NCIs) and DNs has an immunohistochemical profile distinct from that of normal, nuclear FUS. NCIs and DNs are more readily stained than the nuclei by antibodies to the middle portion of FUS. Antibodies to the carboxyl terminal portion, on the other hand, stain the nuclei more readily than NCIs and DNs. Such an immunohistochemical profile of NCIs and DNs was similar to that of cytoplasmic granular FUS staining which we previously reported to be associated with dendrites and synapses. Redistribution of FUS from the nucleus to the cytoplasm could be associated with the formation of abnormal FUS aggregates in FTLD-FUS.

  13. Pathological features of FTLD-FUS in a Japanese population: analyses of nine cases.

    PubMed

    Kobayashi, Zen; Kawakami, Ito; Arai, Tetsuaki; Yokota, Osamu; Tsuchiya, Kuniaki; Kondo, Hiromi; Shimomura, Yoko; Haga, Chie; Aoki, Naoya; Hasegawa, Masato; Hosokawa, Masato; Oshima, Kenichi; Niizato, Kazuhiro; Ishizu, Hideki; Terada, Seishi; Onaya, Mitsumoto; Ikeda, Manabu; Oyanagi, Kiyomitsu; Nakano, Imaharu; Murayama, Shigeo; Akiyama, Haruhiko; Mizusawa, Hidehiro

    2013-12-15

    We investigated the pathological features of frontotemporal lobar degeneration (FTLD) with fused in sarcoma protein (FUS) accumulation (FTLD-FUS) in the Japanese population. Only one out of nine FTLD-FUS cases showed pathology that corresponds to atypical FTLD with ubiquitin-positive inclusions (aFTLD-U). Five were basophilic inclusion body disease (BIBD) and two were neuronal intermediate filament inclusion disease. The last case was unclassifiable and was associated with dystrophic neurites (DNs) as the predominant FUS pathology. The results of this study indicate an ethnic difference from western countries. In Japan, BIBD is the most common subtype of FTLD-FUS and aFTLD-U is rare, a finding which contrasts with aFTLD-U being the most common form in western countries. Immunohistochemical analyses of these FTLD-FUS cases reveal that FUS abnormally accumulated in neuronal cytoplasmic inclusions (NCIs) and DNs has an immunohistochemical profile distinct from that of normal, nuclear FUS. NCIs and DNs are more readily stained than the nuclei by antibodies to the middle portion of FUS. Antibodies to the carboxyl terminal portion, on the other hand, stain the nuclei more readily than NCIs and DNs. Such an immunohistochemical profile of NCIs and DNs was similar to that of cytoplasmic granular FUS staining which we previously reported to be associated with dendrites and synapses. Redistribution of FUS from the nucleus to the cytoplasm could be associated with the formation of abnormal FUS aggregates in FTLD-FUS. PMID:24050818

  14. Early Controversies over Athetosis: I. Clinical Features, Differentiation from other Movement Disorders, Associated Conditions, and Pathology

    PubMed Central

    Lanska, Douglas J.

    2013-01-01

    Background Since the description of athetosis in 1871 by American neurologist William Alexander Hammond (1828–1900) the disorder has been a source of controversy, as were many aspects of Hammond’s career. Methods Primary sources have been used to review controversies in the 50-year period since the initial description of athetosis, in particular those concerning clinical features, differentiation from other movement disorders, associated conditions, and pathology. Controversies concerning treatment will be addressed in a subsequent article. Results Hammond struggled to establish athetosis as a distinct clinical–pathological entity, and had successfully predicted the striatal pathology in his initial case (albeit somewhat serendipitously). Athetosis was, nevertheless, considered by many neurologists to be a form of post-hemiplegic chorea or part of a continuum between chorea and dystonia. European neurologists, and particularly the French, initially ignored or discounted the concept. Additional controversies arose over whether the movements persisted during sleep, whether athetosis was, or could be, associated with imbecility or insanity, and how it should be treated. Discussion Some controversies concerning athetosis served to identify areas where knowledge was insufficient to make accurate statements, despite prior self-assured or even dogmatic statements to the contrary. Other controversies illustrated established prejudices, even if these biases were often only apparent with the greater detachment of hindsight. PMID:23450262

  15. Clinical, Pathological, and Molecular Features of Lung Adenocarcinomas with AXL Expression

    PubMed Central

    Suda, Kenichi; Shimizu, Shigeki; Sakai, Kazuko; Mizuuchi, Hiroshi; Tomizawa, Kenji; Takemoto, Toshiki; Nishio, Kazuto; Mitsudomi, Tetsuya

    2016-01-01

    The receptor tyrosine kinase AXL is a member of the Tyro3-Axl-Mer receptor tyrosine kinase subfamily. AXL affects several cellular functions, including growth and migration. AXL aberration is reportedly a marker for poor prognosis and treatment resistance in various cancers. In this study, we analyzed clinical, pathological, and molecular features of AXL expression in lung adenocarcinomas (LADs). We examined 161 LAD specimens from patients who underwent pulmonary resections. When AXL protein expression was quantified (0, 1+, 2+, 3+) according to immunohistochemical staining intensity, results were 0: 35%; 1+: 20%; 2+: 37%; and 3+: 7% for the 161 samples. AXL expression status did not correlate with clinical features, including smoking status and pathological stage. However, patients whose specimens showed strong AXL expression (3+) had markedly poorer prognoses than other groups (P = 0.0033). Strong AXL expression was also significantly associated with downregulation of E-cadherin (P = 0.025) and CD44 (P = 0.0010). In addition, 9 of 12 specimens with strong AXL expression had driver gene mutations (6 with EGFR, 2 with KRAS, 1 with ALK). In conclusion, we found that strong AXL expression in surgically resected LADs was a predictor of poor prognosis. LADs with strong AXL expression were characterized by mesenchymal status, higher expression of stem-cell-like markers, and frequent driver gene mutations. PMID:27100677

  16. Stratification of Digestive Cancers with Different Pathological Features and Survival Outcomes by MicroRNA Expression

    PubMed Central

    Tang, Senwei; Wu, William K. K.; Li, Xiangchun; Wong, Sunny H.; Wong, Nathalie; Chan, Matthew T. V.; Sung, Joseph J. Y.; Yu, Jun

    2016-01-01

    MicroRNAs (miRNAs) are aberrantly expressed in virtually all cancer types, including digestive cancers. Herein, we aggregated and systematically analyzed miRNA expression profiles of 1765 tumor samples, including esophageal, gastric, liver, pancreatic, colon and rectal cancers, obtained through small RNA sequencing by The Cancer Genome Atlas. We found that digestive cancers of different tissue origins could be differentiated according to their miRNA expression profiles. In particular, esophageal squamous cell carcinoma and esophageal adenocarcinoma exhibited distinct miRNA expression patterns. Thirteen (e.g. miR-135b, miR-182) and sixteen (e.g. miR-139, miR-133a-1, miR-490) miRNAs were commonly upregulated and downregulated in more than four cancer types, respectively. Pertinent to pathological features, low miR-181d expression was associated with microsatellite instability in colon and gastric cancers whereas low miR-106a expression was associated with hepatitis B virus infection in hepatocellular carcinoma. Progression in colon cancer could also be predicted by low let-7f-2 and high miR-106a expression. Molecular subtypes with distinct prognostic outcomes independent of tumor-node-metastasis staging were identified in hepatocellular carcinoma and colon cancer. In total, 4 novel and 6 reported associations between specific miRNAs and patients’ survival were identified. Collectively, novel miRNA markers were identified to stratify digestive cancers with different pathological features and survival outcomes. PMID:27080237

  17. MRL/MpJ mice show unique pathological features after experimental kidney injury.

    PubMed

    Shiozuru, Daichi; Ichii, Osamu; Kimura, Junpei; Nakamura, Teppei; Elewa, Yaser Hosny Ali; Otsuka-Kanazawa, Saori; Kon, Yasuhiro

    2016-02-01

    Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1-positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury.

  18. Imaging features of primary anorectal gastrointestinal stromal tumors with clinical and pathologic correlation

    PubMed Central

    Koch, M.R.; Jagannathan, J.P.; Krajewski, K.M.; Raut, C.P.; Hornick, J.L.; Ramaiya, N.H.

    2012-01-01

    Abstract Purpose: To evaluate the imaging features of anorectal gastrointestinal stromal tumors (GISTs) with clinical and histopathologic correlation. Materials and methods: In this Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, 16 patients (12 men; mean age 66 years (30–89 years)) with pathologically proven anorectal GISTs seen at our institution from January 2001 to July 2011 were identified. Electronic medical records were reviewed to obtain clinical data. Pretreatment imaging studies (computed tomography (CT) in 16 patients, magnetic resonance imaging (MRI) in 9 patients and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT in 8 patients) were evaluated by 2 radiologists until consensus. The location, size and imaging features of the primary tumor and metastases at presentation, if any, were recorded, and correlated with clinical data and pathologic features (histologic type, presence of necrosis, mitotic activity, risk category, immunohistochemical profile). Results: The mean tumor size was 6.9 × 6.0 cm. Of the 16 tumors, 11 (68.7%) were infralevator, 4 (25%) supra and infralevator and 1 (6.3%) supralevator; 9 (56.2%) were exophytic, 6 (37.5%) both exophytic and intraluminal, and 1 (6.3%) was intraluminal. The tumors were iso- to minimally hypoattenuating to muscle on CT, iso- to minimally hypointense on T1-weighted images, hyperintense on T2-weighted images and showed variable enhancement. Necrosis was seen in 4 (25%), and hemorrhage and calcification in 2 (12.5%) patients each. The tumors were FDG avid with a mean maximum standardized uptake value of 11 (8.4–16.8). All tumors were positive for KIT and CD34. Distant metastasis to liver was seen in 1 patient (6.3%) at presentation. Conclusion: Anorectal GISTs are well-circumscribed, non-circumferential, predominantly infralevator, intramural or exophytic, FDG-avid, hypoattenuating masses, and present without

  19. The clinical pathological features, diagnosis, treatment and prognosis of small intestine primary malignant tumors.

    PubMed

    Guo, Xiaochuan; Mao, Zhiyuan; Su, Dan; Jiang, Zhaocai; Bai, Li

    2014-04-01

    The aim of the study was to describe and analyze the clinicopathological features and diagnosis of Chinese patients with small intestine primary malignant tumors and to explore the best therapy to small bowel adenocarcinoma (SBA). More than 26,000 patients with digestive tract malignant tumors received treatment in PLA hospital from 2000 to 2011, and among them, there were 887 patients who had small intestine primary malignant tumors, and 666 of 887 patients had the completed basic clinical documents. We retrospectively analyzed the correlation between clinical and pathological features of the 666 patients and analyzed the survival and prognosis of 173 SBA patients with follow-up data. Both the number of patients with primary malignant tumors of the small intestine and the number of patients who received chemotherapy showed an increasing trend. The ratio of male to female was 1.58:1. The male patients significantly exceed the female patients with tumors of non-ampullary duodenum, jejunum and duodenal ampulla; and most of the patients are over 60 years of age. For patients burdened with either of the pathological types of tumors, the males exceeded the females, but there was no significant difference. Abdominal pain was the main clinical manifestation for patients with tumors of non-ampullary duodenum, jejunum and ileum, and the most common clinical manifestations were jaundice and abdominal pain for patients with ampullary duodenal tumors, adenocarcinoma, neuroendocrine tumors and sarcoma. In addition, patients with stromal tumors were prone to gastrointestinal bleeding. Gastrointestinal endoscopy was the most common examinational procedure. Patients under 60 years of age were prone to surgery and chemotherapy after surgery, and patients over 60 years of age were prone to supportive treatment and chemotherapy without surgery. The medium overall survival of patients who received surgery without chemotherapy, chemotherapy after surgery, chemotherapy without surgery

  20. The Research of Feature Extraction Method of Liver Pathological Image Based on Multispatial Mapping and Statistical Properties

    PubMed Central

    Liu, Huiling; Xia, Bingbing; Yi, Dehui

    2016-01-01

    We propose a new feature extraction method of liver pathological image based on multispatial mapping and statistical properties. For liver pathological images of Hematein Eosin staining, the image of R and B channels can reflect the sensitivity of liver pathological images better, while the entropy space and Local Binary Pattern (LBP) space can reflect the texture features of the image better. To obtain the more comprehensive information, we map liver pathological images to the entropy space, LBP space, R space, and B space. The traditional Higher Order Local Autocorrelation Coefficients (HLAC) cannot reflect the overall information of the image, so we propose an average correction HLAC feature. We calculate the statistical properties and the average gray value of pathological images and then update the current pixel value as the absolute value of the difference between the current pixel gray value and the average gray value, which can be more sensitive to the gray value changes of pathological images. Lastly the HLAC template is used to calculate the features of the updated image. The experiment results show that the improved features of the multispatial mapping have the better classification performance for the liver cancer. PMID:27022407

  1. Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features

    PubMed Central

    Yu, Kun-Hsing; Zhang, Ce; Berry, Gerald J.; Altman, Russ B.; Ré, Christopher; Rubin, Daniel L.; Snyder, Michael

    2016-01-01

    Lung cancer is the most prevalent cancer worldwide, and histopathological assessment is indispensable for its diagnosis. However, human evaluation of pathology slides cannot accurately predict patients' prognoses. In this study, we obtain 2,186 haematoxylin and eosin stained histopathology whole-slide images of lung adenocarcinoma and squamous cell carcinoma patients from The Cancer Genome Atlas (TCGA), and 294 additional images from Stanford Tissue Microarray (TMA) Database. We extract 9,879 quantitative image features and use regularized machine-learning methods to select the top features and to distinguish shorter-term survivors from longer-term survivors with stage I adenocarcinoma (P<0.003) or squamous cell carcinoma (P=0.023) in the TCGA data set. We validate the survival prediction framework with the TMA cohort (P<0.036 for both tumour types). Our results suggest that automatically derived image features can predict the prognosis of lung cancer patients and thereby contribute to precision oncology. Our methods are extensible to histopathology images of other organs. PMID:27527408

  2. New phenotype and pathology features in MYH7-related distal myopathy.

    PubMed

    Tasca, Giorgio; Ricci, Enzo; Penttilä, Sini; Monforte, Mauro; Giglio, Vincenzo; Ottaviani, Pierfrancesco; Camastra, Giovanni; Silvestri, Gabriella; Udd, Bjarne

    2012-07-01

    Laing distal myopathy is an autosomal dominant disease due to mutations in the gene encoding for the human slow-β myosin heavy chain, MYH7. Most reports describe it as a mild, early onset myopathy with involvement usually restricted to foot extensors, hand finger extensors and neck flexors, and unspecific findings on muscle biopsy. We identified the first two Italian families with Laing distal myopathy, harboring two novel mutations in the MYH7 gene and performed clinical, neurophysiological, pathological, muscle MRI and cardiological investigations on affected members from the two families. Subjects from one family presented a moderate-severe phenotype, with proximal together with distal involvement and even loss of ambulation at advanced age. One patient displayed atypical muscle biopsy findings including cytoplasmic bodies and myofibrillar myopathy-like features. Affected members from the second family shared a very mild phenotype, with weakness largely limited to long toe and foot extensors and/or late onset. No patient showed any sign of heart involvement. Our study significantly broadens the clinical and pathological spectrum of Laing distal myopathy. We suggest that MYH7 screening should be considered in undiagnosed late-onset distal myopathy or cytoplasmic body myopathy patients.

  3. Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer's disease.

    PubMed

    Sharoar, M G; Shi, Q; Ge, Y; He, W; Hu, X; Perry, G; Zhu, X; Yan, R

    2016-09-01

    Pathological features in Alzheimer's brains include mitochondrial dysfunction and dystrophic neurites (DNs) in areas surrounding amyloid plaques. Using a mouse model that overexpresses reticulon 3 (RTN3) and spontaneously develops age-dependent hippocampal DNs, here we report that DNs contain both RTN3 and REEPs, topologically similar proteins that can shape tubular endoplasmic reticulum (ER). Importantly, ultrastructural examinations of such DNs revealed gradual accumulation of tubular ER in axonal termini, and such abnormal tubular ER inclusion is found in areas surrounding amyloid plaques in biopsy samples from Alzheimer's disease (AD) brains. Functionally, abnormally clustered tubular ER induces enhanced mitochondrial fission in the early stages of DN formation and eventual mitochondrial degeneration at later stages. Furthermore, such DNs are abrogated when RTN3 is ablated in aging and AD mouse models. Hence, abnormally clustered tubular ER can be pathogenic in brain regions: disrupting mitochondrial integrity, inducing DNs formation and impairing cognitive function in AD and aging brains.

  4. Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer's disease.

    PubMed

    Sharoar, M G; Shi, Q; Ge, Y; He, W; Hu, X; Perry, G; Zhu, X; Yan, R

    2016-09-01

    Pathological features in Alzheimer's brains include mitochondrial dysfunction and dystrophic neurites (DNs) in areas surrounding amyloid plaques. Using a mouse model that overexpresses reticulon 3 (RTN3) and spontaneously develops age-dependent hippocampal DNs, here we report that DNs contain both RTN3 and REEPs, topologically similar proteins that can shape tubular endoplasmic reticulum (ER). Importantly, ultrastructural examinations of such DNs revealed gradual accumulation of tubular ER in axonal termini, and such abnormal tubular ER inclusion is found in areas surrounding amyloid plaques in biopsy samples from Alzheimer's disease (AD) brains. Functionally, abnormally clustered tubular ER induces enhanced mitochondrial fission in the early stages of DN formation and eventual mitochondrial degeneration at later stages. Furthermore, such DNs are abrogated when RTN3 is ablated in aging and AD mouse models. Hence, abnormally clustered tubular ER can be pathogenic in brain regions: disrupting mitochondrial integrity, inducing DNs formation and impairing cognitive function in AD and aging brains. PMID:26619807

  5. Correlation of Computed Tomography with Pathological Features in Angiomatous Nasal Polyps

    PubMed Central

    Dai, Li-Bo; Zhou, Shui-Hong; Ruan, Ling-Xiang; Zheng, Zhou-Jun

    2012-01-01

    Background Angiomatous nasal polyps (ANPs), also known as angiectatic polyps, have rarely been reported in the literature. ANPs are characterized by extensive vascular proliferation and ectasia. ANPs can grow rapidly and exhibit aggressive clinical behavior that could simulate malignancy preoperatively, and they are easily confused with other diseases. In the present study, we analyzed the correlation between the computed tomography (CT) findings of nasal angiomatous polyps and their pathological features. Methods We evaluated CT findings and pathological features of 31 surgically proven ANPs. Results The study population included 16 males and 15 females aged between 27 and 81 years (mean age, 53.5 years). On CT, the masses were heterogeneous; they had a soft tissue density and filled the maxillary and/or nasal cavities. Calcifications were found in 2 of the 31 cases. The lesions showed a clear boundary (15/31). The low-density shading on CT was related to the inflammatory, necrotic, and cystic changes, and the high-density shading on CT was related to hemorrhagic areas of the mass. On contrast-enhanced CT, the center of the lesions was non-enhanced with peripheral intensification due to occlusion or compression of feeder vessels of the polyp center, and the inflammatory cells and neovascularization around the edge of the mass. The most common site of maxillary wall erosion was the medial wall (21/31), followed by the posterior lateral wall (3/31), upper wall (2/31), and septum (3/31). Of these, the nasal cavity and/or maxillary sinus were enlarged in 28 cases. These findings were associated with the chronic progress of nasal angiomatous changes. Conclusions CT of ANPs may demonstrate benign bone changes associated with the lesions and may also reflect the fact that ANPs do not invade peripheral soft tissue. CT demonstrated these lesions consistently and provided information useful for surgical planning. PMID:23300910

  6. The Hybrid Feature Selection Algorithm Based on Maximum Minimum Backward Selection Search Strategy for Liver Tissue Pathological Image Classification

    PubMed Central

    2016-01-01

    We propose a novel feature selection algorithm for liver tissue pathological image classification. To improve the efficiency of feature selection, the same feature values of positive and negative samples are removed in rough selection. To obtain the optimal feature subset, a new heuristic search algorithm, which is called Maximum Minimum Backward Selection (MMBS), is proposed in precise selection. MMBS search strategy has the following advantages. (1) For the deficiency of Discernibility of Feature Subsets (DFS) evaluation criteria, which makes the class of small samples invalid for unbalanced samples, the Weighted Discernibility of Feature Subsets (WDFS) evaluation criteria are proposed as the evaluation strategy of MMBS, which is also available for unbalanced samples. (2) For the deficiency of Sequential Forward Selection (SFS) and Sequential Backward Selection (SBS), which can only add or only delete feature, MMBS decides whether to add the feature to feature subset according to WDFS criteria for each feature firstly; then it decides whether to remove the feature from feature subset according to SBS algorithm. In this way, the better feature subset can be obtained. The experiment results show that the proposed hybrid feature selection algorithm has good classification performance for liver tissue pathological image. PMID:27563344

  7. Cognition, Language, and Clinical Pathological Features of Non-Alzheimer’s Dementias: An Overview

    PubMed Central

    Reilly, Jamie; Rodriguez, Amy; Lamy, Martine; Neils-Strunjas, Jean

    2010-01-01

    There are many distinct forms of dementia whose pharmacological and behavioral management differ. Differential diagnosis among the dementia variants currently relies upon a weighted combination of genetic and protein biomarkers, neuroanatomical integrity, and behavior. Diagnostic specificity is complicated by a high degree of overlap in the initial presenting symptoms across dementia subtypes. For this reason, reliable markers are of considerable diagnostic value. Communication disorders have proven to be among the strongest predictors for discriminating among dementia subtypes. As such, Speech-Language Pathologists may be poised to make an increasingly visible contribution to dementia diagnosis and its ongoing management. The value and durability of this potential contribution, however, demands an improved discipline-wide knowledge base about the unique features associated with different dementia variants. To this end we provide an overview of cognition, language, and clinical pathological features of four of the most common non-Alzheimer’s dementias: Frontotemporal Dementia, Vascular Dementia, Lewy Body Disease Dementia, and Parkinson’s Disease Dementia. PMID:20493496

  8. The comparison of pathology in ferrets infected by H9N2 avian influenza viruses with different genomic features.

    PubMed

    Gao, Rongbao; Bai, Tian; Li, Xiaodan; Xiong, Ying; Huang, Yiwei; Pan, Ming; Zhang, Ye; Bo, Hong; Zou, Shumei; Shu, Yuelong

    2016-01-15

    H9N2 avian influenza virus circulates widely in poultry and has been responsible for sporadic human infections in several regions. Few studies have been conducted on the pathogenicity of H9N2 AIV isolates that have different genomic features. We compared the pathology induced by a novel reassortant H9N2 virus and two currently circulating H9N2 viruses that have different genomic features in ferrets. The results showed that the three viruses can induce infections with various amounts of viral shedding in ferrets. The novel H9N2 induced respiratory infection, but no pathological lesions were observed in lung tissues. The other two viruses induced mild to intermediate pathological lesions in lung tissues, although the clinical signs presented mildly in ferrets. The pathological lesions presented a diversity consistent with viral replication in ferrets. PMID:26638019

  9. Biopsy Quantitative Patohistology and Seral Values of Prostate Specific Antigen-Alpha (1) Antichymotrypsine Complex in Prediction of Adverse Pathology Findings after Radical Prostatectomy.

    PubMed

    Tomasković, Igor; Milicić, Valerija; Tomić, Miroslav; Ruzić, Boris; Ulamec, Monika

    2015-09-01

    In this prospective study we examined the utility of parameters obtained on prostate needle biopsy and prostate specific antigen-alpha(1)-antichymotripsine complex (PSA-ACT) to predict adverse pathologic findings after radical prostatectomy. 45 consecutive patients assigned for radical prostatectomy due to clinically localized prostate cancer were included in the study. Prostate biopsy parameters such as number of positive cores, the greatest percentage of tumor in the positive cores, Gleason score, perineural invasion, unilaterality or bilaterality of the tumor were recorded. PSA-ACT was determined using sandwich immunoassay chemiluminiscent method (Bayer, Tarrytown, New York). We analyzed relationship of preoperative PSA, PSA-ACTand quantitative biopsy parameters with final pathology after prostatectomy. Adverse findings were considered when extracapsular extension of cancer (pT3) was noted. Postoperatively, 29 (64.4%) patients were diagnosed with pT2 disease and 16 (35.6%) with pT3 disease. There was a significant difference in localized vs. locally advanced disease in number of positive biopsy cores (p<0.001), greatest percentage of tumor in the core (p=0.008), localization of the tumor (p=0.003) and perineural invasion (p=0.004). Logistic regression was used to develop a model on the multivariate level. It included number of positive cores and PSA-ACT and was significant on our cohort with the reliability of 82.22%. The combination of PSA-ACT and a large scale of biopsy parameters could be used in prediction of adverse pathologic findings after radical prostatectomy. Clinical decisions and patients counselling could be influenced by these predictors but further confirmation on a larger population is necessary. PMID:26898067

  10. Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features

    SciTech Connect

    Vargas, Carlos; Kestin, Larry L. . E-mail: lkestin@beaumont.edu; Weed, Dan W.; Krauss, Daniel; Vicini, Frank A.; Martinez, Alvaro A.

    2005-03-01

    Purpose: The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT. Methods and materials: Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level {>=}0.1 ng/mL and any postoperative PSA level {>=}0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT. Results: Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA < 0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the

  11. The behavioural/dysexecutive variant of Alzheimer's disease: clinical, neuroimaging and pathological features.

    PubMed

    Ossenkoppele, Rik; Pijnenburg, Yolande A L; Perry, David C; Cohn-Sheehy, Brendan I; Scheltens, Nienke M E; Vogel, Jacob W; Kramer, Joel H; van der Vlies, Annelies E; La Joie, Renaud; Rosen, Howard J; van der Flier, Wiesje M; Grinberg, Lea T; Rozemuller, Annemieke J; Huang, Eric J; van Berckel, Bart N M; Miller, Bruce L; Barkhof, Frederik; Jagust, William J; Scheltens, Philip; Seeley, William W; Rabinovici, Gil D

    2015-09-01

    A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer's disease with a behavioural-predominant presentation (behavioural Alzheimer's disease) and a neuropathological diagnosis of high-likelihood Alzheimer's disease (n = 17) and/or biomarker evidence of Alzheimer's disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer's disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer's disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer's disease: 53%; dysexecutive Alzheimer's disease: 83%) than behavioural (behavioural Alzheimer's disease: 25%; dysexecutive Alzheimer's disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer's disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer's disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer's disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer's disease (typical Alzheimer's disease, n = 58), autopsy-confirmed/Alzheimer's disease biomarker-negative behavioural variant frontotemporal dementia (n = 59

  12. Somatic molecular changes and histo-pathological features of colorectal cancer in Tunisia

    PubMed Central

    Aissi, Sana; Buisine, Marie Pierre; Zerimech, Farid; Kourda, Nadia; Moussa, Amel; Manai, Mohamed; Porchet, Nicole

    2013-01-01

    AIM: To determine correlations between family history, clinical features and mutational status of genes involved in the progression of colorectal cancer (CRC). METHODS: Histo-pathological features and molecular changes [KRAS, BRAF and CTNNB1 genes mutations, microsatellite instability (MSI) phenotype, expression of mismatch repair (MMR) and mucin (MUC) 5AC proteins, mutation and expression analysis of TP53, MLH1 promoter hypermethylation analysis] were examined in a series of 51 unselected Tunisian CRC patients, 10 of them had a proven or probable hereditary disease, on the track of new tumoral markers for CRC susceptibility in Tunisian patients. RESULTS: As expected, MSI and MMR expression loss were associated to the presence of familial CRC (75% vs 9%, P < 0.001). However, no significant associations have been detected between personal or familial cancer history and KRAS (codons 12 and 13) or TP53 (exons 4-9) alterations. A significant inverse relationship has been observed between the presence of MSI and TP53 accumulation (10.0% vs 48.8%, P = 0.0335) in CRC tumors, suggesting different molecular pathways to CRC that in turn may reflect different environmental exposures. Interestingly, MUC5AC expression was significantly associated to the presence of MSI (46.7% vs 8.3%, P = 0.0039), MMR expression loss (46.7% vs 8.3%, P = 0.0039) and the presence of familial CRC (63% vs 23%, P = 0.039). CONCLUSION: These findings suggest that MUC5AC expression analysis may be useful in the screening of Tunisian patients with high risk of CRC. PMID:23983431

  13. C9orf72 BAC Transgenic Mice Display Typical Pathologic Features of ALS/FTD.

    PubMed

    O'Rourke, Jacqueline G; Bogdanik, Laurent; Muhammad, A K M G; Gendron, Tania F; Kim, Kevin J; Austin, Andrew; Cady, Janet; Liu, Elaine Y; Zarrow, Jonah; Grant, Sharday; Ho, Ritchie; Bell, Shaughn; Carmona, Sharon; Simpkinson, Megan; Lall, Deepti; Wu, Kathryn; Daughrity, Lillian; Dickson, Dennis W; Harms, Matthew B; Petrucelli, Leonard; Lee, Edward B; Lutz, Cathleen M; Baloh, Robert H

    2015-12-01

    Noncoding expansions of a hexanucleotide repeat (GGGGCC) in the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Here we report transgenic mice carrying a bacterial artificial chromosome (BAC) containing the full human C9orf72 gene with either a normal allele (15 repeats) or disease-associated expansion (∼100-1,000 repeats; C9-BACexp). C9-BACexp mice displayed pathologic features seen in C9orf72 expansion patients, including widespread RNA foci and repeat-associated non-ATG (RAN) translated dipeptides, which were suppressed by antisense oligonucleotides targeting human C9orf72. Nucleolin distribution was altered, supporting that either C9orf72 transcripts or RAN dipeptides promote nucleolar dysfunction. Despite early and widespread production of RNA foci and RAN dipeptides in C9-BACexp mice, behavioral abnormalities and neurodegeneration were not observed even at advanced ages, supporting the hypothesis that RNA foci and RAN dipeptides occur presymptomatically and are not sufficient to drive neurodegeneration in mice at levels seen in patients. PMID:26637796

  14. Pathological Features and Pathogenesis of the Endomyocardial Form of Restrictive Cardiomyopathy in Cats.

    PubMed

    Kimura, Y; Karakama, S; Hirakawa, A; Tsuchiaka, S; Kobayashi, M; Machida, N

    2016-01-01

    This study reports pathological and molecular features in 41 cases of feline restrictive cardiomyopathy (RCM). Grossly, there were patchy or diffuse areas of endocardial thickening affecting the left ventricle. The more common patchy endocardial lesions occurred as large trabecular or irregular broad bands of fibrous tissue bridging the left ventricular free wall and ventricular septum. Microscopically, regardless of the gross pattern, the thickened endocardium contained various numbers of stellate, spindle-shaped or elongated mesenchymal cells surrounded by fibrous connective tissue. Immunohistochemical findings were indicative of smooth muscle differentiation in mesenchymal cells. These cells proliferated vigorously and produced alcian blue-positive ground substance and collagen fibres; it was considered that the mesenchymal cells contributed to the formation of the endocardial lesions. In addition, multiple left ventricular 'false tendons' were invariably included within the trabecular or broad fibrous bands, providing a framework for formation of those bands. Evidence of endocarditis or endomyocarditis was lacking in all 41 cases, and no viral genomes were detected in any of the DNA or RNA samples obtained from 14 of the hearts. These observations suggest that any relationship between feline RCM and a virus-induced inflammatory response seems unlikely. PMID:27392420

  15. The behavioural features of fatal familial insomnia: A new Italian case with pathological verification.

    PubMed

    Raggi, Alberto; Perani, Daniela; Giaccone, Giorgio; Iannaccone, Sandro; Manconi, Mauro; Zucconi, Marco; Garibotto, Valentina; Marcone, Alessandra; Zamboni, Michele; Limido, Lucia; Tagliavini, Fabrizio; Ferini-Strambi, Luigi; Cappa, Stefano F

    2009-05-01

    We report a new, pathologically verified Italian case of fatal familial insomnia, whose clinical presentation was characterised by complex behavioural disturbances, suggesting wakefulness/NREM/REM combinations.

  16. [Multiple ovarian fibromas in a patient with Gorlin syndrome: US and MR imaging features with pathological correlation].

    PubMed

    Berment, H; Genevois, A; Dacher, J N; Sabourin, J C

    2010-09-01

    We report a case of multiple ovarian fibromas in a 23 year old woman with Gorlin syndrome. We describe the US and MR imaging features with pathological correlation. The fibrous component of the tumors were hypoechoic and attenuating on US with corresponding T2W hypointensity whereas myxoid components were hypoechoic with increased through transmission on US with corresponding T2W hyperintensity.

  17. A retrospective cohort study identifying the principal pathological features useful in the diagnosis of inclusion body myositis

    PubMed Central

    Brady, Stefen; Squier, Waney; Sewry, Caroline; Hanna, Michael; Hilton-Jones, David; Holton, Janice L

    2014-01-01

    Objective The current pathological diagnostic criteria for sporadic inclusion body myositis (IBM) lack sensitivity. Using immunohistochemical techniques abnormal protein aggregates have been identified in IBM, including some associated with neurodegenerative disorders. Our objective was to investigate the diagnostic utility of a number of markers of protein aggregates together with mitochondrial and inflammatory changes in IBM. Design Retrospective cohort study. The sensitivity of pathological features was evaluated in cases of Griggs definite IBM. The diagnostic potential of the most reliable features was then assessed in clinically typical IBM with rimmed vacuoles (n=15), clinically typical IBM without rimmed vacuoles (n=9) and IBM mimics—protein accumulation myopathies containing rimmed vacuoles (n=7) and steroid-responsive inflammatory myopathies (n=11). Setting Specialist muscle services at the John Radcliffe Hospital, Oxford and the National Hospital for Neurology and Neurosurgery, London. Results Individual pathological features, in isolation, lacked sensitivity and specificity. However, the morphology and distribution of p62 aggregates in IBM were characteristic and in a myopathy with rimmed vacuoles, the combination of characteristic p62 aggregates and increased sarcolemmal and internal major histocompatibility complex class I expression or endomysial T cells were diagnostic for IBM with a sensitivity of 93% and specificity of 100%. In an inflammatory myopathy lacking rimmed vacuoles, the presence of mitochondrial changes was 100% sensitive and 73% specific for IBM; characteristic p62 aggregates were specific (91%), but lacked sensitivity (44%). Conclusions We propose an easily applied diagnostic algorithm for the pathological diagnosis of IBM. Additionally our findings support the hypothesis that many of the pathological features considered typical of IBM develop later in the disease, explaining their poor sensitivity at disease presentation and

  18. 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.

  19. Prostate volume and biopsy tumor length are significant predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy

    PubMed Central

    2014-01-01

    Background Gleason pattern 3 less often has molecular abnormalities and often behaves indolent. It is controversial whether low grade small foci of prostate cancer (PCa) on biopsy could avoid immediate treatment or not, because substantial cases harbor unfavorable pathologic results on prostatectomy specimens. This study was designed to identify clinical predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy. Methods Retrospective review of 1040 PCa Japanese patients underwent radical prostatectomy between 2006 and 2013. Of those, 170 patients (16.3%) met the inclusion criteria of clinical stage ≤ cT2a, Gleason score (GS) ≤ 6, up to two positive biopsies, and no more than 50% of cancer involvement in any core. The associations between preoperative data and unfavorable pathologic results of prostatectomy specimens, and oncological outcome were analyzed. The definition of insignificant cancer consisted of pathologic stage ≤ pT2, GS ≤ 6, and an index tumor volume < 0.5 mL (classical) or 1.3 mL (redefined). Results Pathologic stage ≥ pT3, upgraded GS, index tumor volume ≥ 0.5 mL, and ≥ 1.3 mL were detected in 25 (14.7%), 77 (45.3%), 83 (48.8%), and 53 patients (31.2%), respectively. Less than half of cases had classical (41.2%) and redefined (47.6%) insignificant cancer. The 5-year recurrence-free survival was 86.8%, and the insignificant cancers essentially did not relapse regardless of the surgical margin status. MRI-estimated prostate volume, tumor length on biopsy, prostate-specific antigen density (PSAD), and findings of magnetic resonance imaging were associated with the presence of classical and redefined insignificant cancer. Large prostate volume and short tumor length on biopsy remained as independent predictors in multivariate analysis. Conclusions Favorable features of biopsy often are followed by adverse pathologic

  20. Nanotheranostics of Circulating Tumor Cells, Infections and Other Pathological Features In Vivo

    PubMed Central

    Kim, Jin-Woo; Galanzha, Ekaterina I.; Zaharoff, David A.; Griffin, Robert J.; Zharov, Vladimir P.

    2013-01-01

    Many life-threatening diseases are disseminated through biological fluids, such as blood, lymph and cerebrospinal fluid. The migration of tumor cells through the vascular circulation is a mandatory step in metastasis, which is responsible for ∼90% of cancer-associated mortality. Circulating pathogenic bacteria, viruses, or blood clots lead to other serious conditions including bacteremia, sepsis, viremia and infarction. Therefore, technologies capable of detecting circulating tumor cells (CTCs), circulating bacterial cells (CBCs), circulating endothelial cells (CECs), cancer biomarkers such as microparticles and exosomes, which contain important microRNA signatures, and other abnormal features in biological fluids may facilitate early diagnosis and treatment of metastatic cancers, infections and adverse cardiovascular events. Unfortunately, even in a disease setting, circulating abnormal cells are rare events that are easily obscured by the overwhelming background material in whole blood. Existing detection methods mostly rely on ex vivo analyses of limited volumes (a few mL) of whole blood. These small volumes limit the probability of detecting CTCs, CECs, CBCs and other rare phenomena. In vivo detection platforms capable of continuously monitoring the entire circulation may substantially increase the probability of detecting circulating abnormal cells and, in particular, increase the opportunity to identify exceedingly rare and potentially dangerous subsets of these cells, such as circulating cancer stem cells (CCSCs). In addition, in vivo detection technologies capable of destroying and/or capturing circulating abnormal cells may inhibit disease progression. This article reviews novel therapeutic and diagnostic (theranostic) platforms integrating in vivo realtime early diagnosis of CTCs, CECs, CBCs and other abnormal objects in circulation. This critical review particularly focuses on nanotechnology-based theranostic (nanotheranostic) approaches, especially in

  1. Pharmacovigilance from social media: mining adverse drug reaction mentions using sequence labeling with word embedding cluster features

    PubMed Central

    Sarker, Abeed; O’Connor, Karen; Ginn, Rachel

    2015-01-01

    Objective Social media is becoming increasingly popular as a platform for sharing personal health-related information. This information can be utilized for public health monitoring tasks, particularly for pharmacovigilance, via the use of natural language processing (NLP) techniques. However, the language in social media is highly informal, and user-expressed medical concepts are often nontechnical, descriptive, and challenging to extract. There has been limited progress in addressing these challenges, and thus far, advanced machine learning-based NLP techniques have been underutilized. Our objective is to design a machine learning-based approach to extract mentions of adverse drug reactions (ADRs) from highly informal text in social media. Methods We introduce ADRMine, a machine learning-based concept extraction system that uses conditional random fields (CRFs). ADRMine utilizes a variety of features, including a novel feature for modeling words’ semantic similarities. The similarities are modeled by clustering words based on unsupervised, pretrained word representation vectors (embeddings) generated from unlabeled user posts in social media using a deep learning technique. Results ADRMine outperforms several strong baseline systems in the ADR extraction task by achieving an F-measure of 0.82. Feature analysis demonstrates that the proposed word cluster features significantly improve extraction performance. Conclusion It is possible to extract complex medical concepts, with relatively high performance, from informal, user-generated content. Our approach is particularly scalable, suitable for social media mining, as it relies on large volumes of unlabeled data, thus diminishing the need for large, annotated training data sets. PMID:25755127

  2. [Multiple ovarian fibromas in a patient with Gorlin syndrome: US and MR imaging features with pathological correlation].

    PubMed

    Berment, H; Genevois, A; Dacher, J N; Sabourin, J C

    2010-09-01

    We report a case of multiple ovarian fibromas in a 23 year old woman with Gorlin syndrome. We describe the US and MR imaging features with pathological correlation. The fibrous component of the tumors were hypoechoic and attenuating on US with corresponding T2W hypointensity whereas myxoid components were hypoechoic with increased through transmission on US with corresponding T2W hyperintensity. PMID:20814383

  3. [FEATURES MICROECOLOGY GENITAL TRACT IN WOMEN OF REPRODUCTIVE AGE WITH BENIGN CERVICAL PATHOLOGY].

    PubMed

    Koblosh, N D

    2015-01-01

    In the article we may see the results of microbiological investigation of secretion from genital tracts in women with the benign pathology of uterus cervix. The outcomes specify the disorders of microecology of genital tracts in these women following the proliferation of conditionally pathogenic flora, the increase of viral infection and the increase in the frequency of diagnostic of sexually transmitted infections. PMID:27491159

  4. An examination of anatomic variants and incidental peroneal tendon pathologic features: a comprehensive MRI review of asymptomatic lateral ankles.

    PubMed

    Galli, Melissa M; Protzman, Nicole M; Mandelker, Eiran M; Malhotra, Amit D; Schwartz, Edward; Brigido, Stephen A

    2015-01-01

    Intraoperatively, foot and ankle surgeons will encounter peroneal pathologic features in patients with asymptomatic lateral ankles. The purpose of the present study was to review the ankle magnetic resonance imaging (MRI) scans of patients without a history of ankle trauma or lateral ankle pain to determine which anatomic variants correlate with peroneal tendon pathologic features and noted pathophysiology. A total of 500 MRI scans were screened, 108 (41.90 ± 20.42) of which met the inclusion criteria. The peroneus brevis tendon was intact in 104 MRI scans (96.30%), and the peroneus longus tendon was intact in 108 (100.00%). The results of the present study have confirmed statistically significant correlations between the presence of an os perineum and tendinopathy of the peroneus longus [rs(106) = 0.27], undulating peroneal grooves and the severity of peroneal brevis tears [rs(106) = 0.32], a boomerang-shaped peroneus brevis tendon and increasing tendinopathy of the peroneal tendons [brevis (rs(106) = 0.37; longus rs(106) = 0.33], and low-lying muscle bellies and chronic injuries of the superior peroneal retinaculum (rϕ = 0.19). However, the present study did not find evidence to support the presumed correlations between peroneal tendon pathologic findings and hypertrophied peroneal tubercles, low-lying muscle bellies, or the peroneus quartus muscle. Adding to the published data, the present study found a statistically significant correlation between undulating peroneal grooves and an increasing prevalence of osteophytes within the peroneal groove [rs(106) = 0.32]. MRI findings of anatomic variants or peroneal pathologic features might be useful for injury prevention; however, we advise caution from using the findings alone to advocate surgical intervention. To definitively assess causation, prospective, long-term cohort studies are warranted.

  5. Pathological and immunological features of canine necrotising meningoencephalitis and granulomatous meningoencephalitis.

    PubMed

    Uchida, Kazuyuki; Park, Eunsil; Tsuboi, Masaya; Chambers, James K; Nakayama, Hiroyuki

    2016-07-01

    Necrotising meningoencephalitis (NME) and granulomatous meningoencephalitis (GME) are idiopathic inflammatory diseases of the canine central nervous system (CNS). Typical NME occurs predominantly in small breeds of dogs, such as Pug, Maltese and Yorkshire terriers. Although there is no specific breed predisposition to GME, toy and terrier breeds appear to be overrepresented. Recent molecular investigations have identified genetic risk factors for NME in Pug, Maltese and other toy breed dogs; however, details of the pathogenesis of this disease remain to be clarified. NME is characterised pathologically by necrotic lesions with mononuclear cell infiltration in the meninges and perivascular spaces. On the basis of the distribution pattern of major necrotic foci, NME can be divided into cortex dominant and white matter dominant types; the latter is designated necrotising leucoencephalitis (NLE). Lesions in GME are characterised by the accumulation of lymphocytes and macrophages with epithelioid morphology, forming granulomas around blood vessels. Some common genetic factors and/or some additional triggers, such as infection or vaccination, may play a role in the pathogenesis of NME, NLE and GME; however, the host immune responses may define the pathological phenotypes. Different cytokine and chemokine responses are seen in NME, NLE and GME, whilst autoantibodies against astrocytes are detected predominantly in NME. This review focuses on the pathological and immunological characteristics of these canine idiopathic inflammatory CNS disorders. PMID:27240919

  6. Pathological and immunological features of canine necrotising meningoencephalitis and granulomatous meningoencephalitis.

    PubMed

    Uchida, Kazuyuki; Park, Eunsil; Tsuboi, Masaya; Chambers, James K; Nakayama, Hiroyuki

    2016-07-01

    Necrotising meningoencephalitis (NME) and granulomatous meningoencephalitis (GME) are idiopathic inflammatory diseases of the canine central nervous system (CNS). Typical NME occurs predominantly in small breeds of dogs, such as Pug, Maltese and Yorkshire terriers. Although there is no specific breed predisposition to GME, toy and terrier breeds appear to be overrepresented. Recent molecular investigations have identified genetic risk factors for NME in Pug, Maltese and other toy breed dogs; however, details of the pathogenesis of this disease remain to be clarified. NME is characterised pathologically by necrotic lesions with mononuclear cell infiltration in the meninges and perivascular spaces. On the basis of the distribution pattern of major necrotic foci, NME can be divided into cortex dominant and white matter dominant types; the latter is designated necrotising leucoencephalitis (NLE). Lesions in GME are characterised by the accumulation of lymphocytes and macrophages with epithelioid morphology, forming granulomas around blood vessels. Some common genetic factors and/or some additional triggers, such as infection or vaccination, may play a role in the pathogenesis of NME, NLE and GME; however, the host immune responses may define the pathological phenotypes. Different cytokine and chemokine responses are seen in NME, NLE and GME, whilst autoantibodies against astrocytes are detected predominantly in NME. This review focuses on the pathological and immunological characteristics of these canine idiopathic inflammatory CNS disorders.

  7. Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features.

    PubMed

    Wang, Haibo; Cruz-Roa, Angel; Basavanhally, Ajay; Gilmore, Hannah; Shih, Natalie; Feldman, Mike; Tomaszewski, John; Gonzalez, Fabio; Madabhushi, Anant

    2014-10-01

    Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is the mitotic count, which involves quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at multiple high power fields (HPFs) on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Although handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely supervised feature generation methods, there is an appeal in attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. We present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color, and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing the performance

  8. Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features

    PubMed Central

    Wang, Haibo; Cruz-Roa, Angel; Basavanhally, Ajay; Gilmore, Hannah; Shih, Natalie; Feldman, Mike; Tomaszewski, John; Gonzalez, Fabio; Madabhushi, Anant

    2014-01-01

    Abstract. Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is the mitotic count, which involves quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at multiple high power fields (HPFs) on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Although handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely supervised feature generation methods, there is an appeal in attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. We present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color, and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing the

  9. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations

    PubMed Central

    González-Galarza, Faviel F.; Takeshita, Louise Y.C.; Santos, Eduardo J.M.; Kempson, Felicity; Maia, Maria Helena Thomaz; Silva, Andrea Luciana Soares da; Silva, André Luiz Teles e; Ghattaoraya, Gurpreet S.; Alfirevic, Ana; Jones, Andrew R.; Middleton, Derek

    2015-01-01

    It has been 12 years since the Allele Frequency Net Database (AFND; http://www.allelefrequencies.net) was first launched, providing the scientific community with an online repository for the storage of immune gene frequencies in different populations across the world. There have been a significant number of improvements from the first version, making AFND a primary resource for many clinical and scientific areas including histocompatibility, immunogenetics, pharmacogenetics and anthropology studies, among many others. The most widely used part of AFND stores population frequency data (alleles, genes or haplotypes) related to human leukocyte antigens (HLA), killer-cell immunoglobulin-like receptors (KIR), major histocompatibility complex class I chain-related genes (MIC) and a number of cytokine gene polymorphisms. AFND now contains >1400 populations from more than 10 million healthy individuals. Here, we report how the main features of AFND have been updated to include a new section on ‘HLA epitope’ frequencies in populations, a new section capturing the results of studies identifying HLA associations with adverse drug reactions (ADRs) and one for the examination of infectious and autoimmune diseases associated with KIR polymorphisms—thus extending AFND to serve a new user base in these growing areas of research. New criteria on data quality have also been included. PMID:25414323

  10. CT features and pathologic characteristics of IgG4-related systemic disease of submandibular gland.

    PubMed

    Wang, Zhiwei; Feng, Ruie; Chen, Yu; Duan, Miao; Wang, Man; Jin, Zhengyu; Rumboldt, Zoran; Zhang, Zhuhua

    2015-01-01

    The submandibular gland is one of the most frequently affected salivary gland in IgG4-related systemic disease, usually demonstrate homogeneous attenuation on CT imaging as reported, but without much pathological comparison of many cases. This article is to investigate and analyze the typical CT findings and pathologic characteristics of IgG4-related systemic disease (IgG4-RSD) of submandibular gland. A retrospective analysis of the preoperative CT findings in patients with IgG4-RSD of submandibular glands who underwent surgical resection between January 2010 and February 2014 was performed. Twenty patients (16 women) were identified, with a mean age of 58.1±10.2 years. All patients presented with painless submandibular gland swelling. Diffuse gland enlargement, with clear margins and homogeneous density, was found on non-enhanced CT scans in all cases. There were no calcifications or stones within the involved glands. Based on contrast-enhanced CT appearance the patients could be divided into two groups: 11 cases showed homogeneous gland enhancement; and multiple hyperenhancing foci, with a crazy-paving pattern, were detected in 9 cases, which were in consistent with the pathologic findings. The maximum submandibular gland diameter on transverse images was significantly larger (P=0.008) in patients with crazy-paving appearance (32±4 mm) compared to patients with homogeneous enhancement (28±3 mm). It is concluded that the submandibular glands with IgG4-RSD can be characterized by either homogenous appearance or crazy-paving pattern on contrast-enhanced CT imaging.

  11. Contribution of catecholamine reactive intermediates and oxidative stress to the pathologic features of heart diseases.

    PubMed

    Costa, V M; Carvalho, F; Bastos, M L; Carvalho, R A; Carvalho, M; Remião, F

    2011-01-01

    Pathologic heart conditions, particularly heart failure (HF) and ischemia-reperfusion (I/R) injury, are characterized by sustained elevation of plasma and interstitial catecholamine levels, as well as by the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Despite the continuous and extensive research on catecholamines since the early years of the XX(th) century, the mechanisms underlying catecholamine-induced cardiotoxicity are still not fully elucidated. The role of catecholamines in HF, stress cardiomyopathy, I/R injury, ageing, stress, and pheochromocytoma will be thoroughly discussed. Furthermore and although the noxious effects resulting from catecholamine excess have traditionally been linked to adrenoceptors, in fact, several evidences indicate that oxidative stress and the oxidation of catecholamines can have important roles in catecholamine-induced cardiotoxicity. Accordingly, the reactive intermediates formed during catecholamine oxidation have been associated with cardiac toxicity, both in in vitro and in vivo studies. An insight into the influence of ROS, RNS, and catecholamine oxidation products on several heart diseases and their clinical course will be provided. In addition, the source and type of oxidant species formed in some heart pathologies will be referred. In this review a special focus will be given to the research of cardiac pathologies where catecholamines and oxidative stress are involved. An integrated vision of these matters is required and will be provided along this review, namely how the concomitant surge of catecholamines and ROS occurs and how they can be interconnected. The concomitant presence of these factors can elicit peculiar and not fully characterized responses on the heart. We will approach the existing data with new perspectives as they can help explaining several controversial results regarding cardiovascular diseases and the redox ability of catecholamines.

  12. CT features and pathologic characteristics of IgG4-related systemic disease of submandibular gland

    PubMed Central

    Wang, Zhiwei; Feng, Ruie; Chen, Yu; Duan, Miao; Wang, Man; Jin, Zhengyu; Rumboldt, Zoran; Zhang, Zhuhua

    2015-01-01

    The submandibular gland is one of the most frequently affected salivary gland in IgG4-related systemic disease, usually demonstrate homogeneous attenuation on CT imaging as reported, but without much pathological comparison of many cases. This article is to investigate and analyze the typical CT findings and pathologic characteristics of IgG4-related systemic disease (IgG4-RSD) of submandibular gland. A retrospective analysis of the preoperative CT findings in patients with IgG4-RSD of submandibular glands who underwent surgical resection between January 2010 and February 2014 was performed. Twenty patients (16 women) were identified, with a mean age of 58.1±10.2 years. All patients presented with painless submandibular gland swelling. Diffuse gland enlargement, with clear margins and homogeneous density, was found on non-enhanced CT scans in all cases. There were no calcifications or stones within the involved glands. Based on contrast-enhanced CT appearance the patients could be divided into two groups: 11 cases showed homogeneous gland enhancement; and multiple hyperenhancing foci, with a crazy-paving pattern, were detected in 9 cases, which were in consistent with the pathologic findings. The maximum submandibular gland diameter on transverse images was significantly larger (P=0.008) in patients with crazy-paving appearance (32±4 mm) compared to patients with homogeneous enhancement (28±3 mm). It is concluded that the submandibular glands with IgG4-RSD can be characterized by either homogenous appearance or crazy-paving pattern on contrast-enhanced CT imaging. PMID:26884889

  13. Parasellar solitary fibrous tumor of meninges: magnetic resonance imaging features with pathologic correlation.

    PubMed

    Lo, Chung-Ping; Chen, Cheng-Yu; Lin, Chih-Kung; Chin, Shy-Chyi; Juan, Chun-Jung; Hsueh, Chun-Jen

    2004-07-01

    Solitary fibrous tumor (SFT) is a benign mensenchymal neoplasm of spindle-cell origin. The authors report the case of a 50-year-old man with SFT arising from the meninges of the left parasellar region with cavernous sinus involvement. The tumor was demonstrated isointense on T1-weighted and heterogeneously hypointense on T2-weighted magnetic resonance imaging (MRI) with strong contrast enhancement. The preoperative MRI diagnosis was meningioma or hemangiopericytoma. Pathological study revealed an SFT that stained positive immunohistochemically for CD34 and vimentin.

  14. Length-adaptive graph search for automatic segmentation of pathological features in optical coherence tomography images

    NASA Astrophysics Data System (ADS)

    Keller, Brenton; Cunefare, David; Grewal, Dilraj S.; Mahmoud, Tamer H.; Izatt, Joseph A.; Farsiu, Sina

    2016-07-01

    We introduce a metric in graph search and demonstrate its application for segmenting retinal optical coherence tomography (OCT) images of macular pathology. Our proposed "adjusted mean arc length" (AMAL) metric is an adaptation of the lowest mean arc length search technique for automated OCT segmentation. We compare this method to Dijkstra's shortest path algorithm, which we utilized previously in our popular graph theory and dynamic programming segmentation technique. As an illustrative example, we show that AMAL-based length-adaptive segmentation outperforms the shortest path in delineating the retina/vitreous boundary of patients with full-thickness macular holes when compared with expert manual grading.

  15. Clinical and pathological features of childhood-onset nemaline myopathy: a report of four cases.

    PubMed

    Jiang, Chao; Wang, Jianping; Lu, Haidong

    2012-01-01

    We examined whether immunological abnormalities can be found in the specimens of four childhood-onset nemaline myopathy (NM) patients without autoimmune diseases. Pathological examination revealed that nemaline rods were found in all specimens. The immunohistochemical results showed that CD4 positive cells and some other cells were gathered among the necrotic muscle fibers. We conclude that immunological abnormalities are present in the specimens of certain childhood-onset NM patients without autoimmune diseases. Further evaluation of the immunological changes is warranted in childhood-onset NM patients. PMID:22899938

  16. Pathologic Features of Lone Aortic Mobile Thrombus in the Ascending Aorta.

    PubMed

    Endo, Hidehito; Ishii, Hikaru; Tsuchiya, Hiroshi; Takahashi, Yu; Shimoyamada, Hiroaki; Isomura, Aya; Nakajima, Masanori; Hirano, Teruyuki; Ohkura, Yasuo; Kubota, Hiroshi

    2016-10-01

    This report describes the case of a 79-year-old man with aortic mobile thrombus in the ascending aorta, followed by a discussion of the pathologic basis of aortic mobile thrombus formation. The patient underwent replacement of the ascending aorta. Macroscopic examination revealed an aortic wall ulcer with cholesterol-rich atherosclerotic plaque under the aortic mobile thrombus. Microscopic examination showed plaque rupture. These findings are very similar to those of plaque rupture in the coronary artery. We speculate that plaque rupture of localized aortic atherosclerosis is one of the causes of aortic mobile thrombus. PMID:27645970

  17. Pathological features in marine birds affected by the prestige's oil spill in the north of Spain.

    PubMed

    Balseiro, A; Espí, A; Márquez, I; Pérez, V; Ferreras, M C; Marín, J F García; Prieto, J M

    2005-04-01

    A total of 2,465 seabirds, mainly common murres (Uria aalge), razorbills (Alca torda), and puffins (Fratercula arctica) that beached in the northwestern part of Spain after the "Prestige" oil spill on 19 November 2002 were examined by pathological methods. Birds were divided into three groups: dead birds with the body covered (group 1) or uncovered (group 2) by oil and birds recovered alive but which died after being treated at a rescue center (group 3). The main gross lesions were severe dehydration and emaciation. Microscopically, hemosiderin deposits, related to cachexia and/or hemolytic anemia, were observed in those birds harboring oil in the intestine. Severe aspergillosis and ulcers in the ventriculus were found only in group 3 birds, probably because of stress associated with attempted rehabilitation at the rescue center. The mild character of the pathological changes suggests that petroleum oil toxicosis causes multiple sublethal changes that have an effect on the ability of the birds to survive at sea, especially weak and young, inexperienced animals. Dehydration and exhaustion seem to be the most likely cause of death. PMID:16107672

  18. Epidemiological, clinical and pathological features of primary cardiac hemangiosarcoma in dogs: a review of 51 cases.

    PubMed

    Yamamoto, Shinya; Hoshi, Katsuichiro; Hirakawa, Atsushi; Chimura, Syuuichi; Kobayashi, Masayuki; Machida, Noboru

    2013-11-01

    In the study presented here, we aimed to describe the epidemiological, clinical and pathological findings of 51 canine cases with histologically-verified diagnoses of primary cardiac hemangiosarcoma (HSA). The medical data for each dog, including signalment, presenting complaints, physical examination findings, results of various diagnostic testing performed and method of treatment, were checked. In addition, all 51 cases were re-examined pathologically. The tumor occurred most frequently in older Golden Retrievers, followed by Maltese dogs and Miniature Dachshunds. Mass lesions of HSA were found more commonly in the right auricle (RAu) (25/51) and right atrium (RA) (21/51), and the RA masses were significantly (P<0.001) larger than the RAu masses. The echocardiographic detection rate of masses in the RAu group (60%; 15/25) was significantly lower than that in the RA group (95%; 20/21). Survival time was significantly (P<0.05) longer for 5 dogs that received adjuvant chemotherapy after tumor resection than for 12 dogs that did not. In this series, the Maltese (9/51) and Miniature Dachshund (7/51), as well as the Golden Retriever, were represented more frequently than other breeds. The lower echocardiographic detection rate of RAu masses compared with RA masses may be related to tumor size and/or location. The significantly longer survival time for dogs receiving adjuvant chemotherapy indicates that postoperative chemotherapy could be useful for dogs with cardiac HSA.

  19. Major diagnostic and pathological features of iniencephaly based on twenty-four cases.

    PubMed

    Joó, József Gábor; Beke, Artúr; Papp, Csaba; Szigeti, Zsanett; Csaba, Akos; Papp, Zoltán

    2008-01-01

    Iniencephaly is quite a rare malformation the etiology of which is still not fully understood. In the majority of cases it is a grave and lethal condition. It is often complicated by other abnormalities affecting the central nervous system (spina bifida, anencephaly), but malformations involving other organs and systems may also be observed. Based on 24 cases the authors have surveyed the diagnostics of iniencephaly with special regard to the disorders affecting the central and non-central nervous systems. In addition, they have compared the results of prenatal diagnostics and pathological investigations. In the sample, maternal age ranged between 17 and 42 (median 24) years. Positive obstetrical-gynecological and genetic findings in the patients' history have been reported in 4 and 2 cases, respectively. In these cases, the maternal serum alpha-fetoprotein (AFP) values ranged between 0.7 and 3.9 (median 2.0) MoM, while the amniotic fluid AFP values were between 0.9 and 2.7 (median 1.4) MoM. Spina bifida (50%) and anencephaly (42%) were the most commonly occurring complications affecting the central nervous system. Among the non-central nervous system disorders, malformations of the abdominal (omphalocele) and thoracic walls (diaphragmatic hernia) were found most frequently and the tendency to develop associated polyhydramnios was also very high (75%). Pathological investigations revealed developmental disorders such as cleft lip and palate, ventricular septal defect and facial dysmorphism, which are difficult to detect using ultrasonography. PMID:18504373

  20. Clinical and pathologic features of West Nile virus infection in native North American owls (Family strigidae).

    PubMed

    Fitzgerald, S D; Patterson, J S; Kiupel, M; Simmons, H A; Grimes, S D; Sarver, C F; Fulton, R M; Steficek, B A; Cooley, T M; Massey, J P; Sikarskie, J G

    2003-01-01

    Since the initial report of West Nile virus in the northeastern United States in 1999, the virus has spread rapidly westward and southward across the country. In the summer of 2002, several midwestern states reported increased cases of neurologic disease and mortality associated with West Nile virus infection in various native North American owl species. This report summarizes the clinical and pathologic findings for 13 captive and free-ranging owls. Affected species were all in the family Strigidae and included seven snowy owls (Nyctea scandiaca), four great-horned owls (Bubo virginianus), a barred owl (Strix varia), and a short-eared owl (Asio flammeus). Neurologic signs identified included head tilt, uncoordinated flight, paralysis, tremors, and seizures. Owls that died were screened for flaviviral proteins by immunohistochemical staining of formalin-fixed tissues, followed by specific polymerase chain reaction assay to confirm West Nile virus with fresh tissues when available. Microscopic lesions were widespread, involving brain, heart, liver, kidney, and spleen, and were typically nonsuppurative with infiltration by predominantly lymphocytes and plasma cells. Lesions in owls were much more severe than those previously reported in corvids such as crows, which are considered highly susceptible to infection and are routinely used as sentinel species for monitoring for the presence and spread of West Nile virus. This report is the first detailed description of the pathology of West Nile virus infection in Strigiformes and indicates that this bird family is susceptible to natural infection with West Nile virus.

  1. Clinical and pathologic features of West Nile virus infection in native North American owls (Family strigidae).

    PubMed

    Fitzgerald, S D; Patterson, J S; Kiupel, M; Simmons, H A; Grimes, S D; Sarver, C F; Fulton, R M; Steficek, B A; Cooley, T M; Massey, J P; Sikarskie, J G

    2003-01-01

    Since the initial report of West Nile virus in the northeastern United States in 1999, the virus has spread rapidly westward and southward across the country. In the summer of 2002, several midwestern states reported increased cases of neurologic disease and mortality associated with West Nile virus infection in various native North American owl species. This report summarizes the clinical and pathologic findings for 13 captive and free-ranging owls. Affected species were all in the family Strigidae and included seven snowy owls (Nyctea scandiaca), four great-horned owls (Bubo virginianus), a barred owl (Strix varia), and a short-eared owl (Asio flammeus). Neurologic signs identified included head tilt, uncoordinated flight, paralysis, tremors, and seizures. Owls that died were screened for flaviviral proteins by immunohistochemical staining of formalin-fixed tissues, followed by specific polymerase chain reaction assay to confirm West Nile virus with fresh tissues when available. Microscopic lesions were widespread, involving brain, heart, liver, kidney, and spleen, and were typically nonsuppurative with infiltration by predominantly lymphocytes and plasma cells. Lesions in owls were much more severe than those previously reported in corvids such as crows, which are considered highly susceptible to infection and are routinely used as sentinel species for monitoring for the presence and spread of West Nile virus. This report is the first detailed description of the pathology of West Nile virus infection in Strigiformes and indicates that this bird family is susceptible to natural infection with West Nile virus. PMID:14562887

  2. Autonomic involvement in Parkinson's disease: pathology, pathophysiology, clinical features and possible peripheral biomarkers.

    PubMed

    Cersosimo, Maria G; Benarroch, Eduardo E

    2012-02-15

    Autonomic nervous system involvement occurs at early stages in both Parkinson's disease (PD) and incidental Lewy body disease (ILBD), and affects the sympathetic, parasympathetic, and enteric nervous systems (ENS). It has been proposed that alpha-synuclein (α-SYN) pathology in PD has a distal to proximal progression along autonomic pathways. The ENS is affected before the dorsal motor nucleus of the vagus (DMV), and distal axons of cardiac sympathetic nerves degenerate before there is loss of paravertebral sympathetic ganglion neurons. Consistent with neuropathological findings, some autonomic manifestations such as constipation or impaired cardiac uptake of norepinephrine precursors, occur at early stages of the disease even before the onset of motor symptoms. Biopsy of peripheral tissues may constitute a promising approach to detect α-SYN neuropathology in autonomic nerves and a useful early biomarker of PD.

  3. Primary retroperitoneal teratoma in the adult: correlation of MRI features with CT and pathology.

    PubMed

    Bellin, M F; Duron, J J; Curet, P; Dion-Voirin, E; Grellet, J

    1991-01-01

    Primary benign teratoma of the retroperitoneum is a rare tumor in the adult population. Only one case with an MRI examination has been reported in the English literature. This paper describes the CT and MRI features of a retroperitoneal teratoma in a 24-year-old male and discusses the value of MRI in the diagnosis and the preoperative imaging of such a tumor.

  4. Clinical and Anatomical Features as well as Pathological Conditions of Surgically Treated Adult Patients with Occipitalization of the Atlas

    PubMed Central

    Shimizu, Takachika; Fueki, Keisuke; Ino, Masatake; Toda, Naofumi; Tanouchi, Tetsu; Manabe, Nodoka

    2016-01-01

    Background This paper intends to clarify clinical and anatomical features as well as pathological conditions of surgically treated adult patients with occipitalization of the atlas. Methods The authors reviewed 12 consecutive adult patients with occipitalization of the atlas who underwent surgery for myleopathy in our hospital. Mainly using preoperative computed tomography and three-dimensional computed tomography angiography, we investigated their anomalies of the osseous structures and vertebral artery at the cervical spine including the craniovertebral junction (CVJ). We also developed a new classification system for occipitalization of the atlas. Results Atlantoaxial subluxation (AAS) was detected in 9 patients (75%). The condition of AAS was irreducible in 7 patients. Among these 7 patients, deformity at the lateral atlantoaxial joints was detected in 2 patients. C2-3 fusion was detected in 6 patients (67%) among 9 patients with AAS. Anomalies of the VA were detected in 11 patients (92%). Occipitalization of the atlas was classified into three types according to their pathological conditions. In type 1 (2 patients) the medial atlantoaxial joint is semi-dislocated and the lateral atlantoaxial joints are severely deformed. Type 2 (7 patients) exhibits AAS but the lateral atlantoaxial joints are not deformed. Type 3 (3 patients) is not associated with AAS and therefore does not exhibit osseous stenosis at the CVJ. In type 3 the myelopathy was caused by another coexisting condition. Conclusions Occipitalization of the atlas is classified into three types. The main pathological condition in both types 1 and 2 is AAS. Reduction of AAS is essential in both; however, reduction of AAS in type 1 is more technically demanding than in type 2. The pathological conditions of type 3 are completely different from those of the others, so an accurate diagnosis must be made. The new classification system is a useful guide for surgeons when planning surgical strategies. PMID

  5. Manifestations and pathological features of solitary thin-walled cavity lung cancer observed by CT and PET/CT imaging

    PubMed Central

    QI, YUANGANG; ZHANG, QING; HUANG, YONG; WANG, DAOQING

    2014-01-01

    The aim of the present study was to analyze and improve the understanding of computed tomography (CT) and positron emission tomography (PET)/CT imaging and the pathological features of solitary thin-walled cavity lung cancer. A total of 16 patients with pathologically confirmed solitary thin-walled cavity lung cancer were included in the present study. All of the patients received CT scans. Among these, two patients underwent an additional PET/CT examination. The CT and PET/CT images were analyzed and a cross-check analysis of the pathological results was conducted. In total, 16 cases of lesions demonstrated thin-walled cavities on the CT images. Among these cases, three presented with an uneven thickening of the cavity walls, 10 cases exhibited wall nodules and three cases presented with compartments in the cavity. The standard uptake value (SUV) of the cavity wall increased in two patients who underwent PET/CT examinations. The 16 cases of lesions were pathologically confirmed as adenocarcinomas. Light microscopy revealed that the tumor cells, which were observed in 12 cases of lesions, had diffused along the inner cavity wall and the tumor cells of four cases had invaded the bronchial wall. Images of the chest that demonstrated a single thin-walled cavity accompanied by uneven thickening of the cavity wall or wall nodules, in addition to an increase in the SUV and compartments in the cavity, indicated potential lung cancer. Valves formed as a result of bronchial wall damage may have led to the cavity. PMID:24959262

  6. Tau Protein Mediates APP Intracellular Domain (AICD)-Induced Alzheimer’s-Like Pathological Features in Mice

    PubMed Central

    Dawson, Hana N.; Pimplikar, Sanjay W.

    2016-01-01

    Amyloid precursor protein (APP) is cleaved by gamma-secretase to simultaneously generate amyloid beta (Aβ) and APP Intracellular Domain (AICD) peptides. Aβ plays a pivotal role in Alzheimer’s disease (AD) pathogenesis but recent studies suggest that amyloid-independent mechanisms also contribute to the disease. We previously showed that AICD transgenic mice (AICD-Tg) exhibit AD-like features such as tau pathology, aberrant neuronal activity, memory deficits and neurodegeneration in an age-dependent manner. Since AD is a tauopathy and tau has been shown to mediate Aβ–induced toxicity, we examined the role of tau in AICD-induced pathological features. We report that ablating endogenous tau protects AICD-Tg mice from deficits in adult neurogenesis, seizure severity, short-term memory deficits and neurodegeneration. Deletion of tau restored abnormal phosphorylation of NMDA receptors, which is likely to underlie hyperexcitability and associated excitotoxicity in AICD-Tg mice. Conversely, overexpression of wild-type human tau aggravated receptor phosphorylation, impaired adult neurogenesis, memory deficits and neurodegeneration. Our findings show that tau is essential for mediating the deleterious effects of AICD. Since tau also mediates Aβ-induced toxic effects, our findings suggest that tau is a common downstream factor in both amyloid-dependent and–independent pathogenic mechanisms and therefore could be a more effective drug target for therapeutic intervention in AD. PMID:27459671

  7. Pathological features of salivary gland cysts in a Shiba dog with GM1 gangliosidosis: a possible misdiagnosis as malignancy.

    PubMed

    Rahman, Mohammad Mahbubur; Kawaguchi, Hiroaki; Miyoshi, Noriaki; Yabuki, Akira; Nakamoto, Yuya; Ozawa, Tsuyoshi; Yamato, Osamu

    2012-04-01

    Salivary gland cysts are often concurrent with GM1 gangliosidosis in Shiba dogs. Although the etiology is unknown, these cysts may be misdiagnosed as malignant due to the accumulation of foamy cells. The present study investigated the cytological, histopathological, immunohistochemical and electron microscopic characteristics of salivary gland cysts in a Shiba dog affected with GM1 gangliosidosis. The salivary gland masses were surgically enucleated and examined clinicopathologically and pathologically in a 7-month-old Shiba dog with GM1 gangliosidosis. Many large cells with rich cytoplasm including vacuoles of various sizes, i.e., foamy cells, were observed in stamp smears from the cut-surface of the masses and histopathologically in major parts of the cyst wall. Some of these foamy cells presented features similar to a spider-web appearance. The foamy cells were confirmed to have originated from macrophages based on marked immunohistochemical expression of vimentin, HLA-DR, lysozyme and Iba1. An ultrastructural study demonstrated electron-dense vesicular structures in the vacuolated cells. Therefore, the masses were diagnosed pathologically as benign salivary gland cysts with accumulation of foamy cells. In conclusion, the histopathological features of the salivary gland cysts in this Shiba dog were similar to those of lipoma and/or liposarcoma. In such cases, immunohistochemical and ultrastructural examinations were useful in the differential diagnosis. Practitioners, clinical pathologists and pathologists should take GM1 gangliosidosis into consideration when they encounter salivary gland cysts in Shiba dogs.

  8. Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats.

    PubMed

    Imaeda, Masumi; Ishikawa, Hitoshi; Yoshida, Yukari; Takahashi, Takeo; Ohkubo, Yu; Musha, Atsushi; Komachi, Mayumi; Nakazato, Yoichi; Nakano, Takashi

    2014-07-01

    Radiation therapy (RT) has become particularly important recently for treatment of liver tumors, but there are few experimental investigations pertaining to radiation-induced liver injuries over long-term follow-up periods. Thus, the present study examined pathological liver features over a 10-month period using an intraoperative whole-liver irradiation model. Liver function tests were performed in blood samples, whereas cell death, cell proliferation, and fibrotic changes were evaluated pathologically in liver tissues, which were collected from irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function, increased hepatocyte number, and decreased apoptotic cell proportion observed in the 15 Gy group, but not the 30 Gy group, returned to control group levels after 40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than those in the control group after 40 weeks. Azan staining showed a fibrotic pattern in the irradiated liver in the 30 Gy group only, but the expression levels of alpha smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) in both the 15 and 30 Gy groups were significantly higher than those in the control group (P < 0.05). There were differences in the pathological features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF-β1 and α-SMA expression patterns supported the gradual progression of radiation-induced liver fibrosis in both groups. These findings will be useful in the future development of protective drugs for radiation-induced liver injury. PMID:24566720

  9. Some Pathological Features of Lungs from Domestic and Wild Ruminants with Single and Mixed Protostrongylid Infections

    PubMed Central

    Panayotova-Pencheva, Mariana Stancheva; Alexandrov, Marin Tsvyatkov

    2010-01-01

    Lungs of 40 ruminants from Bulgaria with natural small lungworm (Nematoda: Protostrongylidae) infections were investigated, including 16 goats, 15 sheep, 7 mouflons, and 2 chamois. Muellerius capillaris, M. tenuispiculatus, Cystocaulus ocreatus, Neostrongylus linearis, and Protostrongylus brevispiculum infections were predominantly associated with nodular lesions, and Protostrongylus rufescens, Protostrongylus hobmaieri and Protostrongylus rupicaprae were associated with extensive lesions located mainly along the length of the large bronchi. The extent of lung abnormalities was most severe in the sheep. Alveolitis, parasite granulomas, damage of the alveolar septa, hyperplasia of the lung associated lymphoid tissue, and sclerosis of the parenchyma were found upon microscope examinations. In the goats compared to the sheep and mouflons, the terminal bronchi, bronchioles, and alveoli were more affected than the interstitium. Our research shows that the pathological lesions in the lungs of ruminants infected with protostrongylids depend on both the helminth and the host species. To our knowledge, this work is the first to provide data on the pathomorphological lesions in mouflon lungs infected with protostrongylids. PMID:20445790

  10. Hematopoietic tumors of the female genital system: imaging features with pathologic correlation.

    PubMed

    Salem, Usama; Menias, Christine O; Shaaban, Akram; Bhosale, Priya R; Youssef, Ayda; Elsayes, Khaled M

    2014-08-01

    Various hematopoietic neoplasms can involve the female genital system. The most common hematological malignancy that involves the female genital system is lymphoma and secondary involvement is more common than primary genital lymphoma. Rarely, leukemic infiltration and extramedullary plasmacytomas of the female genital tract may also occur. Being infrequent, these lesions are commonly misdiagnosed radiologically. Therefore, understanding these malignancies of the female genital system and recognizing their imaging features are of utmost clinical importance. Although definitive diagnosis can be made only by histological analysis, imaging of these tumors plays an important role in detecting lesion extensions, guiding biopsies, staging disease, planning therapy, and detecting recurrence.

  11. A note on the stability and discriminability of graph-based features for classification problems in digital pathology

    NASA Astrophysics Data System (ADS)

    Cruz-Roa, Angel; Xu, Jun; Madabhushi, Anant

    2015-01-01

    Nuclear architecture or the spatial arrangement of individual cancer nuclei on histopathology images has been shown to be associated with different grades and differential risk for a number of solid tumors such as breast, prostate, and oropharyngeal. Graph-based representations of individual nuclei (nuclei representing the graph nodes) allows for mining of quantitative metrics to describe tumor morphology. These graph features can be broadly categorized into global and local depending on the type of graph construction method. While a number of local graph (e.g. Cell Cluster Graphs) and global graph (e.g. Voronoi, Delaunay Triangulation, Minimum Spanning Tree) features have been shown to associated with cancer grade, risk, and outcome for different cancer types, the sensitivity of the preceding segmentation algorithms in identifying individual nuclei can have a significant bearing on the discriminability of the resultant features. This therefore begs the question as to which features while being discriminative of cancer grade and aggressiveness are also the most resilient to the segmentation errors. These properties are particularly desirable in the context of digital pathology images, where the method of slide preparation, staining, and type of nuclear segmentation algorithm employed can all dramatically affect the quality of the nuclear graphs and corresponding features. In this paper we evaluated the trade off between discriminability and stability of both global and local graph-based features in conjunction with a few different segmentation algorithms and in the context of two different histopathology image datasets of breast cancer from whole-slide images (WSI) and tissue microarrays (TMA). Specifically in this paper we investigate a few different performance measures including stability, discriminability and stability vs discriminability trade off, all of which are based on p-values from the Kruskal-Wallis one-way analysis of variance for local and global

  12. Influence of clinical and pathologic features on the pathologist's diagnosis of mycosis fungoides: a pilot study.

    PubMed

    Rovner, Rebecca; Smith, Hayden L; Katz, Peter J; Liu, Vincent

    2015-07-01

    Although clinicopathologic correlation is critical in the diagnosis of early mycosis fungoides (MF), how clinical information directly affects the pathologist's interpretation is unknown. This pilot study aimed to assess the influence of provided clinical information and specific histopathologic features on the histopathologic diagnosis of MF vs. its inflammatory simulants. A computerized survey recorded diagnostic impressions by 24 dermatopathologists of 30 hematoxylin-eosin stained images, including 15 MF images and 15 dermatitis images. Images were accompanied by concordant clinical descriptions (33%), no clinical information (33%) or discordant clinical descriptions (33%). Percentage of correctly classified MF histopathologic images for the three scenarios of concordant clinical information, no clinical information or discordant clinical information were 32% (kappa 0.19), 56% (kappa 0.12) and 16% (kappa 0.33), respectively. The percentage of correctly classified slides presented with no clinical information was different from the other two groups (p < 0.0001). Pautrier collections were most associated with correct classification. Clinical information may play a significant role in the histopathologic diagnosis of MF, although there may be some value in initial blinded histopathologic interpretation. Specific histopathologic features differ in relative importance in the diagnosis of MF.

  13. Optimization of a 3D Dynamic Culturing System for In Vitro Modeling of Frontotemporal Neurodegeneration-Relevant Pathologic Features.

    PubMed

    Tunesi, Marta; Fusco, Federica; Fiordaliso, Fabio; Corbelli, Alessandro; Biella, Gloria; Raimondi, Manuela T

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer's disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may be

  14. Optimization of a 3D Dynamic Culturing System for In Vitro Modeling of Frontotemporal Neurodegeneration-Relevant Pathologic Features.

    PubMed

    Tunesi, Marta; Fusco, Federica; Fiordaliso, Fabio; Corbelli, Alessandro; Biella, Gloria; Raimondi, Manuela T

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer's disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may be

  15. Examining the relation of osteochondral lesions of the talus to ligamentous and lateral ankle tendinous pathologic features: a comprehensive MRI review in an asymptomatic lateral ankle population.

    PubMed

    Galli, Melissa M; Protzman, Nicole M; Mandelker, Eiran M; Malhotra, Amit D; Schwartz, Edward; Brigido, Stephen A

    2014-01-01

    Given the frequency and burden of ankle sprains, the pathologic features identified on magnetic resonance imaging (MRI) scans are widely known in the symptomatic population. Ankle MRI pathologic features in the asymptomatic population, however, are poorly understood. Such examinations are rarely undertaken unless an ankle has been injured or is painful. We report the systematic MRI findings from the reports of 108 consecutive asymptomatic lateral ankles (104 patients). Our purpose was to (1) report the prevalence of osteochondral lesions of the talus (OLTs) and pathologic features of the medial and lateral ligaments, peroneal tendons, and superior peroneal retinaculum (SPR); (2) correlate the presence of OLTs with the pathologic features of the medial and lateral ligaments, peroneal tendons, and SPR; and (3) correlate ligamentous discontinuity with the peroneal pathologic features, OLTs, and SPR pathologic features. A total of 16 OLTs (14.81%) were present (13 medial and 3 lateral). Of the 16 patients with OLTs, 8 (50.00%) had concomitant peroneal pathologic findings. Healthy medial and lateral ligaments were noted in 41 patients (37.96%), and ligamentous discontinuity was grade I in 25 (23.15%), II in 32 (29.63%), III in 5 (4.63%), and grade IV in 5 patients (4.63%). A weak positive correlation was found between attenuation or tears of the superficial deltoid and medial OLTs (phi coefficient = 0.23, p = .0191) and a moderate positive correlation between tears of the posterior talofibular ligament and lateral OLTs (phi coefficient = 0.30, p = .0017). Additionally, a moderate positive correlation between ligamentous discontinuity and tendinopathy of the peroneus brevis was noted [Spearman's coefficient(106) = 0.29, p = .0024]. These findings add to the evidence of concomitant pathologic features in the asymptomatic population. To definitively assess causation and evaluate the clinical evolution of radiologic findings, future, prospective, longitudinal

  16. RET/PTC Translocations and Clinico-Pathological Features in Human Papillary Thyroid Carcinoma

    PubMed Central

    Romei, Cristina; Elisei, Rossella

    2012-01-01

    Thyroid carcinoma is the most frequent endocrine cancer accounting for 5–10% of thyroid nodules. Papillary histotype (PTC) is the most prevalent form accounting for 80% of all thyroid carcinoma. Although much is known about its epidemiology, pathogenesis, clinical, and biological behavior, the only documented risk factor for PTC is the ionizing radiation exposure. Rearrangements of the Rearranged during Transfection (RET) proto-oncogene are found in PTC and have been shown to play a pathogenic role. The first RET rearrangement, named RET/PTC, was discovered in 1987. This rearrangement constitutively activates the transcription of the RET tyrosine-kinase domain in follicular cell, thus triggering the signaling along the MAPK pathway and an uncontrolled proliferation. Up to now, 13 different types of RET/PTC rearrangements have been reported but the two most common are RET/PTC1 and RET/PTC3. Ionizing radiations are responsible for the generation of RET/PTC rearrangements, as supported by in vitro studies and by the evidence that RET/PTC, and particularly RET/PTC3, are highly prevalent in radiation induced PTC. However, many thyroid tumors without any history of radiation exposure harbor similar RET rearrangements. The overall prevalence of RET/PTC rearrangements varies from 20 to 70% of PTCs and they are more frequent in childhood than in adulthood thyroid cancer. Controversial data have been reported on the relationship between RET/PTC rearrangements and the PTC prognosis. RET/PTC3 is usually associated with a more aggressive phenotype and in particular with a greater tumor size, the solid variant, and a more advanced stage at diagnosis which are all poor prognostic factors. In contrast, RET/PTC1 rearrangement does not correlate with any clinical–pathological characteristics of PTC. Moreover, the RET protein and mRNA expression level did not show any correlation with the outcome of patients with PTC and no correlation between RET/PTC rearrangements and the

  17. Detection Rate, Distribution, Clinical and Pathological Features of Colorectal Serrated Polyps

    PubMed Central

    Cao, Hai-Long; Chen, Xue; Du, Shao-Chun; Song, Wen-Jing; Wang, Wei-Qiang; Xu, Meng-Que; Wang, Si-Nan; Piao, Mei-Yu; Cao, Xiao-Cang; Wang, Bang-Mao

    2016-01-01

    Background: Colorectal serrated polyp is considered as histologically heterogeneous lesions with malignant potential in western countries. However, few Asian studies have investigated the comprehensive clinical features of serrated polyps in symptomatic populations. The aim of the study was to evaluate the features of colorectal serrated polyps in a Chinese symptomatic population. Methods: Data from all consecutive symptomatic patients were documented from a large colonoscopy database and were analyzed. Chi-square test or Fisher's exact test and logistic regression analysis were used for the data processing. Results: A total of 9191 (31.7%) patients were detected with at least one colorectal polyp. The prevalence of serrated polyps was 0.53% (153/28,981). The proportions of hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA) of all serrated polyps were 41.2%, 7.2%, and 51.6%, respectively, which showed a lower proportion of HP and SSA/P and a higher proportion of TSA. Serrated polyps appeared more in males and elder patients while there was no significant difference in the subtype distribution in gender and age. The proportions of large and proximal serrated polyps were 13.7% (21/153) and 46.4% (71/153), respectively. In total, 98.9% (89/90) serrated adenomas were found with dysplasia. Moreover, 14 patients with serrated polyps were found with synchronous advanced colorectal neoplasia, and large serrated polyps (LSPs) (odds ratio: 3.446, 95% confidence interval: 1.010–11.750, P < 0.05), especially large HPs, might have an association with synchronous advanced neoplasia (AN). Conclusions: The overall detection rate of colorectal serrated polyps in Chinese symptomatic patient population was low, and distribution pattern of three subtypes is different from previous reports. Moreover, LSPs, especially large HPs, might be associated with an increased risk of synchronous AN. PMID:27748334

  18. Correlation of HOXD3 promoter hypermethylation with clinical and pathologic features in screening prostate biopsies

    PubMed Central

    Chen, Leonard N; Rubin, Rachel S; Othepa, Eugide; Cer, Caroline; Yun, Elizabeth; Agarwal, Raghunath P; Collins, Brian T; McGeagh, Kevin; Pahira, John; Bandi, Guarav; Kowalczyk, Keith; Kumar, Deepak; Dritschilo, Anatoly; Collins, Sean P; Bostwick, David G; Lynch, John H; Suy, Simeng

    2014-01-01

    BACKGROUND Molecular markers that can discriminate indolent cancers from aggressive ones may improve the management of prostate cancer and minimize unnecessary treatment. Aberrant DNA methylation is a common epigenetic event in cancers and HOXD3 promoter hypermethylation (H3PH) has been found in prostate cancer. Our objective was to evaluate the relationship between H3PH and clinicopathologic features in screening prostate biopsies. METHODS Ninety-two patients who underwent a prostate biopsy at our institution between October 2011 and May 2012 were included in this study. The core with the greatest percentage of the highest grade disease was analyzed for H3PH by methylation-specific PCR. Correlational analysis was used to analyze the relationship between H3PH and various clinical parameters. Chi-square analysis was used to compare H3PH status between benign and malignant disease. RESULTS Of the 80 biopsies with HOXD3 methylation status assessable, 66 sets were confirmed to have cancer. In the 14 biopsies with benign disease there was minimal H3PH with the mean percentage of methylation reference (PMR) of 0.7%. In contrast, the HOXD3 promoter was hypermethylated in 16.7% of all cancers and in 50% of high risk tumors with an average PMR of 4.3% (P = 0.008). H3PH was significantly correlated with age (P = 0.013), Gleason score (P = 0.031) and the maximum involvement of the biopsy core (P = 0.035). CONCLUSIONS H3PH is associated with clinicopathologic features. The data indicate that H3PH is more common in older higher risk patients. More research is needed to determine the role of this marker in optimizing management strategies in men with newly diagnosed prostate cancer. Prostate 74:714–721, 2014. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:24847526

  19. Clinical and pathological features of common gill diseases of cultured salmonids in Ontario

    PubMed Central

    Speare, David J.; Ferguson, Hugh W.

    1989-01-01

    We reviewed the clinical presentations and histopathology of 118 diagnostic submissions of trout with infectious gill diseases from commercial trout farms within Ontario. Bacterial gill disease (BGD) (56%) and nodular gill disease (NGD) (26.2%) together accounted for 82.2% of these submissions. Submissions of fish with BGD occurred in every month of the year, but were proportionally more frequent in late winter and spring than in late summer and fall. Chemotherapy of groups of fish with gill diseases was common prior to submission, but the success rate of such treatment was low (29% for BGD; 21% for NGD). Specific therapeutic protocols implemented following etiological diagnosis of BGD were successful in 80% of the previously unresponsive cases and in 88.8% of previously untreated cases. The gills of trout collected within 48-96 h of treatment and apparent clinical recovery lacked bacteria and necrotic epithelial cells, but features such as lamellar fusion and epithelial hyperplasia were similar between recovered and affected fish. ImagesFigure 1.Figure 2.Figure 4.Figure 5.Figure 6.Figure 7.Figure 8. PMID:17423456

  20. S-phase fractions of colorectal carcinomas related to pathologic and clinical features

    SciTech Connect

    Meyer, J.S.; Prioleau, P.G.

    1981-09-01

    The S-phase fractions (SPFs) of epithelial cells in 100 resected colorectal carcinomas were measured by in vitro exposure to tritiated thymidine and autoradiography. The frequency distribution of SPFs was gaussian with a median of 17.8 per hundred in 90 unirradiated carcinomas, whereas in ten carcinomas given radiation therapy preoperatively, it was positively skewed with a median of 6.9. Analysis of the unirradiated carcinomas showed no relationship between SPF and various clinical and morphologic features that included age, race, sex, site, size, Dukes' stage, histologic grade of the tumor, number of metastasis-bearing regional lymph nodes, presence of adenomas of the large bowel, survival or relapse-free survival of the patient, or SPF or adjacent normal colorectal crypts. The results show no evidence that colorectal carcinomas can be divided into kinetic subsets. The spatial orientation of labeled cells in autoradiographs indicated presence of a nonproliferative fraction of cells in many tumors that may modulate response to radiation therapy and chemotherapy.

  1. Clinical & pathological features of acute toxicity due to Cassia occidentalis in vertebrates.

    PubMed

    Vashishtha, V M; John, T J; Kumar, Amod

    2009-07-01

    Cassia occidentalis is an annual shrub found in many countries including India. Although bovines and ovines do not eat it, parts of the plant are used in some traditional herbal medicines. Several animal studies have documented that fresh or dried beans are toxic. Ingestion of large amounts by grazing animals has caused serious illness and death. The toxic effects in large animals, rodents and chicken are on skeletal muscles, liver, kidney and heart. The predominant systems involved depend upon the animal species and the dose of the beans consumed. Brain functions are often affected. Gross lesions at necropsy consist of necrosis of skeletal muscle fibres and hepatic centrilobular necrosis; renal tubular necrosis is less frequent. Muscle and liver cell necrosis is reflected in biochemical abnormalities. The median lethal dose (LD(50)) is 1 g/kg for mice and rats. Toxicity is attributed to various anthraquinones and their derivatives and alkaloids, but the specific toxins have not been identified. Data on human toxicity are extremely scarce. This review summarizes information available on Cassia toxicity in animals and compares it with toxic features reported in children. The clinical spectrum and histopathology of C. occidentalis poisoning in children resemble those of animal toxicity, affecting mainly hepatic, skeletal muscle and brain tissues. The case-fatality rate in acute severe poisoning is 75-80 per cent in children. PMID:19700797

  2. Herpes Simplex Virus Type 1 infection: overview on relevant clinico-pathological features.

    PubMed

    Arduino, Paolo G; Porter, Stephen R

    2008-02-01

    Herpes Simplex Virus Type 1 (HSV-1) is a nuclear replicating enveloped virus, usually acquired through direct contact with infected lesions or body fluids (typically saliva). The prevalence of HSV-1 infection increases progressively from childhood, the seroprevalence being inversely related to socioeconomic background. Primary HSV-1 infections in children are either asymptomatic or following an incubation period of about 1 week gives rise to mucocutaneous vesicular eruptions. Herpetic gingivostomatitis typically affects the tongue, lips, gingival, buccal mucosa and the hard and soft palate. Most primary oro-facial HSV infection is caused by HSV-1, infection by HSV-2 is increasingly common. Recurrent infections, which occur at variable intervals, typically give rise to vesiculo-ulcerative lesions at mucocutaneous junctions particularly the lips (herpes labialis). Recurrent HSV-1 infection within the mouth is uncommon in otherwise healthy patients, although in immunocompromised patients, recurrent infection can be more extensive and/or aggressive. The diagnosis of common herpetic infection can usually be based upon the clinical history and presenting features. Confirmatory laboratory diagnosis is, however, required when patients are, or may be, immunocompromised.

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

    PubMed Central

    Lin, Yang; 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. PMID:27738631

  4. Usual interstitial pneumonia end-stage features from explants with radiologic and pathological correlations.

    PubMed

    Rabeyrin, Maud; Thivolet, Françoise; Ferretti, Gilbert R; Chalabreysse, Lara; Jankowski, Adrien; Cottin, Vincent; Pison, Christophe; Cordier, Jean-François; Lantuejoul, Sylvie

    2015-08-01

    Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe idiopathic interstitial pneumonia, with typical high-resolution computed tomography (HRCT) features and histologic pattern of usual interstitial pneumonia (UIP); its main differential diagnosis is fibrotic nonspecific interstitial pneumonia (F-NSIP). Usual interstitial pneumonia was mainly described from lung biopsies, and little is known on explants. Twenty-two UIP/IPF explants were analyzed histologically and compared with previous open lung biopsies (OLBs; n = 11) and HRCT (n = 19), when available. Temporospatial heterogeneity and subpleural and paraseptal fibrosis were similarly found in UIP/IPF explants and OLB (91%-95%). Fibroblastic foci were found in 82% of OLBs and 100% of explants, with a higher mean score in explants (P = .023). Honeycombing was present in 64% of OLBs and 95% of explants, with a higher mean score in explants (P = .005). Almost 60% of UIP/IPF explants showed NSIP areas and 41% peribronchiolar fibrosis; inflammation, bronchiolar metaplasia, and vascular changes were more frequent in UIP/IPF explants; and Desquamative Interstitial Pneumonia (DIP)-like areas were not common (18%-27%). Numerous large airspace enlargements with fibrosis were frequent in UIP/IPF explants (59%). On HRCT, honeycombing was observed in 95% of the cases and ground-glass opacities in 53%, correlating with NSIP areas or acute exacerbation at histology. Six patients had combined IPF and emphysema. Lesions were more severe in UIP/IPF explants, reflecting the worsening of the disease. Usual interstitial pneumonia/IPF explants more frequently presented with confounding lesions such as NSIP areas, peribronchiolar fibrosis, and airspace enlargements with fibrosis sometimes associated with emphysema. PMID:26025258

  5. Effects of clinical, laboratuary and pathological features on successful sperm retrieval in non-obstructive azoospermia

    PubMed Central

    Güneri, Çağrı; Alkibay, Turgut; Tunç, Lütfi

    2016-01-01

    Objective The study aims to evaluate the correlation of testicular sperm extraction (TESE) and histopathology with various features of non-obstructive azoospermia (NOA) cases who consulted to our university-based infertility clinic, and the probability of prompting couples about TESE success and to investigate the cost reduction chance through cost-beneficial aspects. Material and methods One hundred and twenty-five patients were enrolled in this study. Age, unprotected intercourse period, age of puberty, and concomittant diseases were noted. Testicular volumes were measured. The correlations between genetic test results and serum levels of Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), free testosterone, prolactine were investigated. Results The incidence of NOA among infertile men was found to be 15.1%. Median age of the cases was 33.1 years. Decrease in TESE success rate was seen in the group aged >30, and those who practiced unprotected intercourse for more than 10 years. TESE success rate was 40 percent. The required negative correlation between FSH levels, and testicular volume was not observed when the patient had additional diseases and/or genitourinary surgery. FSH and LH levels were significantly different between TESE- positive and negative groups (p=0.006, and p=0.001 respectively). Success rate in bilateral TESE group was 14.2%, and 96% of TESE- negative patients had bilateral TESE. Fifteen of 118 patients had Y chromosome microdeletions. These results were similar in both TESE- positive and negative group. Conclusion None of the parameters investigated herein predicted succesful TESE outcomes. However, in cases with increased FSH and AZFa/AZFb deletion before application of bilateral TESE, in cases of increased FSH and AZFa/AZFb deletion, detailed information should be given to these patients about low success rates and risk of disease inheritance which may reduce procedural costs. Knowing groups with poor prognosis, may help

  6. Effects of clinical, laboratuary and pathological features on successful sperm retrieval in non-obstructive azoospermia

    PubMed Central

    Güneri, Çağrı; Alkibay, Turgut; Tunç, Lütfi

    2016-01-01

    Objective The study aims to evaluate the correlation of testicular sperm extraction (TESE) and histopathology with various features of non-obstructive azoospermia (NOA) cases who consulted to our university-based infertility clinic, and the probability of prompting couples about TESE success and to investigate the cost reduction chance through cost-beneficial aspects. Material and methods One hundred and twenty-five patients were enrolled in this study. Age, unprotected intercourse period, age of puberty, and concomittant diseases were noted. Testicular volumes were measured. The correlations between genetic test results and serum levels of Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), free testosterone, prolactine were investigated. Results The incidence of NOA among infertile men was found to be 15.1%. Median age of the cases was 33.1 years. Decrease in TESE success rate was seen in the group aged >30, and those who practiced unprotected intercourse for more than 10 years. TESE success rate was 40 percent. The required negative correlation between FSH levels, and testicular volume was not observed when the patient had additional diseases and/or genitourinary surgery. FSH and LH levels were significantly different between TESE- positive and negative groups (p=0.006, and p=0.001 respectively). Success rate in bilateral TESE group was 14.2%, and 96% of TESE- negative patients had bilateral TESE. Fifteen of 118 patients had Y chromosome microdeletions. These results were similar in both TESE- positive and negative group. Conclusion None of the parameters investigated herein predicted succesful TESE outcomes. However, in cases with increased FSH and AZFa/AZFb deletion before application of bilateral TESE, in cases of increased FSH and AZFa/AZFb deletion, detailed information should be given to these patients about low success rates and risk of disease inheritance which may reduce procedural costs. Knowing groups with poor prognosis, may help

  7. Pathological features and proposed diagnostic criteria of porcine periweaning failure-to-thrive syndrome.

    PubMed

    Huang, Y; Harding, J C S

    2015-05-01

    Porcine periweaning failure-to-thrive syndrome (PFTS) is a clinical syndrome characterized by anorexia and progressive debilitation of newly weaned pigs. The objectives of the current case-control study were to describe the histopathologic features of PFTS in North America and test for selected pathogens in case and control pigs on 8 farms allegedly fulfilling the clinical definition of PFTS. Based on observations during farm visits, 5 farms fully met the case definition (PFTS farms), whereas 3 farms only partially fulfilled the definition (NON-PFTS farms). Necropsy and histopathologic examination were performed on case (n = 8 or 9) and control (n = 4) pigs from each farm. Superficial gastritis, which was mainly localized in the fundus and characterized by attenuation of superficial foveolar cells, was significantly more frequent in case pigs from PFTS farms compared with all the other pigs (odds ratio [OR], 16.7). The same was found for thymic atrophy (OR, 30.1) and small intestinal (SI) villous atrophy in the duodenum (OR, 28.7), jejunum (OR, 67.4), and ileum (OR, 56.3). All pigs with PFTS had at least 2 of these 3 lesions: gastritis, thymic atrophy, and SI villous atrophy. PFTS was not associated with any relevant porcine pathogen tested. We propose the diagnosis of PFTS be based on the fulfillment of the clinical case definition, the presence of the above lesions, and exclusion of other common swine diseases and pathogens. However, PFTS can be ruled out if debilitated pigs do not have at least 2 of the above 3 lesions.

  8. Oral squamous cell carcinoma: clinicopathological features from 346 cases from a single Oral Pathology service during an 8-year period

    PubMed Central

    PIRES, Fábio Ramôa; RAMOS, Amanda Barreto; de OLIVEIRA, Jade Bittencourt Coutinho; TAVARES, Amanda Serra; da LUZ, Priscilla Silva Ribeiro; dos SANTOS, Teresa Cristina Ribeiro Bartholomeu

    2013-01-01

    Epidemiological data from oral squamous cell carcinoma (OSCC) is mostly derived from North American, European and East Asian populations. Objective The aim of this study was to report the demographic and clinicopathological features from OSCC diagnosed in an Oral Pathology service in southeastern Brazil in an 8-year period. Material and Methods All OSCC diagnosed from 2005 to 2012 were reviewed, including histological analysis of all hematoxylin and eosin stained slides and review of all demographic and clinical information from the laboratory records. Results A total of 346 OSCC was retrieved and males represented 67% of the sample. Mean age of the patients was 62.3 years-old and females were affected a decade older than males (p<0.001). Mean time of complaint with the tumors was 10 months and site distribution showed that the border of the tongue (37%), alveolar mucosa/gingiva (20%) and floor of mouth/ventral tongue (19%) were the most common affected sites. Mean size of the tumors was 3.4 cm, with no differences for males and females (p=0.091) and males reported both tobacco and alcohol consumption more frequently than females. Histological grade of the tumors revealed that 27%, 40% and 21% of the tumors were, respectively, classified as well-, moderately- and poorly-differentiated OSCC, 26 cases (7.5%) were microinvasive OSCC and 17 cases were OSCC variants. OSCC in males mostly affected the border of tongue, floor of mouth/ventral tongue and alveolar mucosa/gingival, while they were more frequent on the border of tongue, alveolar mucosa/gingival and buccal mucosa/buccal sulcus in females (p=0.004). Conclusions The present data reflect the epidemiological characteristics of OSCC diagnosed in a public Oral Pathology laboratory in southeastern Brazil and have highlighted several differences in clinicopathological features when comparing male and female OSCC-affected patients. PMID:24212993

  9. Correlation of increased MALAT1 expression with pathological features and prognosis in cancer patients: a meta-analysis.

    PubMed

    Shi, X S; Li, J; Yang, R H; Zhao, G R; Zhou, H P; Zeng, W X; Zhou, M

    2015-12-29

    Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a potential cancer biomarker, yet the mechanism by which it influences the development of cancer remains unknown. In this study, we aimed to correlate MALAT1 expression with pathological features and prognosis in cancer patients. Several databases were searched using combinations of keywords relating to MALAT1 and cancer. After selection of relevant cohort studies according to strict criteria, a meta-analysis was conducted. Twelve studies were analyzed, involving 958 cancer patients. Elevated MALAT1 expression was associated with poor prognosis and larger tumors [prognosis: hazard ratio = 3.11, 95% confidence interval (CI) = 1.98-4.23, P = 0.000; tumor size: odds ratio (OR) = 0.40, 95%CI = 0.21-0.74, P = 0.003]. However, no connection with histological grade, T-stage, lymph node (LN) metastasis, or distant metastasis was established (all P > 0.05). A correlation between increased expression and poor prognosis was observed in the large and small sample-size subgroups (all P< 0.05), as was a relationship with large tumor size (OR = 0.30, 95%CI = 0.13-0.71, P = 0.006). Expression was correlated with T-stage and distant metastasis in the small sample-size subgroup (all P < 0.05), but no association was detected regarding histological grade, LN metastasis in either subgroup (all P > 0.05). Our findings demonstrate that elevated MALAT1 expression correlates with large tumor size, advanced tumor stage, and poor prognosis, and might therefore be utilized to evaluate clinical pathological features and prognostic out come for cancer patients.

  10. Optimization of a 3D Dynamic Culturing System for In Vitro Modeling of Frontotemporal Neurodegeneration-Relevant Pathologic Features

    PubMed Central

    Tunesi, Marta; Fusco, Federica; Fiordaliso, Fabio; Corbelli, Alessandro; Biella, Gloria; Raimondi, Manuela T.

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer’s disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may

  11. [Multidetector CT and magnetic resonance imaging features of solitary fibrous tumors in the pelvis and the relevant pathologic basis changes].

    PubMed

    Li, Xueming; Ren, Jing; Zhou, Peng; Cao, Ying; Cheng, Zhuzhong; Yu, Jianqun; Xu, Guohui

    2015-02-01

    In order to investigate the features of multidetector CT (MDCT) and magnetic resonance imaging (MRI) as well as the corresponding pathogic basis of solitary fibrous tumor (SFT) in the pelvis, we collected the clinical data of 13 patients with pathologically confirmed SFT in pelvis, and retrospectively reviewed the MDCT and MRI appearances. Of these enrolled patients, 6 received MDCT scans, 5 underwent MRI scans, and 2 underwent both MDCT and MRI examinations. Shown on the MDCT and MRI, the maximum diameters of the masses ranged from 4.0 to 25.2 cm (averaged 11.8 cm). Six masses were lobulated, and seven were round or oval. In addition, all masses were well-defined and displaced the adjacent structures to some degrees. On the computed tomography, all masses were of isodensity on unenhanced scans in general, among which five masses were demonstrated with hypodense areas. On the MRI T1-weighted image, all lesions were isointense, of which patchy hypointense areas were detected in 3 cases and radial hypointense areas were in 3 cases, and the other one was presented with homogenous intensity. On T2-weighted images, most of the lesions were mixed hyperintense, of which 3 cases were of heterogenous hyperintesity, radial hypointense areas were detected in 3 patients, and the other one was homogenously intense. On enhanced computed tomography and MRI, large supplying vessels were found in 4 cases; 12 cases showed moderate to conspicuous enhancement, and the other one was presented with mild homogenous enhancement. Of the patients with moderate to conspicuous enhancement, patchy areas of non-enhancement were detected in 7 cases, radial areas of progressive enhancement were detected in 3 cases, and the remained 2 cases showed homogenous enhancement. On pathology, the radial area presented as progressive enhancement was fibrosis. During the follow-ups after surgery, 2 patients had local recurrence and 1 had metastasis to liver. In conclusion, the SFT in the pelvis are commonly

  12. [Multidetector CT and magnetic resonance imaging features of solitary fibrous tumors in the pelvis and the relevant pathologic basis changes].

    PubMed

    Li, Xueming; Ren, Jing; Zhou, Peng; Cao, Ying; Cheng, Zhuzhong; Yu, Jianqun; Xu, Guohui

    2015-02-01

    In order to investigate the features of multidetector CT (MDCT) and magnetic resonance imaging (MRI) as well as the corresponding pathogic basis of solitary fibrous tumor (SFT) in the pelvis, we collected the clinical data of 13 patients with pathologically confirmed SFT in pelvis, and retrospectively reviewed the MDCT and MRI appearances. Of these enrolled patients, 6 received MDCT scans, 5 underwent MRI scans, and 2 underwent both MDCT and MRI examinations. Shown on the MDCT and MRI, the maximum diameters of the masses ranged from 4.0 to 25.2 cm (averaged 11.8 cm). Six masses were lobulated, and seven were round or oval. In addition, all masses were well-defined and displaced the adjacent structures to some degrees. On the computed tomography, all masses were of isodensity on unenhanced scans in general, among which five masses were demonstrated with hypodense areas. On the MRI T1-weighted image, all lesions were isointense, of which patchy hypointense areas were detected in 3 cases and radial hypointense areas were in 3 cases, and the other one was presented with homogenous intensity. On T2-weighted images, most of the lesions were mixed hyperintense, of which 3 cases were of heterogenous hyperintesity, radial hypointense areas were detected in 3 patients, and the other one was homogenously intense. On enhanced computed tomography and MRI, large supplying vessels were found in 4 cases; 12 cases showed moderate to conspicuous enhancement, and the other one was presented with mild homogenous enhancement. Of the patients with moderate to conspicuous enhancement, patchy areas of non-enhancement were detected in 7 cases, radial areas of progressive enhancement were detected in 3 cases, and the remained 2 cases showed homogenous enhancement. On pathology, the radial area presented as progressive enhancement was fibrosis. During the follow-ups after surgery, 2 patients had local recurrence and 1 had metastasis to liver. In conclusion, the SFT in the pelvis are commonly

  13. Molecular profiles of BRCA1-mutated and matched sporadic breast tumours: relation with clinico-pathological features

    PubMed Central

    Berns, E M J J; Staveren, I L van; Verhoog, L; Ouweland, A M W van de; Gelder, M Meijer-van; Meijers-Heijboer, H; Portengen, H; Foekens, J A; Dorssers, L C J; Klijn, J G M

    2001-01-01

    About 5–10% of breast cancers are hereditary; a genetically and clinically heterogeneous disease in which several susceptibility genes, including BRCA1, have been identified. While distinct tumour features can be used to estimate the likelihood that a breast tumour is caused by a BRCA1 germline mutation it is not yet possible to categorize a BRCA1 mutated tumour. The aim of the present study is to molecularly classify BRCA1 mutated breast cancers by resolving gene expression patterns of BRCA1 and matched sporadic surgical breast tumour specimens. The expression profiles of 6 frozen breast tumour tissues with a proven BRCA1 gene mutation were weighed against those from 12 patients without a known family history but who had similar clinico-pathological characteristics. In addition two fibroblast cultures, the breast cancer cell-line HCC1937 and its corresponding B-lymphoblastoid cell line (heterozygous for mutation BRCA1 5382insC) and an epithelial ovarian cancer cell line (A2780) were studied. Using a high density membrane based array for screening of RNA isolated from these samples and standard algorithms and software, we were able to distinguish subgroups of sporadic cases and a group consisting mainly of BRCA1-mutated breast tumours. Furthermore this pilot analysis revealed a gene cluster that differentially expressed genes related to cell substrate formation, adhesion, migration and cell organization in BRCA1-mutated tumours compared to sporadic breast tumours. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11506493

  14. Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease.

    PubMed

    Yamanaka, S; Johnson, M D; Grinberg, A; Westphal, H; Crawley, J N; Taniike, M; Suzuki, K; Proia, R L

    1994-10-11

    Tay-Sachs disease, the prototype of the GM2 gangliosidoses, is a catastrophic neurodegenerative disorder of infancy. The disease is caused by mutations in the HEXA gene resulting in an absence of the lysosomal enzyme, beta-hexosaminidase A. As a consequence of the enzyme deficiency, GM2 ganglioside accumulates progressively, beginning early in fetal life, to excessive amounts in the central nervous system. Rapid mental and motor deterioration starting in the first year of life leads to death by 2-4 years of age. Through the targeted disruption of the mouse Hexa gene in embryonic stem cells, we have produced mice with biochemical and neuropathologic features of Tay-Sachs disease. The mutant mice displayed < 1% of normal beta-hexosaminidase A activity and accumulated GM2 ganglioside in their central nervous system in an age-dependent manner. The accumulated ganglioside was stored in neurons as membranous cytoplasmic bodies characteristically found in the neurons of Tay-Sachs disease patients. At 3-5 months of age, the mutant mice showed no apparent defects in motor or memory function. These beta-hexosaminidase A-deficient mice should be useful for devising strategies to introduce functional enzyme and genes into the central nervous system. This model may also be valuable for studying the biochemical and pathologic changes occurring during the course of the disease.

  15. Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease

    SciTech Connect

    Proia, R.L.; Yamanaka, S.; Johnson, M.D.

    1994-09-01

    Tay-Sachs disease, the prototype of the G{sub M2} gangliosidoses, is a catastrophic neurodegenerative disorder of infancy. The disease is caused by mutations in the HEXA gene resulting in an absence of the lysosomal enzyme, {beta}-hexosaminidase A. As consequence of the enzyme deficiency, G{sub M2} ganglioside accumulates progressively, beginning early in fetal life, to excessive amounts in the central nervous system (CNS). Rapid mental and motor deterioration starting in the first year of life leads to death by 2 to 4 years of age. Through the targeted disruption of the Hexa gene in embryonic stem cells, we have produced mice with biochemical and neuropathologic features of Tay-Sachs disease. The mutant mice exhibited less than 1% of normal {beta}-hexosaminidase A activity and accumulated G{sub M2} ganglioside in their CNS in an age-dependent manner. The accumulated ganglioside was stored in neurons as membranous cytoplasmic bodies characteristically found in the neurons of Tay-Sachs disease patients. At three to five months of age the mutant mice showed no apparent defects in motor or memory function. These {beta}-hexosaminidase A deficient mice should be useful for devising strategies to introduce functional enzymes and genes into the CNS. This model may also be valuable for studying the biochemical and pathologic changes occurring during the course of the disease.

  16. Pathologic features of dilated cardiomyopathy with localized noncompaction in a child with deletion 1p36 syndrome.

    PubMed

    Pearce, F Bennett; Litovsky, Silvio H; Dabal, Robert J; Robin, Nathaniel; Dure, Leon J; George, James F; Kirklin, James K

    2012-01-01

    Dilated cardiomyopathy and ventricular noncompaction have been reported in association with deletion 1p36 syndrome. Previous descriptions include echocardiographic and/or gross pathologic descriptions. There are no previous reports of microscopic findings. We report a case with descriptions of echocardiographic, gross pathologic, and microscopic findings.

  17. Spatial-Temporal [{sup 18}F]FDG-PET Features for Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiation Therapy

    SciTech Connect

    Tan, Shan; Kligerman, Seth; Chen, Wengen; Lu, Minh; Kim, Grace; Feigenberg, Steven; D'Souza, Warren D.; Suntharalingam, Mohan; Lu, Wei

    2013-04-01

    Purpose: To extract and study comprehensive spatial-temporal {sup 18}F-labeled fluorodeoxyglucose ([{sup 18}F]FDG) positron emission tomography (PET) features for the prediction of pathologic tumor response to neoadjuvant chemoradiation therapy (CRT) in esophageal cancer. Methods and Materials: Twenty patients with esophageal cancer were treated with trimodal therapy (CRT plus surgery) and underwent [{sup 18}F]FDG-PET/CT scans both before (pre-CRT) and after (post-CRT) CRT. The 2 scans were rigidly registered. A tumor volume was semiautomatically delineated using a threshold standardized uptake value (SUV) of ≥2.5, followed by manual editing. Comprehensive features were extracted to characterize SUV intensity distribution, spatial patterns (texture), tumor geometry, and associated changes resulting from CRT. The usefulness of each feature in predicting pathologic tumor response to CRT was evaluated using the area under the receiver operating characteristic curve (AUC) value. Results: The best traditional response measure was decline in maximum SUV (SUV{sub max}; AUC, 0.76). Two new intensity features, decline in mean SUV (SUV{sub mean}) and skewness, and 3 texture features (inertia, correlation, and cluster prominence) were found to be significant predictors with AUC values ≥0.76. According to these features, a tumor was more likely to be a responder when the SUV{sub mean} decline was larger, when there were relatively fewer voxels with higher SUV values pre-CRT, or when [{sup 18}F]FDG uptake post-CRT was relatively homogeneous. All of the most accurate predictive features were extracted from the entire tumor rather than from the most active part of the tumor. For SUV intensity features and tumor size features, changes were more predictive than pre- or post-CRT assessment alone. Conclusion: Spatial-temporal [{sup 18}F]FDG-PET features were found to be useful predictors of pathologic tumor response to neoadjuvant CRT in esophageal cancer.

  18. Chromosome region maintenance 1 expression and its association with clinical pathological features in primary carcinoma of the liver

    PubMed Central

    XIE, QIAO-LING; LIU, YUE; ZHU, YING

    2016-01-01

    Liver cancer is the third leading cause of cancer-associated mortality worldwide. Recurrence and metastasis are the major factors affecting the prognosis; thus, investigation of the underlying molecular mechanisms of invasion and metastasis, and detection of novel drug target may improve the mortality rate of liver cancer patients. Chromosome region maintenance 1 (CRM1) recognizes specific leucine-rich nuclear export signal sequences, and its overexpression is associated with tumor-suppressor gene inactivation, proliferation, invasion and resistance to chemotherapy. The aim of the present study was to examine the association of CRM1 expression with the clinical and pathological features of primary liver cancer. In total, 152 cases diagnosed with liver cancer were included. CRM1 expression was detected in cancer tissues and adjacent normal tissues by immunohistochemical assay. No statistically significant difference was found between the CRM1 expression levels in tumor and adjacent normal tissues (P=0.106). However, CRM1 expression in adjacent normal tissues was higher compared with that in tumor tissues in the negative hepatitis B envelope antigen (HBeAg; P=0.029) and low differentiation (P=0.004) groups. In tumor tissues, CRM1 expression was significantly correlated with differentiation (P=0.045), whereas in adjacent normal tissues, CRM1 expression was significantly correlated with the tumor diameter (P=0.004). Therefore, it can be concluded that CRM1 is highly expressed in both tumor and adjacent normal tissues. Furthermore, CRM1 expression is associated with the tumor differentiation degree and diameter. Lower differentiation and larger tumor diameter resulted in higher CRM1 expression in adjacent normal tissues, and higher tendency for invasion and metastasis. In addition, the risk of invasion and metastasis remains in chronic hepatitis B patients with negative HBeAg. PMID:27347018

  19. Predicting Pathological Features at Radical Prostatectomy in Patients with Prostate Cancer Eligible for Active Surveillance by Multiparametric Magnetic Resonance Imaging

    PubMed Central

    de Cobelli, Ottavio; Terracciano, Daniela; Tagliabue, Elena; Raimondi, Sara; Bottero, Danilo; Cioffi, Antonio; Jereczek-Fossa, Barbara; Petralia, Giuseppe; Cordima, Giovanni; Almeida, Gilberto Laurino; Lucarelli, Giuseppe; Buonerba, Carlo; Matei, Deliu Victor; Renne, Giuseppe; Di Lorenzo, Giuseppe; Ferro, Matteo

    2015-01-01

    Purpose The aim of this study was to investigate the prognostic performance of multiparametric magnetic resonance imaging (mpMRI) and Prostate Imaging Reporting and Data System (PIRADS) score in predicting pathologic features in a cohort of patients eligible for active surveillance who underwent radical prostatectomy. Methods A total of 223 patients who fulfilled the criteria for “Prostate Cancer Research International: Active Surveillance”, were included. Mp–1.5 Tesla MRI examination staging with endorectal coil was performed at least 6–8 weeks after TRUS-guided biopsy. In all patients, the likelihood of the presence of cancer was assigned using PIRADS score between 1 and 5. Outcomes of interest were: Gleason score upgrading, extra capsular extension (ECE), unfavorable prognosis (occurrence of both upgrading and ECE), large tumor volume (≥0.5ml), and seminal vesicle invasion (SVI). Receiver Operating Characteristic (ROC) curves and Decision Curve Analyses (DCA) were performed for models with and without inclusion of PIRADS score. Results Multivariate analysis demonstrated the association of PIRADS score with upgrading (P<0.0001), ECE (P<0.0001), unfavorable prognosis (P<0.0001), and large tumor volume (P = 0.002). ROC curves and DCA showed that models including PIRADS score resulted in greater net benefit for almost all the outcomes of interest, with the only exception of SVI. Conclusions mpMRI and PIRADS scoring are feasible tools in clinical setting and could be used as decision-support systems for a more accurate selection of patients eligible for AS. PMID:26444548

  20. Clinical-Pathologic Features and Long-Term Outcomes of Tubular Carcinoma of the Breast Compared With Invasive Ductal Carcinoma Treated With Breast Conservation Therapy

    SciTech Connect

    Liu, Gene-Fu F.; Yang Qifeng; Haffty, Bruce G.; Moran, Meena S.

    2009-12-01

    Purpose: To evaluate our institutional experience of treating tubular carcinoma of the breast (TC) and invasive ductal carcinoma (IDC) with conservative surgery and radiation therapy, to compare clinical-pathologic features and long-term outcomes. Methods and Materials: A review of our institution's tumor registry from 1975 to 2007, followed by a central pathology review of available slides, yielded 71 cases of Stage I/II TC and 2,238 cases of Stage I/II IDC treated with breast conservation therapy. Clinical-pathologic features and outcomes were analyzed by subtype to detect significant differences. Results: The median follow-up was 7 years. The TC cohort presented more frequently with pT1 disease (97% vs. 80%, p = 0.0007), pN0 disease (95% vs. 74%, p = 0.0004), hormone-receptor positivity (ER+, 89% vs. 62%, p = 0.0001; PR+, 81% vs. 52%, p = 0.0001), and HER-2 negativity (89% vs. 71%, p = 0.04). Clinical outcomes also favored the TC cohort, with lower rates of breast cancer-related death (1% vs. 10%; p = 0.0109) and distant metastasis (1% vs. 13%; p = 0.0028) and higher rates of 10-year overall (90% vs. 80%; p = 0.033), cause-specific (99% vs. 86%; p = 0.011), and disease-free (99% vs. 82%; p = 0.003) survival. There was a nonsignificant trend toward improved breast cancer relapse-free survival for the TC cohort (95% vs. 87%; p = 0.062) but no difference in nodal relapse-free survival or contralateral breast cancer relapse-free survival (all p values >0.05) between the cohorts. Conclusion: Our institutional experience suggests that TC, when compared with IDC, is associated with more favorable clinical-pathologic features and comparable, if not superior, outcomes after breast conservation therapy, suggesting the appropriateness of a conservative approach to this rare subtype.

  1. TU-C-12A-09: Modeling Pathologic Response of Locally Advanced Esophageal Cancer to Chemo-Radiotherapy Using Quantitative PET/CT Features, Clinical Parameters and Demographics

    SciTech Connect

    Zhang, H; Chen, W; Kligerman, S; D’Souza, W; Suntharalingam, M; Lu, W; Tan, S; Kim, G

    2014-06-15

    Purpose: To develop predictive models using quantitative PET/CT features for the evaluation of tumor response to neoadjuvant chemo-radiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: This study included 20 patients who underwent tri-modality therapy (CRT + surgery) and had {sup 18}F-FDG PET/CT scans before initiation of CRT and 4-6 weeks after completion of CRT but prior to surgery. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model. Conclusion: The SVM model using all features

  2. Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy Using Spatial-Temporal {sup 18}F-FDG PET Features, Clinical Parameters, and Demographics

    SciTech Connect

    Zhang, Hao; Tan, Shan; Chen, Wengen; Kligerman, Seth; Kim, Grace; D'Souza, Warren D.; Suntharalingam, Mohan; Lu, Wei

    2014-01-01

    Purpose: To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials: This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV]{sub max}, tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher

  3. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease.

    PubMed

    Wolf, Heike; Damme, Markus; Stroobants, Stijn; D'Hooge, Rudi; Beck, Hans Christian; Hermans-Borgmeyer, Irm; Lüllmann-Rauch, Renate; Dierks, Thomas; Lübke, Torben

    2016-09-01

    Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1) was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6)-GlcNAc(β1-N)-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS). On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis.

  4. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease

    PubMed Central

    Wolf, Heike; Stroobants, Stijn; D'Hooge, Rudi; Hermans-Borgmeyer, Irm; Lüllmann-Rauch, Renate; Dierks, Thomas; Lübke, Torben

    2016-01-01

    ABSTRACT Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1) was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6)-GlcNAc(β1-N)-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS). On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis. PMID:27491075

  5. Levels and actions of neuroactive steroids in the nervous system under physiological and pathological conditions: Sex-specific features.

    PubMed

    Melcangi, Roberto C; Giatti, Silvia; Garcia-Segura, Luis M

    2016-08-01

    Neuroactive steroids regulate the physiology of the central and peripheral nervous system, exert neuroprotective actions and represent interesting tools for therapeutic strategies against neurodegenerative and psychiatric disorders. Sex differences in their levels are detected not only under physiological conditions but are also modified in a sex-dependent way in different pathological alterations such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, traumatic brain injury, spinal cord injury, stroke, diabetic encephalopathy, psychiatric disorders and peripheral neuropathy. Interestingly, many of these disorders show sex differences in their incidence, symptomatology and/or neurodegenerative outcome. The neuroprotective actions of neuroactive steroids, together with the sex specific regulation of its levels might provide the basis to design sex-specific neuroprotective therapies. Indeed, some experiments here discussed suggest the viability of this approach. PMID:26657814

  6. Differences in pathological and clinical features of breast cancer in Arab as compared to Jewish women in Northern Israel.

    PubMed

    Zidan, Jamal; Sikorsky, Natalya; Basher, Walid; Sharabi, Adi; Friedman, Eitan; Steiner, Mariana

    2012-08-15

    Breast cancer (BC) does not affect ethnic groups equally. BC mortality is higher in Israeli Palestinian Arab women than among Israeli Jewish women. This study aims to compare clinical, biological and pathological characteristics of breast cancer in the two populations. Records of 1,140 women with BC treated at Northern Israel between 2002 and 2007 were reviewed: 872 Jews and 268 Arabs. Age at diagnosis, tumor stage, pathological differentiation, estrogen receptor (ER) and HER-2 expression were evaluated. The main age at diagnosis was 49.9 years for Arabs and 59.4 years for Jews (p < 0.0001). Mean tumor size was < 2 cm in 25% of Arabs and 53% of Jews (p < 0.0001). Lymph node metastases presented in 64.6% of Arabs and 37.2% of Jews (p < 0.0001). Stage I disease was 19% in Arab and 49.2% in Jewish women while Stages III and IV disease was 42% and 11.3% respectively (p < 0.001). ER was positive in 69% of Arabs and in 78.5% of Jews (p < 0.001). Poorly differentiated tumors were found in 28.8% of Arabs vs. 12.8% in Jews (p < 0.0001). Overexpression of HER-2 was present in 35.4% of Arab and 22% of Jewish women (p < 0.001). We found that race is an important predictive factor for breast cancer. Arab women are diagnosed at younger age, with more advanced stage and biologically more aggressive disease than in Jewish women. Socioeconomic factors alone are not sufficient to explain significant effects of race on tumor characteristics. Findings suggest a different genetic susceptibility in the two populations which needs further research.

  7. Pathological features of cantharidin-induced toxic cardiomyopathy: lack of correlation between electron-microscopic and histopathologic myocardial damage.

    PubMed

    Friesen, J M; Ferris, J A; Rabkin, S S; Fung, H Y

    1979-01-01

    Electron-microscopic evidence of the cardiotoxic effects of cantharidin administered to rabbits was observed. No correlation was found between the electron-microscopic changes and the light-microscopic features as assessed by special histological stains. The reasons for this are discussed.

  8. Significant differences in demographic, clinical, and pathological features in relation to smoking and alcohol consumption among 1,633 head and neck cancer patients

    PubMed Central

    Moyses, Raquel Ajub; López, Rossana Verónica Mendoza; Cury, Patrícia Maluf; Siqueira, Sheila Aparecida Coelho; Curioni, Otávio Alberto; de Gois Filho, José Francisco; Figueiredo, David Livingstone Alves; Head; GENCAPO, Neck Genome Project; Tajara, Eloiza Helena; Michaluart, Pedro

    2013-01-01

    OBJECTIVE: As a lifestyle-related disease, social and cultural disparities may influence the features of squamous cell carcinoma of the head and neck in different geographic regions. We describe demographic, clinical, and pathological aspects of squamous cell carcinoma of the head and neck according to the smoking and alcohol consumption habits of patients in a Brazilian cohort. METHODS: We prospectively analyzed the smoking and alcohol consumption habits of 1,633 patients enrolled in five São Paulo hospitals that participated in the Brazilian Head and Neck Genome Project – Gencapo. RESULTS: The patients who smoked and drank were younger, and those who smoked were leaner than the other patients, regardless of alcohol consumption. The non-smokers/non-drinkers were typically elderly white females who had more differentiated oral cavity cancers and fewer first-degree relatives who smoked. The patients who drank presented significantly more frequent nodal metastasis, and those who smoked presented less-differentiated tumors. CONCLUSIONS: The patients with squamous cell carcinoma of the head and neck demonstrated demographic, clinical, and pathological features that were markedly different according to their smoking and drinking habits. A subset of elderly females who had oral cavity cancer and had never smoked or consumed alcohol was notable. Alcohol consumption seemed to be related to nodal metastasis, whereas smoking correlated with the degree of differentiation. PMID:23778492

  9. Expression of Estrogen Receptor Beta Predicts Oncologic Outcome of pT3 Upper Urinary Tract Urothelial Carcinoma Better Than Aggressive Pathological Features

    PubMed Central

    Luo, Hao Lun; Sung, Ming Tse; Tsai, Eing Mei; Lin, Chang Shen; Lee, Nai Lun; Chung, Yueh-Hua; Chiang, Po Hui

    2016-01-01

    Upper urinary tract urothelial carcinoma (UT-UC) is rare and treatment options or prognostic markers are limited. There is increasing evidence indicating that urothelial carcinoma may be an endocrine-related cancer. The aim of this study was to analyze the prognostic effect of estrogen receptor beta (ERβ) on the outcome of UT-UC. From 2005 to 2012, this study included 105 patients with pT3 UT-UC. Perioperative factors, pathological features, and ERβ immunostaining were reviewed and prognostic effects were examined by multivariate analysis. This study divided patients into either the ERβ-high (n = 52) or ERβ-low (n = 53) group and analyzed their oncologic outcomes. All pathological features except infiltrating tumor architecture (significantly higher incidence in ERβ-low group, p = 0.004) are symmetric in both groups. Low ERβ expression was significantly correlated with local recurrence and distant metastasis in univariate analysis (p = 0.035 and 0.004, respectively) and multivariate analysis (p = 0.05 and 0.008, respectively). Cell line study also proved that knock down of ERβ cause less UTUC proliferation and migration. In addition, ERβ agonist also enhanced the cytotoxic and migration inhibition effect of cisplatin and ERβ antagonist cause the UTUC cell more resistant to cisplatin. This result may help identify patients in need of adjuvant therapy or develop potential targeted therapy. PMID:27052470

  10. High Pretreatment D-Dimer Levels Correlate with Adverse Clinical Features and Predict Poor Survival in Patients with Natural Killer/T-Cell Lymphoma

    PubMed Central

    Sun, Peng; Yan, Shu-mei; Liu, Pan-pan; Li, Zhi-ming; Jiang, Wen-qi

    2016-01-01

    Pretreatment plasma D-dimer levels have been reported to predict survival in several types of malignancies. The aim of this study was to evaluate the prognostic value of D-dimer levels in patients with newly diagnosed natural killer/T-cell lymphoma (NKTCL). The cut-off value of D-dimer to predict survival was set as 1.2 μg/mL based on the receiver operating curve analysis. Patients with a D-dimer level ≥ 1.2 μg/mL had significantly more adverse clinical features, including poor performance status, advanced stage diseases, B symptoms, elevated serum lactic dehydrogenase levels, involvement of regional lymph nodes, more extranodal diseases, and higher International Prognostic Index and natural killer/T-cell lymphoma prognostic index scores. A D-dimer level ≥ 1.2 μg/mL was significantly associated with inferior 3-year overall survival (OS, 13.0 vs. 68.5%, P < 0.001). In the multivariate analysis, a D-dimer level ≥ 1.2 μg/mL remained an independent predictor for worse OS (HR: 3.13, 95% CI: 1.47–6.68, P = 0.003) after adjusting for other confounding prognostic factors. Among patients with Ann Arbor stage I-II diseases, those with a D-dimer level ≥ 1.2 μg/mL had a significantly worse survival than those with a D-dimer level < 1.2 μg/mL (3 year-OS: 76.2 vs. 22.2%, P < 0.001). Survival of early-stage patients with a high D-dimer level was similar to that of the advanced-stage patients. In conclusion, pretreatment plasma D-dimer level may serve as a simple but effective predictor of prognosis in patients with NKTCL. PMID:27032016

  11. High Pretreatment D-Dimer Levels Correlate with Adverse Clinical Features and Predict Poor Survival in Patients with Natural Killer/T-Cell Lymphoma.

    PubMed

    Bi, Xi-wen; Wang, Liang; Zhang, Wen-wen; Sun, Peng; Yan, Shu-mei; Liu, Pan-pan; Li, Zhi-ming; Jiang, Wen-qi

    2016-01-01

    Pretreatment plasma D-dimer levels have been reported to predict survival in several types of malignancies. The aim of this study was to evaluate the prognostic value of D-dimer levels in patients with newly diagnosed natural killer/T-cell lymphoma (NKTCL). The cut-off value of D-dimer to predict survival was set as 1.2 μg/mL based on the receiver operating curve analysis. Patients with a D-dimer level ≥ 1.2 μg/mL had significantly more adverse clinical features, including poor performance status, advanced stage diseases, B symptoms, elevated serum lactic dehydrogenase levels, involvement of regional lymph nodes, more extranodal diseases, and higher International Prognostic Index and natural killer/T-cell lymphoma prognostic index scores. A D-dimer level ≥ 1.2 μg/mL was significantly associated with inferior 3-year overall survival (OS, 13.0 vs. 68.5%, P < 0.001). In the multivariate analysis, a D-dimer level ≥ 1.2 μg/mL remained an independent predictor for worse OS (HR: 3.13, 95% CI: 1.47-6.68, P = 0.003) after adjusting for other confounding prognostic factors. Among patients with Ann Arbor stage I-II diseases, those with a D-dimer level ≥ 1.2 μg/mL had a significantly worse survival than those with a D-dimer level < 1.2 μg/mL (3 year-OS: 76.2 vs. 22.2%, P < 0.001). Survival of early-stage patients with a high D-dimer level was similar to that of the advanced-stage patients. In conclusion, pretreatment plasma D-dimer level may serve as a simple but effective predictor of prognosis in patients with NKTCL.

  12. Pulmonary infantile hemangioma presenting as a mass in a premature male infant: a case report focusing on pathological features.

    PubMed

    Siaghani, Parwiz J; Chavez, Claire; Anselmo, Dean M; Shane, Lisa

    2015-01-01

    Infantile hemangiomas are the most common benign neoplasm of infancy, with most occurring in the head and neck region. Predisposing factors include prematurity, low birth weight, multiple gestations, advanced maternal age, and chorionic villous sampling. In addition, white women, particularly those with a family history, are also at a higher risk. However, pulmonary infantile hemangiomas are exceedingly rare, with only a few case reports in the literature. Infantile hemangiomas should be considered in the differential diagnosis of a pulmonary mass in the early pediatric population. We present a case of pulmonary infantile hemangioma in a premature male infant successfully managed by surgical excision, with an emphasis on the pathogenesis and histologic features.

  13. Clinical and pathological features and treatment of AIDS-related cutaneous Kaposi's sarcoma in Chinese Han patients.

    PubMed

    Zheng, X-K; Lu, S-H; Liu, J-F; Lai, Y-R

    2015-01-01

    This retrospective study aimed to observe the clinicopathological features and immunological phenotypes, and explore effective treatment and prognosis for 12 Chinese Han patients with acquired immunodeficiency syndrome-related cutaneous Kaposi's sarcoma. All 12 patients were human immunodeficiency virus-positive, and underwent the standard highly active antiretroviral therapy (HAART). Skin lesions mainly presented as purple, or rufous papules, or plaques; skin biopsy showed diffuse or flaky infiltration of spindle cells, active proliferation of slit-like vasculature, erythrocyte exudation, hemosiderin deposition, and inflammatory cell infiltration. Immunohistochemical analysis showed the expression of Ubiquitin C-terminal hydrolase L1 (+), and CD31 (+) in T-cells; factor VIII (+) and HHF-35 (+) in the proliferating vascular endothelial cells; vimentin (+) and S-100 protein (-) in the vessel wall; and CD34 (+++) in the spindle cells of 6 cases, with 1 case of negative CD34 expression. Four patients with confined lesions underwent surgery and microwave therapy, and received a favorable prognosis. Two patients with limited lesions underwent microwave therapy, and the lesions subsided. Of six patients with widely distributed sarcomas, five underwent microwave therapy and one received combined chemotherapy; five attained significant efficacy, and one died. There were no significant differences in the clinicopathological features and immunological phenotypes between the Chinese Han patients and those from other populations. Along with basal HAART, patients in early stages, with sarcomas <2 cm in diameter should undergo surgery and microwave therapy, while patients with sarcomas >2 cm in diameter should undergo chemotherapy and microwave therapy.

  14. Mouse Models of Acute Respiratory Distress Syndrome: A Review of Analytical Approaches, Pathologic Features, and Common Measurements.

    PubMed

    Aeffner, Famke; Bolon, Brad; Davis, Ian C

    2015-12-01

    Acute respiratory distress syndrome (ARDS) is a severe pulmonary reaction requiring hospitalization, which is incited by many causes, including bacterial and viral pneumonia as well as near drowning, aspiration of gastric contents, pancreatitis, intravenous drug use, and abdominal trauma. In humans, ARDS is very well defined by a list of clinical parameters. However, until recently no consensus was available regarding the criteria of ARDS that should be evident in an experimental animal model. This lack was rectified by a 2011 workshop report by the American Thoracic Society, which defined the main features proposed to delineate the presence of ARDS in laboratory animals. These should include histological changes in parenchymal tissue, altered integrity of the alveolar capillary barrier, inflammation, and abnormal pulmonary function. Murine ARDS models typically are defined by such features as pulmonary edema and leukocyte infiltration in cytological preparations of bronchoalveolar lavage fluid and/or lung sections. Common pathophysiological indicators of ARDS in mice include impaired pulmonary gas exchange and histological evidence of inflammatory infiltrates into the lung. Thus, morphological endpoints remain a vital component of data sets assembled from animal ARDS models.

  15. The frequency, clinical significance, and pathological features of chronic chorioamnionitis: a lesion associated with spontaneous preterm birth.

    PubMed

    Kim, Chong Jai; Romero, Roberto; Kusanovic, Juan Pedro; Yoo, Wonsuk; Dong, Zhong; Topping, Vanessa; Gotsch, Francesca; Yoon, Bo Hyun; Chi, Je Geun; Kim, Jung-Sun

    2010-07-01

    chorioamnionitis than in those without chronic chorioamnionitis (P<0.05). We propose that chronic chorioamnionitis defines a common placental pathological lesion among the preterm labor and preterm prelabor rupture of membranes groups, especially in cases of late preterm birth. Its association with villitis of unknown etiology and the chemokine profile in amniotic fluid suggests an immunological origin, akin to transplantation rejection and graft-versus-host disease in the chorioamniotic membranes.

  16. Clinical and pathological features of kidney transplant patients with concurrent polyomavirus nephropathy and rejection-associated endarteritis

    PubMed Central

    McGregor, Stephanie M; Chon, W James; Kim, Lisa; Chang, Anthony; Meehan, Shane M

    2015-01-01

    AIM: To describe the clinicopathologic features of concurrent polyomavirus nephropathy (PVN) and endarteritis due to rejection in renal allografts. METHODS: We searched our electronic records database for cases with transplant kidney biopsies demonstrating features of both PVN and acute rejection (AR). PVN was defined by the presence of typical viral cytopathic effect on routine sections and positive polyomavirus SV40 large-T antigen immunohistochemistry. AR was identified by endarteritis (v1 by Banff criteria). All cases were subjected to chart review in order to determine clinical presentation, treatment course and outcomes. Outcomes were recorded with a length of follow-up of at least one year or time to nephrectomy. RESULTS: Of 94 renal allograft recipients who developed PVN over an 11-year period at our institution, we identified 7 (7.4%) with viral cytopathic changes, SV40 large T antigen staining, and endarteritis in the same biopsy specimen, indicative of concurrent PVN and AR. Four arose after reduction of immunosuppression (IS) (for treatment of PVN in 3 and tuberculosis in 1), and 3 patients had no decrease of IS before developing simultaneous concurrent disease. Treatment consisted of reduced oral IS and leflunomide for PVN, and anti-rejection therapy. Three of 4 patients who developed endarteritis in the setting of reduced IS lost their grafts to rejection. All 3 patients with simultaneous PVN and endarteritis cleared viremia and were stable at 1 year of follow up. Patients with endarteritis and PVN arising in a background of reduced IS had more severe rejection and poorer outcome. CONCLUSION: Concurrent PVN and endarteritis may be more frequent than is currently appreciated and may occur with or without prior reduction of IS. PMID:26722657

  17. B-cell and T-cell lymphomas of the breast: clinical--pathological features of 53 cases.

    PubMed

    Gualco, Gabriela; Bacchi, Carlos E

    2008-10-01

    Breast involvement by non-Hodgkin lymphomas is rare. We studied the morphological, immunophenotypical, and clinical features of 53 cases of malignant lymphomas involving the breast in a population of Brazilian patients. Most of the cases were of B-cell phenotype. Four of the patients with primary breast lymphomas had T-cell lymphomas, 3 had CD30-positive anaplastic large cell lymphomas, and 1 had panniculitis-like T-cell lymphoma. Most patients presented with an incidental breast mass. Secondary breast lymphoma was seen in 19 patients and most commonly occurred as part of widespread nodal disease. Two patients presented with bilateral breast involvement. The most prevalent histological subtype was also diffuse large B-cell lymphoma, followed by follicular lymphoma. This study shows that the broad morphological and immunophenotypical spectrum of malignant lymphoma of the breast occurring in a large series of Brazilian patients has many similarities with that seen in Western countries, with a higher proportion of high-grade lymphomas in both primary and secondary cases.

  18. Primary and secondary T-cell lymphomas of the breast: clinico-pathologic features of 11 cases.

    PubMed

    Gualco, Gabriela; Chioato, Lucimara; Harrington, William J; Weiss, Lawrence M; Bacchi, Carlos E

    2009-07-01

    Breast involvement by non-Hodgkin lymphomas is rare, and exceptional for T-cell lymphomas; we studied the morphologic, immunophenotypic, and clinical features of 11 patients with T-cell non-Hodgkin lymphomas involving the breast. Four cases fulfilled the definition criteria for primary breast lymphomas, 3 females and 1 male, with a median age of 51 years. One primary breast lymphomas was T-cell lymphoma unspecified, other was subcutaneous panniculitis-like T-cell lymphoma, and 2 cases were anaplastic large cell lymphomas. One of the anaplastic large cell lymphoma cases was found surrounding a silicone breast implant and presented as clinically as mastitis; whereas the other case occurred in a man. T-cell lymphoma secondarily involved the breast in 7 patients, all women and 1 bilateral, with a median age of 29 years. These secondary breast lymphomas occurred as part of widespread nodal or leukemic disease. Three patients had adult T-cell leukemia/lymphoma, including the patient with bilateral lesions, 3 others had precursor T-lymphoblastic lymphoma/leukemia, and the other presented with a peripheral-T-cell lymphoma non otherwise specified type. Breast T-cell lymphomas are very infrequent and are morphologically and clinically heterogeneous.

  19. Calpain mediates pulmonary vascular remodeling in rodent models of pulmonary hypertension, and its inhibition attenuates pathologic features of disease.

    PubMed

    Ma, Wanli; Han, Weihong; Greer, Peter A; Tuder, Rubin M; Toque, Haroldo A; Wang, Kevin K W; Caldwell, R William; Su, Yunchao

    2011-11-01

    Pulmonary hypertension is a severe and progressive disease, a key feature of which is pulmonary vascular remodeling. Several growth factors, including EGF, PDGF, and TGF-β1, are involved in pulmonary vascular remodeling during pulmonary hypertension. However, increased knowledge of the downstream signaling cascades is needed if effective clinical interventions are to be developed. In this context, calpain provides an interesting candidate therapeutic target, since it is activated by EGF and PDGF and has been reported to activate TGF-β1. Thus, in this study, we examined the role of calpain in pulmonary vascular remodeling in two rodent models of pulmonary hypertension. These data showed that attenuated calpain activity in calpain-knockout mice or rats treated with a calpain inhibitor resulted in prevention of increased right ventricular systolic pressure, right ventricular hypertrophy, as well as collagen deposition and thickening of pulmonary arterioles in models of hypoxia- and monocrotaline-induced pulmonary hypertension. Additionally, inhibition of calpain in vitro blocked intracellular activation of TGF-β1, which led to attenuated Smad2/3 phosphorylation and collagen synthesis. Finally, smooth muscle cells of pulmonary arterioles from patients with pulmonary arterial hypertension showed higher levels of calpain activation and intracellular active TGF-β. Our data provide evidence that calpain mediates EGF- and PDGF-induced collagen synthesis and proliferation of pulmonary artery smooth muscle cells via an intracrine TGF-β1 pathway in pulmonary hypertension. PMID:22005303

  20. Clinical and pathologic features of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism.

    PubMed

    Greenlee, Justin J; Smith, Jodi D; West Greenlee, M Heather; Nicholson, Eric M

    2012-01-01

    The majority of bovine spongiform encephalopathy (BSE) cases have been ascribed to the classical form of the disease. H-type and L-type BSE cases have atypical molecular profiles compared to classical BSE and are thought to arise spontaneously. However, one case of H-type BSE was associated with a heritable E211K mutation in the prion protein gene. The purpose of this study was to describe transmission of this unique isolate of H-type BSE when inoculated into a calf of the same genotype by the intracranial route. Electroretinograms were used to demonstrate preclinical deficits in retinal function, and optical coherence tomography was used to demonstrate an antemortem decrease in retinal thickness. The calf rapidly progressed to clinical disease (9.4 months) and was necropsied. Widespread distribution of abnormal prion protein was demonstrated within neural tissues by western blot and immunohistochemistry. While this isolate is categorized as BSE-H due to a higher molecular mass of the unglycosylated PrP(Sc) isoform, a strong labeling of all 3 PrP(Sc) bands with monoclonal antibodies 6H4 and P4, and a second unglycosylated band at approximately 14 kDa when developed with antibodies that bind in the C-terminal region, it is unique from other described cases of BSE-H because of an additional band 23 kDa demonstrated on western blots of the cerebellum. This work demonstrates that this isolate is transmissible, has a BSE-H phenotype when transmitted to cattle with the K211 polymorphism, and has molecular features that distinguish it from other cases of BSE-H described in the literature.

  1. "High-grade" central acellular carcinoma and matrix-producing carcinoma of the breast: correlation between ultrasonographic findings and pathological features.

    PubMed

    Yamaguchi, Rin; Tanaka, Maki; Mizushima, Yasuko; Hirai, Yoshitake; Yamaguchi, Miki; Terasaki, Hiroshi; Yokoyama, Toshiro; Tsuchiya, Shin-ichi; Nakashima, Osamu; Yano, Hirohisa

    2011-09-01

    High-grade carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrixproducing carcinoma (MPC) are aggressive tumors that both have a central myxomatous acellular zone. Their characteristic morphology may be useful in diagnostic imaging. Ultrasonographic findings based on the Breast Imaging Recording and Data System (BI-RADS) and detailed histological features were evaluated in 11 cases of CAC and 2 cases of MPC to characterize their features. Safranin-O staining was undertaken for the evaluation of central acellular zones in these tumors. Overall, ultrasonography demonstrated heterogeneous hyperechoic lesions in the center of the hypoechoic mass. Posterior echo enhancement was observed in all but 1 case. One case was classified as malignant and the others as "borderline." Histologically, cancer tissue was located in the periphery of the tumor with a ring-like structure and fewer cellular central areas comprising hyaline cartilage myxoid material such as those stained by safranin-O. The present study showed that the pathological findings of CACs and MPCs accurately reflect the ultrasonographic findings. Tumors that showed hyperechoic areas in the center of the hypoechoic mass, with posterior echo enhancement indicating acellular zones composed by myxochondroid material, and that were also relatively round on ultrasonography may be benign, but evaluation is required to exclude CAC and MPC.

  2. Clinical-pathological features and treatment modalities associated with recurrence in DCIS and micro-invasive carcinoma: Who to treat more and who to treat less.

    PubMed

    Toss, Angela; Palazzo, Juan; Berger, Adam; Guiles, Frances; Sendecki, Jocelyn Andrel; Simone, Nicole; Anne, Rani; Avery, Tiffany; Jaslow, Rebecca; Lazar, Melissa; Tsangaris, Theodore; Cristofanilli, Massimo

    2016-10-01

    The primary aim in the management of DCIS is the prevention of recurrence and contralateral tumor. Risk factors for DCIS recurrence and appropriate treatments are still widely debated. Adjuvant therapies after surgical resection reduce recurrences and contralateral disease, but these treatments have significant financial costs, side effects and there is a group of low-risk patients who would not gain additional benefit. The aim of our analysis was to identify clinical-pathological features and treatment modalities associated with recurrence in DCIS and microinvasive carcinoma. In the Thomas Jefferson University Cancer Registry of Philadelphia, we identified 865 patients with DCIS or micro-invasive carcinoma treated between 2003 and 2013. Associations between recurrence and demographic factors (age at diagnosis, ethnicity), biological features (ER, PR and HER2) and treatment modalities (surgery, radiotherapy and endocrine treatment) were assessed. Our single institution register-based study showed that distribution of age at diagnosis and biological features did not significantly differ among ethnic groups. Younger women and micro-invasive carcinoma patients were more likely to undergo mastectomy, while African Americans were more likely to take endocrine therapy and undergo radiotherapy. In our sample only ER/PR negative DCIS were associated with significantly higher recurrence rate. Moreover, we reported a high rate of HER2 positive recurrences, suggesting that expression of this oncogene may represent a potential biomarker for DCIS at high risk of recurrence. To better define the molecular profile of the subgroup at worse prognosis might help to identify biomarkers predictive of recurrence or second tumors, identifying patients candidates for more appropriate treatments. PMID:27506636

  3. Expression profile of SIX family members correlates with clinic-pathological features and prognosis of breast cancer: A systematic review and meta-analysis.

    PubMed

    Xu, Han-Xiao; Wu, Kong-Ju; Tian, Yi-Jun; Liu, Qian; Han, Na; He, Xue-Lian; Yuan, Xun; Wu, Gen Sheng; Wu, Kong-Ming

    2016-07-01

    Sineoculis homeobox homolog (SIX) family proteins, including SIX1, SIX2, SIX3, SIX4, SIX5, and SIX6, have been implicated in the initiation and progression of breast cancer, but the role of each member in breast tumor is not fully understood. We conducted a systematic review and meta-analysis to evaluate the association between the mRNA levels of all 6 members and clinic-pathological characteristics and clinical outcome of breast cancer patients based on the PRISMA statement criteria.ArrayExpress and Oncomine were searched for eligible databases published up to December 10, 2015. The association between the mRNA expression of SIX family members and clinic-pathological features and prognosis was measured by the odds ratio (OR), hazard ratio (HR), and the corresponding 95% confidence interval (CI), respectively. All statistical analyses were performed using STATA software.In total, 20 published Gene Expression Omnibus (GEO) databases with 3555 patients were analyzed. Our analysis revealed that patients with SIX1 overexpression had worse overall survival (OS) (HR: 1.28, 95% CI: 1.03-1.58) and shorter relapse-free survival (RFS) (HR: 1.28, 95% CI: 1.05-1.56), and much worse prognosis for luminal breast cancer patients with SIX1 overexpression (OS: HR: 1.64, 95% CI: 1.13-2.39; RFS: HR: 1.43, 95% CI: 1.06-1.93). We found that patients with higher SIX2 level had shorter time to both relapse and metastasis. However, high SIX3 mRNA level was a protective factor for OS and RFS of basal-like breast cancer patients.Our study suggested that members of SIX family played distinct roles in breast cancer. Detailed analysis of the expression of the SIX family members might provide useful information to predict breast cancer progression and prognosis.

  4. Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry.

    PubMed

    Chen, Ying-Bei; Brannon, A Rose; Toubaji, Antoun; Dudas, Maria E; Won, Helen H; Al-Ahmadie, Hikmat A; Fine, Samson W; Gopalan, Anuradha; Frizzell, Norma; Voss, Martin H; Russo, Paul; Berger, Michael F; Tickoo, Satish K; Reuter, Victor E

    2014-05-01

    cytoplasmic staining without nuclear labeling, unlike the pattern seen with confirmed HLRCC tumors. Sequencing revealed no germline or somatic FH alterations in 14 tumors that either exhibited only cytoplasmic 2SC staining (n=5) or were negative for 2SC (n=9), despite their HLRCC-like morphologic features. Our results emphasize the pivotal role of pathologic examination in the diagnosis of HLRCC patients and indicate immunohistochemical detection of 2SC as a useful ancillary tool in the differentiation of HLRCC renal tumors from other high-grade renal cell carcinomas. PMID:24441663

  5. Differentiating Smoking-Related Interstitial Fibrosis (SRIF) from Usual Interstitial Pneumonia (UIP) with Emphysema Using CT Features Based on Pathologically Proven Cases

    PubMed Central

    Chae, Kum Ju; Jin, Gong Yong; Jung, Hyun Nyeong; Kwon, Keun Sang; Choi, Hyemi; Lee, Yong Chul; Chung, Myoung Ja; Park, Ho Sung

    2016-01-01

    Objective To differentiate smoking-related interstitial fibrosis (SRIF) from usual interstitial pneumonia (UIP) with emphysema on CT in combined pulmonary fibrosis and emphysema (CPFE) patients. Materials and Methods This study was approved by the institutional review board and informed consent was waived. We included 65 patients who underwent lung biopsy under the suspicion of UIP pattern on HRCT, and after radiologic-pathologic correlation, they were divided into three groups: UIP without emphysema (n = 30), UIP with emphysema (n = 26), and SRIF (n = 9). The quantitative extent of emphysema in the entire lung was visually assessed and fibrotic patterns were qualitatively analyzed based on six characteristics (asymmetry, juxta-subpleural sparing, emphysema beside the honeycombing area, absence of ground grass attenuation/reticulation in honeycombing area, inhomogeneous honeycombing, and absence of honeycombing in the upper lobes). Kaplan-Meier analysis was used for survival analysis, and logistic regression with a receiver operating characteristic curve was used to predict the possibility of SRIF. Results In qualitative analysis of fibrotic patterns, SRIF tended to exhibit more than three of six fibrotic features, whereas UIP with emphysema demonstrated about two of these characteristics (p = 0.035). In addition, SRIF had a higher extent of emphysema than UIP with emphysema when they have same amount of fibrosis (p = 0.014). In patients with SRIF, 5-year survival rate was 85.7%, while it was 40.7% in UIP with emphysema patients (p = 0.035). Conclusion Fibrotic CT patterns and survival rate differed between SRIF and UIP with emphysema among CPFE patients, which explains the variable prognosis of CPFE. PMID:27611866

  6. Clinical and pathological features of toxoplasmosis in free-ranging common wombats (Vombatus ursinus) with multilocus genotyping of Toxoplasma gondii type II-like strains.

    PubMed

    Donahoe, Shannon L; Šlapeta, Jan; Knowles, Graeme; Obendorf, David; Peck, Sarah; Phalen, David N

    2015-04-01

    Toxoplasma gondii is a cosmopolitan zoonotic protozoan parasite with the capacity to infect virtually any warm blooded vertebrate species. Australian native marsupials are thought to be highly susceptible to toxoplasmosis; however, most reports are in captive animals and little is known about T. gondii associated disease in free-ranging marsupials, including wombats (Vombatus ursinus). This study describes the clinical and pathological features of eight cases of toxoplasmosis in free-ranging common wombats in Tasmania and New South Wales (NSW) from 1992 to 2013, including a morbidity and mortality event investigated in the Southern Highlands NSW in the autumn of 2010. The diagnosis of T. gondii infection was confirmed using either immunohistochemistry, molecular diagnostics or both. Utilizing the combination of direct DNA sequencing of B1, SAG1, 5'- and 3'-SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico DNA markers and virtual RFLP to genetically characterize two of the T. gondii strains, we found a nonarchetypal type II-like strain (ToxoDB PCR-RFLP genotype #1) and an atypical type II-like strain (ToxoDB PCR-RFLP genotype #3) to be the causal agents of toxoplasmosis in wombats from the 2010 morbidity and mortality event. This study suggests that T. gondii may act as a significant disease threat to free-ranging common wombats. Our findings indicate neurologic signs are a very common clinical presentation in common wombats with toxoplasmosis and T. gondii infection should be considered as a likely differential diagnosis for any common wombat exhibiting signs of blindness, head tilt, circling and changes in mentation. PMID:25463314

  7. Clinical and pathological features of toxoplasmosis in free-ranging common wombats (Vombatus ursinus) with multilocus genotyping of Toxoplasma gondii type II-like strains.

    PubMed

    Donahoe, Shannon L; Šlapeta, Jan; Knowles, Graeme; Obendorf, David; Peck, Sarah; Phalen, David N

    2015-04-01

    Toxoplasma gondii is a cosmopolitan zoonotic protozoan parasite with the capacity to infect virtually any warm blooded vertebrate species. Australian native marsupials are thought to be highly susceptible to toxoplasmosis; however, most reports are in captive animals and little is known about T. gondii associated disease in free-ranging marsupials, including wombats (Vombatus ursinus). This study describes the clinical and pathological features of eight cases of toxoplasmosis in free-ranging common wombats in Tasmania and New South Wales (NSW) from 1992 to 2013, including a morbidity and mortality event investigated in the Southern Highlands NSW in the autumn of 2010. The diagnosis of T. gondii infection was confirmed using either immunohistochemistry, molecular diagnostics or both. Utilizing the combination of direct DNA sequencing of B1, SAG1, 5'- and 3'-SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico DNA markers and virtual RFLP to genetically characterize two of the T. gondii strains, we found a nonarchetypal type II-like strain (ToxoDB PCR-RFLP genotype #1) and an atypical type II-like strain (ToxoDB PCR-RFLP genotype #3) to be the causal agents of toxoplasmosis in wombats from the 2010 morbidity and mortality event. This study suggests that T. gondii may act as a significant disease threat to free-ranging common wombats. Our findings indicate neurologic signs are a very common clinical presentation in common wombats with toxoplasmosis and T. gondii infection should be considered as a likely differential diagnosis for any common wombat exhibiting signs of blindness, head tilt, circling and changes in mentation.

  8. A novel NREM and REM parasomnia with sleep breathing disorder associated with antibodies against IgLON5: a case series, pathological features, and characterization of the antigen

    PubMed Central

    Sabater, Lidia; Gaig, Carles; Gelpi, Ellen; Bataller, Luis; Lewerenz, Jan; Torres-Vega, Estefanía; Contreras, Angeles; Giometto, Bruno; Compta, Yaroslau; Embid, Cristina; Vilaseca, Isabel; Iranzo, Alex; Santamaría, Joan; Dalmau, Josep; Graus, Francesc

    2014-01-01

    ) against IgLON5, member of a family of neuronal cell adhesion molecules. Only 1/285 controls (with progressive supranuclear palsy) had IgLON5 antibodies. Neuropathology showed neuronal loss and extensive deposits of hyperphosphorylated tau mainly involving the tegmentum of the brainstem and hypothalamus. Interpretation IgLON5-antibodies identify a unique NREM and REM parasomnia with sleep breathing dysfunction and pathological features suggesting a tauopathy. Funding Fondo de Investigaciones Sanitarias. Centros de Investigación Biomédica en Red de enfermedades neurodegenerativas (CIBERNED) and Respiratorias (CIBERES), Ministerio de Economía y Competitividad, Fundació la Marató TV3 and the National Institutes of Health. PMID:24703753

  9. Computational Pathology

    PubMed Central

    Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.

    2016-01-01

    Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131

  10. Musculoskeletal Pathology.

    PubMed

    Peat, Frances J; Kawcak, Christopher E

    2015-08-01

    The current understanding of pathology as it relates to common diseases of the equine musculoskeletal system is reviewed. Conditions are organized under the fundamental categories of developmental, exercise-induced, infectious, and miscellaneous pathology. The overview of developmental pathology incorporates the new classification system of juvenile osteochondral conditions. Discussion of exercise-induced pathology emphasizes increased understanding of the contribution of cumulative microdamage caused by repetitive cyclic loading. Miscellaneous musculoskeletal pathology focuses on laminitis, which current knowledge indicates should be regarded as a clinical syndrome with a variety of possible distinct mechanisms of structural failure that are outlined in this overview. PMID:26037607

  11. Osler's pathology.

    PubMed

    Pai, S A

    2000-12-01

    Sir William Osler, one of the giants of clinical medicine, had his initial training as a pathologist. He was one of the physicians responsible for the impact that autopsies have had on medicine. He also contributed to the development of laboratory medicine. Osler made significant discoveries in anatomic pathology and hematology. His expertise was restricted not just to human pathology, but also to veterinary pathology. His mentors played a fundamental role in his achievements in academics.

  12. Pathology Gross Photography: The Beginning of Digital Pathology.

    PubMed

    Rampy, B Alan; Glassy, Eric F

    2016-03-01

    The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale. PMID:26851666

  13. Pathology Gross Photography: The Beginning of Digital Pathology.

    PubMed

    Rampy, B Alan; Glassy, Eric F

    2015-06-01

    The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale.

  14. ISMP Adverse Drug Reactions

    PubMed Central

    2013-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24421544

  15. Oral pathology.

    PubMed

    Niemiec, Brook A

    2008-05-01

    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  16. Therapeutic Approach of a High Functioning Individual With Traumatic Brain Injury and Subsequent Emotional Volatility With Features of Pathological Laughter and Crying With Dextromethorphan/Quinidine.

    PubMed

    Garcia-Baran, Dynela; Johnson, Thomas M; Wagner, Joyce; Shen, Joann; Geers, Michelle

    2016-03-01

    Pathological laughing and crying, or pseudobulbar affect (PBA), has been described in patients with neurological disorders such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, stroke, and traumatic brain injury (TBI) since the 19th century (Schiffer 2005). The syndrome is characterized by inappropriate episodes of laughing or crying after minor stimuli. It was first coined a disinhibition of cortical control by Kinnier Wilson in 1924. It was observed in brain disease and seen with mild TBI. It can impair social and occupational function and is largely underrecognized in clinical settings. PBA is usually treated with antidepressants and dopaminergic agents. In this case we treated a military recruit with TBI with Nuedexta-a dextromethorphan/Quinidine derivative with a subsequent decrease in his episodes. PMID:27015166

  17. Therapeutic Approach of a High Functioning Individual With Traumatic Brain Injury and Subsequent Emotional Volatility With Features of Pathological Laughter and Crying With Dextromethorphan/Quinidine.

    PubMed

    Garcia-Baran, Dynela; Johnson, Thomas M; Wagner, Joyce; Shen, Joann; Geers, Michelle

    2016-03-01

    Pathological laughing and crying, or pseudobulbar affect (PBA), has been described in patients with neurological disorders such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, stroke, and traumatic brain injury (TBI) since the 19th century (Schiffer 2005). The syndrome is characterized by inappropriate episodes of laughing or crying after minor stimuli. It was first coined a disinhibition of cortical control by Kinnier Wilson in 1924. It was observed in brain disease and seen with mild TBI. It can impair social and occupational function and is largely underrecognized in clinical settings. PBA is usually treated with antidepressants and dopaminergic agents. In this case we treated a military recruit with TBI with Nuedexta-a dextromethorphan/Quinidine derivative with a subsequent decrease in his episodes.

  18. Therapeutic Approach of a High Functioning Individual With Traumatic Brain Injury and Subsequent Emotional Volatility With Features of Pathological Laughter and Crying With Dextromethorphan/Quinidine

    PubMed Central

    Garcia-Baran, Dynela; Johnson, Thomas M.; Wagner, Joyce; Shen, Joann; Geers, Michelle

    2016-01-01

    Abstract Pathological laughing and crying, or pseudobulbar affect (PBA), has been described in patients with neurological disorders such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, stroke, and traumatic brain injury (TBI) since the 19th century (Schiffer 2005). The syndrome is characterized by inappropriate episodes of laughing or crying after minor stimuli. It was first coined a disinhibition of cortical control by Kinnier Wilson in 1924. It was observed in brain disease and seen with mild TBI. It can impair social and occupational function and is largely underrecognized in clinical settings. PBA is usually treated with antidepressants and dopaminergic agents. In this case we treated a military recruit with TBI with Nuedexta—a dextromethorphan/Quinidine derivative with a subsequent decrease in his episodes. PMID:27015166

  19. [Features of the influence of functional pathology of the digestive system combining with neurocirculatory dystonia on quality of life of students' population].

    PubMed

    Chirva, O V

    2013-11-01

    The study of 139 persons from organized student population is presented. The results of the frequency of occurrence of functional diseases of the digestive system combining with neurocirculatory dystonia in this age group are illustrated. It is shown that all indices of the quality of life are decreased in patients with comorbid functional disorders according to the results of the questionnaire «SF-36 Health Status Survey» (SF-36). The most pronounced reduction was set for such indices as RP, GH, VT, RE and MH and was more typical for patients with irritable bowel syndrome and the "overlap syndrome" of functional disorders of the digestive system combining with the autonomic dysfunction. High degree of reduction of the "mental health component» (MH sum) in all groups was demonstrated which confirms the particular impact of functional pathology on the psychological state of young persons.

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

    PubMed

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

    2011-02-01

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

  1. Pathologic and Molecular Features Correlate With Long-Term Outcome After Adjuvant Therapy of Resected Primary GI Stromal Tumor: The ACOSOG Z9001 Trial

    PubMed Central

    Corless, Christopher L.; Ballman, Karla V.; Antonescu, Cristina R.; Kolesnikova, Violetta; Maki, Robert G.; Pisters, Peter W.T.; Blackstein, Martin E.; Blanke, Charles D.; Demetri, George D.; Heinrich, Michael C.; von Mehren, Margaret; Patel, Shreyaskumar; McCarter, Martin D.; Owzar, Kouros; DeMatteo, Ronald P.

    2014-01-01

    Purpose The ACOSOG (American College of Surgeons Oncology Group) Z9001 (Alliance) study, a randomized, placebo-controlled trial, demonstrated that 1 year of adjuvant imatinib prolonged recurrence-free survival (RFS) after resection of primary GI stromal tumor (GIST). We sought to determine the pathologic and molecular factors associated with patient outcome. Patients and Methods There were 328 patients assigned to the placebo arm and 317 to the imatinib arm. Median patient follow-up was 74 months. There were 645 tumor specimens available for mitotic rate or mutation analysis. Results RFS remained superior in the imatinib arm (hazard ratio, 0.6; 95% CI, 0.43 to 0.75; Cox model–adjusted P < .001). On multivariable analysis of patients in the placebo arm, large tumor size, small bowel location, and high mitotic rate were associated with lower RFS, whereas tumor genotype was not significantly associated with RFS. Multivariable analysis of patients in the imatinib arm yielded similar findings. When comparing the two arms, imatinib therapy was associated with higher RFS in patients with a KIT exon 11 deletion of any type, but not a KIT exon 11 insertion or point mutation, KIT exon 9 mutation, PDGFRA mutation, or wild-type tumor, although some of these patient groups were small. Adjuvant imatinib did not seem to alter overall survival. Conclusion Our findings show that tumor size, location, and mitotic rate, but not tumor genotype, are associated with the natural history of GIST. Patients with KIT exon 11 deletions assigned to 1 year of adjuvant imatinib had a longer RFS. PMID:24638003

  2. Pathological features of lymphoid proliferations of the salivary glands: lymphoepithelial sialadenitis versus low-grade B-cell lymphoma of the malt type.

    PubMed

    Carbone, A; Gloghini, A; Ferlito, A

    2000-12-01

    Lymphoid proliferations of the salivary glands can be either reactive or neoplastic. Reactive lesions include the lymphoepithelial sialadenitis (LESA; also known as myoepithelial sialadenitis [MESA]) of Sjogren's syndrome. Lymphomas of the salivary glands are predominantly B-cell type and include extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. The spectrum of histopathologic features of LESA/MESA includes 1) "fully benign lymphoid infiltrate," with or without an associated lymphoid follicular structure, without immunoglobulin (Ig) light chain restriction in B-cells, and without any features of aggressive behavior, and 2) "lymphoproliferative lesions," with or without areas of Ig light chain restriction in B-cells, with the usual presence of centrocyte-like cells. A more or less pronounced lymphoepithelial aggressiveness may be present without definite evidence of malignancy. B-cell clones are detected in over 50% of cases of LESA/MESA by molecular genetic methods, but this does not correlate with morphological or clinical evidence of overt lymphoma. On the other hand, "marginal zone B-cell lymphoma of the MALT type" of the salivary glands produces a dense lymphoid infiltrate diffusely involving the gland, with obliteration of acini. The centrocyte-like cells form broad "halos" around the epithelial cell nests and broad strands between lymphoepithelial lesions, often linking together several lymphoepithelial lesions. Further, lymphoma cells express monotypic surface Ig, and in the majority of the cases, the plasma cells are also monoclonal. In conclusion, the diagnosis of LESA/MESA versus marginal zone B-cell lymphoma of the MALT type still relies on the evaluation of morphological features. It seems that molecular genetic analysis has little or no practical role in the clinical diagnosis of salivary gland lymphoma in a setting of LESA/MESA and Sjögren's syndrome.

  3. Selected cases from the Arkadi M. Rywlin international pathology slide series: granular cell nevus of congenital type: a melanocytic proliferation exhibiting distinct morphologic, immunohistochemical, and ultrastructural features.

    PubMed

    De Pellegrin, Alessandro; Luzar, Bostjan; Suster, Saul; Falconieri, Giovanni

    2015-07-01

    A case of combined melanocytic nevus characterized by extensive granular cytoplasmic changes is described. Clinically, the lesion presented as an irregular, slightly asymmetric, and raised pigmented lesion of back with indistinct borders. Microscopically, a congenital pattern of distribution of melanocytes could be recognized growing along follicular and adnexal units. Melanocytes were arranged in sheets of epithelioid cells with abundant granular cytoplasm. A minor component featuring conventional dermal melanocytes was also present. Mitotic figures were not recognized. Immunohistochemistry was positive for Melan A and S100 protein in both conventional melanocytes and granular cells. In addition, the granular cells were also strongly positive for HMB45 and NKI-C3. The proliferative marker Ki67/MIB1 was nonreactive. Ultrastructural examination showed large cells with round to oval nuclei and numerous scattered cytoplasmic granules showing features consistent with lysosomes or autophagosomes. No premelanosomes, glycogen, lipid, or other distinctive organelles could be identified. Clinical follow-up at 2 years was uneventful. This unusual lesion may represent a peculiar dermal melanocytic proliferation in which the abundant granular cytoplasm is most likely due to degeneration of melanosomes induced by autophagocytic activity. The striking cytoplasmic granularity observed in this lesion may lead to confusion with other conditions, thus warranting adding granular cell nevus to the phenotypic spectrum of benign melanocytic proliferations.

  4. Comparison of the pathologic and pathogenic features in six different regions of postmortem brains of three patients with fatal familial insomnia.

    PubMed

    Xie, Wu-Ling; Shi, Qi; Xia, Sheng-Li; Zhang, Bao-Yun; Gong, Han-Shi; Wang, Shao-Bin; Xu, Yin; Guo, Yan; Tian, Chan; Zhang, Jin; Xu, Bian-Li; Liu, Yong; Dong, Xiao-Ping

    2013-01-01

    Fatal familial insomnia (FFI) is an autosomal dominant prion disease clinically characterized by rapidly progressive insomnia, prominent autonomic alterations and behavioral disturbance. The D178N mutation of the prion protein gene (PRNP) on chromosome 20 in conjunction with methionine at codon 129 is a molecular feature. Although the neuropathological characteristics of FFI are well documented, the neuropathologic and pathogenic features of FFI patients remain poorly understood. Six brain regions of postmortem brains from 3 FFI patients were examined using immunohistochemistry, western blot analyses and quantitative real-time PCR. In all 3 brain specimens, reactive astrogliosis was found to be more severe in the thalamus than in the cortex regions. Western blot analyses showed that all three brains expressed PrP, but only 2 were associated with significantly weak proteinase K (PK) resistance. However, the conformational stabilities of PrPSc in the 3 FFI brains were significantly weaker than those presented in a G114V genetic Creutzfeldt-Jakob disease (gCJD) case. Immunohistochemistry and western blot analyses showed comparable amounts of neuron-specific enolase (NSE)-positive stained cells and NSE protein among the different regions in the three brains. In addition, the transcriptional levels of glial fibrillary acidic protein (GFAP) and NSE-specific mRNAs were coincident with the expression of these proteins. In conclusion, in the present study, we described the detailed regional neuropathology of FFI cases.

  5. Primary intestinal-type glandular lesions of the vagina: clinical, pathologic, and immunohistochemical features of 14 cases ranging from benign polyp to adenoma to adenocarcinoma.

    PubMed

    Staats, Paul N; McCluggage, W Glenn; Clement, Philip B; Young, Robert H

    2014-05-01

    Primary intestinal-type glandular lesions of the vagina are rare. We report a series of 14 lesions, including 1 intestinal-type polyp without neoplastic features, 3 adenomas (2 with high-grade dysplasia), and 10 adenocarcinomas. Patients ranged in age from 20 to 86 years (mean 60 y) and presented with vaginal bleeding or a mass. No history of diethylstilbestrol exposure, adenosis, or endometriosis was elicited in any patient. The lesions were mostly polypoid, small (0.8 to 2.0 cm), and located in the posterior (6 cases) and lower (7 cases) vagina. One carcinoma metastasized to a para-aortic lymph node; the others were confined to the vagina. The neoplasms exhibited histologic features identical to those seen in primary large intestinal tumors, including variable numbers of goblet cells and in 1 case neuroendocrine cells. Five of the adenocarcinomas contained areas consistent with a precursor adenoma. In 3 cases, a benign urothelium-lined duct was adjacent to the lesion, and in 2 patients benign intestinal-type epithelium was present; no other potential benign precursor lesions were seen. Immunohistochemical analysis was performed on 6 cases; the tumors were positive for CDX-2 (6/6), CK20 (5/6), CEA (5/5), CK7 (4/6), and CA-125 (2/4) and were negative for ER (0/6) and p16 (0/2). Clinical outcome data were available in 3 patients with adenocarcinomas; 1 died of disease in <1 year, and 2 were alive with no evidence of disease at 2 and 7 years. The pertinent literature is reviewed, and the potential origin and differential diagnosis of these lesions are discussed. PMID:24722061

  6. [Clinical pathology].

    PubMed

    Dimitrijević, Jovan

    2006-05-01

    This work describes the basic elements of pathology used in clinical practice. Pathology plays an important role in clinical and scientific work, but only a few areas of pathology will be covered. Although the contribution of oncological and surgical pathology to therapy is the most well known, the cases chosen here will involve infectious pathology, diseases of the kidney and the liver, autoimmune diseases, as well as organ transplantation. Especially important is the description of methods that enable more accurate morphological diagnoses, such as histochemistry, immunohistochemistry, immunofluorescence, and electronic microscopy. Previous experience and joint work with clinical doctors have enabled the definition of significant morphological elements as well as of essential methods of pathohistological diagnosis. Besides, as is often the case, although disease symptoms are difficult to discern and biochemical results do not show significant changes compared to normal values, the results of biopsy come as a surprise to clinical doctors. For example, in virus hepatitis B involving so-called asymptomatic HBsAg carriers, we discovered every morphological form of hepatitis, from minimal lesions to chronic, persistent, and active hepatitis. With hepatitis C, certain morphological lesions point to the etiopathogenesis of this disease and thus help to confirm the diagnosis and to instigate therapy on time. Another significant experience involves kidney biopsies in cases when clinical findings are asymptomatic. Often, in such cases, morphological findings point to glomerulonephritis and glomerulopathy at different stages. Timely and subtle morphological diagnostics offer a more precise explanation for the pathological injury of tissues than other diagnostic methods. In this way, by adopting new methods, the work of pathologists is included more and more in everyday clinical practice. The inclusion of pathologists in a transplantation team makes sure a proper selection of

  7. Solitary fibrous tumors and hemangiopericytomas of the meninges: overlapping pathological features and common prognostic factors suggest the same spectrum of tumors.

    PubMed

    Bouvier, Corinne; Métellus, Philippe; de Paula, André Maues; Vasiljevic, Alexandre; Jouvet, Anne; Guyotat, Jacques; Mokhtari, Karima; Varlet, Pascale; Dufour, Henry; Figarella-Branger, Dominique

    2012-07-01

    Meningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) are distinct entities in the World Health Organization (WHO) classification of central nervous system (CNS) tumors while they belong to the same spectrum of tumors in other locations. Well-defined histological prognostic factors are also lacking for these tumors. In order to clarify the relationship between SFT and HPC and to find histological and immunohistochemical prognostic factors, we carried out a retrospective study in 89 patients. The following histological parameters were recorded: hypercellularity, collagenic areas, cytonuclear atypias, necrosis, mitotic count per 10 high-power fields, vasculo-nervous adherences defined by engulfment of vessel or nerve by the tumor, brain infiltration. We found overlapping histological and immunohistochemical features between SFT and HPC. The most relevant histological prognostic factors in the whole cohort for both progression-free survival (PFS) and overall survival (OS) in univariate analysis were hypercellularity, high mitotic count (>5 per 10 high-power fields) and necrosis. On the basis of these results, we propose a new grading scheme for these tumors which was of pronostic value for both PFS and OS in uni- and multivariate analysis. As extent of surgery was also a prognostic factor for both PFS and OS in univariate analysis, we propose that management of SFT/HPC might be based both on quality of removal and histological grade.

  8. Clinical and pathological features of Burkitt lymphoma showing expression of BCL2--an analysis including gene expression in formalin-fixed paraffin-embedded tissue.

    PubMed

    Masqué-Soler, Neus; Szczepanowski, Monika; Kohler, Christian W; Aukema, Sietse M; Nagel, Inga; Richter, Julia; Siebert, Reiner; Spang, Rainer; Burkhardt, Birgit; Klapper, Wolfram

    2015-11-01

    The differential diagnosis between Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) can be challenging. BL has been reported to express less BCL2 than DLBCL, but this issue has not been analysed systematically. BL expressing BCL2 can be considered to be MYC/BCL2 co-expressors, a feature that is associated with poorer outcome in DLBCL but that has not been correlated with outcome in BL so far. We analysed the expression of BCL2 in 150 cases of conventionally diagnosed BL using two different BCL2 antibodies. BCL2 expression was detected in 23% of the cases, though the expression varied in intensity and number of positive cells. We did not detect any relevant differences in clinical presentation and outcome between BCL2-positive and BCL2-negative BL in a subgroup of 43 cases for which detailed clinical data were available. An independent cohort of 17 BL with expression of BCL2 were analysed molecularly, with 13 of 17 cases classified as molecularly defined BL (Burkitt Lymphoma) using gene expression profiling on formalin-fixed paraffin-embedded tissues. The four lymphomas diagnosed molecularly as intermediates did not differ in clinical presentation and outcome from molecularly defined BL. PMID:26218299

  9. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  10. [Pathology of lung cancer].

    PubMed

    Theegarten, D; Hager, T

    2016-09-01

    Lung cancer is the leading cause of cancer death in men and the second most frequent cause in women. The pathology of lung tumors is of special relevance concerning therapy and prognosis and current classification systems have to be taken into consideration. The results of molecular tissue subtyping allow further classification and therapeutic options. The histological entities are mainly associated with typical X‑ray morphological features. PMID:27495784

  11. Prediction of Low versus High Recurrence Scores in Estrogen Receptor-Positive, Lymph Node-Negative Invasive Breast Cancer on the Basis of Radiologic-Pathologic Features: Comparison with Oncotype DX Test Recurrence Scores.

    PubMed

    Dialani, Vandana; Gaur, Shantanu; Mehta, Tejas S; Venkataraman, Shambhavi; Fein-Zachary, Valerie; Phillips, Jordana; Brook, Alexander; Slanetz, Priscilla J

    2016-08-01

    Purpose To review mammographic, ultrasonographic (US), and magnetic resonance (MR) imaging features and pathologic characteristics of estrogen receptor (ER)-positive, lymph node-negative invasive breast cancer and to determine the relationship of these characteristics to Oncotype DX (Genomic Health, Redwood City, Calif) test recurrence scores (ODRS) for breast cancer recurrence. Materials and Methods This institutional review board-approved retrospective study was performed in a single large academic medical center. The study population included patients with ER-positive, lymph node-negative invasive breast cancer who underwent genomic testing from January 1, 2009, to December 31, 2013. Imaging features of the tumor were classified according to the Breast Imaging Reporting and Data System lexicon by breast imagers who were blinded to the ODRS. Mammography was performed in 86% of patients, US was performed in 84%, and MR imaging was performed in 33%, including morphologic and kinetic evaluation. Images from each imaging modality were evaluated. Each imaging finding, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, and tumor grade were then individually correlated with ODRS. Analysis of variance was used to determine differences for each imaging feature. Regression analysis was used to calculate prediction of recurrence on the basis of imaging features combined with histopathologic features. Results The 319 patients had a mean age ± standard deviation of 55 years ± 8.7 (range, 31-82 years). Imaging features with a positive correlation with ODRS included a well-circumscribed oval mass (P = .024) at mammography, vascularity (P = .047) and posterior enhancement (P = .004) at US, and lobulated mass (P = .002) at MR imaging. Recurrence scores were predicted by using these features in combination with PR and HER2 status and tumor grade by using the threshold of more than 30 as a high recurrence score. With a regression tree, there

  12. African American Men With Very Low–Risk Prostate Cancer Exhibit Adverse Oncologic Outcomes After Radical Prostatectomy: Should Active Surveillance Still Be an Option for Them?

    PubMed Central

    Sundi, Debasish; Ross, Ashley E.; Humphreys, Elizabeth B.; Han, Misop; Partin, Alan W.; Carter, H. Ballentine; Schaeffer, Edward M.

    2013-01-01

    Purpose Active surveillance (AS) is a treatment option for men with very low–risk prostate cancer (PCa); however, favorable outcomes achieved for men in AS are based on cohorts that under-represent African American (AA) men. To explore whether race-based health disparities exist among men with very low–risk PCa, we evaluated oncologic outcomes of AA men with very low–risk PCa who were candidates for AS but elected to undergo radical prostatectomy (RP). Patients and Methods We studied 1,801 men (256 AA, 1,473 white men, and 72 others) who met National Comprehensive Cancer Network criteria for very low–risk PCa and underwent RP. Presenting characteristics, pathologic data, and cancer recurrence were compared among the groups. Multivariable modeling was performed to assess the association of race with upgrading and adverse pathologic features. Results AA men with very low–risk PCa had more adverse pathologic features at RP and poorer oncologic outcomes. AA men were more likely to experience disease upgrading at prostatectomy (27.3% v 14.4%; P < .001), positive surgical margins (9.8% v 5.9%; P = .02), and higher Cancer of the Prostate Risk Assessment Post-Surgical scoring system (CAPRA-S) scores. On multivariable analysis, AA race was an independent predictor of adverse pathologic features (odds ratio, [OR], 3.23; P = .03) and pathologic upgrading (OR, 2.26; P = .03). Conclusion AA men with very low–risk PCa who meet criteria for AS but undergo immediate surgery experience significantly higher rates of upgrading and adverse pathology than do white men and men of other races. AA men with very low–risk PCa should be counseled about increased oncologic risk when deciding among their disease management options. PMID:23775960

  13. Alexander's disease: clinical, pathologic, and genetic features.

    PubMed

    Johnson, Anne B; Brenner, Michael

    2003-09-01

    Alexander's disease, a rare and fatal disorder of the central nervous system, most commonly affects infants and young children but can also occur in older children and sometimes adults. In infants and young children, it causes developmental delay, psychomotor retardation, paraparesis, feeding problems, usually megalencephaly, often seizures, and sometimes hydrocephalus. Juvenile cases often do not have megalencephaly and tend to have predominant pseudobulbar and bulbar signs. In both groups, characteristic magnetic resonance imaging findings have been described. In adult cases, the signs are variable, can resemble multiple sclerosis, and might include palatal myoclonus. In all cases, the examination of brain tissue shows the presence of widely distributed Rosenthal fibers. Almost all cases have recently been found to have a heterozygous, missense, point mutation in the gene for glial fibrillary acidic protein, which provides a new diagnostic tool. In most cases, the mutation appears to occur de novo, not being present in either parent, but some adult cases are familial.

  14. Pathologic features of fatal shark attacks.

    PubMed

    Byard, R W; Gilbert, J D; Brown, K

    2000-09-01

    To examine the pattern of injuries in cases of fatal shark attack in South Australian waters, the authors examined the files of their institution for all cases of shark attack in which full autopsies had been performed over the past 25 years, from 1974 to 1998. Of the seven deaths attributed to shark attack during this period, full autopsies were performed in only two cases. In the remaining five cases, bodies either had not been found or were incomplete. Case 1 was a 27-year-old male surfer who had been attacked by a shark. At autopsy, the main areas of injury involved the right thigh, which displayed characteristic teeth marks, extensive soft tissue damage, and incision of the femoral artery. There were also incised wounds of the right wrist. Bony injury was minimal, and no shark teeth were recovered. Case 2 was a 26-year-old male diver who had been attacked by a shark. At autopsy, the main areas of injury involved the left thigh and lower leg, which displayed characteristic teeth marks, extensive soft tissue damage, and incised wounds of the femoral artery and vein. There was also soft tissue trauma to the left wrist, with transection of the radial artery and vein. Bony injury was minimal, and no shark teeth were recovered. In both cases, death resulted from exsanguination following a similar pattern of soft tissue and vascular damage to a leg and arm. This type of injury is in keeping with predator attack from underneath or behind, with the most severe injuries involving one leg. Less severe injuries to the arms may have occurred during the ensuing struggle. Reconstruction of the damaged limb in case 2 by sewing together skin, soft tissue, and muscle bundles not only revealed that no soft tissue was missing but also gave a clearer picture of the pattern of teeth marks, direction of the attack, and species of predator.

  15. Breast carcinosarcoma: clinical and pathological features.

    PubMed

    Mele, Marco; Jensen, Lisbeth L; Vahl, Pernille; Funder, Jonas Amstrup

    2015-01-01

    Carcinosarcoma of the breast is an extremely rare and highly aggressive breast tumor.It has two distinct malignant cell lines involving epithelial (carcinomatous) and mesenchymal (sarcomatous) components. The literature on the topic is sparse. We report a rare case of carcinosarcoma of the breast containing a small fraction of a pancytokeratin positive sarcomatous-appearing cell population i.e. a metaplastic cell population. The patient was treated with a multidisciplinary approach.

  16. Microscopic Disease Extension in Three Dimensions for Non-Small-Cell Lung Cancer: Development of a Prediction Model Using Pathology-Validated Positron Emission Tomography and Computed Tomography Features

    SciTech Connect

    Loon, Judith van; Siedschlag, Christian; Stroom, Joep; Blauwgeers, Hans; Suylen, Robert-Jan van; Knegjens, Joost; Rossi, Maddalena; Baardwijk, Angela van; Boersma, Liesbeth; Klomp, Houke; Vogel, Wouter; Burgers, Sjaak; Gilhuijs, Kenneth

    2012-01-01

    Purpose: One major uncertainty in radiotherapy planning of non-small-cell lung cancer concerns the definition of the clinical target volume (CTV), meant to cover potential microscopic disease extension (MDE) around the macroscopically visible tumor. The primary aim of this study was to establish pretreatment risk factors for the presence of MDE. The secondary aim was to establish the impact of these factors on the accuracy of positron emission tomography (PET) and computed tomography (CT) to assess the total tumor-bearing region at pathologic examination (CTV{sub path}). Methods and Materials: 34 patients with non-small-cell lung cancer who underwent CT and PET before lobectomy were included. Specimens were examined microscopically for MDE. The gross tumor volume (GTV) on CT and PET (GTV{sub CT} and GTV{sub PET}, respectively) was compared with the GTV and the CTV at pathologic examination, tissue deformations being taken into account. Using multivariate logistic regression, image-based risk factors for the presence of MDE were identified, and a prediction model was developed based on these factors. Results: MDE was found in 17 of 34 patients (50%). The MDE did not exceed 26 mm in 90% of patients. In multivariate analysis, two parameters (mean CT tumor density and GTV{sub CT}) were significantly associated with MDE. The area under the curve of the two-parameter prediction model was 0.86. Thirteen tumors (38%, 95% CI: 24-55%) were identified as low risk for MDE, being potential candidates for reduced-intensity therapy around the GTV. In the low-risk group, the effective diameter of the GTV{sub CT/PET} accurately represented the CTV{sub path}. In the high-risk group, GTV{sub CT/PET} underestimated the CTV{sub path} with, on average, 19.2 and 26.7 mm, respectively. Conclusions: CT features have potential to predict the presence of MDE. Tumors identified as low risk of MDE show lower rates of disease around the GTV than do high-risk tumors. Both CT and PET accurately

  17. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence.

  18. Adverse Stress, Hippocampal Networks, and Alzheimer's Disease

    PubMed Central

    Rothman, Sarah M.; Mattson, Mark P.

    2009-01-01

    Recent clinical data have implicated chronic adverse stress as a potential risk factor in the development of Alzheimer's disease (AD) and data also suggest that normal, physiological stress responses may be impaired in AD. It is possible that pathology associated with AD causes aberrant responses to chronic stress, due to potential alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Recent work in rodent models of AD suggests that chronic adverse stress exacerbates the cognitive deficits and hippocampal pathology that are present in the AD brain. This review summarizes recent findings obtained in experimental AD models regarding the influence of chronic adverse stress on the underlying cellular and molecular disease processes including the potential role of glucocorticoids. Emerging findings suggest that both AD and chronic adverse stress affect hippocampal neural networks in a similar fashion. We describe alterations in hippocampal plasticity that occur in both chronic stress and AD including dendritic remodeling, neurogenesis and long-term potentiation. Finally, we outline potential roles for oxidative stress and neurotrophic factor signaling as key determinants of the impact of chronic stress on the plasticity of neural networks and AD pathogenesis. PMID:19943124

  19. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence. PMID:23850228

  20. Nanotechnology: Toxicologic Pathology

    PubMed Central

    Hubbs, Ann F.; Sargent, Linda M.; Porter, Dale W.; Sager, Tina M.; Chen, Bean T.; Frazer, David G.; Castranova, Vincent; Sriram, Krishnan; Nurkiewicz, Timothy R.; Reynolds, Steven H.; Battelli, Lori A.; Schwegler-Berry, Diane; McKinney, Walter; Fluharty, Kara L.; Mercer, Robert R.

    2015-01-01

    Nanotechnology involves technology, science, and engineering in dimensions less than 100 nm. A virtually infinite number of potential nanoscale products can be produced from many different molecules and their combinations. The exponentially increasing number of nanoscale products will solve critical needs in engineering, science, and medicine. However, the virtually infinite number of potential nanotechnology products is a challenge for toxicologic pathologists. Because of their size, nanoparticulates can have therapeutic and toxic effects distinct from micron-sized particulates of the same composition. In the nanoscale, distinct intercellular and intracellular translocation pathways may provide a different distribution than that obtained by micron-sized particulates. Nanoparticulates interact with subcellular structures including microtubules, actin filaments, centrosomes, and chromatin; interactions that may be facilitated in the nanoscale. Features that distinguish nanoparticulates from fine particulates include increased surface area per unit mass and quantum effects. In addition, some nanotechnology products, including the fullerenes, have a novel and reactive surface. Augmented microscopic procedures including enhanced dark-field imaging, immunofluorescence, field-emission scanning electron microscopy, transmission electron microscopy, and confocal microscopy are useful when evaluating nanoparticulate toxicologic pathology. Thus, the pathology assessment is facilitated by understanding the unique features at the nanoscale and the tools that can assist in evaluating nanotoxicology studies. PMID:23389777

  1. [Pathological horseshoe kidney. Therapeutic aspects].

    PubMed

    Bennani, S; Touijer, A; Aboutaieb, R; el Mrini, M; Benjelloun, S

    1994-01-01

    The authors report the various therapeutic modalities of uropathies associated with horseshoe kidney, based on a series of 20 pathologic horseshoe kidneys, associated with 12 cases of renal stones, 5 ureteropelvic junction obstructions, 3 kidney tumors, 2 cases of pyonephrosis and finally 1 traumatic horseshoe kidney. The specific anatomic and surgical features of this uncommon malformation are emphasized and the therapeutic features of each uropathy associated with horseshoe kidney are discussed. PMID:7825982

  2. Adverse reactions to cosmetics.

    PubMed

    Gendler, E

    1987-06-01

    Adverse reactions to cosmetics can be irritant or allergic and are most often caused by fragrances or preservatives. Preservatives include formaldehyde, formaldehyde releasers, and parabens. Other agents that cause allergy are paraphenylenediamine in hair dyes and toluene sulfonamide formaldehyde resin in nail polishes.

  3. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  4. Adverse reactions to cosmetics.

    PubMed

    Dogra, A; Minocha, Y C; Kaur, S

    2003-01-01

    Adverse reaction to cosmetics constitute a small but significant number of cases of contact dermatitis with varied appearances. These can present as contact allergic dermatitis, photodermatitis, contact irritant dermatitis, contact urticaria, hypopigmentation, hyperpigmentation or depigmentation, hair and nail breakage. Fifty patients were included for the study to assess the role of commonly used cosmetics in causing adverse reactions. It was found that hair dyes, lipsticks and surprisingly shaving creams caused more reaction as compared to other cosmetics. Overall incidence of contact allergic dermatitis seen was 3.3% with patients own cosmetics. Patch testing was also done with the basic ingredients and showed positive results in few cases where casual link could be established. It is recommended that labeling of the cosmetics should be done to help the dermatologists and the patients to identify the causative allergen in cosmetic preparation.

  5. [Adverse effects of antidepressive agents in hospitalized geriatric patients].

    PubMed

    Korínková, V; Kolibás, E; Králová, M; Novotný, V; Konceoj, V A; Pjatnickij, A N; Andrusenkova, M P

    1992-11-01

    The frequency, intensity and profile of adverse effects of antidepressants was studied in elderly patients. The series consisted of 102 patients with depression admitted to hospitals in Bratislava and Moscow. The adverse effects of amitriptyline (Amitriptylin Spofa) and maprotiline (Ludiomil Ciba-Geigy) were compared. The assessment done on days 0, 7, and 28 of treatment showed that xerostomia had the highest occurrence rate with both preparations studied. In patients treated with amitriptyline adverse effects were more severe and were recorded more frequently, requiring treatment withdrawal in 3 patients. The overall intensity of adverse effects was significantly higher with amitriptyline (p < 0.05). In the group of patients treated with amitriptyline the adverse effects were more marked in those with severe somatic pathology. The risk of amitriptyline treatment in elderly patients is being emphasized along with the need for monitoring and correcting adverse effects of the treatment. Although maprotiline exhibited a lower occurrence rate of adverse effects, cardiac functions should be regularly checked in patients with preexisting cardiac pathology. (Tab. 2, Fig. 3, Ref. 6.).

  6. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  7. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  8. Vaccine adverse events.

    PubMed

    Follows, Jill

    2012-01-01

    Millions of adults are vaccinated annually against the seasonal influenza virus. An undetermined number of individuals will develop adverse events to the influenza vaccination. Those who suffer substantiated vaccine injuries, disabilities, and aggravated conditions may file a timely, no-fault and no-cost petition for financial compensation under the National Vaccine Act in the Vaccine Court. The elements of a successful vaccine injury claim are described in the context of a claim showing the seasonal influenza vaccination was the cause of Guillain-Barré syndrome.

  9. [Adverse events prevention ability].

    PubMed

    Aparo, Ugo Luigi; Aparo, Andrea

    2007-03-01

    The issue of how to address medical errors is the key to improve the health care system performances. Operational evidence collected in the last five years shows that the solution is only partially linked to future technological developments. Cultural and organisational changes are mandatory to help to manage and drastically reduce the adverse events in health care organisations. Classical management, merely based on coordination and control, is inadequate. Proactive, self-organising network based structures must be put in place and managed using adaptive, fast evolving management tools. PMID:17484160

  10. [Adverse events prevention ability].

    PubMed

    Aparo, Ugo Luigi; Aparo, Andrea

    2007-03-01

    The issue of how to address medical errors is the key to improve the health care system performances. Operational evidence collected in the last five years shows that the solution is only partially linked to future technological developments. Cultural and organisational changes are mandatory to help to manage and drastically reduce the adverse events in health care organisations. Classical management, merely based on coordination and control, is inadequate. Proactive, self-organising network based structures must be put in place and managed using adaptive, fast evolving management tools.

  11. Screening for adverse events.

    PubMed

    Karson, A S; Bates, D W

    1999-02-01

    Adverse events (AEs) in medical patients are common, costly, and often preventable. Development of quality improvement programs to decrease the number and impact of AEs demands effective methods for screening for AEs on a routine basis. Here we describe the impact, types, and potential causes of AEs and review various techniques for identifying AEs. We evaluate the use of generic screening criteria in detail and describe a recent study of the sensitivity and specificity of individual generic screening criteria and combinations of these criteria. In general, the most sensitive screens were the least specific and no small sub-set of screens identified a large percentage of adverse events. Combinations of screens that were limited to administrative data were the least expensive, but none were particularly sensitive, although in practice they might be effective since routine screening is currently rarely done. As computer systems increase in sophistication sensitivity will improve. We also discuss recent studies that suggest that programs that screen for and identify AEs can be useful in reducing AE rates. While tools for identifying AEs have strengths and weaknesses, they can play an important role in organizations' quality improvement portfolios. PMID:10468381

  12. Adverse events related to blood transfusion

    PubMed Central

    Sahu, Sandeep; Hemlata; Verma, Anupam

    2014-01-01

    The acute blood transfusion reactions are responsible for causing most serious adverse events. Awareness about various clinical features of acute and delayed transfusion reactions with an ability to assess the serious reactions on time can lead to a better prognosis. Evidence-based medicine has changed today's scenario of clinical practice to decrease adverse transfusion reactions. New evidence-based algorithms of transfusion and improved haemovigilance lead to avoidance of unnecessary transfusions perioperatively. The recognition of adverse events under anaesthesia is always challenging. The unnecessary blood transfusions can be avoided with better blood conservation techniques during surgery and with anaesthesia techniques that reduce blood loss. Better and newer blood screening methods have decreased the infectious complications to almost negligible levels. With universal leukoreduction of red blood cells (RBCs), selection of potential donors such as use of male donors only plasma and restriction of RBC storage, most of the non-infectious complications can be avoided. PMID:25535415

  13. SNOMED CT in pathology.

    PubMed

    García-Rojo, Marcial; Daniel, Christel; Laurinavicius, Arvydas

    2012-01-01

    Pathology information systems have been using SNOMED II for many years, and in most cases, they are in a migration process to SNOMED CT. COST Action IC0604 (EURO-TELEPATH) has considered terminology normalization one of its strategic objectives. This paper reviews the use of SNOMED CT in healthcare, with a special focus in pathology. Nowadays, SNOMED CT is mainly used for concept search and coding of clinical data. Some ontological errors found in SNOMED CT are described. The Integrating the Healthcare Enterprise (IHE) initiative has fostered the use of SNOMED CT, also in Pathology, as recommended in the Supplement Anatomic Pathology Structured Reports of the IHE Anatomic Pathology Technical Framework. Rule governing concept post-coordination is also described. Some recent initiatives are trying to define a SNOMED CT subset for Pathology. The Spanish Society of Pathology has defined a subset for specimens and procedures in Pathology. Regarding diagnosis coding, the morphological abnormality sub-hierarchy of SNOMED CT need to be significantly extended and improved to become useful for pathologists. A consensus is needed to encode pathology reports with the adequate hierarchies and concepts. This will make the implementation of pathology structured reports more feasible.

  14. Application of Molecular Pathology in Endocrine Pathology.

    PubMed

    Linke, Ebru Serinsoz; Tezel, Gaye Güler

    2015-01-01

    Rapid growth in knowledge of cell and molecular biology led to the increased usage of molecular techniques in anatomical pathology. This is also due to the advances achieved in the techniques introduced in the last few years which are less laborious as compared to the techniques used at the beginning of the "molecular era". The initial assays were also very expensive and were not performed except for selected centers. Moreover, the clinicians were not sure how to make use of the accumulating molecular information. That situation has also changed and molecular techniques are being performed in a wide variety of medical settings which also has a reflection on the endocrine system pathology among other organ systems. This review will provide an update of genetic changes observed in different endocrine system pathologies and their diagnostic, therapeutic and prognostic values.

  15. Handheld computing in pathology

    PubMed Central

    Park, Seung; Parwani, Anil; Satyanarayanan, Mahadev; Pantanowitz, Liron

    2012-01-01

    Handheld computing has had many applications in medicine, but relatively few in pathology. Most reported uses of handhelds in pathology have been limited to experimental endeavors in telemedicine or education. With recent advances in handheld hardware and software, along with concurrent advances in whole-slide imaging (WSI), new opportunities and challenges have presented themselves. This review addresses the current state of handheld hardware and software, provides a history of handheld devices in medicine focusing on pathology, and presents future use cases for such handhelds in pathology. PMID:22616027

  16. Transgenerational inheritance of stress pathology.

    PubMed

    Matthews, Stephen G; Phillips, David I

    2012-01-01

    It is becoming increasingly evident that maternal exposure to adversity during pregnancy leads to life-long effects in offspring. While there appears to be some commonality in the effects of maternal stress on endocrine and behavioral outcomes in the first generation offspring, it is clear that effects are highly dependent on species, sex and age, as well as on the time in pregnancy when stress is experienced. Recent studies have identified that the effects of maternal stress are not confined to the first generation and that they can extend over multiple generations. These effects are also evident in humans. While our understanding of the potential mechanisms by which transgenerational programming of the stress response occurs remain largely undetermined, recent studies have begun to identify potential mechanisms of transfer. These include modified maternal adaptations to pregnancy, altered maternal behavior and transgenerational epigenetic programming. Such transgenerational programming of stress responses and pathologies has important societal consequences as it could provide a biological explanation for the generational persistence of human behaviors in populations exposed to adversity.

  17. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation.

    PubMed

    Calafate, Sara; Buist, Arjan; Miskiewicz, Katarzyna; Vijayan, Vinoy; Daneels, Guy; de Strooper, Bart; de Wit, Joris; Verstreken, Patrik; Moechars, Diederik

    2015-05-26

    Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  18. Opportunities in Speech Pathology.

    ERIC Educational Resources Information Center

    Newman, Parley W.

    The importance of speech is discussed and speech pathology is described. Types of communication disorders considered are articulation disorders, aphasia, facial deformity, hearing loss, stuttering, delayed speech, voice disorders, and cerebral palsy; examples of five disorders are given. Speech pathology is investigated from these aspects: the…

  19. Uterine pathology and infertility.

    PubMed

    Flamigni, C; Gianaroli, L; Ferraretti, A P; Jasonni, V M; Melega, C; Possati, G

    1985-01-01

    The authors describe the factors influencing implantation with reference to uterine pathology; the role that it plays both in the case of failure of implantation and in the case of repeated abortions is discussed and the techniques of treatment in the presence of uterine pathology affecting fertility are listed.

  20. Radiographic pathology for technologists

    SciTech Connect

    Mace, J.D.; Kowalczyk, N.

    1988-01-01

    This book explains the fundamentals of disease mechanisms and relates this to the practice of radiologic science. Each chapter begins with a discussion of normal anatomy and physiology, then covers pathology and demonstrates how the pathology appears on film. Imaging modalities such as computed tomography, MRI, and ultrasound are also discussed. Clinical case studies are included.

  1. Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases.

    PubMed

    Lewis, J E; Olsen, K D; Sebo, T J

    2001-06-01

    Pathologic factors of predictive value for carcinoma ex pleomorphic adenoma (CXPA), an aggressive salivary gland malignancy, are poorly defined. Because residual mixed tumor may be relatively inconspicuous and various carcinoma subtypes are encountered, misdiagnosis is common. To describe the pathologic features and identify potential prognostic factors, we retrospectively examined 73 cases of CXPA of the major salivary glands treated at Mayo Clinic. Paraffin section immunostaining for keratins (AE1/AE3, CK7, CK20), epithelial membrane antigen, carcinoembryonic antigen, vimentin, actin, S-100 protein, glial fibrillary acidic protein, and p53 and c-erbB-2 oncoproteins was performed in 69 cases. DNA content and proliferation indices were determined by digital image analysis of Feulgen- and MIB-I-stained sections, retrospectively. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The carcinoma component was predominant in 82% of tumors. Adenocarcinoma not otherwise specified (31 cases) and salivary duct carcinoma (24 cases) were the most frequent histologic subtypes. Sixty-two tumors were high grade (Broders 3 or 4). Residual mixed tumor was extensively hyalinized in 54 cases. Pathologic features significantly associated with overall survival included pathologic stage (P =.009), tumor size (P =.012), grade (P =.005), proportion of carcinoma (P =.004), extent of invasion (P =.002), and proliferation index of carcinoma (P =.03). Of 4 patients with intracapsular (noninvasive) carcinoma, none had an adverse outcome. The immunohistochemical profile of CXPA included positive staining reactions in the malignant component for AE1/AE3 in 97% of cases, CK7 in 94%, epithelial membrane antigen in 86%, carcinoembryonic antigen in 75%, vimentin in 52%, and S-100 protein in 29%. Expression of p53 and c-erbB-2 oncoproteins was detected in 41% and 30% of the carcinomas, respectively, but neither was associated with

  2. Adverse Reactions to Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    Meyer, Roger E. , Ed.

    This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

  3. Relationship between magnification and resolution in digital pathology systems.

    PubMed

    Sellaro, Tiffany L; Filkins, Robert; Hoffman, Chelsea; Fine, Jeffrey L; Ho, Jon; Parwani, Anil V; Pantanowitz, Liron; Montalto, Michael

    2013-08-22

    Many pathology laboratories are implementing digital pathology systems. The image resolution and scanning (digitization) magnification can vary greatly between these digital pathology systems. In addition, when digital images are compared with viewing images using a microscope, the cellular features can vary in size. This article highlights differences in magnification and resolution between the conventional microscopes and the digital pathology systems. As more pathologists adopt digital pathology, it is important that they understand these differences and how they ultimately translate into what the pathologist can see and how this may impact their overall viewing experience.

  4. Adverse events occurring after smallpox vaccination.

    PubMed

    Lane, J Michael; Goldstein, Joel

    2003-07-01

    We reviewed the literature on adverse events reported to occur after smallpox vaccination. Nearly one-half of the United States population is vaccinia-naïve and may be at risk for development of serious adverse events. We describe the clinical features of postvaccinial central nervous system disease, progressive vaccinia, eczema vaccinatum, accidental implantations, "generalized vaccinia," and the common erythematous and/or urticarial rashes. In the 1960s, death occurred approximately once in every million primary vaccinations, with fatalities resulting from progressive vaccinia, postvaccinial encephalitis, and eczema vaccinatum. Death in revaccinees occurred less commonly and almost entirely from progressive vaccinia. In today's population, death rates might be higher because of the increased prevalence of immune deficiency and atopic dermatitis.

  5. [Gunshot wounds: forensic pathology].

    PubMed

    Lorin de la Grandmaison, Geoffroy

    2012-02-01

    Gunshot wounds are among the most complex traumatic lesions encountered in forensic pathology. At the time of autopsy, careful scrutiny of the wounds is essential for correct interpretation of the lesions. Complementary pathological analysis has many interests: differentiation between entrance and exit wounds, estimation of firing distance, differentiation between vital and post mortem wounds and wounds dating. In case of multiple headshots, neuropathological examination can provide arguments for or against suicide. Sampling of gunshot wounds at autopsy must be systematic. Pathological data should be confronted respectively to autopsy and death scene investigation data and also ballistic studies. Forensic pathologist must be aware of the limits of optic microscopy.

  6. Psychological adverse effects of cannabis smoking: a tentative classification.

    PubMed

    Nigrete, J C

    1973-01-20

    This paper stresses the need for an early definition and description of the "deviant" cannabis smoker in North America. Attention is called to the fact that on this continent heavy smokers have not yet been separated as "problem" users from other smokers.A comprehensive review of possible psychological adverse effects of the drug is made. The following classification is suggested: a) Severe intoxications, b) Pathological intoxications, c) Acute cannabis psychoses, d) Subacute and chronic cannabis psychoses and e) Residual conditions.

  7. Psychological adverse effects of cannabis smoking: a tentative classification.

    PubMed

    Nigrete, J C

    1973-01-20

    This paper stresses the need for an early definition and description of the "deviant" cannabis smoker in North America. Attention is called to the fact that on this continent heavy smokers have not yet been separated as "problem" users from other smokers.A comprehensive review of possible psychological adverse effects of the drug is made. The following classification is suggested: a) Severe intoxications, b) Pathological intoxications, c) Acute cannabis psychoses, d) Subacute and chronic cannabis psychoses and e) Residual conditions. PMID:4569453

  8. Colorectal carcinoma: Pathologic aspects

    PubMed Central

    Fleming, Matthew; Ravula, Sreelakshmi; Tatishchev, Sergei F.

    2012-01-01

    Colorectal carcinoma is one of the most common cancers and one of the leading causes of cancer-related death in the United States. Pathologic examination of biopsy, polypectomy and resection specimens is crucial to appropriate patient managemnt, prognosis assessment and family counseling. Molecular testing plays an increasingly important role in the era of personalized medicine. This review article focuses on the histopathology and molecular pathology of colorectal carcinoma and its precursor lesions, with an emphasis on their clinical relevance. PMID:22943008

  9. Determinants of pathologic mineralization.

    PubMed

    Kirsch, Thorsten

    2008-01-01

    Physiologic mineralization is necessary for the formation of skeletal tissues and for their appropriate functions during adulthood. Mineralization has to be controlled and restricted to specific regions. If the mineralization process occurs in regions that normally do not mineralize, there can be severe consequences (pathologic or ectopic mineralization). Recent findings have indicated that physiologic and pathologic mineralization events are initiated by matrix vesicles, membrane-enclosed particles released from the plasma membranes of mineralization-competent cells. The understanding of how these vesicles are released from the plasma membrane and initiate the mineralization process may provide novel therapeutic strategies to prevent pathologic mineralization. In addition, other regulators (activators and inhibitors) of physiologic mineralization have been identified and characterized, and there is evidence that the same factors also contribute to the regulation of pathologic mineralization. Finally, programmed cell death (apoptosis) may be a contributor to physiologic mineralization and if occurring after tissue injury may induce pathologic mineralization and mineralization-related differentiation events in the injured and surrounding areas. This review describes how the understanding of mechanisms and factors regulating physiologic mineralization can be used to develop new therapeutic strategies to prevent pathologic or ectopic mineralization events.

  10. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  11. Adverse effects of anabolic steroids.

    PubMed

    Hickson, R C; Ball, K L; Falduto, M T

    1989-01-01

    Anabolic steroids are used therapeutically for various disorders and as ergogenic aids by athletes to augment strength, muscular development, and to enhance performance. There is a wide range of concomitant temporary and permanent adverse effects with steroid administration. Several well-documented adverse actions of these hormones may develop rapidly within several weeks or less (i.e. altered reproductive function) or require up to several years of steroid intake (i.e. liver carcinoma). More recent studies indicate that glucose intolerance, insulin resistance, increased cardiovascular disease risk profiles, cerebral dangers, musculoskeletal injuries, prostate cancer, psychosis and schizophrenic episodes, among others, accompany anabolic steroid intake. There is, at present, no evidence to support the claim that athletes are less susceptible to adverse effects than those individuals receiving hormone treatment in a clinical setting. Based on the available information which has accumulated primarily from cross-sectional, short term longitudinal, and case studies, there is a need: (a) to develop a comprehensive battery of specific and sensitive markers of adverse effects, particularly those that would be able to detect the onset of adverse actions; and (b) to conduct controlled long term longitudinal studies in order to fully understand the extensiveness and mechanisms involved in the occurrence of adverse effects.

  12. Pathologies Associated with the p53 Response

    PubMed Central

    Gudkov, Andrei V.; Komarova, Elena A.

    2010-01-01

    Although p53 is a major cancer preventive factor, under certain extreme stress conditions it may induce severe pathologies. Analyses of animal models indicate that p53 is largely responsible for the toxicity of ionizing radiation or DNA damaging drugs contributing to hematopoietic component of acute radiation syndrome and largely determining severe adverse effects of cancer treatment. p53-mediated damage is strictly tissue specific and occurs in tissues prone to p53-dependent apoptosis (e.g., hematopoietic system and hair follicles); on the contrary, p53 can serve as a survival factor in tissues that respond to p53 activation by cell cycle arrest (e.g., endothelium of small intestine). There are multiple experimental indications that p53 contributes to pathogenicity of acute ischemic diseases. Temporary reversible suppression of p53 by small molecules can be an effective and safe approach to reduce severity of p53-associated pathologies. PMID:20595398

  13. Molecular systems evaluation of oligomerogenic APPE693Q and fibrillogenic APPKM670/671NL/PSEN1Δexon9 mouse models identifies shared molecular features with human Alzheimer’s brain molecular pathology

    PubMed Central

    Readhead, Ben; Haure-Mirande, Jean-Vianney; Zhang, Bin; Haroutunian, Vahram; Gandy, Sam; Schadt, Eric E.; Dudley, Joel T.; Ehrlich, Michelle E.

    2016-01-01

    matrix regulation and neurogenesis, as well as strong overlap with AD associated co-expression network structures. The strong overlap in molecular systems features supports the relevance of these findings from the AD mouse models to human AD. PMID:26552589

  14. Molecular Pathology Informatics.

    PubMed

    Roy, Somak

    2015-06-01

    Molecular informatics (MI) is an evolving discipline that will support the dynamic landscape of molecular pathology and personalized medicine. MI provides a fertile ground for development of clinical solutions to bridge the gap between clinical informatics and bioinformatics. Rapid adoption of next generation sequencing (NGS) in the clinical arena has triggered major endeavors in MI that are expected to bring a paradigm shift in the practice of pathology. This brief review presents a broad overview of various aspects of MI, particularly in the context of NGS based testing. PMID:26065793

  15. Complexity and forensic pathology.

    PubMed

    Jones, Richard Martin

    2015-12-01

    It has become increasingly apparent that nonlinearity and complexity are the norm in human physiological systems, the relevance of which is informing an enhanced understanding of basic pathological processes such as inflammation, the host response to severe trauma, and critical illness. This article will explore how an understanding of nonlinear systems and complexity might inform the study of the pathophysiology of deaths of medicolegal interest, and how 'complexity thinking' might usefully be incorporated into modern forensic medicine and forensic pathology research, education and practice.

  16. Reinforcement pathology and obesity.

    PubMed

    Carr, Katelyn A; Daniel, Tinuke Oluyomi; Lin, Henry; Epstein, Leonard H

    2011-09-01

    Obesity is, in part, a result of positive energy balance or energy intake exceeding physiological needs. Excess energy intake is determined by a series of food choices over time. These choices involve both motivational and executive function processes. Problems arise when there is excessive motivation to eat and low impulse control, a situation we have termed reinforcement pathology. Motivational and executive function processes have also been implicated in the development of drug dependence and addiction. In this review we discuss the application of reinforcement pathology to obesity, and implications of this approach for obesity treatment. PMID:21999693

  17. Reinforcement pathology and obesity.

    PubMed

    Carr, Katelyn A; Daniel, Tinuke Oluyomi; Lin, Henry; Epstein, Leonard H

    2011-09-01

    Obesity is, in part, a result of positive energy balance or energy intake exceeding physiological needs. Excess energy intake is determined by a series of food choices over time. These choices involve both motivational and executive function processes. Problems arise when there is excessive motivation to eat and low impulse control, a situation we have termed reinforcement pathology. Motivational and executive function processes have also been implicated in the development of drug dependence and addiction. In this review we discuss the application of reinforcement pathology to obesity, and implications of this approach for obesity treatment.

  18. Adrenoleukodystrophy: molecular genetics, pathology, and Lorenzo's oil.

    PubMed

    Moser, H W; Powers, J M; Smith, K D

    1995-07-01

    Knowledge about adrenoleukodystrophy (ALD), a disorder which was described first in 1923, has increased greatly during recent years. The principal biochemical abnormality, the presumed enzyme defect, and the gene defect, have been defined. A dietary therapy has been proposed and attracted world-wide attention through a motion picture. Nevertheless, many questions remain and cannot be answered without a more fundamental understanding of pathology and pathogenesis. This article will provide a review of the history, clinical features, pathology, biochemistry, and the gene defect, and then appraise current efforts to clarify pathogenesis and develop therapeutic approaches.

  19. [Cartilage tumors : Pathology and radiomorphology].

    PubMed

    Uhl, M; Herget, G; Kurz, P

    2016-06-01

    Primary cartilage-forming tumors of the bone are frequent entities in the daily work of skeletal radiologists. This article describes the correlation of pathology and radiology in cartilage-forming skeletal tumors, in particular, enchondroma, osteochondroma, periosteal chondromas, chondroblastoma and various forms of chondrosarcoma. After reading, the radiologist should be able to deduce the different patterns of cartilage tumors on radiographs, CT, and MRI from the pathological aspects. Differentiation of enchondroma and chondrosarcoma is a frequent diagnostic challenge. Some imaging parameters, e. g., deep cortical scalloping (more than two thirds of the cortical thickness), cortical destruction, or a soft-tissue mass, are features of a sarcoma. Osteochondromas are bony protrusions with a continuous extension of bone marrow from the parent bone, the host cortical bone runs continuously from the osseous surface of the tumor into the shaft of the osteochondroma and the osteochondroma has a cartilage cap. Chondromyxoid fibromas are well-defined lytic and eccentric lesions of the metaphysis of the long bones, with nonspecific MRI findings. Chondroblastomas have a strong predilection for the epiphysis of long tubular bones and develop an intense perifocal bone marrow edema. Dedifferentiated chondrosarcomas are bimorphic lesions with a low-grade chondrogenic component and a high-grade noncartilaginous component. Most chondrogenic tumors have a predilection with regard to site and age at manifestation. PMID:27233920

  20. Pathology of growth hormone excess.

    PubMed

    Kovacs, K

    1988-09-01

    This paper briefly reviews the pathology of growth hormone excess. Prolonged oversecretion of growth hormone is associated with elevated serum growth hormone as well as somatomedian C levels and the clinical signs and symptoms of acromegaly or gigantism. Morphologic studies, including immunohistochemistry and electron microscopy, revealed that several distinct morphologic lesions can be present in the pituitary gland of patients with acromegaly or gigantism. Although substantial progress has been achieved during the last two decades, more work is required to correlate the morphologic features of adenoma cells with their biologic behavior. We feel that the future can be viewed with optimism and further exciting results can be expected by the interaction of pathologists, clinical endocrinologists and basic scientists. PMID:3070506

  1. Pathological Gambling Subtypes

    ERIC Educational Resources Information Center

    Vachon, David D.; Bagby, R. Michael

    2009-01-01

    Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…

  2. Pathological Gambling: Psychiatric Models

    ERIC Educational Resources Information Center

    Westphal, James R.

    2008-01-01

    Three psychiatric conceptual models: addictive, obsessive-compulsive spectrum and mood spectrum disorder have been proposed for pathological gambling. The objectives of this paper are to (1) evaluate the evidence base from the most recent reviews of each model, (2) update the evidence through 2007 and (3) summarize the status of the evidence for…

  3. Pathological fractures in children

    PubMed Central

    De Mattos, C. B. R.; Binitie, O.; Dormans, J. P.

    2012-01-01

    Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated. PMID:23610658

  4. Next-Generation Pathology.

    PubMed

    Caie, Peter D; Harrison, David J

    2016-01-01

    The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

  5. Personality Pathology and Interpersonal Problem Stability

    PubMed Central

    Wright, Aidan G.C.; Scott, Lori N.; Stepp, Stephanie D.; Hallquist, Michael N.; Pilkonis, Paul A.

    2014-01-01

    Personality disorders (PDs) are often described as stable, which ignores the important dynamic processes and shifts that are observed clinically in individuals with PD. The current study examined patterns of variability in problematic interpersonal functioning, a core feature of personality pathology. Participants (N=150) were assessed for personality pathology at baseline and also completed the Inventory of Interpersonal Problems–Circumplex Scales at baseline and every three months over the course of a year. Baseline PD was used to predict individual means and variability parameters in generalized interpersonal distress, agentic problems, and communal problems across repeated assessments. Disorders associated with disinhibition predicted variability in generalized distress and agentic problems, whereas only antagonism related disorders predicted variability in communal problems. These associations reveal dynamic processes involved in multiple dimensions of personality pathology and suggest that future research on instability is needed that expands beyond the historical focus on borderline PD. PMID:25562539

  6. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  7. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  8. Adverse Childhood Experiences and Hallucinations

    ERIC Educational Resources Information Center

    Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

    2005-01-01

    Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

  9. Pathology informatics fellowship training: Focus on molecular pathology

    PubMed Central

    Mandelker, Diana; Lee, Roy E.; Platt, Mia Y.; Riedlinger, Gregory; Quinn, Andrew; Rao, Luigi K. F.; Klepeis, Veronica E.; Mahowald, Michael; Lane, William J.; Beckwith, Bruce A.; Baron, Jason M.; McClintock, David S.; Kuo, Frank C.; Lebo, Matthew S.; Gilbertson, John R.

    2014-01-01

    Background: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques. Methods and Results: Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program's core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology. Conclusions: The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists. PMID:24843823

  10. Lone atrial fibrillation: Pathologic or not?

    PubMed

    Chambers, Patrick William

    2007-01-01

    Atrial fibrillation risk has been strongly associated with increasing age and visceral obesity. These characteristics are strongly associated with diabetes, decreased heart rate variability, and chronic inflammation. Lone atrial fibrillation (LAF) on the other hand exhibits a predilection for the physically fit and the middle aged, especially males. Given these opposing features it is postulated that pathologic AF is due to cardiac fibrosis and other age related changes while LAF is due to physiologic neurohormonal changes related to autonomic tone, insulin sensitivity, and electrolyte imbalance and that pathologic AF and LAF can be reliably differentiated via an anthropometric approach using weight, height, hip, and waist measurements. An anthropometric study is undertaken from an LAF database to test this hypothesis. Such individuals in addition to being younger and predominantly male appear to be taller with less central adiposity vs. those with pathologic AF. The ramifications of these findings with respect to insulin resistance, sympathetic tone, inflammation and hypertension, often associated with pathologic atrial fibrillation, are discussed. Speculation is drawn about possible etiologic link with mitral valve prolapse, which is commonly encountered in the tall and thin and which shares multiple clinical features with LAF. PMID:17005327

  11. [Czech eponyms in pathology].

    PubMed

    Steiner, Ivo

    2013-01-01

    The 24th European Congress of Pathology taking place in Prague is an opportunity to remind our society of the Czech names appearing as eponyms in pathological terminology: Karel Rokitanský - R. protuberance in dermoid cyst; R. thrombogenic theory of atherosclerosis; Mayer - R. - Küster - Hauser - Winckel syndrome (congenital malformation of the vagina and uterus); Václav Treitz - T. duodenal ligament; T. retroperitoneal hernia; T. uremic colitis; Vilém Dušan Lambl - L. excrescences of heart valves; Lamblia (Giardia) intestinalis, and also the foundation of urological cytology; Stanislav Provázek - Prowazek - Halberstädter bodies (trachoma), Rickettsia Prowazeki (typhus fever); Josef Vaněk - V. tumor (gastric inflammatory fibroid polyp), and also discovery of the etiology of pneumocystic pneumonia; Otto Jírovec - Pneumocystis Jiroveci; Blahoslav Bednář - B. tumor (pigmented dermatofibrosarcoma protuberans).

  12. [Pathology of implants].

    PubMed

    Mittermayer, C; Eblenkamp, M; Richter, H A; Zwadlo-Klarwasser, G; Bhardwaj, R S; Klosterhalfen, B

    2002-01-01

    Progress in the surgery of implants and biomaterials can be accomplished by: 1. Painstakingly analysing and registering of defaulting implants after explantation within a "National Registry of Implant Pathology". 2. Development of a DNA-microarray named "Implantat/Chronic Wound" in order to discover the differential transcriptional activities of cells brought into contact with different foreign surfaces. 3. Predictive cell-engineering combined with custom-made implant surfaces with the aim of optimal patient care.

  13. Adverse reactions to fragrances. A clinical review.

    PubMed

    de Groot, A C; Frosch, P J

    1997-02-01

    This article reviews side-effects of fragrance materials present in cosmetics with emphasis on clinical aspects: epidemiology, types of adverse reactions, clinical picture, diagnostic procedures, and the sensitizers. Considering the ubiquitous occurrence of fragrance materials, the risk of side-effects is small. In absolute numbers, however, fragrance allergy is common, affecting approximately 1% of the general population. Although a detailed profile of patients sensitized to fragrances needs to be elucidated, common features of contact allergy are: axillary dermatitis, dermatitis of the face (including the eyelids) and neck, well-circumscribed patches in areas of "dabbing-on" perfumes (wrists, behind the ears) and (aggravation of) hand eczema. Depending on the degree of sensitivity, the severity of dermatitis may range from mild to severe with dissemination and even erythroderma. Airborne or "connubial" contact dermatitis should always be suspected. Other less frequent adverse reactions to fragrances are photocontact dermatitis, immediate contact reactions and pigmentary changes. The fragrance mix, although very useful for the detection of sensitive patients, both causes false-positive and false-negative reactions, and detects only 70% of perfume-allergic patients. Therefore, future research should be directed at increasing the sensitivity and the specificity of the mix. Relevance is said to be established in 50-65% of positive reactions, but accurate criteria are needed. Suggestions are made for large-scale investigation of several fragrances on the basis of literature data and frequency of use in cosmetics. The literature on adverse reactions to balsam of Peru (an indicator for fragrance sensitivity), essential oils (which currently appear to be used more in aromatherapy than in perfumery) and on fragrances used as flavours and spices in foods and beverages is not discussed in detail, but pertinent side-effects data are tabulated and relevant literature is

  14. Cutaneous Adverse Effects of Neurologic Medications.

    PubMed

    Bahrani, Eman; Nunneley, Chloe E; Hsu, Sylvia; Kass, Joseph S

    2016-03-01

    Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication.

  15. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance.

    PubMed

    Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee

    2015-10-01

    Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis, funisitis, and chorionic vasculitis and represent a host response (maternal or fetal) to a chemotactic gradient in the amniotic cavity. While acute chorioamnionitis is evidence of a maternal host response, funisitis and chorionic vasculitis represent fetal inflammatory responses. Intraamniotic infection generally has been considered to be the cause of acute chorioamnionitis and funisitis; however, recent evidence indicates that "sterile" intraamniotic inflammation, which occurs in the absence of demonstrable microorganisms induced by "danger signals," is frequently associated with these lesions. In the context of intraamniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient that favors the migration of neutrophils from the maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals that are released during the course of cellular stress or cell death can also induce the release of neutrophil chemokines. The prevalence of chorioamnionitis is a function of gestational age at birth, and present in 3-5% of term placentas and in 94% of placentas delivered at 21-24 weeks of gestation. The frequency is higher in patients with spontaneous labor, preterm labor, clinical chorioamnionitis (preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are the hallmarks of the fetal inflammatory response syndrome, a condition characterized by an elevation in the fetal plasma concentration of interleukin-6, and associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multiorgan fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults: a risk factor for short- and long-term complications (ie, sterile inflammation in fetuses, neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental disease. Illustrations of the lesions and diagrams of the mechanisms of disease are provided.

  16. [Clinico-pathologic features of occupational allergic eczema].

    PubMed

    Allegri, F; Palminteri, G

    2003-01-01

    The Authors study the fundamental role of individual predisposition in professional eczema. They remark the relation between medicine and dermatology and, particularly, the possible interference of immediate hypersensibility. PMID:14979135

  17. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance.

    PubMed

    Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee

    2015-10-01

    Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis, funisitis, and chorionic vasculitis and represent a host response (maternal or fetal) to a chemotactic gradient in the amniotic cavity. While acute chorioamnionitis is evidence of a maternal host response, funisitis and chorionic vasculitis represent fetal inflammatory responses. Intraamniotic infection generally has been considered to be the cause of acute chorioamnionitis and funisitis; however, recent evidence indicates that "sterile" intraamniotic inflammation, which occurs in the absence of demonstrable microorganisms induced by "danger signals," is frequently associated with these lesions. In the context of intraamniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient that favors the migration of neutrophils from the maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals that are released during the course of cellular stress or cell death can also induce the release of neutrophil chemokines. The prevalence of chorioamnionitis is a function of gestational age at birth, and present in 3-5% of term placentas and in 94% of placentas delivered at 21-24 weeks of gestation. The frequency is higher in patients with spontaneous labor, preterm labor, clinical chorioamnionitis (preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are the hallmarks of the fetal inflammatory response syndrome, a condition characterized by an elevation in the fetal plasma concentration of interleukin-6, and associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multiorgan fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults: a risk factor for short- and long-term complications (ie, sterile inflammation in fetuses, neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental disease. Illustrations of the lesions and diagrams of the mechanisms of disease are provided. PMID:26428501

  18. Acute Lymphocytic Leukemia in Adults. Pathologic Features and Prognosis.

    PubMed

    Marinescu, Cristina; Vlădăreanu, Ana-Maria; Mihai, Felicia

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is a malignant neoplasm of the lymphocyte precursor cells. Among adults it is a relatively rare neoplasm with a curability rate around 30% at 5 years. Currently, the diagnosis and classification of ALL is a multistep procedure that relies on the simultaneous application of multiple techniques that include: cytomorphology, immunophenotype and cytogenetic assays. Some of them have important clinical implications for both diagnosis and predicting response to specific treatment regimens, while the role of others is still to be defined. Over the years, several prognostic factors have been identified and today a risk stratification at diagnosis and during the follow-up is based on the characteristics of the leukemic cells.

  19. Pathologic features of naturally occurring juvenile polyarteritis in beagle dogs.

    PubMed

    Snyder, P W; Kazacos, E A; Scott-Moncrieff, J C; HogenEsch, H; Carlton, W W; Glickman, L T; Felsburg, P J

    1995-07-01

    Eighteen young Beagle dogs (eight males and 10 females), ages 6-40 months, with canine juvenile polyarteritis syndrome (CJPS), a naturally occurring vasculitis and perivasculitis of unknown etiology, were necropsied, and their tissues were examined by histopathologic and histochemical methods. The condition is characterized by recurring episodes of an acute onset of fever (> 40 C) and neck pain that persist for 3-7 days. The major histopathologic alterations were a systemic vasculitis and perivasculitis. During the febrile, painful period of CJPS, the vascular lesions ranged from a histiocytic-lymphocytic periarterial infiltration to transmural arterial inflammation with concomitant fibrinoid necrosis and vascular thrombosis. Massive periarterial accumulations of inflammatory cells were common and often extended into adjacent tissues. The small- to medium-sized muscular arteries of the heart, cranial mediastinum, and cervical spinal meninges were consistently involved. Vasculitis occasionally occurred in other organ systems. The vascular lesions in dogs examined during clinically normal periods consisted of intimal and medial fibrosis, ruptured elastic laminae, and mild perivasculitis; these lesions were probably related to previous episodes of vasculitis. Eight dogs that had experienced repeated acute episodes also developed splenic, hepatic, and renal amyloidosis. The clinical signs, laboratory abnormalities, and the vascular lesions suggest that the condition may be immune-system mediated. CJPS may serve as a naturally occurring animal model of human immune-system-mediated vasculitides such as polyarteritis nodosa, infantile polyarteritis, and Kawasaki disease.

  20. Ocular toxoplasmosis II: clinical features, pathology and management

    PubMed Central

    Butler, Nicholas J; Furtado, João M; Winthrop, Kevin L; Smith, Justine R

    2014-01-01

    The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis. PMID:22712598

  1. Epidemiology, pathology and clinical features of genital mycoses--1981 status.

    PubMed

    Senft, H H; Korte, W

    1982-01-01

    The clinical picture of candidal vaginitis was described for the first time in 1792. The connection with yeasts was already discovered in the 19th century. Not until the last 35 years, however, have the epidemiologic aspects of genital mycoses and the diagnostic and therapeutic principles been systematically developed. The rise in the incidence of the disease is due to several factors: the administration of corticosteroids, cystostatic agents, and oral contraceptives as well as socioeconomic circumstances. Two serious complications of vaginal yeast infection in pregnant women should be noted: the amniotic infection syndrome and neonatal contamination at the time of delivery. Vulvovaginitis is one of the most common genital diseases in childhood and adolescence. Mycoses can be diagnosed in daily gynecological practice by simple, reliable methods, but only culture on prepared media or by incubation of standardized plates can be depended upon to establish or rule out a mycosis. Effective antimycotics with a broad spectrum of activity have been developed in the last 15 years. We have been primarily concerned with clotrimazole because of our own investigations and impartial comparisons with other fungicidal drugs. Studies of patient compliance have shown that the diseased women accept short-term therapy most readily. However, appropriate control examinations are needed to document the results of treatment. PMID:6761085

  2. Pharmacogenomics of adverse drug reactions

    PubMed Central

    2013-01-01

    Considerable progress has been made in identifying genetic risk factors for idiosyncratic adverse drug reactions in the past 30 years. These reactions can affect various tissues and organs, including liver, skin, muscle and heart, in a drug-dependent manner. Using both candidate gene and genome-wide association studies, various genes that make contributions of varying extents to each of these forms of reactions have been identified. Many of the associations identified for reactions affecting the liver and skin involve human leukocyte antigen (HLA) genes and for reactions relating to the drugs abacavir and carbamazepine, HLA genotyping is now in routine use prior to drug prescription. Other HLA associations are not sufficiently specific for translation but are still of interest in relation to underlying mechanisms for the reactions. Progress on non-HLA genes affecting adverse drug reactions has been less, but some important associations, such as those of SLCO1B1 and statin myopathy, KCNE1 and drug-induced QT prolongation and NAT2 and isoniazid-induced liver injury, are considered. Future prospects for identification of additional genetic risk factors for the various adverse drug reactions are discussed. PMID:23360680

  3. Advances in salivary gland pathology.

    PubMed

    Cheuk, W; Chan, J K C

    2007-07-01

    This review summarizes the new findings on salivary gland pathology under the following categories: immunohistochemistry; molecular genetics; newly recognized tumour types; known tumour entities with new findings; and progression of salivary gland tumours. In the application of immunohistochemistry, CD117 can aid in highlighting the luminal cell component of various salivary gland tumours, whereas p63 or maspin can aid in highlighting the abluminal cell component. A high Ki67 index remains the most useful marker to predict adverse outcome in salivary gland carcinoma. Specific chromosomal translocations are recognized in pleomorphic adenoma (with translocation involving PLGA1 or HMGA2 gene) and mucoepidermoid carcinoma (with MECT1-MAML2 gene fusion). Newly recognized entities include: sclerosing polycystic adenosis (with recent molecular evidence supporting its neoplastic nature), sclerosing mucoepidermoid carcinoma with eosinophilia, keratocystoma, adenoma with additional stromal component (lymphadenoma, lipoadenoma and adenofibroma), cribriform adenocarcinoma of the tongue and signet ring adenocarcinoma of minor salivary gland. Known tumour entities with new findings include: salivary duct carcinoma (with newly recognized mucinous, micropapillary and sarcomatoid variants), intraductal carcinoma (with controversies in terminology), mucoepidermoid carcinoma (with newly proposed grading parameters and oncocytic variant), epithelial-myoepithelial carcinoma (with newly recognized morphological variants), small cell carcinoma (with most cases being related to Merkel cell carcinoma), extranodal marginal zone B-cell lymphoma (with specific chromosomal translocation) and chronic sclerosing sialadenitis (being a component of IgG4-related sclerosing disease). Progression of salivary gland tumours can take the form of malignant transformation of a benign tumour, progression from low-grade to high-grade carcinoma, dedifferentiation, or stromal invasion of an in situ carcinoma.

  4. Molecular pathology in real time.

    PubMed

    Ryška, Aleš

    2016-03-01

    With the development of sophisticated individualized therapeutic approaches, the role of pathology in classification of tumors is enormously increasing. The solely morphological characterization of neoplastic process is no more sufficient for qualified decision on optimal therapeutic approach. Thus, morphologic diagnosis must be supplemented by molecular analysis of the lesion with emphasis on the detection of status of certain markers used as predictive factors for targeted therapy. Both intrinsic and acquired types of intratumor heterogeneity have an impact at various moments of cancer diagnostics and therapy. The primary heterogeneity of neoplastic tissue represents a significant problem in patients, where only limited biopsy samples from the primary tumor are available for diagnosis, such as core needle biopsy specimens in breast cancer, transthoracic or endobronchial biopsies in lung cancer, or endoscopic biopsies in gastric cancer. Detection of predictive markers may be influenced by this heterogeneity, and the marker detection may be falsely negative or (less probably) falsely positive. In addition, as these markers are often detected in the tissue samples from primary tumor, the differences between molecular features of the primary lesion and its metastases may be responsible for failure of systemic therapy in patients with discordant phenotype between primary and metastatic disease. The fact of tumor heterogeneity must be taken into consideration already in establishing pathological diagnosis. One has to be aware that limited biopsy specimen must not always be fully representative of the entire tumor volume. To overcome these limitations, there does not exist one single simple solution. Examination of more tissue (preference of surgical resection specimens over biopsies, whenever possible), use of ultra-sensitive methods able to identify the minute subclones as a source of possible resistance to treatment, and detection of secondary molecular events from

  5. Unravelling adverse reactions to NSAIDs using systems biology.

    PubMed

    Perkins, James R; Sanak, Marek; Canto, Gabriela; Blanca, Miguel; Cornejo-García, José Antonio

    2015-03-01

    We introduce the reader to systems biology, using adverse drug reactions (ADRs), specifically hypersensitivity reactions to multiple non-steroidal anti-inflammatory drugs (NSAIDs), as a model. To disentangle the different processes that contribute to these reactions - from drug intake to the appearance of symptoms - it will be necessary to create high-throughput datasets. Just as crucial will be the use of systems biology to integrate and make sense of them. We review previous work using systems biology to study related pathologies such as asthma/allergy, and NSAID metabolism. We show examples of their application to NSAIDs-hypersensitivity using current datasets. We describe breakthroughs in high-throughput technology and speculate on their use to improve our understanding of this and other drug-induced pathologies.

  6. Pathologic and physiologic phimosis

    PubMed Central

    McGregor, Thomas B.; Pike, John G.; Leonard, Michael P.

    2007-01-01

    OBJECTIVE To review the differences between physiologic and pathologic phimosis, review proper foreskin care, and discuss when it is appropriate to seek consultation regarding a phimotic foreskin. SOURCES OF INFORMATION This paper is based on selected findings from a MEDLINE search for literature on phimosis and circumcision referrals and on our experience at the Children’s Hospital of Eastern Ontario Urology Clinic. MeSH headings used in our MEDLINE search included “phimosis,” “referral and consultation,” and “circumcision.” Most of the available articles about phimosis and foreskin referrals were retrospective reviews and cohort studies (levels II and III evidence). MAIN MESSAGE Phimosis is defined as the inability to retract the foreskin. Differentiating between physiologic and pathologic phimosis is important, as the former is managed conservatively and the latter requires surgical intervention. Great anxiety exists among patients and parentsregarding non-retractile foreskins. Most phimosis referrals seen in pediatric urology clinics are normal physiologically phimotic foreskins. Referrals of patients with physiologic phimosis to urology clinics can create anxiety about the need for surgery among patients and parents, while unnecessarily expanding the waiting list for specialty assessment. Uncircumcised penises require no special care. With normal washing, using soap and water, and gentle retraction during urination and bathing, most foreskins will become retractile over time. CONCLUSION Physiologic phimosis is often seen by family physicians. These patients and their parents require reassurance of normalcy and reinforcement of proper preputial hygiene. Consultation should be sought when evidence of pathologic phimosis is present, as this requires surgical management. PMID:17872680

  7. Confounders in interpreting pathology for safety and risk assessment

    SciTech Connect

    Wolf, Douglas C. . E-mail: wolf.doug@epa.gov; 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 be 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.

  8. Marketing the pathology practice.

    PubMed

    Berkowitz, E N

    1995-07-01

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

  9. Psychological adverse effects of cannabis smoking: a tentative classification

    PubMed Central

    Negrete, J. C.

    1973-01-01

    This paper stresses the need for an early definition and description of the “deviant” cannabis smoker in North America. Attention is called to the fact that on this continent heavy smokers have not yet been separated as “problem” users from other smokers. A comprehensive review of possible psychological adverse effects of the drug is made. The following classification is suggested: a) Severe intoxications, b) Pathological intoxications, c) Acute cannabis psychoses, d) Subacute and chronic cannabis psychoses and e) Residual conditions. PMID:4569453

  10. Competition among differentiated health plans under adverse selection.

    PubMed

    Olivella, Pau; Vera-Hernández, Marcos

    2007-03-01

    Market power and adverse selection are prevalent features of the market for pre-paid health plans. However, most of the literature on adverse selection considers extreme cases: either perfect competition or monopoly. If instead health plans are horizontally differentiated, then (i) profits derived from each low risk are higher than from each high risk and (ii) when the profits derived from each high risk are negative (cross-subsidization), a health authority as informed as the health plans can implement a Pareto-improvement. Both local and global deviations from cross-subsidization are addressed within a Nash equilibrium framework. PMID:16971005

  11. Ghent Pathology 2011.

    PubMed

    Ryu, Doojin

    2014-03-01

    This study examines the intraday formation process of transaction prices and bid-ask spreads in theKOSPI 200 futures market. By extending the structural model ofMadhavan,Richardson, andRoomans (1997), I develop a unique cross-market model that can decompose spread components and explain intraday price formation for the futures market by using the order flow information from theKOSPI 200 options market, which is a market that is closely related to the futures market as well as considered to be one of the most remarkable options market in the world. The empirical results indicate that the model implied spread and the permanent component of the spread that results from informed trading tend to be underestimated without the inclusion of options market information. Furthermore, the results imply that trades of in-the-money options, which have high delta values, generally incur a more adverse information cost component (the permanent spread component) of the futures market than those of out-of-the-money options, which have relatively low delta values. Finally, I find that the adverse information cost component that is estimated from the cross-market model exhibits a nearlyU-shape intraday pattern; however, it sharply decreases at the end of the trading day.

  12. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects.

  13. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects. PMID:27357302

  14. Adverse Effects of Electroconvulsive Therapy.

    PubMed

    Andrade, Chittaranjan; Arumugham, Shyam Sundar; Thirthalli, Jagadisha

    2016-09-01

    Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. PMID:27514303

  15. Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank.

    PubMed

    Bieniek, Kevin F; Ross, Owen A; Cormier, Kerry A; Walton, Ronald L; Soto-Ortolaza, Alexandra; Johnston, Amelia E; DeSaro, Pamela; Boylan, Kevin B; Graff-Radford, Neill R; Wszolek, Zbigniew K; Rademakers, Rosa; Boeve, Bradley F; McKee, Ann C; Dickson, Dennis W

    2015-12-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future

  16. [Molecular pathology of schizophrenia].

    PubMed

    Uezato, Akihito; Nishikawa, Toru

    2013-04-01

    Dopamine hypothesis has dominated as a molecular pathology of schizophrenia over the past few decades and anti-dopaminergic drugs are currently the most widespread available treatment option. Converging lines of evidence suggest altered regulation of other neurotransmitters including glutamate, GABA and acetylcholine, results in the dysregulation of dopaminergic neurons in schizophrenia, and is involved in the comprehensive symptoms such as positive, negative, and cognitive dysfunction. In the prefrontal cortex of patients with schizophrenia; dysfunctional NMDA-type glutamate receptors on GABAergic interneurons cause disinhibition of pyramidal glutamatergic neurons, resulting in increase in the firing of dopaminergic neurons. Cognitive dysfunction of schizophrenia may be a representation of asynchronous glutamatergic and GABAergic neurons. In addition to the effects of NMDA receptor modulators including D-serine, emerging evidences of the roles of nicotinic acetylcholine receptors on glutamatergic and dopaminergic regulations suggest new treatment options for schizophrenia.

  17. Molecular Pathology and Biomarkers.

    PubMed

    Ha, Patrick K; Stenman, Göran

    2016-01-01

    The field of salivary gland tumor biology is quite broad, given the numerous subtypes of both benign and malignant tumors originating from the major and minor salivary glands. Knowledge about the molecular pathology of these lesions is still limited, and there are few clinically useful diagnostic and prognostic biomarkers. However, recent discoveries of certain key genomic alterations, such as chromosome translocations, copy number alterations, and mutations, provide new insights into the molecular pathogenesis of these lesions and may help to better define them. It is also hoped that this new knowledge can help to guide therapy, but this translation has been somewhat slow to develop, perhaps due to the rarity of these tumors and the lack of large, randomized studies. However, because of the limitations inherent in what surgery and radiation can provide, there is an urgent need for understanding of the mechanisms of carcinogenesis in these tumors individually, so that chemotherapy and/or targeted therapy can be rationally selected.

  18. Imaging of pituitary pathology.

    PubMed

    Buchfelder, Michael; Schlaffer, Sven

    2014-01-01

    Modern imaging techniques play a vital role in the diagnosis, surveillance, and treatment monitoring of patients with pituitary disease. For its high soft tissue contrast, magnetic resonance (MR) imaging provides detailed information about the localization and extent of a lesion. It is thus, to date, the most important imaging technique for documenting or ruling out structural lesions. It is usually the first and only imaging procedure to be employed in pituitary pathology. While large pituitary adenomas are reliably depicted in standard T1-weighted sequences, small microadenomas, such as in Cushing's disease, may only become visible if repeat studies, sophisticated techniques and high-field scanners are employed. For monitoring treatment effects after surgical procedures, drug applications, or irradiation, follow-up studies with identical parameters should be employed, preferably at the same investigation site. Some space is devoted to intraoperative imaging, which not only allows assessment of how radical tumor resection needs to be during pituitary tumor surgery, but also provides extremely accurate structural data for neuronavigation. Less frequent lesions, such as craniopharyngiomas, meningiomas, germ cell tumors, gliomas, skull base tumors, hypothalamic hamartomas, vascular malformations, inflammatory and developmental lesions and other, even less frequent pathologies should be considered in the differential diagnosis. The particular strength of computed tomography (CT) is the direct depiction of calcification, a weakness of MRI, and the high resolution of bone structures at the skull base. This chapter presents the characteristics of both frequent and less commonly encountered tumoral lesions, with an emphasis on computed tomography and magnetic resonance imaging. PMID:25248586

  19. Pathologic tooth migration.

    PubMed

    Brunsvold, Michael A

    2005-06-01

    Pathologic tooth migration (PTM) is a common complication of moderate to severe periodontitis and is often the motivation for patients to seek periodontal therapy. In this review of the literature, available information concerning prevalence, etiology, treatment, and prevention of pathologic tooth migration is summarized. Prevalence of PTM among periodontal patients has been reported to range from 30.03% to 55.8%. A survey of the literature regarding chief complaints of periodontal patients support these high prevalence findings. The etiology of PTM appears to be multifactorial. Periodontal bone loss appears to be a major factor in the etiology of PTM. Many aspects of occlusion can contribute to abnormal migration of teeth, and more than one of those factors may be present in an individual patient. Soft tissue forces of the tongue, cheeks, and lips are known to cause tooth movement and in some situations can cause PTM. Also considered important in the etiology of PTM is pressure produced from inflammatory tissues within periodontal pockets. Because extrusion is a common form of PTM, clinical observations support the theory that eruption forces sometimes play a role in the etiology of PTM. Many oral habits have been associated with PTM which are often difficult for the therapist to detect. Most cases of severe PTM require a team approach to achieve success. Periodontal, orthodontic, and prosthodontic treatment are often required. Many patient variables enter into the selection of treatment for PTM. In early stages of PTM, spontaneous correction of migrated teeth sometimes occurs after periodontal therapy. Light intrusive forces are used successfully to treat extrusion and flaring forms of PTM. Based on the literature reviewed, it appears that many cases of PTM could be prevented through the early diagnosis and treatment of periodontal disease, occlusal contributing factors, gingival enlargement, and oral habits. PMID:15948679

  20. [Pathology of Charcot-Marie-Tooth Disease].

    PubMed

    Oka, Nobuyuki

    2016-01-01

    Although genetic testing is available, nerve biopsy is useful in selected patients for the diagnosis of Charcot-Marie-Tooth disease (CMT). These are sporadic cases of hereditary neuropathy, or familial cases in which genetic testing is negative. CMT is caused by mutations of various genes. The pathological features of CMT have mostly been investigated using nerve biopsy, which may shed light on the presumed functions of mutated gene products. PMP22 duplication in CMT1A induces numerous large onion bulb lesions (OB). Compared to chronic inflammatory demyelinating polyradiculoneuropathy, the differential features of CMT1A are patchy distribution of OB and non-inflammatory lesions. CMT1B also manifests as OB, but presents abnormal compaction of myelin sheaths caused by uncompacted myelin or excessive myelin folding. CMT2 includes axonal neuropathies and many causative genes have been found. CMT2A (MFN2 mutation) shows abnormal mitochondria with a spherical morphology instead of tubular in the longitudinal direction. CMT4 consists of autosomal recessive forms with demyelinating pathology. Most subtypes have mutations of genes relating to myelin maintenance, and pathologically, they show abnormal folding of the myelin structure.

  1. Clinical and Pathological Characteristics of Organized Hematoma

    PubMed Central

    Ohta, Nobuo; Watanabe, Tomoo; Ito, Tsukasa; Kubota, Toshinori; Suzuki, Yusuke; Ishida, Akihiro; Aoyagi, Masaru; Matsubara, Atsushi; Izuhara, Kenji; Kakehata, Seiji

    2013-01-01

    Objective. To study the clinical and pathological characteristics of patients with organized hematoma with malignant features in maxillary sinuses. Subjects and Methods. This was a retrospective study of five patients who were treated surgically for organized hematoma. The preoperative CT and MRI findings were studied clinically. The expressions of CD31, CD34, and periostin in surgical samples were investigated by immunohistochemistry. Results. The clinical features of organized hematoma, such as a mass expanding from the maxillary sinus with bone destruction, resembled those of maxillary carcinoma. However, CT and MRI provided sufficient and useful information to differentiate this condition from malignancy. Surgical resection was the first-line treatment because of the presence of a firm capsule. Characteristic histopathological findings were a mixture of dilated vessels, hemorrhage, fibrin exudation, fibrosis, hyalinization, and neovascularization. The expressions of periostin, CD31, and CD34 were observed in organized hematoma of the maxillary sinus. Conclusion. The expressions of periostin, CD31, and CD34 were observed in organized hematoma of the maxillary sinus. Organized hematoma is characterized pathologically by a mixture of bleeding, dilated vessels, hemorrhage, fibrin exudation, fibrosis, hyalinization, and neovascularization. CT and MRI show heterogeneous findings reflecting a mixture of these pathological entities. PMID:23533421

  2. [Pathological diagnosis of Hodgkin lymphoma].

    PubMed

    Tamaru, Jun-ichi

    2014-03-01

    This lymphoma was recognized by Thomas Hodgkin in 1832. In 1865, Samuel Wilks named it Hodgkin disease. Now, the term Hodgkin lymphoma (HL) is acceptable over Hodgkin disease. Since the neoplastic cells of the disease is well-recognized to be a lymphoid cell, especially B lymphocyte. In WHO classification published in 2008, HLs are divided into two entities: Classical HL and nodular lymphocyte predominat HL. The former is composed of four different subtypes: nodular sclerosis (NS), mixed cellularity (MC), lymphocyte rich (LR), and lymphocyte depletion (LD). HL is characterized by the morphological feature comprising a minority of neoplastic cells, Hodgkin/Reed-Sternberg cells and popcorn (LP) cells and a majority of non-neoplastic reactive cells. Antigen receptor gene analyses by prevailing molecular methods and flow cytometry are not appropriate method for the diagnosis of HL, because of small number of neoplastic cells. They are, however, very useful in the differential diagnosis to rule out other lymphomas. Even the present when science progressed, pathological (morphological and immunohistochemical) examination is very worth for diagnosis of HL. PMID:24724402

  3. Differential diagnosis of cerebral hemispheric pathology: multimodal approach.

    PubMed

    Moritani, T; Smoker, W R K; Lee, H K; Sato, Y

    2011-06-01

    This article gives a comprehensive review and illustrations of the imaging features of various pathological conditions and clinical syndromes associated with cerebral hemispheric involvement. The various conditions are described and defined to provide a basis for the differential diagnostics. The hypotheses relating to the pathology of the various syndromes are discussed with special emphasis on excitotoxic mechanisms for explaining the subsequent cerebral hemiatrophy. PMID:21528369

  4. Visceral pathology of hereditary tyrosinemia type I.

    PubMed

    Russo, P; O'Regan, S

    1990-08-01

    The major pathological findings in 23 patients with hereditary tyrosinemia type I seen at the Hôpital Sainte-Justine over a 23-year period are reviewed in combination with findings in the literature. Hepatic and renal alterations are given special emphasis. Hepatic changes differ in the acute and chronic forms of the disease. The former is characterized by alterations shared by several hepatopathies of infancy, whereas the latter is characterized by established cirrhosis, frequently of a mixed macro- and micronodular type, with a frightening propensity for the development of hepatocellular carcinoma. Renal changes reflect tubular injury, resulting in Fanconi syndrome, with tubular dilatation, nephrocalcinosis, and involution of epithelial cells. A significant proportion of patients also reveal some degree of glomerulosclerosis and interstitial fibrosis, indicating at least the need for careful assessment and follow-up of renal function, particularly in light of the adverse renal effects of immunosuppressive regimens used in liver transplantation. PMID:2378357

  5. Nontraditional applications in clinical pathology.

    PubMed

    Jordan, Holly L; Register, Thomas C; Tripathi, Niraj K; Bolliger, Anne Provencher; Everds, Nancy; Zelmanovic, David; Poitout, Florence; Bounous, Denise I; Wescott, Debra; Ramaiah, Shashi K

    2014-10-01

    Most published reviews of preclinical toxicological clinical pathology focus on the fundamental aspects of hematology, clinical chemistry, coagulation, and urinalysis in routine toxicology animal species, for example, rats, mice, dogs, and nonhuman primates. The objective of this continuing education course was to present and discuss contemporary examples of nonroutine applications of clinical pathology endpoints used in the drug development setting. Area experts discussed bone turnover markers of laboratory animal species, clinical pathology of pregnant and growing laboratory animals, clinical pathology of nonroutine laboratory animal species, and unique applications of the Siemens Advia(®) hematology analyzer. This article is a summary based on a presentation given at the 31st Annual Symposium of the Society of Toxicologic Pathology, during the Continuing Education Course titled "Nontraditional Applications of Clinical Pathology in Drug Discovery and Preclinical Toxicology."

  6. Pathology of drug-associated gastrointestinal disease.

    PubMed

    Price, Ashley B

    2003-11-01

    A large number of drugs have gastrointestinal side-effects of which diarrhoea or constipation, nausea and vomiting are amongst the commonest. In relatively few are there diagnostic pathological changes and this review draws attention to the most common. Incriminating a drug as a cause of specific pathological changes requires the drug to be associated with the changes, for the latter to resolve when the drug is withdrawn and for them to re-appear when a patient is rechallenged with the drug. Individual histological features such as apoptosis, tissue infiltration by eosinophils and increased intra-epithelial lymphocytes within the gut mucosa can be clues to an iatrogenic aetiology but these are by no means specific. Amongst the few pathognomonic patterns of drug reactions is pseudomembranous colitis and diaphragm disease. These, along with others such as reactive gastritis and the collagenous and lymphocytic forms of microscopic colitis, in which drugs have also been implicated, are described here. PMID:14651719

  7. Pathology of renal diseases in the tropics.

    PubMed

    Boonpucknavig, Vijitr; Soontornniyomkij, Virawudh

    2003-01-01

    Renal diseases unique to the tropics are those that occur in association with infectious diseases including dengue hemorrhagic fever, typhoid fever, shigellosis, leptospirosis, lepromatous leprosy, malaria, opisthorchiasis, and schistosomiasis. These renal complications can be classified on the basis of their clinical and pathologic characteristics into acute transient reversible glomerulonephritis, chronic progressive irreversible glomerulonephritis, amyloidosis, and acute renal failure (ARF) resulting from acute tubular necrosis, acute tubulointerstitial nephritis, and thrombotic microangiopathy. Certain primary glomerular diseases including immunoglobulin (Ig) M nephropathy and focal segmental and global glomerulosclerosis are prevalent in some tropical countries. Renal complications of venomous snakebites also are common in the tropics. This article discusses and summarizes important works in the literature in respect to the clinical syndromes, pathologic features, and pathogenesis of tropical renal diseases both in humans and experimental animal models.

  8. Adverse reactions to food additives.

    PubMed

    Simon, R A

    1986-01-01

    There are thousands of agents that are intentionally added to the food that we consume. These include preservatives, stabilizers, conditioners, thickeners, colorings, flavorings, sweeteners, antioxidants, etc. etc. Yet only a surprisingly small number have been associated with hypersensitivity reactions. Amongst all the additives, FD&C dyes have been most frequently associated with adverse reactions. Tartrazine is the most notorious of them all; however, critical review of the medical literature and current Scripps Clinic studies would indicate that tartrazine has been confirmed to be at best only occasionally associated with flares of urticaria or asthma. There is no convincing evidence in the literature of reactivity to the other azo or nonazo dyes. This can also be said of BHA/BHT, nitrites/nitrates and sorbates. Parabens have been shown to elicit IgE mediated hypersensitivity reactions when used as pharmaceutical preservatives; however, as with the other additives noted above, ingested parabens have only occasionally been associated with adverse reactions. MSG, the cause of the 'Chinese restaurant syndrome' has only been linked to asthma in one report. Sulfiting agents used primarily as food fresheners and to control microbial growth in fermented beverages have been established as the cause of any where from mild to severe and even fatal reactions in at least 5% of the asthmatic population. Other reactions reported to follow sulfite ingestion include anaphylaxis, gastro intestinal complaints and dermatological eruptions. The prevalence of these non asthmatic reactions is unknown. The mechanism of sulfite sensitive asthma is also unknown but most likely involves hyperreactivity to inhale SO2 in the great majority of cases; however, there are reports of IgE mediated reactions and other sulfite sensitive asthmatics have been found with low levels of sulfite oxidase; necessary to oxidize endogenous sulfite to sulfate.

  9. [Diagnostic significance of pathologic synkinesis for detection of pyramidal pathology].

    PubMed

    Baliasnyĭ, M M

    1991-01-01

    Five types of pathological synkinesis (++blepharo-ocular, ++blepharo-facial, ++bucco-manual, ++digito-digital on the hands, ++pedo-digital) are described. They are of definite importance for revealing pyramidal pathology including its early stages as well as for objective evaluation and observation of the time-course of changes in the illness. PMID:1654715

  10. [Diagnostic significance of pathologic synkinesis for detection of pyramidal pathology].

    PubMed

    Baliasnyĭ, M M

    1991-01-01

    Five types of pathological synkinesis (++blepharo-ocular, ++blepharo-facial, ++bucco-manual, ++digito-digital on the hands, ++pedo-digital) are described. They are of definite importance for revealing pyramidal pathology including its early stages as well as for objective evaluation and observation of the time-course of changes in the illness.

  11. Scientific and Regulatory Policy Committee: Recommended ("Best") Practices for Determining, Communicating, and Using Adverse Effect Data from Nonclinical Studies.

    PubMed

    Kerlin, Roy; Bolon, Brad; Burkhardt, John; Francke, Sabine; Greaves, Peter; Meador, Vince; Popp, James

    2016-02-01

    Recommendations (best practices) are provided by the Society of Toxicologic Pathology's Adversity Working Group for making consistent interpretations of test article-related effects as "adverse" and assigning a "no observed adverse effect level" (NOAEL) in nonclinical toxicity studies. Adverse is a term indicating "harm" to the test animal, while nonadverse indicates lack of harm. Adverse findings in the study reports should be defined in relation to effects on the test species used and within the context of the given study. Test article-related effects should be described on their own merits, and decisions to consider them as adverse or nonadverse should be justified. Related effects may be discussed together; in particular, markers of toxicity that are not in and of themselves adverse ideally should be discussed in conjunction with the causal toxicity to determine adversity. Adverse findings should be identified in subreports (clinical data, pathology data, etc.) if sufficient information is available, and/or in the final study report as individual or grouped findings, but study NOAELs should be established at the level of the overall study report. Interpretations such as "not biologically relevant" or "not toxicologically important" should be avoided unless defined and supported by scientific rationale. Decisions defining adverse findings and the NOAEL in final study reports should combine the expertise of all contributing scientific disciplines. Where possible, use of NOAELs in data tables should be linked to explanatory text that places them in context. Ideally, in nonclinical summary documents, NOAELs from multiple studies are considered together in defining the most important adverse responses in the most sensitive species. These responses are then considered along with an understanding of their likely mechanisms, as well as other information such as variability in species sensitivity, comparative pathology, reversibility and progression, kinetics, and

  12. Forest pathology in Hawaii

    USGS Publications Warehouse

    Gardner, D.E.

    2003-01-01

    Native Hawaiian forests are characterised by a high degree of endemism, including pathogens as well as their hosts. With the exceptions of koa (Acacia koa Gray), possibly maile (Alyxia oliviformis Gaud.), and, in the past, sandalwood (Santalum spp.), forest species are of little commercial value. On the other hand, these forests are immensely important from a cultural, ecological, and evolutionary standpoint. Forest disease research was lacking during the mid-twentieth century, but increased markedly with the recognition of ohia (Metrosideros polymorpha Gaud.) decline in the 1970s. Because many pathogens are themselves endemic, or are assumed to be, having evolved with their hosts, research emphasis in natural areas is on understanding host-parasite interactions and evolutionary influences, rather than disease control. Aside from management of native forests, attempts at establishing a commercial forest industry have included importation of several species of pine, Araucaria, and Eucalyptus as timber crops, and of numerous ornamentals. Diseases of these species have been introduced with their hosts. The attacking of native species by introduced pathogens is problematic - for example, Armillaria mellea (Vahl ex Fr.) Que??l. on koa and mamane (Sophora chrysophylla (Salisb.) Seem.). Much work remains to be done in both native and commercial aspects of Hawaiian forest pathology.

  13. Microchimerism in endocrine pathology.

    PubMed

    Rust, Daniel W; Bianchi, Diana W

    2009-01-01

    Chimerism in an individual refers to the coexistence of cells arising from two distinct organisms. It can arise iatrogenically via transplant or blood transfusion, and physiologically via twin to twin transfer, or from trafficking between mother and fetus during pregnancy. Many of the diseases associated with microchimerism affect the endocrine system (e.g., autoimmune thyroid disease and diabetes mellitus type 1). Microchimerism is relevant to endocrine pathology because (a) it is associated with pregnancy, a condition of complex endocrine physiology; (b) materno-fetal and feto-maternal cellular migration must involve the placenta, itself an endocrine organ; and (c) in some species, chimerism results in states of intersexuality, a condition intimately involved with endocrine physiology. Studies of feto-maternal microchimerism in the thyroid have documented the presence of fetal cells in association with Hashimoto thyroiditis, Graves' disease, thyroid adenoma, and papillary thyroid carcinoma. Studies of materno-fetal microchimerism have documented the presence of maternal cells in juvenile diabetes and other pediatric conditions. Microchimerism plays a potential role in the repair of diseased thyroid and pancreatic tissues.

  14. Rabies: ocular pathology.

    PubMed Central

    Haltia, M; Tarkkanen, A; Kivelä, T

    1989-01-01

    Ocular pathology in the first European case of human bat-borne rabies is described. The patient was a 30-year-old bat scientist who seven weeks after bat bite developed neurological symptoms and died 23 days later. Rabies virus antigens were detected in brain smears. After extensive virological studies the virus turned out to be a rabies-related virus, closely resembling the Duvenhage virus isolated from bats in South Africa in 1980. By light microscopy focal chronic inflammatory infiltration of the ciliary body and of the choroid was found. PAS-positive exudate was seen in the subretinal and in the outer plexiform layers of the retina, and retinal veins showed endothelial damage and perivascular inflammation. Many of the retinal ganglion cells were destroyed. The presence of rabies-related viral antigen in the retinal ganglion cells was shown by positive cytoplasmic immunofluorescence, though electron microscopy failed to identify definite viral structures in the retina. By immunohistochemistry glial fibrillary acidic protein was observed in the Müller's cells, which are normally negative for this antigen but express it as a reactive change when the retina is damaged. Synaptophysin, a constituent of presynaptic vesicles of normal retinal neurons, was not detected in the retina. Images PMID:2920157

  15. Pathology of bovine tuberculosis.

    PubMed

    Domingo, M; Vidal, E; Marco, A

    2014-10-01

    Bovine tuberculosis (bTB) is a chronic granulomatous caseous-necrotising inflammatory process that mainly affects the lungs and their draining lymph nodes (Ln.). The pathological changes associated with bTB infection reflect the interplay between the host defence mechanisms and the mycobacterial virulence factors and the balance between the immunologic protective responses and the damaging inflammatory processes. Inhalation is the most common infection route and causes lesions of the nasopharynx and lower respiratory tract, including its associated lymph nodes. The initial infection (primary complex) may be followed by chronic (post-primary) tuberculosis or may be generalised. Goat tuberculosis often produces liquefactive necrosis and caverns, similarly to human TB. The assessment of the severity of TB lesions is crucial for vaccine trials. Semi-quantitative gross lesion scoring systems have been developed for cattle, but imaging technology has allowed the development of more standardised, objective, and quantitative methods, such as multi-detector computed tomography (MDCT), which provides quantitative measures of lesion volume. PMID:24731532

  16. Adverse events in healthcare: learning from mistakes.

    PubMed

    Rafter, N; Hickey, A; Condell, S; Conroy, R; O'Connor, P; Vaughan, D; Williams, D

    2015-04-01

    Large national reviews of patient charts estimate that approximately 10% of hospital admissions are associated with an adverse event (defined as an injury resulting in prolonged hospitalization, disability or death, caused by healthcare management). Apart from having a significant impact on patient morbidity and mortality, adverse events also result in increased healthcare costs due to longer hospital stays. Furthermore, a substantial proportion of adverse events are preventable. Through identifying the nature and rate of adverse events, initiatives to improve care can be developed. A variety of methods exist to gather adverse event data both retrospectively and prospectively but these do not necessarily capture the same events and there is variability in the definition of an adverse event. For example, hospital incident reporting collects only a very small fraction of the adverse events found in retrospective chart reviews. Until there are systematic methods to identify adverse events, progress in patient safety cannot be reliably measured. This review aims to discuss the need for a safety culture that can learn from adverse events, describe ways to measure adverse events, and comment on why current adverse event monitoring is unable to demonstrate trends in patient safety.

  17. Pathways by which Abeta facilitates tau pathology.

    PubMed

    Blurton-Jones, Mathew; Laferla, Frank M

    2006-12-01

    Since the initial description one hundred years ago by Dr. Alois Alzheimer, the disorder that bears his name has been characterized by the occurrence of two brain lesions: amyloid plaques and neurofibrillary tangles (NFTs). Yet the precise relationship between beta-amyloid (Abeta) and tau, the two proteins that accumulate within these lesions, has proven elusive. Today, a growing body of work supports the notion that Abeta may directly or indirectly interact with tau to accelerate NFT formation. Here we review recent evidence that Abeta can adversely affect distinct molecular and cellular pathways, thereby facilitating tau phosphorylation, aggregation, mis-localization, and accumulation. Studies are presented that support four putative mechanisms by which Abeta may facilitate the development of tau pathology. A great deal of work suggests that Abeta may drive tau pathology by activating specific kinases, providing a straightforward mechanism by which Abeta may enhance tau hyperphosphorylation and NFT formation. In the AD brain, Abeta also triggers a massive inflammatory response and pro-inflammatory cytokines can in turn indirectly modulate tau phosphorylation. Mounting evidence also suggests that Abeta may inhibit tau degradation via the proteasome. Lastly, Abeta and tau may indirectly interact at the level of axonal transport and evidence is presented for two possible scenarios by which axonal transport deficits may play a role. We propose that the four putative mechanisms described in this review likely mediate the interactions between Abeta and tau, thereby leading to the development of AD neurodegeneration.

  18. Eccrine spiradenoma: clinical and pathologic study of 49 tumors.

    PubMed

    Mambo, N C

    1983-10-01

    A clinical and pathologic study of 49 eccrine spiradenomas occurring in 46 patients is presented. The study showed that pain and/or tenderness are not such characteristic clinical features of this tumor as has previously been suggested; either or both were present in only 23% of the 35 patients with well-documented clinical histories. Some pathologic features, not previously documented in this tumor, were seen and included: cylindromatous foci, aggregates of stromal clear cells, clear cells lining ducts and ulceration of the overlying epidermis. Two tumors had undergone malignant transformation, but there were no recurrences in the 35 patients with adequate follow-up.

  19. The Pathology of Acute Liver Failure.

    PubMed

    Lefkowitch, Jay H

    2016-05-01

    Acute liver failure (ALF) is a rare and severe liver disease that usually develops in 8 weeks or less in individuals without preexisting liver disease. Its chief causes worldwide are hepatitis virus infections (hepatitis A, B, and E) and drug hepatotoxicity (particularly intentional or unintentional acetaminophen toxicity). Massive hepatic necrosis is often seen in liver specimens in ALF and features marked loss of hepatocytes, variable degrees of inflammation, and a stereotypic proliferation of bile ductular structures (neocholangioles) derived from activated periportal hepatic progenitor cells. This paper reviews the liver pathology in ALF, including forms of zonal necrosis and their etiologies. PMID:27058243

  20. Exercise hypertension: an adverse prognosis?

    PubMed

    Smith, Ryan G; Rubin, Stanley A; Ellestad, Myrvin H

    2009-01-01

    We sought to clarify the prognostic importance of an "exaggerated" or "hypertensive" systolic blood pressure response to exercise during an exercise test. Studies evaluating the prognosis for cardiovascular events and cardiovascular mortality in those with hypertension during exercise testing were systematically reviewed. Fourteen studies were identified. Six studies were of healthy volunteers or hypertensives. Eight studies were in subjects with known or suspected heart disease. Without established heart disease, exercise hypertension predicted cardiovascular events and cardiovascular death. However, two of the six studies included a multivariate analysis; both demonstrated no independent association. Studies in subjects with known or suspected heart disease demonstrated that exercise hypertension predicted fewer cardiac events and lesser mortality or, after multivariate adjustment, no associated risk. In a healthy population, a higher exercise blood pressure may indicate hypertension or prehypertension, instead of normal vascular function, and an associated long-term adverse prognosis. In a population with a high burden of heart disease, the highest risk subjects with the most extensive cardiac disease may not be capable of generating pressure or workload to allow the manifestation of exercise systolic hypertension. By comparison, therefore, those with exercise hypertension have a better prognosis. PMID:20409979

  1. Adverse effects of antihypertensive drugs.

    PubMed

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  2. The pathology roadmap in Parkinson disease

    PubMed Central

    Surmeier, D. James; Sulzer, David

    2013-01-01

    An under-appreciated clue about pathogenesis in Parkinson disease (PD) is the distribution of pathology in the early and middle stages of the disease. This pathological ‘roadmap’ shows that in addition to dopaminergic neurons in the substantia nigra pars compacta (SNc), a significant number of other central and peripheral neuronal populations exhibit Lewy pathology, phenotypic dysregulation or frank degeneration in PD patients. This spatially distributed, at-risk population of neurons shares a number of features, including autonomously generated activity, broad action potentials, low intrinsic calcium buffering capacity and long, poorly myelinated, highly branched axons. Many, and perhaps all, of these traits add to the metabolic burden in these neurons, suggesting that mitochondrial deficits could drive pathogenesis in PD—in agreement with a large segment of the literature. What is less clear is how this neuronal phenotype might shape the susceptibility to proteostatic dysfunction or to the spread of α-synuclein fibrils deposited in the extracellular space. The review explores the literature on these issues and their translational implications. PMID:23324593

  3. Pathology of Mouse Models of Accelerated Aging.

    PubMed

    Harkema, L; Youssef, S A; de Bruin, A

    2016-03-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience," which aims at elucidating the molecular mechanisms involved in aging. Progeroid mouse models are frequently used in geroscience as they provide insight into the molecular mechanisms that are involved in the highly complex process of natural aging. This review provides an overview of the most commonly reported nonneoplastic macroscopic and microscopic pathologic findings in progeroid mouse models (eg, osteoporosis, osteoarthritis, degenerative joint disease, intervertebral disc degeneration, kyphosis, sarcopenia, cutaneous atrophy, wound healing, hair loss, alopecia, lymphoid atrophy, cataract, corneal endothelial dystrophy, retinal degenerative diseases, and vascular remodeling). Furthermore, several shortcomings in pathologic analysis and descriptions of these models are discussed. Progeroid mouse models are valuable models for aging, but thorough knowledge of both the mouse strain background and the progeria-related phenotype is required to guide interpretation and translation of the pathology data. PMID:26864891

  4. 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). PMID:27100343

  5. Reversibility of Adverse, Calcineurin-Dependent Cardiac Remodeling

    PubMed Central

    Berry, Jeff M.; Le, Vien; Rotter, David; Battiprolu, Pavan K.; Grinsfelder, Bennett; Tannous, Paul; Burchfield, Jana S.; Czubryt, Michael; Backs, Johannes; Olson, Eric N.; Rothermel, Beverly A.; Hill, Joseph A.

    2011-01-01

    Background Studies to dissect the role of calcineurin in pathological cardiac remodeling have relied heavily on murine models, where genetic gain- and loss-of-function manipulations are initiated at or before birth. However, the great majority of clinical cardiac pathology occurs in adults. Yet, nothing is known about the effects of calcineurin when its activation commences in adulthood. Further, despite the fact that ventricular hypertrophy is a well established risk factor for heart failure, the relative pace and progression of these two major phenotypic features of heart disease are unknown. Methods and Results We engineered mice harboring in cardiomyocytes a constitutively active calcineurin transgene driven by a tetracycline-responsive promoter element. Expression of the mutant calcineurin transgene was initiated for variable lengths of time to determine the natural history of disease pathogenesis, and to determine when, if ever, these events are reversible. Activation of the calcineurin transgene in adult mice triggered rapid and robust cardiac growth with features characteristic of pathological hypertrophy. Concentric hypertrophy preceded the development of systolic dysfunction, fetal gene activation, fibrosis, and clinical heart failure. Further, cardiac hypertrophy reversed spontaneously when calcineurin activity was turned off, and expression of fetal genes reverted to baseline. Fibrosis, a prominent feature of pathological cardiac remodeling, manifested partial reversibility. Conclusions Together, these data establish and define the deleterious effects of calcineurin signaling in adult heart and reveal that calcineurin-dependent hypertrophy with concentric geometry precedes systolic dysfunction and heart failure. Furthermore, these findings demonstrate that during much of the disease process, calcineurin-dependent remodeling remains reversible. PMID:21700928

  6. Adverse effects of general anaesthetics.

    PubMed

    Berthoud, M C; Reilly, C S

    1992-01-01

    This review deals with the adverse reactions associated with general anaesthetic agents in current use. These reactions fall into 2 categories; those which are more common, predictable and often closely related, and those which are rare, unpredictable and carry a high mortality. Both inhalational and intravenous anaesthetic agents affect the central nervous and cardio-respiratory systems in a dose-related manner. Neuronal inhibition results in decreasing levels of consciousness and depression of the medullary vital centres which can lead to cardiorespiratory failure. Both groups of agents have some depressant effect on the myocardium and vascular smooth muscle leading to a fall in cardiac output and hypotension. Centrally-mediated respiratory depression is common to both groups and the inhalational agents have a direct effect on lung physiology. The most important idiosyncratic reactions to the volatile agents are malignant hyperpyrexia and 'halothane hepatitis'. Malignant hyperpyrexia has an incidence of 1:12,000 with a mortality of about 24%. It is triggered most often by halothane together with suxamethonium. Post halothane hepatic necrosis is rare. Evidence points to 2 distinct syndromes; direct toxicity from the products of reductive metabolism, and a more serious illness, immunologically mediated via haptens formed by liver proteins and the products of oxidative metabolism. Prolonged nitrous oxide exposure can cause bone marrow depression and life-threatening pressure effects by expansion of air-filled spaces within the body. The idiosyncratic reactions to the intravenous agents include anaphylactoid reactions (which are rare) and triggering of acute porphyria. Etomidate is immunologically 'clean', but it inhibits cortisol synthesis. PMID:1418699

  7. Early adversity, neural development, and inflammation.

    PubMed

    Chiang, Jessica J; Taylor, Shelley E; Bower, Julienne E

    2015-12-01

    Early adversity is a risk factor for poor mental and physical health. Although altered neural development is believed to be one pathway linking early adversity to psychopathology, it has rarely been considered a pathway linking early adversity to poor physical health. However, this is a viable pathway because the central nervous system is known to interact with the immune system via the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). In support of this pathway, early adversity has been linked to changes in neural development (particularly of the amygdala, hippocampus, and prefrontal cortex), HPA axis and ANS dysregulation, and higher levels of inflammation. Inflammation, in turn, can be detrimental to physical health when prolonged. In this review, we present these studies and consider how altered neural development may be a pathway by which early adversity increases inflammation and thus risk for adverse physical health outcomes.

  8. [Cutaneous adverse effects of TNFalpha antagonists].

    PubMed

    Failla, V; Sabatiello, M; Lebas, E; de Schaetzen, V; Dezfoulian, B; Nikkels, A F

    2012-01-01

    The TNFalpha antagonists, including adalimumab, etanercept and infliximab, represent a class of anti-inflammatory and immunosuppressive drugs. Although cutaneous adverse effects are uncommon, they are varied. There is no particular risk profile to develop cutaneous adverse effects. The principal acute side effects are injection site reactions and pruritus. The major long term cutaneous side effects are infectious and inflammatory conditions. Neoplastic skin diseases are exceptional. The association with other immunosuppressive agents can increase the risk of developing cutaneous adverse effects. Some adverse effects, such as lupus erythematosus, require immediate withdrawal of the biological treatment, while in other cases temporary withdrawal is sufficient. The majority of the other cutaneous adverse effects can be dealt without interrupting biologic treatment. Preclinical and clinical investigations revealed that the new biologics, aiming IL12/23, IL23 and IL17, present a similar profile of cutaneous adverse effects, although inflammatory skin reactions may be less often encountered compared to TNFalpha antagonists.

  9. Myoepithelial cells in pathology.

    PubMed

    Balachander, N; Masthan, K M K; Babu, N Aravindha; Anbazhagan, V

    2015-04-01

    Myoepithelial cells are a normal constituent of the salivary acini and ducts and are found between the epithelial cells and the basement membrane. Microscopically myoepithelial cells are thin and spindle-shaped and ultrastructurally they possess a number of Cytoplasmic processes that extend between and over the acinar and ductal-lining cells, and they show features of both smooth muscle and epithelium. They play a vital role during expulsion of saliva and regulates the electrolytic exchange. They also perform as tumor suppressors and are considered to play a very important role in differentiation of various salivary gland tumors and help in the diagnosis of tumors. Neoplastic myoepithelial cells in both benign and malignant tumors can take numerous forms including epithelioid, plasmacytoid, spindle and clear cell variant, and this variability largely accounts for difficulties in histopathological diagnosis.

  10. Digital pathology and anatomic pathology laboratory information system integration to support digital pathology sign-out

    PubMed Central

    Guo, Huazhang; Birsa, Joe; Farahani, Navid; Hartman, Douglas J.; Piccoli, Anthony; O’Leary, Matthew; McHugh, Jeffrey; Nyman, Mark; Stratman, Curtis; Kvarnstrom, Vanja; Yousem, Samuel; Pantanowitz, Liron

    2016-01-01

    Background: The adoption of digital pathology offers benefits over labor-intensive, time-consuming, and error-prone manual processes. However, because most workflow and laboratory transactions are centered around the anatomical pathology laboratory information system (APLIS), adoption of digital pathology ideally requires integration with the APLIS. A digital pathology system (DPS) integrated with the APLIS was recently implemented at our institution for diagnostic use. We demonstrate how such integration supports digital workflow to sign-out anatomical pathology cases. Methods: Workflow begins when pathology cases get accessioned into the APLIS (CoPathPlus). Glass slides from these cases are then digitized (Omnyx VL120 scanner) and automatically uploaded into the DPS (Omnyx® Integrated Digital Pathology (IDP) software v.1.3). The APLIS transmits case data to the DPS via a publishing web service. The DPS associates scanned images with the correct case using barcode labels on slides and information received from the APLIS. When pathologists remotely open a case in the DPS, additional information (e.g. gross pathology details, prior cases) gets retrieved from the APLIS through a query web service. Results: Following validation of this integration, pathologists at our institution have signed out more than 1000 surgical pathology cases in a production environment. Integration between the APLIS and DPS enabled pathologists to review digital slides while simultaneously having access to pertinent case metadata. The introduction of a digital workflow eliminated costly manual tasks involving matching of glass slides and avoided delays waiting for glass slides to be delivered. Conclusion: Integrating the DPS and APLIS were instrumental for successfully implementing a digital solution at our institution for pathology sign-out. The integration streamlined our digital sign-out workflow, diminished the potential for human error related to matching slides, and improved the sign

  11. Image Analysis in Surgical Pathology.

    PubMed

    Lloyd, Mark C; Monaco, James P; Bui, Marilyn M

    2016-06-01

    Digitization of glass slides of surgical pathology samples facilitates a number of value-added capabilities beyond what a pathologist could previously do with a microscope. Image analysis is one of the most fundamental opportunities to leverage the advantages that digital pathology provides. The ability to quantify aspects of a digital image is an extraordinary opportunity to collect data with exquisite accuracy and reliability. In this review, we describe the history of image analysis in pathology and the present state of technology processes as well as examples of research and clinical use. PMID:27241112

  12. Utilization management in anatomic pathology.

    PubMed

    Lewandrowski, Kent; Black-Schaffer, Steven

    2014-01-01

    There is relatively little published literature concerning utilization management in anatomic pathology. Nonetheless there are many utilization management opportunities that currently exist and are well recognized. Some of these impact only the cost structure within the pathology department itself whereas others reduce charges for third party payers. Utilization management may result in medical legal liabilities for breaching the standard of care. For this reason it will be important for pathology professional societies to develop national utilization guidelines to assist individual practices in implementing a medically sound approach to utilization management.

  13. Cue reactivity in active pathological, abstinent pathological, and regular gamblers.

    PubMed

    Sodano, Ruthlyn; Wulfert, Edelgard

    2010-03-01

    Twenty-one treatment-seeking pathological gamblers, 21 pathological gamblers in recovery, and 21 recreational gamblers watched two video-taped exciting gambling scenarios and an exciting roller-coaster control scenario while their arousal (heart rate and subjective excitement) and urge to gamble were being measured. The gamblers did not differ significantly in cue-elicited heart rate elevations or excitement. However, the active pathological gamblers reported significantly greater urges to gamble across all cues compared to the abstinent pathological gamblers and, with marginal significance (p = 0.06), also compared to the social gamblers. Further exploration of these findings revealed that active pathological gamblers experience urges to gamble in response to exciting situations, whether or not they are gambling related, whereas abstinent and social gamblers only report urges to an exciting gambling-related cue. This suggests that for pathological gamblers excitement itself, irrespective of its source, may become a conditioned stimulus capable of triggering gambling behavior. Implications for treatment and future research are discussed. PMID:19662519

  14. The Archives of Pathology & Laboratory Medicine: The Most Widely Read Pathology Journal Today.

    PubMed

    Allen, Timothy Craig

    2016-09-01

    The Archives of Pathology & Laboratory Medicine was first published in 1926 as a subspecialty journal of the American Medical Association. It became the official journal of the College of American Pathologists in 1995. Under the dynamic leadership of its most recent editor-in-chief, Philip T. Cagle, MD, and his vibrant editorial board, the Archives has nearly doubled its impact factor and become the most widely read general pathology journal today. Dr Cagle has consistently added leading pathologists to the editorial board, and the collective expertise of these individuals is clearly evident in new, cutting-edge journal masthead sections. The Archives has featured innovative content in the field of digital pathology, including articles on the utilization of smart phones in pathology and incorporation of whole-slide images and videos into the content of articles. Special sections have characterized the Archives during the current editorial board's tenure and have proven immensely popular with the journal's readership. As the Archives celebrates its 90th anniversary, its editorial board remains committed to providing insightful and relevant medical knowledge. The journal's open access Web site ( www.archivesofpathology.org ) allows the dissemination of this knowledge to every corner of the globe at no expense to those who wish to be educated or improve their medical practice. PMID:27139152

  15. Meckel on developmental pathology.

    PubMed

    Opitz, John M; Schultka, Rüdiger; Göbbel, Luminita

    2006-01-15

    cartilage named after him, and as having interpreted, correctly, the developmental nature of the "Meckel" diverticulum. It is virtually unknown that Meckel also first enuntiated the concept and distinction between primary and secondary malformations/anomalies, introduced the notion of heredity into the causal analysis of congenital anomalies, was the father of syndromology (the Meckel syndrome), had a clear understanding of pleiotropy and heterogeneity, and can unequivocally be regarded as the father of developmental pathology. In hindsight, and inspite of much professional success, Meckel emerges as a tragic figure in the history of biology, his life cut short at 52 without an ability to incorporate cell theory and the embryological insights of his younger contemporaries into his intellectual edifice which might have made it possible for him to finally and clearly see "analogy" (now homology), of which he was the greatest expert in his era, as incontrovertible evidence for descent. In that case, Darwin and Haeckel might have even had the courtesy of a tip-of-the-hat in Meckel's direction. PMID:16353245

  16. Objective pathological diagnosis of coal worker's pneumoconiosis

    SciTech Connect

    Fisher, E.R.; Watkins, G.; Lam, N.V.; Tsuda, H.; Hermann, C.; Johal, J.; Liu, H.

    1981-05-08

    Pertinent pathological features of lungs obtained at autopsies from 99 coal miners were compared with those observed in the lungs of 268 male town dwellers of comparable age who were not occupationally related to the coal mining or other industries at risk for development of pneumoconiosis. The degree of anthracotic pigment deposition and severity of type of pigmented lesion with its accompanying reticulum fiber formation and fibrosis were significantly greater in lungs of miners. There was a high degree of overlap in degree of pigment deposition, particularly those quantitated as grades 1 and 2 and in lesions regarded as types 1 and 2. The greatest divergence was observed for prevalence of nodular pulmonary lesions (type 4). There was also a considerable divergence in the type 3 alteration characterized by nonnodular aggregates of carbon-laden macrophages accompanied by minimal reactive fibrosis. It appears that an objective pathological diagnosis of coal workers' pneumoconiosis (CWP) can be rendered only by the demonstration of type 4 lesions. Approximately 25% of coal miners exhibited unequivocal features of CWP. No significant differences concerning incidence or types of emphysema or frequency of chronic cor pulmonale were encountered between the two populations.

  17. Objective pathological diagnosis of coal workers' pneumoconiosis

    SciTech Connect

    Fisher, E.R.; Watkins, G.; Lam, N.V.; Tsuda, H.; Hermann, C.; Johal, J.; Liu, H.

    1981-05-08

    Pertinent pathological features of lungs obtained at autopsies from 99 coal miners were compared with those observed in the lungs of 268 male town dwellers of comparable age who were not occupationally related to the coal mining or other industries at risk for development of pneumoconiosis. The degree of anthracotic pigment deposition and severity of type of pigmented lesion with its accompanying reticulum fiber formation and fibrosis were significantly greater in lungs of miners. There was a high degree of overlap in degrees of pigment deposition, particularly those quantitated as grades 1 and 2 and in lesions regarded as types 1 and 2. The greatest divergence was observed for prevalence of nodular pulmonary lesions (type 4). There was also a considerable divergence in the type 3 alteration characterized by nonnodular aggregates of carbon-laden macrophages accompanied by minimal reactive fibrosis. It appears that an objective pathological diagnosis of coal workers' pneumoconiosis can be rendered only by the demonstration of type 4 lesions. Approximately 25% of coal miners exhibited unequivocal features of CWP. No significant differences concerning incidence or types of emphysema or frequency of chronic cor pulmonale were encountered between the two populations.

  18. Assessment of breast pathologies using nonlinear microscopy

    PubMed Central

    Tao, Yuankai K.; Shen, Dejun; Sheikine, Yuri; Ahsen, Osman O.; Wang, Helen H.; Schmolze, Daniel B.; Johnson, Nicole B.; Brooker, Jeffrey S.; Cable, Alex E.; Connolly, James L.; Fujimoto, James G.

    2014-01-01

    Rapid intraoperative assessment of breast excision specimens is clinically important because up to 40% of patients undergoing breast-conserving cancer surgery require reexcision for positive or close margins. We demonstrate nonlinear microscopy (NLM) for the assessment of benign and malignant breast pathologies in fresh surgical specimens. A total of 179 specimens from 50 patients was imaged with NLM using rapid extrinsic nuclear staining with acridine orange and intrinsic second harmonic contrast generation from collagen. Imaging was performed on fresh, intact specimens without the need for fixation, embedding, and sectioning required for conventional histopathology. A visualization method to aid pathological interpretation is presented that maps NLM contrast from two-photon fluorescence and second harmonic signals to features closely resembling histopathology using hematoxylin and eosin staining. Mosaicking is used to overcome trade-offs between resolution and field of view, enabling imaging of subcellular features over square-centimeter specimens. After NLM examination, specimens were processed for standard paraffin-embedded histology using a protocol that coregistered histological sections to NLM images for paired assessment. Blinded NLM reading by three pathologists achieved 95.4% sensitivity and 93.3% specificity, compared with paraffin-embedded histology, for identifying invasive cancer and ductal carcinoma in situ versus benign breast tissue. Interobserver agreement was κ = 0.88 for NLM and κ = 0.89 for histology. These results show that NLM achieves high diagnostic accuracy, can be rapidly performed on unfixed specimens, and is a promising method for intraoperative margin assessment. PMID:25313045

  19. Uncommon Manifestations of Intervertebral Disk Pathologic Conditions.

    PubMed

    Diehn, Felix E; Maus, Timothy P; Morris, Jonathan M; Carr, Carrie M; Kotsenas, Amy L; Luetmer, Patrick H; Lehman, Vance T; Thielen, Kent R; Nassr, Ahmad; Wald, John T

    2016-01-01

    Beyond the familiar disk herniations with typical clinical features, intervertebral disk pathologic conditions can have a wide spectrum of imaging and clinical manifestations. The goal of this review is to illustrate and discuss unusual manifestations of intervertebral disk pathologic conditions that radiologists may encounter, including disk herniations in unusual locations, those with atypical imaging features, and those with uncommon pathophysiologic findings. Examples of atypical disk herniations presented include dorsal epidural, intradural, symptomatic thoracic (including giant calcified), extreme lateral (retroperitoneal), fluorine 18 fluorodeoxyglucose-avid, acute intravertebral (Schmorl node), and massive lumbar disk herniations. Examples of atypical pathophysiologic conditions covered are discal cysts, fibrocartilaginous emboli to the spinal cord, tiny calcified disks or disk-level spiculated osteophytes causing spinal cerebrospinal fluid (CSF) leak and intracranial hypotension, and pediatric acute calcific discitis. This broad gamut of disease includes a variety of sizes of disk pathologic conditions, from the tiny (eg, the minuscule calcified disks causing high-flow CSF leaks) to the extremely large (eg, giant calcified thoracic intradural disk herniations causing myelopathy). A spectrum of clinical acuity is represented, from hyperacute fibrocartilaginous emboli causing spinal cord infarct, to acute Schmorl nodes, to chronic intradural herniations. The entities included are characterized by a range of clinical courses, from the typically devastating cord infarct caused by fibrocartilaginous emboli, to the usually spontaneously resolving pediatric acute calcific discitis. Several conditions have important differential diagnostic considerations, and others have relatively diagnostic imaging findings. The pathophysiologic findings are well understood for some of these entities and poorly defined for others. Radiologists' knowledge of this broad scope of

  20. American Society for Clinical Pathology

    MedlinePlus

    ... for Clinical Pathology Expands List of Commonly Used Tests and Treatments Physicians and Patients Should Question CMS Listens to ASCP, Gives Providers more Flexibility in MACRA Implementation ePolicy News September 2016 Urge ...

  1. Detection of peripheral nerve pathology

    PubMed Central

    Seelig, Michael J.; Baker, Jonathan C.; Mackinnon, Susan E.; Pestronk, Alan

    2013-01-01

    Objective: To compare accuracy of ultrasound and MRI for detecting focal peripheral nerve pathology, excluding idiopathic carpal or cubital tunnel syndromes. Methods: We performed a retrospective review of patients referred for neuromuscular ultrasound to identify patients who had ultrasound and MRI of the same limb for suspected brachial plexopathy or mononeuropathies, excluding carpal/cubital tunnel syndromes. Ultrasound and MRI results were compared to diagnoses determined by surgical or, if not performed, clinical/electrodiagnostic evaluation. Results: We identified 53 patients who had both ultrasound and MRI of whom 46 (87%) had nerve pathology diagnosed by surgical (n = 39) or clinical/electrodiagnostic (n = 14) evaluation. Ultrasound detected the diagnosed nerve pathology (true positive) more often than MRI (43/46 vs 31/46, p < 0.001). Nerve pathology was correctly excluded (true negative) with equal frequency by MRI and ultrasound (both 6/7). In 25% (13/53), ultrasound was accurate (true positive or true negative) when MRI was not. These pathologies were typically (10/13) long (>2 cm) and only occasionally (2/13) outside the MRI field of view. MRI missed multifocal pathology identified with ultrasound in 6 of 7 patients, often (5/7) because pathology was outside the MRI field of view. Conclusions: Imaging frequently detects peripheral nerve pathology and contributes to the differential diagnosis in patients with mononeuropathies and brachial plexopathies. Ultrasound is more sensitive than MRI (93% vs 67%), has equivalent specificity (86%), and better identifies multifocal lesions than MRI. In sonographically accessible regions ultrasound is the preferred initial imaging modality for anatomic evaluation of suspected peripheral nervous system lesions. PMID:23553474

  2. The Role of Speech Pathology and Audiology in Special Education.

    ERIC Educational Resources Information Center

    Bakare, C. A.

    1976-01-01

    Speech and language disorder is seen as a characteristic feature in most of the areas of exceptionalities identified as the hearing impaired, the visually impaired, the mentally retarded, the physically handicapped, and learning disabilities. Commonalities of speech pathology/audiology and special education are discussed. (MLW)

  3. Strategic approaches to adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for organizing biological and toxicological knowledge in a manner that supports extrapolation of data pertaining to the initiation or early progression of toxicity to an apical adverse outcome that occurs at a level of org...

  4. Understanding adverse events: human factors.

    PubMed Central

    Reason, J

    1995-01-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  5. Understanding adverse events: human factors.

    PubMed

    Reason, J

    1995-06-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  6. Multiple adverse experiences and child cognitive development.

    PubMed

    Guinosso, Stephanie A; Johnson, Sara B; Riley, Anne W

    2016-01-01

    During childhood and adolescence, children's social environments shape their cognitive development. Children exposed to multiple adversities in their social environment are more likely to have poorer cognitive outcomes. These findings have prompted interest among pediatric and public health communities to screen and connect youth to appropriate interventions that ameliorate the detrimental effects of adverse exposures. Such intervention efforts can be improved with a stronger conceptual understanding of the relationship between multiple adverse exposures and child cognitive development. This includes disentangling adverse exposures from other risk factors or underlying mechanisms, specifying mechanisms of action, and determining when adverse exposures are most detrimental. This review summarizes findings from the literature on each of these areas and proposes a conceptual model to guide further research and intervention.

  7. Adverse effects of anabolic steroids in athletes.

    PubMed

    Kibble, M W; Ross, M B

    1987-09-01

    The effects of anabolic steroid use on athletic performance and the adverse effects associated with the use of anabolic steroids are reviewed. Anabolic steroids increase protein synthesis in skeletal muscles and reverse catabolic processes. Because of these properties, some athletes use anabolic steroids in an attempt to improve their athletic performance. However, studies indicate that increases in muscle mass and strength during anabolic steroid administration are observed only in athletes who already are weight-trained and who continue intensive training while maintaining high-protein, high-calorie diets. Adverse effects attributed to anabolic steroid use occur frequently. Serious adverse effects include hepatic and endocrine dysfunction; cardiovascular and behavioral changes also are reported. Some of the adverse effects associated with the use of these agents are irreversible, particularly in women. The use of anabolic steroids to improve athletic performance has become prevalent. However, the reported benefits are tempered by numerous adverse reactions.

  8. Adulthood personality correlates of childhood adversity

    PubMed Central

    Carver, Charles S.; Johnson, Sheri L.; McCullough, Michael E.; Forster, Daniel E.; Joormann, Jutta

    2014-01-01

    Objective: Childhood adversity has been linked to internalizing and externalizing disorders and personality disorders in adulthood. This study extends that research by examining several personality measures as correlates of childhood adversity. Method: In a college sample self-reports were collected of childhood adversity, several scales relating to personality, and current depression symptoms as a control variable. The personality-related scales were reduced to four latent variables, which we termed anger/aggression, extrinsic focus, agreeableness, and engagement. Results: Controlling for concurrent depressive symptoms and gender, higher levels of reported childhood adversity related to lower agreeableness and to higher anger/aggression and extrinsic focus. Conclusions: Findings suggest that early adversity is linked to personality variables relevant to the building of social connection. PMID:25484874

  9. Managing adverse effects of glaucoma medications

    PubMed Central

    Inoue, Kenji

    2014-01-01

    Glaucoma is a chronic, progressive disease in which retinal ganglion cells disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma eye drops have hypotensive effects and like all other medications are associated with adverse effects. Adverse reactions may either result from the main agent or from preservatives used in the drug vehicle. The preservative benzalkonium chloride, is one such compound that causes frequent adverse reactions such as superficial punctate keratitis, corneal erosion, conjunctival allergy, and conjunctival injection. Adverse reactions related to main hypotensive agents have been divided into those affecting the eye and those affecting the entire body. In particular, β-blockers frequently cause systematic adverse reactions, including bradycardia, decrease in blood pressure, irregular pulse and asthma attacks. Prostaglandin analogs have distinctive local adverse reactions, including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation, and upper eyelid deepening. No systemic adverse reactions have been linked to prostaglandin analog eye drop usage. These adverse reactions may be minimized when they are detected early and prevented by reducing the number of different eye drops used (via fixed combination eye drops), reducing the number of times eye drops are administered, using benzalkonium chloride-free eye drops, using lower concentration eye drops, and providing proper drop instillation training. Additionally, a one-time topical medication can be given to patients to allow observation of any adverse reactions, thereafter the preparation of a topical medication with the fewest known adverse reactions can be prescribed. This does require precise patient monitoring and inquiries about patient symptoms following medication use. PMID:24872675

  10. CBT for eating disorders: The impact of early changes in eating pathology on later changes in personality pathology, anxiety and depression.

    PubMed

    Turner, Hannah; Marshall, Emily; Wood, Francesca; Stopa, Lusia; Waller, Glenn

    2016-02-01

    Whilst studies have consistently identified early symptom reduction as an important predictor of treatment outcome, the impact of early change on common comorbid features has not been investigated. This study of CBT for eating disorders explored patterns of early change in eating pathology and longer-term change in personality pathology, anxiety and depression. It also explored the impact of early change in eating pathology on overall change in personality pathology, anxiety and depression. Participants were 179 adults diagnosed with eating disorders who were offered a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment and following the 6th session. They also completed measures of personality disorder cognitions, anxiety and depression at the start and end of treatment. There were significant changes in eating pathology over the first six sessions of treatment. Significant improvements were also seen in personality disorder pathology, anxiety and depression by the end of therapy. Effect sizes were medium to large for both completer and intention to treat analyses. Early changes in eating pathology were associated with later changes in common comorbid features, with early reduction in restraint being a key predictor. These findings demonstrate that early symptom change can be achieved in CBT for eating disorders when delivered in routine clinical practice. Such change has long-term benefits that go beyond the domain of eating pathology, enhancing change in personality pathology, anxiety and depression.

  11. Introduction: human pathology within the broad scope of comparative pathology.

    PubMed

    Kaiser, H E

    1996-01-01

    Pathologic integration is the basic phenomenon of comparative pathology. Since man evolved as earth's most influential species, he was unequally influenced the progression and prevention of diseases in himself and other species. This has both positive and negative ramifications. Positive influences have been life-style, the prolongation of life under healthy conditions and medical progress as seen in the treatment of diabetes mellitus, dental hygiene and other factors, such as the decrease of infectious and parasitic diseases, which are still dominating factors in developing nations. Negative influences are side effects of medical treatments, the appearance of occupational, and certain recreational diseases. These are the pathologic effects of man's life-style to which car accidents, smoking and other factors can be added. Different species are affected by environmental changes such as pollution, ozone, acidic rain, polluted food, and transmission of different diseases from one species to another. Interspecies-specifically the direct influence of man in the extermination of other species, or the indirect influence such as through pollutants in the environment producing chain reactions in different species, can be distinguished. The physical environment has been changed as can be seen in air pollution in large cities, the damage to the ozone layer and the increase of malignant melanoma in certain regions of western Australia. The industrialized nations are dominated by non-infectious diseases such as atherosclerosis and neoplasms, whereas in the developing nations parasitic and infectious diseases stand in the fore-front. Particular diseases like acquired immunodeficiency syndrome increase in both types of nations. These diseases may have developed from other species, e.g. the plague which was originally a disease of rodents, especially rats where it was transmitted by the flea, Xenopsylla cheopis, Rothschild. The principle of foremost importance is the disruption

  12. Adverse drug reactions in an elderly outpatient population.

    PubMed

    Schneider, J K; Mion, L C; Frengley, J D

    1992-01-01

    The prevalence of adverse drug reactions (ADRs) in elderly outpatients was investigated, along with factors that might be associated with their occurrence. The medical records of elderly patients attending an interdisciplinary geriatric clinic and a general medical clinic during 1988 were audited to collect a variety of demographic and treatment data and to detect documentation of first-time ADRs. Subjects were classified as having had an ADR if a physician documented this or if a relevant symptom was noted in the record and a score of 1 or above was obtained on the Adverse Drug Reaction Probability Scale. The presence of potential drug interactions was also assessed. The sample size was 463 patients, of whom 332 attended the medical clinic and 131 attended the geriatric clinic. Potential drug interactions were identified in the records of 143 subjects (31%). There were 107 documented ADRs in 97 patients (21%). Of these patients, 86 were noted by the physicians as having had an ADR. Twelve patients were hospitalized as a direct result of an ADR. Significant risk factors for ADRs were attendance in the geriatric clinic, the use of potentially harmful drug combinations, and the use of drugs that require therapeutic monitoring. Patient age and the number of drugs had no association with ADRs. In the elderly population studied, patients with frailty arising from multiple pathologies were more likely to have ADRs than the more robust elderly, even when their therapeutic regimens were simplified. PMID:1570873

  13. Collateral Adverse Outcomes After Lumbar Spine Surgery.

    PubMed

    Daniels, Alan H; Gundle, Kenneth; Hart, Robert A

    2016-01-01

    Collateral adverse outcomes are the expected or unavoidable results of a procedure that is performed in a standard manner and typically experienced by the patient. Collateral adverse outcomes do not result from errors, nor are they rare. Collateral adverse outcomes occur as the direct result of a surgical procedure and must be accepted as a trade-off to attain the intended benefits of the surgical procedure. As such, collateral adverse outcomes do not fit into the traditional definition of a complication or adverse event. Examples of collateral adverse outcomes after lumbar spine arthrodesis include lumbar stiffness, postoperative psychological stress, postoperative pain, peri-incisional numbness, paraspinal muscle denervation, and adjacent-level degeneration. Ideally, a comparison of interventions for the treatment of a clinical condition should include information on both the negative consequences (expected and unexpected) and potential benefits of the treatment options. The objective evaluation and reporting of collateral adverse outcomes will provide surgeons with a more complete picture of invasive interventions and, thus, the improved ability to assess alternative treatment options. PMID:27049197

  14. Communication skills in diagnostic pathology.

    PubMed

    Lehr, Hans-Anton; Bosman, Fred T

    2016-01-01

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

  15. General features

    SciTech Connect

    Wallace, R.E.

    1990-01-01

    The San Andreas fault system, a complex of faults that display predominantly large-scale strike slip, is part of an even more complex system of faults, isolated segments of the East Pacific Rise, and scraps of plates lying east of the East Pacific Rise that collectively separate the North American plate from the Pacific plate. This chapter briefly describes the San Andreas fault system, its setting along the Pacific Ocean margin of North America, its extent, and the patterns of faulting. Only selected characteristics are described, and many features are left for depictions on maps and figures.

  16. Relationship between pathological gambling, alcoholism and drug addiction.

    PubMed

    Baldo, V; Cristofoletti, M; Majori, S; Cibin, M; Peron, C; Dal Zotto, A; Zampieri, N; Saia, M; Trivello, R

    2006-01-01

    The aim of this survey was to evaluate the distribution of pathological gamblers treated in an alcohol or drug addiction treatment program run by the Italian National Health Service providing assistance to alcohol and drug abusers in Venice (North east Italy) from September 1 to December 31, 2001. Each drug- or alcohol-dependent patient retained for treatment for at least one month was administrated an anonymous precoded questionnaire to collect personal and socio-demographic features. The South Oaks Gambling Screen (SOGS) was used to measure pathological gambling and the Symptom Checklist-90-Revised (SCL-90-R) to measure psychological distress levels and psychiatric symptoms. Among the 113 enrolled subjects we found a greater prevalence of pathological gamblers among drug users than among alcoholics and drug abusers were younger than alcoholics; moreover, there was a prevalence of single status, low schooling, and a low-medium income despite full-time occupation. Only pathological gamblers revealed a significant positive correlation with a family history of gambling and reached positive scores (>1.5) for some likely psychiatric symptoms. Abuse disorders and pathological gambling are frequently associated with multidependence personality traits. Preventing substance abuse may reduce the pathological gambling rates and better results can be obtained with educational campaigns beginning earlier in life. PMID:16649512

  17. Pathologic studies of fatal cases in outbreak of hand, foot, and mouth disease, Taiwan.

    PubMed Central

    Shieh, W. J.; Jung, S. M.; Hsueh, C.; Kuo, T. T.; Mounts, A.; Parashar, U.; Yang, C. F.; Guarner, J.; Ksiazek, T. G.; Dawson, J.; Goldsmith, C.; Chang, G. J.; Oberste, S. M.; Pallansch, M. A.; Anderson, L. J.; Zaki, S. R.

    2001-01-01

    In 1998, an outbreak of enterovirus 71-associated hand, foot, and mouth disease occurred in Taiwan. Pathologic studies of two fatal cases with similar clinical features revealed two different causative agents, emphasizing the need for postmortem examinations and modern pathologic techniques in an outbreak investigation. PMID:11266307

  18. The pathology of shin splints.

    PubMed

    Kues, J M

    1990-01-01

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

  19. [Pathology of the vitreomacular interface].

    PubMed

    Pop, Monica; Gheorghe, Alina

    2014-01-01

    Vitreous role in the pathophysiology of retinal diseases has increased importantly over the recent years. This was possible using Optical Coherence Tomography which reviewed the way the vitreoretinal interface should be looked at and defined and classified new pathologies such as Vitreoretinal Traction Syndrome. Vitreous is not an empty space but an important anatomical structure with role in ocular physiology. With age biochemical changes occur so that vitreous starts to liquefy. Once the vitreous is liquefied (sinchisis) it collapses and passes in the retrohialoid space (sineresis). In complete PVD besides sinchisis there is a weakness of the adherence between the posterior cortex and ILM with total detachment of posterior cortex. Abnormal adhesions are associated with incomplete PVD. The definition and understanting of vitreoretinal pathology is an active and continuous process, PVD being the trigger of a lot of retinal pathologies: epiretinal membrane, macular hole, tractional macular oedema, VMTS, myopic traction maculopathy, exacerbations of exudative ARMD.

  20. Revised histopathological consensus classification of joint implant related pathology.

    PubMed

    Krenn, V; Morawietz, L; Perino, G; Kienapfel, H; Ascherl, R; Hassenpflug, G J; Thomsen, M; Thomas, P; Huber, M; Kendoff, D; Baumhoer, D; Krukemeyer, M G; Natu, S; Boettner, F; Zustin, J; Kölbel, B; Rüther, W; Kretzer, J P; Tiemann, A; Trampuz, A; Frommelt, L; Tichilow, R; Söder, S; Müller, S; Parvizi, J; Illgner, U; Gehrke, T

    2014-12-01

    This extended classification of joint implant related pathology is a practical histopathologic classification based on defined morphological criteria covering the complete spectrum of pathohistologic changes in periprosthetic tissues. These changes may occur as a consequence of endoprosthetic replacement of large joints and may lead to a reduction in the prosthesis survival rate. We describe the established consensus classification of the periprosthetic membrane, in which aseptic and septic prosthetic loosening can be subdivided into four histological types, as well as histopathological criteria for additional significant pathologies including endoprosthetic-associated arthrofibrosis, particle-induced immunological, inflammatory and toxic mechanisms (adverse reactions), and bone tissue pathologies. These characteristic tissue alterations and their relationships are summarized in the extended classification. Since particle heterogeneity in periprosthetic tissue is high and particle identification is a necessary part of diagnosis, the identification of different types of particles is described in the histopathological particle algorithm. The morphological qualities of prosthetic material particles and the demarcation between abrasion and non-abrasion endogenous particles are also summarized. This feasible classification which is based on low cost standard tissue processing and examination and on well-defined diagnostic criteria is a solid platform for the histological diagnosis of implant associated pathologies providing a stable and reproducible tool for the surgical pathologist. Since this classification is suitable for standardized histopathological diagnostics, it might also provide a useful data set for joint arthroplasty registers, particularly for registers based on so-called routine data.

  1. Towards a Role for Clinical Pathology Diagnostics for Childhood Maltreatment

    PubMed Central

    Bearer, EL; Ji, J; Trickett, P; Kaplan, CD; Mennen, F

    2015-01-01

    Recent reports from the Center for Disease Control and Kaiser Permanente demonstrate that early life adverse experience leads to morbidity and mortality in adulthood. To date there are no objective tests that help care-givers or local child protective services make informed decisions for children with a history of abuse, neglect or trauma. This is the first report from a new group of trans-disciplinary investigators describing a new approach to identify the biological impact of childhood maltreatment using clinical pathology testing. Such new quantitative measurements will be useful to identify children at risk for poor mental and physical health outcomes and to follow response to interventions. PMID:26640822

  2. Optimal breast cancer pathology manifesto.

    PubMed

    Tot, T; Viale, G; Rutgers, E; Bergsten-Nordström, E; Costa, A

    2015-11-01

    This manifesto was prepared by a European Breast Cancer (EBC) Council working group and launched at the European Breast Cancer Conference in Glasgow on 20 March 2014. It sets out optimal technical and organisational requirements for a breast cancer pathology service, in the light of concerns about variability and lack of patient-centred focus. It is not a guideline about how pathology services should be performed. It is a call for all in the cancer community--pathologists, oncologists, patient advocates, health administrators and policymakers--to check that services are available that serve the needs of patients in a high quality, timely way.

  3. Optimal breast cancer pathology manifesto.

    PubMed

    Tot, T; Viale, G; Rutgers, E; Bergsten-Nordström, E; Costa, A

    2015-11-01

    This manifesto was prepared by a European Breast Cancer (EBC) Council working group and launched at the European Breast Cancer Conference in Glasgow on 20 March 2014. It sets out optimal technical and organisational requirements for a breast cancer pathology service, in the light of concerns about variability and lack of patient-centred focus. It is not a guideline about how pathology services should be performed. It is a call for all in the cancer community--pathologists, oncologists, patient advocates, health administrators and policymakers--to check that services are available that serve the needs of patients in a high quality, timely way. PMID:26283037

  4. [Fibronectin, aging and related pathologies].

    PubMed

    Labat-Robert, J; Chevalier, X

    1991-01-01

    It could be demonstrated that plasma and tissue fibronectin (FN) increase with age. Some age dependent diseases as diabetes, osteoarthritis and Werner syndrome produce also an increase of tissue fibronectin biosynthesis. Plasma fibronectin decreases in diabetes and in breast cancer. Alternative splicing of the FN gene appears also to vary with age and in some related pathologies. Nutritional status and UV light also influence FN biosynthesis. It appears therefore that the determination of plasma FN and its isoforms as well as the study of tissue FN may be of interest for the study of chronological aging and related pathologies. PMID:1835421

  5. Current diagnosis of temporomandibular pathologies.

    PubMed

    Learreta, Jorge A; Matos, Jane L F; Matos, Marcelo Freire; Durst, Andreas C

    2009-04-01

    The current scientific knowledge of TMJ pathologies points to the importance of etiological research and the need for differential diagnosis using the most modem technological resources. Those include MRI, computed tomography, serologic studies, genetic mapping, and bioelectronic instruments which allow clinicians to study, understand, and measure respectively, the structural changes of soft and hard tissues, infections, genetic susceptibility for autoimmune diseases, and stomatognathic function. The purpose of this article is an overview of the current knowledge and related tools for the diagnosis of TMJ pathologies.

  6. Childhood adversities and psychosis: evidence, challenges, implications

    PubMed Central

    Morgan, Craig; Gayer‐Anderson, Charlotte

    2016-01-01

    There is a substantial body of research reporting evidence of associations between various forms of childhood adversity and psychosis, across the spectrum from experiences to disorder. This has been extended, more recently, to include studies of cumulative effects, of interactions with other factors, of specific effects, and of putative biological and psychological mechanisms. In this paper we evaluate this research and highlight the remaining methodological issues and gaps that temper, but do not dismiss, conclusions about the causal role of childhood adversity. We also consider the emerging work on cumulative, synergistic, and specific effects and on mechanisms; and discuss the broader implications of this line of research for our understanding of psychosis. We conclude that the current balance of evidence is that childhood adversities – particularly exposure to multiple adversities involving hostility and threat – do, in some people, contribute to the onset of psychotic experiences and psychotic disorders. PMID:27265690

  7. RACIAL RESIDENTIAL SEGREGATION AND ADVERSE BIRTH OUTCOMES

    EPA Science Inventory

    INTRODUCTION. The disparity between black and white women's adverse birth outcomes has been subject to much investigation, yet the factors underlying its persistence remain elusive, which has encouraged research on neighborhood-level influences, including racial residential segr...

  8. Encouraging spontaneous reporting of adverse effects.

    PubMed

    2015-02-01

    One priority when organising surveillance of health products is to remove barriers to reporting adverse effects. One way to encourage reporting is by providing regular feedback, as practised by the German drug bulletin arznei-telegramm, for example. PMID:25802925

  9. Adverse Outcome Pathways: From Definition to Application

    EPA Science Inventory

    A challenge for both human health and ecological toxicologists is the transparent application of mechanistic (e.g., molecular, biochemical, histological) data to risk assessments. The adverse outcome pathway (AOP) is a conceptual framework designed to meet this need. Specifical...

  10. 27 CFR 22.107 - Pathological laboratories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Pathological laboratories... Pathological laboratories. (a) Pathological laboratories, not operated by a hospital or sanitarium, may... sanitariums. If a pathological laboratory does not exclusively conduct analyses or tests for hospitals...

  11. 27 CFR 22.107 - Pathological laboratories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Pathological laboratories... Pathological laboratories. (a) Pathological laboratories, not operated by a hospital or sanitarium, may... sanitariums. If a pathological laboratory does not exclusively conduct analyses or tests for hospitals...

  12. 27 CFR 22.107 - Pathological laboratories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Pathological laboratories... Pathological laboratories. (a) Pathological laboratories, not operated by a hospital or sanitarium, may... sanitariums. If a pathological laboratory does not exclusively conduct analyses or tests for hospitals...

  13. 27 CFR 22.107 - Pathological laboratories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Pathological laboratories... Pathological laboratories. (a) Pathological laboratories, not operated by a hospital or sanitarium, may... sanitariums. If a pathological laboratory does not exclusively conduct analyses or tests for hospitals...

  14. 27 CFR 22.107 - Pathological laboratories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Pathological laboratories... Pathological laboratories. (a) Pathological laboratories, not operated by a hospital or sanitarium, may... sanitariums. If a pathological laboratory does not exclusively conduct analyses or tests for hospitals...

  15. Broken or maladaptive? Altered trajectories in neuroinflammation and behavior after early life adversity

    PubMed Central

    Ganguly, Prabarna; Brenhouse, Heather C.

    2014-01-01

    Exposure to adversity and stress early in development yields vulnerability to mental illnesses throughout the lifespan. Growing evidence suggests that this vulnerability has mechanistic origins involving aberrant development of both neurocircuitry and neuro-immune activity. Here we review the current understanding of when and how stress exposure initiates neuroinflammatory events that interact with brain development. We first review how early life adversity has been associated with various psychopathologies, and how neuroinflammation plays a role in these pathologies. We then summarize data and resultant hypotheses describing how early life adversity may particularly alter neuro-immune development with psychiatric consequences. Finally, we review how sex differences contribute to individualistic vulnerabilities across the lifespan. We submit the importance of understanding how stress during early development might cause outright neural or glial damage, as well as experience-dependent plasticity that may insufficiently prepare an individual for sex-specific or life-stage specific challenges. PMID:25081071

  16. Domoic Acid Toxicologic Pathology: A Review

    PubMed Central

    Pulido, Olga M.

    2008-01-01

    Domoic acid was identified as the toxin responsible for an outbreak of human poisoning that occurred in Canada in 1987 following consumption of contaminated blue mussels [Mytilus edulis]. The poisoning was characterized by a constellation of clinical symptoms and signs. Among the most prominent features described was memory impairment which led to the name Amnesic Shellfish Poisoning [ASP]. Domoic acid is produced by certain marine organisms, such as the red alga Chondria armata and planktonic diatom of the genus Pseudo-nitzschia. Since 1987, monitoring programs have been successful in preventing other human incidents of ASP. However, there are documented cases of domoic acid intoxication in wild animals and outbreaks of coastal water contamination in many regions world-wide. Hence domoic acid continues to pose a global risk to the health and safety of humans and wildlife. Several mechanisms have been implicated as mediators for the effects of domoic acid. Of particular importance is the role played by glutamate receptors as mediators of excitatory neurotransmission and the demonstration of a wide distribution of these receptors outside the central nervous system, prompting the attention to other tissues as potential target sites. The aim of this document is to provide a comprehensive review of ASP, DOM induced pathology including ultrastructural changes associated to subchronic oral exposure, and discussion of key proposed mechanisms of cell/tissue injury involved in DOM induced brain pathology and considerations relevant to food safety and human health. PMID:18728725

  17. Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients

    PubMed Central

    Hejazi, Mohammad Esmayil; Shafiifar, Afsaneh; Mashayekhi, Siminozar

    2016-01-01

    Background: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. Materials and Methods: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients’ demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. Results: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. Conclusion: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID:27403173

  18. [Psychic experience of pathological machine gamblers].

    PubMed

    Avtonomov, D A

    2011-01-01

    The author presents results of the psychopathological phenomena and subjective experience study of 38 patients with the verified diagnosis "Pathological addiction to gambling" (F63.0) without psychotic disorders. In 84,2% cases, the patients preferred slot machine gambling. The causes of such preferences were analyzed. The phenomenology of the psychic experience of the patients who are slot machine gamblers is presented. With the formation of the addiction, the gamblers began to think about slot machines as human beings (creatures), feel attachment to them, see the individuality in them, and experience slot machines as live and real partners in imaginative or even verbal dialogs. Two main "forms of contact" with slot machines were elicited and described: verbal and non-verbal. The gambler has been gradually depleted the image of himself and experiences the "loss of contact" with his own features, qualities, wishes, and intentions. The data obtained may be helpful in psychotherapeutic and rehabilitative work with such patients. PMID:22027663

  19. The fibromatoses: CT-pathologic correlation.

    PubMed

    Francis, I R; Dorovini-Zis, K; Glazer, G M; Lloyd, R V; Amendola, M A; Martel, W

    1986-11-01

    Although CT has been used in the evaluation of benign fibroblastic tumors (fibromatoses), data are lacking on radiologic-histopathologic correlation. In an attempt to explain the variable CT appearance of these lesions, a retrospective analysis was carried out of CT findings and histopathologic features in nine patients with fibromatoses. In three of four patients who had precontrast CT scans, the tumors were hyperdense relative to muscle, whereas in one patient the lesion was hypodense. The postenhancement appearance was variable. The pathologic specimens were analyzed and graded for collagen content, cellular content, tumor necrosis, and tumor vascularity. No consistent relationship could be established between the CT appearance of these lesions and their histologic appearance.

  20. Learning Biology with Plant Pathology.

    ERIC Educational Resources Information Center

    Carroll, Juliet E.

    This monograph contains 10 plant pathology experiments that were written to correspond to portions of a biology curriculum. Each experiment is suitable to a biology topic and designed to encourage exploration of those biological concepts being taught. Experiments include: (1) The Symptoms and Signs of Disease; (2) Koch's Postulates; (3)…

  1. Giving your heart to pathology.

    PubMed

    Klaassen, Jim

    2015-10-17

    Jim KIaassen recently joined Axiom Veterinary Laboratories as a clinical pathologist. During his career, Dr Klaassen has worked in small animal practice, lectured in clinical pathology, undertaken preclinical research and held senior roles in commercial veterinary laboratories in the USA, including as chief medical officer of Antech Diagnostics.

  2. Surgical pathology of urologic diseases

    SciTech Connect

    Javadpour, N.; Barsky, S.H.

    1987-01-01

    This text details recent advances in methods for detecting, diagnosing, and managing genitourinary diseases. Included are chapters on imaging techniques (including magnetic resonance imaging, computed tomography, and ultrasound; tumor markers (such as alphafetoprotein, human chorionic gonadotropin, prostatic specific antigen, and T-antigens); immunocytochemistry; pediatric urologic pathology; and other key topics.

  3. THE PATHOLOGY OF MENTAL RETARDATION.

    ERIC Educational Resources Information Center

    CROME, L.; STERN, J.

    DATA FROM RECENT COMPREHENSIVE STUDIES OF THE PATHOLOGY OF MENTAL RETARDATION ARE ASSEMBLED, INCLUDING MATERIAL ON ETIOLOGY, MORPHOLOGY, BIOCHEMISTRY, AND LABORATORY DIAGNOSIS. AREAS COVERED ARE (1) GENETIC CAUSES OF MENTAL RETARDATION, (2) DISORDERS OF GESTATION, (3) BIRTH INJURY, (4) GENERAL CONSIDERATIONS OF POSTNATAL CAUSES OF MENTAL…

  4. Vertical Feature Mask Feature Classification Flag Extraction

    Atmospheric Science Data Center

    2013-03-28

      Vertical Feature Mask Feature Classification Flag Extraction This routine demonstrates extraction of the ... in a CALIPSO Lidar Level 2 Vertical Feature Mask feature classification flag value. It is written in Interactive Data Language (IDL) ...

  5. Hepatocellular Carcinoma, Fibrolamellar Variant: Diagnostic Pathologic Criteria and Molecular Pathology Update. A Primer

    PubMed Central

    Sergi, Consolato M.

    2015-01-01

    Fibrolamellar hepatocellular carcinoma (FL-HCC) is generally a fairly rare event in routine pathology practice. This variant of hepatocellular carcinoma (HCC) is peculiarly intriguing and,in addition, poorly understood. Young people or children are often the target individuals with this type of cancer. Previously, I highlighted some pathology aspects of FL-HCC, but in this review, the distinctive clinico-pathologic features of FL-HCC and the diagnostic pathologic criteria of FL-HCC are fractionally reviewed and expanded upon. Further, molecular genetics update data with reference to this specific tumor are particularly highlighted as a primer for general pathologists and pediatric histopathologists. FL-HCC may present with metastases, and regional lymph nodes may be sites of metastatic spread. However, peritoneal and pulmonary metastatic foci have also been reported. To the best of our knowledge, FL-HCC was initially considered having an indolent course, but survival outcomes have recently been updated reconsidering the prognosis of this tumor. Patients seem to respond well to surgical resection, but recurrences are common. Thus, alternative therapies, such as chemotherapy and radiation, are ongoing. Overall, it seems that this aspect has not been well-studied for this variant of HCC and should be considered as target for future clinical trials. Remarkably, FL-HCC data seem to point to a liver neoplasm of uncertain origin and unveiled outcome. A functional chimeric transcript incorporating DNAJB1 and PRKACA was recently added to FL-HCC. This sensational result may give remarkable insights into the understanding of this rare disease and potentially provide the basis for its specific diagnostic marker. Detection of DNAJB1-PRKACA seems to be, indeed, a very sensitive and specific finding in supporting the diagnosis of FL-HCC. In a quite diffuse opinion, prognosis of this tumor should be reconsidered following the potentially mandatory application of new molecular

  6. The Value of Large Sections in Surgical Pathology

    PubMed Central

    Foschini, Maria P.; Baldovini, Chiara; Ishikawa, Yuko; Eusebi, Vincenzo

    2012-01-01

    Large format sections (LS) first have been introduced in breast pathology more than a century ago. Since then, they constituted for longtime a research tool to better understand breast microanatomy and the relationship between radiological images and pathological features. Similarly LS have been used to study neoplastic, inflammatory, and degenerative diseases affecting various organs, as brain, lung, gastrointentinal tract, bone, urinary tract, prostate, and placenta. Currently LS are mostly applied to diagnostic routine to better stage tumours such as prostate and breast carcinomas or to correlate radiologic imaging to gross specimens. The purpose of the present paper is to review the historical background and the basis of the applications of LS in surgical pathology, with special emphasis on breast tumours. PMID:23227346

  7. [Principles of pathological diagnosis in children with congenital abnormalities].

    PubMed

    Ivanovskaia, T E; Kogoi, T F; Voloshchuk, I N

    1983-01-01

    The features of establishment of pathological diagnosis in children with congenital malformations (CM) are discussed. An analysis of 1058 autopsy records of the centralized department of pathology of the Children's Clinical Hospital No. 1, Moscow, was carried out. CM were found in 236 cases (22.3% of the total number of autopsies). In 117 cases (49.6% of all CM observations) CM was the main disease, in 82 (34.7%) observations CM were combined with other diseases. In the establishment of pathological diagnosis in cases of combined diseases, the epidemiological situation, the importance of one or another process for statistical generalizations should be taken into consideration. In our opinion, preference should be given to cases of intrauterine, highly contagious, and nosocomial infections. In 37 (15.7%) observations CM exerted no effect on the course of the disease and was classified as the background condition.

  8. Pathology and sensitivity of current clinical criteria in corticobasal syndrome.

    PubMed

    Ouchi, Haruka; Toyoshima, Yasuko; Tada, Mari; Oyake, Mutsuo; Aida, Izumi; Tomita, Itsuro; Satoh, Akira; Tsujihata, Mitsuhiro; Takahashi, Hitoshi; Nishizawa, Masatoyo; Shimohata, Takayoshi

    2014-02-01

    The aim of this study was to investigate corticobasal syndrome with respect to underlying pathologies, the ability of current clinical criteria to detect early stages of disease, and symptoms and signs predicting background pathologies. We retrospectively analyzed the clinicopathological findings from patients with corticobasal syndrome. We also analyzed whether those findings fulfilled the diagnostic criteria for corticobasal degeneration (CBD). Finally, we investigated characteristic clinical features that are specific to each background pathology. Of 10 consecutive autopsied patients who had corticobasal syndrome (mean age ± standard deviation, 67.9 ± 9.3 years; male:female ratio, 6:4), three had corticobasal degeneration pathology, three had progressive supranuclear palsy, three had Alzheimer's disease, and one had atypical four-repeat tauopathy. Nine patients fulfilled Mayo criteria, and all 10 patients fulfilled modified Cambridge criteria at the later stage, but only two patients fulfilled either clinical criteria within 2 years of disease onset. Five patients fulfilled the clinical criteria for possible CBD (p-CBD), and one patient fulfilled the clinical research criteria for probable sporadic CBD (cr-CBD) at the later stage. Only two patients fulfilled the criteria for either p-CBD or cr-CBD within 2 years of disease onset. Although we could not find any predictive characteristic clinical features that were specific to CBD pathology, only patients with progressive supranuclear palsy developed apraxia of eyelid opening and cerebellar ataxia. Myoclonus and memory impairment, especially if they appear at an early stage of the disease, may predict Alzheimer's disease pathology. Sensitivity of the available clinical criteria for corticobasal syndrome was poor within 2 years of disease onset.

  9. The Complement System and Adverse Pregnancy Outcomes

    PubMed Central

    Regal, Jean F.; Gilbert, Jeffrey S.; Burwick, Richard M.

    2015-01-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the feta allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092

  10. ADVERSE DRUG REACTIONS IN THE ORAL CAVITY.

    PubMed

    Boras, Vanja Vučićević; Andabak-Rogulj, Ana; Brailo, Vlaho; Šimunković, Sonja Kraljević; Gabrić, Dragana; Vrdoljak, Danko Velimir

    2015-06-01

    Every medication may lead to adverse effects, even when used in standard doses and mode of application. In the oral cavity, adverse effects may affect every part of oral mucosa and are the result of medications taken either locally or systemically. Oral adverse reactions to drugs are not typical and therefore sometimes not easy to recognize. On diagnosing adverse side effects in the oral cavity, experienced clinician will usually diagnose the condition on the basis of detailed medical history and clinical finding. However, the only objective evidence for the offending drug is 're-challenge', i.e. exposure to the drug after its discontinuation. It carries a huge risk of anaphylactic reaction; therefore it has to be performed in a controlled hospital setting. Therapy is based on immediate exclusion of the offending drug and, if lesions are present in the oral cavity, topical or systemic corticosteroid therapy is prescribed. This article gives a review of patients with oral adverse drug reactions referred to the Department of Oral Medicine in Zagreb.

  11. Putative adverse outcome pathways relevant to neurotoxicity

    PubMed Central

    Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028

  12. The complement system and adverse pregnancy outcomes.

    PubMed

    Regal, Jean F; Gilbert, Jeffrey S; Burwick, Richard M

    2015-09-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the fetal allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child.

  13. Histopathological Features of Brain Arteriovenous Malformations in Japanese Patients

    PubMed Central

    HERMANTO, Yulius; TAKAGI, Yasushi; YOSHIDA, Kazumichi; ISHII, Akira; KIKUCHI, Takayuki; FUNAKI, Takeshi; MINEHARU, Yohei; MIYAMOTO, Susumu

    2016-01-01

    Clinical features of high risk brain arteriovenous malformations (BAVMs) are well characterized. However, pathological evidences about the differences that are possessed by high risk patients are still lacking. We reviewed archived routine hematoxylin-eosin specimens from a total of 54 surgical treated BAVMs. The histopathological features in nidus were semi-quantitatively analyzed. We obtained the pathological differences of BAVMs nidus between several clinical features. Among the analyzed pathological features, the significant differences were observed in degree of venous enlargement and intimal hyperplasia. Juvenile, female, diffuse nidus, high Spetzler-Martin grade, and low flow patients had a lesser degree of those parameters compared to adult, male, compact nidus, low Spetzler-Martin grade and high flow patients. High risk profiles of BAVMs patients were well-reflected in the nidus pathology. Therefore, juvenile, female, diffuse nidus, and low flow in Japanese BAVMs patients might have different vascular remodeling process that predispose to higher tendency of hemorrhage. PMID:27053330

  14. Pathology effects at radiation doses below those causing increased mortality

    NASA Technical Reports Server (NTRS)

    Carnes, Bruce A.; Gavrilova, Natalia; Grahn, Douglas

    2002-01-01

    Mortality data from experiments conducted at the Argonne National Laboratory (ANL) on the long-term effects of external whole-body irradiation on B6CF(1) mice were used to investigate radiation-induced effects at intermediate doses of (60)Co gamma rays or fission-spectrum neutrons either delivered as a single exposure or protracted over 60 once-weekly exposures. Kaplan-Meier analyses were used to identify the lowest dose in the ANL data (within radiation quality, pattern of exposure, and sex) at which radiation-induced mortality caused by primary tumors could be detected (approximately 1-2 Gy for gamma rays and 10-15 cGy for neutrons). Doses at and below these levels were then examined for radiation-induced shifts in the spectrum of pathology detected at death. To do this, specific pathology events were pooled into larger assemblages based on whether they were cancer, cardiovascular disease or non-neoplastic diseases detected within the lungs and pleura, liver and biliary tract, reproductive organs, or urinary tract. Cancer and cardiovascular disease were further subdivided into categories based on whether they caused death, contributed to death, or were simply observed at death. Counts of how often events falling within each of these combined pathology categories occurred within a mouse were then used as predictor variables in logistic regression to determine whether irradiated mice could be distinguished from control mice. Increased pathology burdens were detected in irradiated mice at doses lower than those causing detectable shifts in mortality-22 cGy for gamma rays and 2 cGy for neutrons. These findings suggest that (1) models based on mortality data alone may underestimate radiation effects, (2) radiation may have adverse health consequences (i.e. elevated health risks) even when mortality risks are not detected, and (3) radiation-induced pathologies other than cancer do occur, and they involve multiple organ systems.

  15. A Novel Small Molecule Modulator of Amyloid Pathology.

    PubMed

    Lovell, Mark A; Lynn, Bert C; Fister, Shuling; Bradley-Whitman, Melissa; Murphy, M Paul; Beckett, Tina L; Norris, Christopher M

    2016-05-01

    Because traditional approaches to drug development for Alzheimer's disease are becoming increasingly expensive and in many cases disappointingly unsuccessful, alternative approaches are required to shift the paradigm. Following leads from investigations of dihydropyridine calcium channel blockers, we observed unique properties from a class of functionalized naphthyridines and sought to develop these as novel therapeutics that minimize amyloid pathology without the adverse effects associated with current therapeutics. Our data show methyl 2,4-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridine-1-carboxylate (BNC-1) significantly decreases amyloid burden in a well-established mouse model of amyloid pathology through a unique mechanism mediated by Elk-1, a transcriptional repressor of presenilin-1. Additionally, BNC-1 treatment leads to increased levels of synaptophysin and synapsin, markers of synaptic integrity, but does not adversely impact presenilin-2 or processing of Notch-1, thus avoiding negative off target effects associated with pan-gamma secretase inhibition. Overall, our data show BNC-1 significantly decreases amyloid burden and improves markers of synaptic integrity in a well-established mouse model of amyloid deposition by promoting phosphorylation and activation of Elk-1, a transcriptional repressor of presenilin-1 but not presenilin-2. These data suggest BNC-1 might be a novel, disease-modifying therapeutic that will alter the pathogenesis of Alzheimer's disease. PMID:27163808

  16. Interleukin-22: immunobiology and pathology

    PubMed Central

    Dudakov, Jarrod A.; Hanash, Alan M.; van den Brink, Marcel R.M.

    2015-01-01

    Interleukin-22 (IL-22) is a recently described IL-10 family cytokine that is produced by T-helper (Th)-17 cells, γδ T cells, NKT cells and newly described innate lymphoid cells (ILCs). Knowledge of IL-22 biology has rapidly evolved since its discovery in 2000, and a role for IL-22 has been identified in numerous tissues including the intestines, lung, liver, kidney, thymus, pancreas and skin. IL-22 primarily targets non-hematopoietic epithelial and stromal cells where it can promote proliferation and play a role in tissue regeneration. In addition, IL-22 regulates host defense at barrier surfaces. However, IL-22 has also been linked to several conditions involving inflammatory tissue pathology. In this review, we will assess the current understanding of this cytokine, including its physiologic and pathologic effects on epithelial cell function. PMID:25706098

  17. α-Synuclein: Experimental Pathology.

    PubMed

    Hasegawa, Masato; Nonaka, Takashi; Masuda-Suzukake, Masami

    2016-01-01

    α-Synuclein, which is present as a small, soluble, cytosolic protein in healthy subjects, is converted to amyloid-like fibrils in diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Bulk synthesis of purified α-synuclein has made it more convenient to study the nature of the normal protein and the mechanism of its conversion to an abnormal form in vitro and in vivo. Synthetic α-synuclein fibrils and pathological α-synuclein from diseased brains can act as triggers to convert normal α-synuclein to an abnormal form via prion-like mechanisms. In this article, we describe the experimental pathologies of α-synuclein both in vitro and in vivo in human and animal models. Prion-like spreading of abnormal α-synuclein from cell to cell can account for the progression of these α-synucleinopathies. PMID:27481772

  18. Rotator cuff and subacromial pathology.

    PubMed

    Yablon, Corrie M; Jacobson, Jon A

    2015-07-01

    Both MRI and ultrasound (US) demonstrate equivalent accuracy in the evaluation of the rotator cuff. Both modalities have their advantages, disadvantages, and pitfalls. Radiography is an important complementary modality in that it can demonstrate occult sources of shoulder pain. MRI is recommended for the evaluation of shoulder pain in patients < 40 years of age because labral pathology is frequently identified. However, in patients > 40 years, US should be the first-line modality because the incidence of rotator cuff pathology increases with age. US is useful to guide procedures such as subacromial injection and calcific tendinosis lavage. Radiologists should be knowledgeable of both MRI and US of the shoulder to tailor these examinations to the specific needs of their patients.

  19. Pathological Significance of Mitochondrial Glycation

    PubMed Central

    Pun, Pamela Boon Li; Murphy, Michael P.

    2012-01-01

    Glycation, the nonenzymatic glycosylation of biomolecules, is commonly observed in diabetes and ageing. Reactive dicarbonyl species such as methylglyoxal and glyoxal are thought to be major physiological precursors of glycation. Because these dicarbonyls tend to be formed intracellularly, the levels of advanced glycation end products on cellular proteins are higher than on extracellular ones. The formation of glycation adducts within cells can have severe functional consequences such as inhibition of protein activity and promotion of DNA mutations. Although several lines of evidence suggest that there are specific mitochondrial targets of glycation, and mitochondrial dysfunction itself has been implicated in disease and ageing, it is unclear if glycation of biomolecules specifically within mitochondria induces dysfunction and contributes to disease pathology. We discuss here the possibility that mitochondrial glycation contributes to disease, focussing on diabetes, ageing, cancer, and neurodegeneration, and highlight the current limitations in our understanding of the pathological significance of mitochondrial glycation. PMID:22778743

  20. Quality in pathology laboratory practice.

    PubMed

    Weinstein, S

    1995-06-01

    Quality refers not only to analytical quality control, a traditional area of laboratory excellence, but to the entire science of quality management. As measures of quality, structural indicators refer to staffing and physical facilities, process indicators to the institutions operations and, perhaps most importantly, outcome indicators address the ultimate patient care uses that pathology information is put to. Comparison of performance to peer laboratories, external quality control, is a practical, if limited, yardstick of performance. Customer satisfaction and turn-around-time of tests are receiving more recent attention as quality measures. Blood banking, because of its inherently complex cycle from donor phlebotomy to product infusion, requires special considerations with regard to quality management. Reporting of anatomical pathology, where the only gold standard is a consensus of experts, also does not lend itself to classical numerical quality assessment. PMID:7670717

  1. Pathology of traumatic brain injury.

    PubMed

    Finnie, John W

    2014-12-01

    Although traumatic brain injury (TBI) is frequently encountered in veterinary practice in companion animals, livestock and horses, inflicted head injury is a common method of euthanasia in domestic livestock, and malicious head trauma can lead to forensic investigation, the pathology of TBI has generally received little attention in the veterinary literature. This review highlights the pathology and pathogenesis of cerebral lesions produced by blunt, non-missile and penetrating, missile head injuries as an aid to the more accurate diagnosis of neurotrauma cases. If more cases of TBI in animals that result in fatality or euthanasia are subjected to rigorous neuropathological examination, this will lead to a better understanding of the nature and development of brain lesions in these species, rather than extrapolating data from human studies. PMID:25178417

  2. Adverse reaction; patent blue turning patient blue.

    PubMed

    Joshi, Meera; Hart, Matthew; Ahmed, Farid; McPherson, Sandy

    2012-11-30

    The authors report a severe anaphylactic reaction to Patent Blue V dye used in sentinel node biopsy for lymphatic mapping during breast cancer surgery to stage the axilla. Patent Blue dye is the most widely used in the UK; however, adverse reactions have been reported with the blue dye previously. This case highlights that reactions may not always be immediately evident and to be vigilant in all patients that have undergone procedures using blue dye. If the patients are not responding appropriately particularly during an anaesthetic, one must always think of a possible adverse reaction to the dye. All surgical patients should give consent for adverse reactions to patent blue dye preoperatively. Alternative agents such as methylene blue are considered.

  3. The multisystem adverse effects of NSAID therapy.

    PubMed

    James, D S

    1999-11-01

    The clinical utility of nonsteroidal anti-inflammatory drugs (NSAIDs) to manage pain and inflammation is limited by adverse side effects. Although effective analgesic and anti-inflammatory agents, NSAIDs are associated with side effects that are a consequence of nonspecific inhibition of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). The primary adverse events associated with NSAID therapy are upper gastrointestinal (GI) ulceration, perforation, or bleeding, all of which involve mucosal damage of varying severity and can be asymptomatic and occur with little warning. Clinicians who prescribe NSAIDs should be able to identify patients who are at risk of an NSAID-induced GI adverse event and to detect and manage the event should one occur. The use of COX-2-specific inhibitors to manage pain and inflammation may minimize the risks of NSAID-associated toxicities.

  4. Adverse health consequences of the Iraq War.

    PubMed

    Levy, Barry S; Sidel, Victor W

    2013-03-16

    The adverse health consequences of the Iraq War (2003-11) were profound. We conclude that at least 116,903 Iraqi non-combatants and more than 4800 coalition military personnel died over the 8-year course. Many Iraqi civilians were injured or became ill because of damage to the health-supporting infrastructure of the country, and about 5 million were displaced. More than 31,000 US military personnel were injured and a substantial percentage of those deployed suffered post-traumatic stress disorder, traumatic brain injury, and other neuropsychological disorders and their concomitant psychosocial problems. Many family members of military personnel had psychological problems. Further review of the adverse health consequences of this war could help to minimise the adverse health consequences of, and help to prevent, future wars.

  5. Identifying Adverse Drug Events by Relational Learning.

    PubMed

    Page, David; Costa, Vítor Santos; Natarajan, Sriraam; Barnard, Aubrey; Peissig, Peggy; Caldwell, Michael

    2012-07-01

    The pharmaceutical industry, consumer protection groups, users of medications and government oversight agencies are all strongly interested in identifying adverse reactions to drugs. While a clinical trial of a drug may use only a thousand patients, once a drug is released on the market it may be taken by millions of patients. As a result, in many cases adverse drug events (ADEs) are observed in the broader population that were not identified during clinical trials. Therefore, there is a need for continued, post-marketing surveillance of drugs to identify previously-unanticipated ADEs. This paper casts this problem as a reverse machine learning task, related to relational subgroup discovery and provides an initial evaluation of this approach based on experiments with an actual EMR/EHR and known adverse drug events. PMID:24955289

  6. Insulin dysfunction and Tau pathology

    PubMed Central

    El Khoury, Noura B.; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

    2013-01-01

    The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia. PMID:24574966

  7. Diagnostic pathology in 2012: development of digital pathology in an open access journal

    PubMed Central

    2013-01-01

    Abstract Herein we describe and interpret the digital world of diagnostic surgical pathology, and take the in Pathology leading Open Access Journal Diagnostic Pathology as example. Virtual slide http://www.diagnosticpathology.diagnomx.eu/vs/1944221953867351 PMID:23305209

  8. The molecular pathology of haemophilia.

    PubMed

    Larner, A J

    1987-06-01

    The great success of recombinant DNA technology in unravelling the pathology of the thalassaemias at a molecular level has encouraged the application of these methods to other single gene disorders of man in the hope of gaining a deeper insight into the biochemical defects underlying them. An example of this approach is provided by the sex-linked recessive disorders of blood clotting: haemophilia and Christmas disease. These clinically indistinguishable, life-long disorders result from the deficiency or abnormality of the clotting proteins factor VIII and factor IX, respectively, which both participate in the activation of factor X in the intrinsic pathway of blood coagulation. This paper looks at the information concerning the molecular biology and pathology of the haemophilias which has recently been forthcoming. The genes for factor VIII and factor IX have both been successfully cloned within the past five years, with that of factor VIII, achieved in 1984, being a particular tour de force. It encompasses 0.1 per cent of the human X chromosome and is the largest gene yet characterised. Gene cloning is the starting point from which gene probes can be designed to elucidate the molecular pathology of the haemophilias. The implications of these discoveries for the practice of clinical medicine are reviewed, with special emphasis on prenatal diagnosis and carrier detection by means of restriction fragment length polymorphisms, and replacement therapy with recombinant factor VIII.

  9. Factorial Structure of Pathological Personality as Evaluated by Peers

    PubMed Central

    Thomas, Cannon; Turkheimer, Eric; Oltmanns, Thomas F.

    2015-01-01

    This study explored how individuals apply features of personality disorders (PDs) to peers. Members of groups nominated peers who exhibited symptoms for each of the 10 PDs in the DSM–IV. Data were gathered in 2 samples: 1st-year college students (n = 1,440) and Air Force recruits (n = 2,075). The peer method reliably identified group members exhibiting specific PD features. Factor analyses identified a clearly interpretable structure relevant to the pathological personality constructs being assessed. The structure replicated well across samples and showed expected relationships to broader models of normal personality. However, cross-method correlations of factor scores were only moderate, suggesting that peer reports are reliably different from self-reports regarding the presence of pathological personality traits. PMID:12653416

  10. Metals and cholesterol: two sides of the same coin in Alzheimer’s disease pathology

    PubMed Central

    Wong, Bruce X.; Hung, Ya Hui; Bush, Ashley I.; Duce, James A.

    2014-01-01

    Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease. It begins years prior to the onset of clinical symptoms, such as memory loss and cognitive decline. Pathological hallmarks of AD include the accumulation of β-amyloid in plaques and hyperphosphorylated tau in neurofibrillary tangles. Copper, iron, and zinc are abnormally accumulated and distributed in the aging brain. These metal ions can adversely contribute to the progression of AD. Dysregulation of cholesterol metabolism has also been implicated in the development of AD pathology. To date, large bodies of research have been carried out independently to elucidate the role of metals or cholesterol on AD pathology. Interestingly, metals and cholesterol affect parallel molecular and biochemical pathways involved in AD pathology. The possible links between metal dyshomeostasis and altered brain cholesterol metabolism in AD are reviewed. PMID:24860500

  11. The pathology of cartilage in chondrodysplasias.

    PubMed

    Hwang, W S; Tock, E P; Tan, K L; Tan, L K

    1979-01-01

    The pathology of four types of chondrodysplasias, viz., type II achondrogenesis, thanatophoric dwarfism, Saldino-Noonan syndrome, and chondrodysplasia punctata were studied. In each of these disorders, cells with features similar to the chief and dark chondrocytes of normal hyaline cartilage were seen to be altered in different ways. There was a total absence of chief cells in type II achondrogenesis. All the chondrocytes present were of one variety at different states of maturation, with the fully matured cell having features of dark chondrocytes. The absence of chief cells was associated with marked diminution of interlacunar matrix and failure of growth plate development. The chief chondrocytes in thanatophoric dwarfism appeared diminished in number. They were probably abnormal functionally as evident by their lack of cytoplasmic vacuolation and the formation of thick, occasionally branched collagen in the matrix. The growth plate was stunted and poorly developed. Striking changes involving the dark cells were noted in Saldino-Noonan syndrome, where unusually elongated dark cells were found in groups within abnormal cystic spaces. The chief cells were large and contained abnormal cytoplasmic filaments. There was no formation of a growth plate. In chondrodysplasia punctata, the chief cells were enlarged and abnormally vacuolated. The matrix showed excessive aggregates of coarse granular material. In addition, there were focal accumulations of highly abnormal chief and dark cells with abnormal matrix which contained increased amount of keratan sulphate and culminated in spotty calcification. PMID:469631

  12. Vaginal Fluid Inflammatory Biomarkers and the Risk of Adverse Neonatal Outcomes in Women with PPROM.

    PubMed

    Dorfeuille, Nydia; Morin, Valérie; Tétu, Amélie; Demers, Suzanne; Laforest, Geneviève; Gouin, Katy; Piedboeuf, Bruno; Bujold, Emmanuel

    2016-08-01

    Objective The purpose of this study was to evaluate the predictive value of vaginal fluid biomarkers for chorioamnionitis and adverse perinatal outcomes in women with preterm premature rupture of membranes (PPROM). Methods We recruited women with PPROM, without clinical chorioamnionitis, between 22 and 36 weeks' gestation. Vaginal fluid was collected on admission for the measurement of metalloproteinase-8 (MMP-8), interleukin-6 (IL-6), lactate, and glucose concentration. Placental pathology and neonatal charts were reviewed. Primary outcomes were histological chorioamnionitis and adverse neonatal neurological outcomes (intraventricular hemorrhage grade 2 or 3, periventricular leukomalacia, or hypoxic/ischemic encephalopathy). Linear regression analyses were used to adjust for gestational age at PPROM. Results Twenty-seven women were recruited at a mean gestational age of 31.6 ± 3.1 weeks, including 25 (93%) with successful collection of vaginal fluid sample. Histological chorioamnionitis and adverse neonatal neurological outcomes were observed in nine (33%) and four (15%) cases, respectively. In univariate analysis, MMP-8, IL-6, glucose, and lactate concentrations in vaginal fluid were associated with the risk of chorioamnionitis but not anymore after adjustment for gestational age at PPROM. MMP-8 concentration was the only biomarker associated with adverse neurological outcome, and it remained significant after adjustment for gestational age at PPROM (p = 0.02). Conclusion Vaginal fluid inflammatory biomarkers at admission for PPROM could predict adverse perinatal outcomes. PMID:27120475

  13. Corpus callosum: normal imaging appearance, variants and pathologic conditions.

    PubMed

    Battal, B; Kocaoglu, M; Akgun, V; Bulakbasi, N; Tayfun, C

    2010-12-01

    Various types of lesions can occur within the corpus callosum (CC) which is a white matter tract communicating corresponding regions of the cerebral hemispheres. Magnetic resonance imaging is the modality of choice for the evaluation of the CC. In addition, diffusion weighted imaging and diffusion tensor imaging can provide additional information about the CC. The aim of this study is to illustrate the imaging features of the corpus callosum and its pathologies. PMID:21199431

  14. Maternal floor infarction: management of an underrecognized pathology.

    PubMed

    Al-Sahan, Nada; Grynspan, David; von Dadelszen, Peter; Gruslin, Andrée

    2014-01-01

    Maternal floor infarction is a relatively rare condition characterized clinically by severe early onset fetal growth restriction with features of uteroplacental insufficiency. It has a very high recurrence rate and carries a significant risk or fetal demise. Pathological characteristics include massive and diffuse fibrin deposition along the decidua basalis and the perivillous space of the basal plate. We present a case of recurrent maternal floor infarction and propose diagnostic clues as well as potential therapeutic options.

  15. Imaging Spectrum of Cerebellar Pathologies: A Pictorial Essay

    PubMed Central

    Arora, Richa

    2015-01-01

    Summary The cerebellum is a crucial structure of hindbrain which helps in maintaining motor tone, posture, gait and also coordinates skilled voluntary movements including eye movements. Cerebellar abnormalities have different spectrum, presenting symptoms and prognosis as compared to supratentorial structures and brainstem. This article intends to review the various pathological processes involving the cerebellum along with their imaging features on MR, which are must to know for all radiologists, neurologists and neurosurgeons for their prompt diagnosis and management. PMID:25806100

  16. DSM-III-R and ICD-10 personality disorder features among women experiencing two types of self-reported homesickness: an exploratory study.

    PubMed

    Eurelings-Bontekoe, E H; Brouwers, E; Verschuur, M; Duijsens, I

    1998-08-01

    This study investigated the intensity of DSM-III-R and ICD-10 personality disorder features among females experiencing self-reported homesickness. Three groups were compared: (a) a group of women experiencing chronic feelings of homesickness (CHS); (b) a group of women experiencing episodic attacks of homesickness, each time they go on holidays (EHS); and (c) a group of healthy control females, recruited from the general population (HC). This study aimed to investigate whether the homesick participants showed stronger features of personality pathology than the controls and whether those who report experiencing chronic feelings of homesickness showed stronger features of personality pathology than those who at the moment of testing were not in an actual state of homesickness. Glass effect sizes revealed that the DSM-III-R avoidant and dependent and the ICD-10 anxious and dependent traits were most strongly associated with either type of homesickness. Finally, CHS was particularly associated with passive-aggressive traits and EHS with sadistic traits. Based on the stories of 21 homesick women, a link between adverse attachment experiences in childhood and certain personality features on the one hand and homesickness on the other is tentatively suggested.

  17. From the radiologic pathology archives imaging of osteonecrosis: radiologic-pathologic correlation.

    PubMed

    Murphey, Mark D; Foreman, Kristopher L; Klassen-Fischer, Mary K; Fox, Michael G; Chung, Ellen M; Kransdorf, Mark J

    2014-01-01

    Osteonecrosis is common and represents loss of blood supply to a region of bone. Common sites affected include the femoral head, humeral head, knee, femoral/tibial metadiaphysis, scaphoid, lunate, and talus. Symptomatic femoral head osteonecrosis accounts for 10,000-20,000 new cases annually in the United States. In contradistinction, metadiaphyseal osteonecrosis is often occult and asymptomatic. There are numerous causes of osteonecrosis most commonly related to trauma, corticosteroids, and idiopathic. Imaging of osteonecrosis is frequently diagnostic with a serpentine rim of sclerosis on radiographs, photopenia in early disease at bone scintigraphy, and maintained yellow marrow at MR imaging with a serpentine rim of high signal intensity (double-line sign) on images obtained with long repetition time sequences. These radiologic features correspond to the underlying pathology of osseous response to wall off the osteonecrotic process and attempts at repair with vascularized granulation tissue at the reactive interface. The long-term clinical importance of epiphyseal osteonecrosis is almost exclusively based on the likelihood of overlying articular collapse. MR imaging is generally considered the most sensitive and specific imaging modality both for early diagnosis and identifying features that increase the possibility of this complication. Treatment subsequent to articular collapse and development of secondary osteoarthritis typically requires reconstructive surgery. Malignant transformation of osteonecrosis is rare and almost exclusively associated with metadiaphyseal lesions. Imaging features of this dire sequela include aggressive bone destruction about the lesion margin, cortical involvement, and an associated soft-tissue mass. Recognizing the appearance of osteonecrosis, which reflects the underlying pathology, improves radiologic assessment and is important to guide optimal patient management. PMID:25019438

  18. Late-onset inflammatory adverse reactions related to soft tissue filler injections.

    PubMed

    Alijotas-Reig, Jaume; Fernández-Figueras, Maria Teresa; Puig, Lluís

    2013-08-01

    An ever-increasing number of persons seek medical solutions to improve the appearance of their aging skin or for aesthetic and cosmetic indications in diverse pathological conditions, such as malformations, trauma, cancer, and orthopedic, urological, or ophthalmological conditions. Currently, physicians have many different types of dermal and subdermal fillers, such as non-permanent, permanent, reversible, or non-reversible materials. Despite the claims of manufacturers and different authors that fillers are non-toxic and non-immunogenic or that complications are very uncommon, unwanted side effects do occur with all compounds used. Implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions, including inflammation, thrombosis, and excessive fibrosis. Usually, these adverse reactions are associated with the accumulation of large numbers of mononuclear cells. The adverse reactions related to fillers comprise a broad range of manifestations, which may appear early or late and range from local to systemic. Clinicians should be aware of them since the patient often denies the antecedent of injection or is unaware of the material employed. Most of these adverse effects seem to have an immunological basis, the fillers acting more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies; management of both acute and systemic reactions is often difficult, and requires anti-inflammatory and occasionally immunosuppressive therapy. The clinical, pathological, and therapeutic aspects of inflammatory and immune-mediated late-onset adverse reactions related to soft tissue filler injections are thoroughly reviewed herein.

  19. Congruence Couple Therapy for Pathological Gambling

    ERIC Educational Resources Information Center

    Lee, Bonnie K.

    2009-01-01

    Couple therapy models for pathological gambling are limited. Congruence Couple Therapy is an integrative, humanistic, systems model that addresses intrapsychic, interpersonal, intergenerational, and universal-spiritual disconnections of pathological gamblers and their spouses to shift towards congruence. Specifically, CCT's theoretical…

  20. Adverse outcome pathway (AOP) development and evaluation

    EPA Science Inventory

    The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be mea...

  1. The adverse outcome pathway knowledge base

    EPA Science Inventory

    The rapid advancement of the Adverse Outcome Pathway (AOP) framework has been paralleled by the development of tools to store, analyse, and explore AOPs. The AOP Knowledge Base (AOP-KB) project has brought three independently developed platforms (Effectopedia, AOP-Wiki, and AOP-X...

  2. Linezolid Induced Adverse Drug Reactions - An Update.

    PubMed

    Kishor, Kamal; Dhasmana, Neha; Kamble, Shashank Shivaji; Sahu, Roshan Kumar

    2015-01-01

    Treatment regimen recommended for resistant tuberculosis consists of various drugs and these drugs are prescribed for at least 12-15 months. Such a long duration therapy and high dose of antibiotics result in adverse drug reactions (ADRs). ADRs may lead to various complications in disease management like replacement of drugs, dose increment, therapy withdrawal, etc. Linezolid is one of those drugs, practiced as an anti-mycobacterial agent and it is an important member of drug regimen for MDR and XDR tuberculosis. Linezolid is a broad spectrum antibiotic known for its unique mechanism of inhibition of resistant pathogenic strains. However, it causes serious adverse effects like thrombocytopenia, optic neuropathy, peripheral neuropathy, lactic acidosis, etc. Literature suggests that Linezolid can cause severe ADRs which affect patient compliance and hinder in therapy to a larger extent. Recent studies confirm the possibility of ADRs to be predicted with genetic make-up of individuals. To effectively deliver the available treatment regimen and ensure patient compliance, it is important to manage ADRs more efficiently. The role of pharmacogenomics in reducing adverse drug effects has been recently explored. In the present review, we discussed about Linezolid induced adverse drug reactions, mechanisms and genetic associations. PMID:26424176

  3. Pharmacogenomics and adverse drug reactions in children

    PubMed Central

    Rieder, Michael J.; Carleton, Bruce

    2014-01-01

    Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children. PMID:24795743

  4. Adverse Effects of Common Drugs: Dietary Supplements.

    PubMed

    Felix, Todd Matthew; Karpa, Kelly Dowhower; Lewis, Peter R

    2015-09-01

    Dietary supplement-induced adverse effects often resolve quickly after discontinuation of the offending product, especially in younger patients. The potential for unwanted outcomes can be amplified in elderly patients or those taking multiple prescription drugs, especially where interactions exist with drugs metabolized by cytochrome P450 enzymes. Attributing injury or illness to a specific supplement can be challenging, especially in light of multi-ingredient products, product variability, and variability in reporting, as well as the vast underreporting of adverse drug reactions. Clinicians prescribing a new drug or evaluating a patient with a new symptom complex should inquire about use of herbal and dietary supplements as part of a comprehensive evaluation. Clinicians should report suspected supplement-related adverse effects to the local or state health department, as well as the Food and Drug Administration's MedWatch program (available at https://www.safetyreporting.hhs.gov). Clinicians should consider discussing suspected adverse effects involving drugs, herbal products, or dietary supplements with their community- and hospital-based pharmacists, and explore patient management options with medical or clinical toxicology subspecialists.

  5. Reducing Adverse Impact: One City's Efforts.

    ERIC Educational Resources Information Center

    Prewitt, Jeff

    Following a workshop on "Innovations in Employment Testing that Improve Validity and Reduce Adverse Impact," the City of Louisville (Kentucky) implemented a strategy to develop a comprehensive testing and recruiting program for police recruits. To improve candidate expectations and preparation, the following activities were undertaken: intense…

  6. Helping Student Teachers Avoid Adverse Legal Actions.

    ERIC Educational Resources Information Center

    Peach, Larry; Reddick, Thomas L.

    1984-01-01

    Discusses five areas of the school environment lending themselves to the possibility of teacher and student teacher liability: negligence, malpractice, rights to privacy, field trips, and search of students and school property. Suggests specific guidelines for decreasing the possibility of adverse legal action. (NEC)

  7. Adverse effects of fillers and their histopathology.

    PubMed

    Haneke, Eckart

    2014-12-01

    Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options.

  8. Resilience in the Face of Adversity.

    ERIC Educational Resources Information Center

    Patterson, Jerry

    2001-01-01

    "Resilience" is the capacity for moving ahead under adverse circumstances. School superintendents are advised to stay upbeat and mindful of "both-and" opportunities; stay focused on what they care about; remain flexible and tolerant of ambiguity; be proactive, not reactive; and apply resilience-conserving strategies during tough times. (MLH)

  9. Adverse Effects of Psychotropic Medications on Sleep.

    PubMed

    Doghramji, Karl; Jangro, William C

    2016-09-01

    Psychotropic medications such as antidepressants, antipsychotics, stimulants, and benzodiazepines are widely prescribed. Most of these medications are thought to exert their effects through modulation of various monoamines as well as interactions with receptors such as histamine and muscarinic cholinergic receptors. Through these interactions, psychotropics can also have a significant impact on sleep physiology, resulting in both beneficial and adverse effects on sleep. PMID:27514301

  10. [Analysis of Spontaneously Reported Adverse Events].

    PubMed

    Nakamura, Mitsuhiro

    2016-01-01

    Observational study is necessary for the evaluation of drug effectiveness in clinical practice. In recent years, the use of spontaneous reporting systems (SRS) for adverse drug reactions has increased and they have become an important resource for regulatory science. SRS, being the largest and most well-known databases worldwide, are one of the primary tools used for postmarketing surveillance and pharmacovigilance. To analyze SRS, the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report Database (JADER) are reviewed. Authorized pharmacovigilance algorithms were used for signal detection, including the reporting odds ratio. An SRS is a passive reporting database and is therefore subject to numerous sources of selection bias, including overreporting, underreporting, and a lack of a denominator. Despite the inherent limitations of spontaneous reporting, SRS databases are a rich resource and data mining index that provide powerful means of identifying potential associations between drugs and their adverse effects. Our results, which are based on the evaluation of SRS databases, provide essential knowledge that could improve our understanding of clinical issues.

  11. Adverse effects of fillers and their histopathology.

    PubMed

    Haneke, Eckart

    2014-12-01

    Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options. PMID:25536126

  12. Alopecia in Systemic Amyloidosis: Trichoscopic-Pathologic Correlation

    PubMed Central

    Miteva, Mariya; Wei, Erin; Milikowski, Clara; Tosti, Antonella

    2015-01-01

    Alopecia in systemic amyloidosis is very rare and has been described as individual cases of diffuse nonscarring alopecia and a case of alopecia universalis. We report the trichoscopic findings in alopecia associated with systemic amyloidosis. The most prominent feature was a salmon colored halo (0.3-1 mm in diameter) surrounding the follicular ostia. Other features included broken hairs and black dots. The salmon colored halo correlated on pathology with the perifollicular deposition of amyloid. The horizontal sections showed that the sebaceous glands were preserved which supports the nonscarring pattern of the alopecia. PMID:26903748

  13. Pathology of testicular germ cell tumors.

    PubMed

    Brodsky, G L

    1991-12-01

    The pathology report on a testicular germ cell tumor should include the following information: Tumor type: The histologic type of tumor present. If the tumor is of mixed type, the components should be listed, in order of relative abundance. The pathologist may endeavor to give a numeric estimate of the percentages of each element. Staging information: The size of the tumor should be listed. Local spread--into rete testis, tunica albuginea, epididymis, and spermatic cord--should be listed. If the cord is involved, possible involvement of its surgical resection margin should be assessed. Vascular/lymphatic invasion should be assessed for its presence or absence. Status of the remainder of the testis: Evidence of cryptorchidism or other dysgenetic features should be mentioned. Such features may imply a greater risk for the development of a contralateral tumor. Also, the presence of normal spermatogenesis elsewhere in the uninvolved testis should be reported. This finding may suggest a relatively decreased risk for contralateral tumor development and is a likely indicator of fertility should the patient consider sperm banking prior to retroperitoneal surgery and chemotherapy. The finding of mature sperm in the epididymis is an easy way to confirm spermatogenesis in the testis. Incidental findings: Lipomas or hydroceles of the cord, adrenal rests, and adnexal cysts may be found. The pathologist plays a crucial role in the diagnosis of germ cell tumors. In addition to elucidating tumor type, the pathologist is relied upon for precise local staging and for the classification of metastases, all of which have important implications in determining optimal therapy. As the clinical management of germ cell tumors evolves, the pathologist will continue to play a role in defining those features that have a bearing on patient outcome.

  14. Genetic–pathologic characterization of myeloproliferative neoplasms

    PubMed Central

    Kim, Yonggoo; Park, Joonhong; Jo, Irene; Lee, Gun Dong; Kim, Jiyeon; Kwon, Ahlm; Choi, Hayoung; Jang, Woori; Chae, Hyojin; Han, Kyungja; Eom, Ki-Seong; Cho, Byung-Sik; Lee, Sung-Eun; Yang, Jinyoung; Shin, Seung-Hwan; Kim, Hyunjung; Ko, Yoon Ho; Park, Haeil; Jin, Jong Youl; Lee, Seungok; Jekarl, Dong Wook; Yahng, Seung-Ah; Kim, Myungshin

    2016-01-01

    Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more myeloid lineages. The current study demonstrates that three driver mutations were detected in 82.6% of 407 MPNs with a mutation distribution of JAK2 in 275 (67.6%), CALR in 55 (13.5%) and MPL in 6 (1.5%). The mutations were mutually exclusive in principle except in one patient with both CALR and MPL mutations. The driver mutation directed the pathologic features of MPNs, including lineage hyperplasia, laboratory findings and clinical presentation. JAK2-mutated MPN showed erythroid, granulocytic and/or megakaryocytic hyperplasia whereas CALR- and MPL-mutated MPNs displayed granulocytic and/or megakaryocytic hyperplasia. The lineage hyperplasia was closely associated with a higher mutant allele burden and peripheral cytosis. These findings corroborated that the lineage hyperplasia consisted of clonal proliferation of each hematopoietic lineage acquiring driver mutations. Our study has also demonstrated that bone marrow (BM) fibrosis was associated with disease progression. Patients with overt fibrosis (grade ⩾2) presented an increased mutant allele burden (P<0.001), an increase in chromosomal abnormalities (P<0.001) and a poor prognosis (P<0.001). Moreover, among patients with overt fibrosis, all patients with wild-type JAK2/CALR/MPL (triple-negative) showed genomic alterations by genome-wide microarray study and revealed the poorest overall survival, followed by JAK2-mutated MPNs. The genetic–pathologic characteristics provided the information for understanding disease pathogenesis and the progression of MPNs. The prognostic significance of the driver mutation and BM fibrosis suggests the necessity of a prospective therapeutic strategy to improve the clinical outcome. PMID:27444979

  15. [Urothelial carcinoma. Does surgical pathology learn from molecular pathology?].

    PubMed

    Hofstädter, F

    2008-11-01

    The question is raised whether the new theories about initiation and progression of urothelial carcinoma gained by molecular techniques show effects on the classification and histopathological diagnosis. As fundamental new concepts are considered: two pathways of tumor progression, clonality of synchronous and metachronous tumors, tumor-analogous molecular findings in flat lesions, and stromal invasion as dominant principle of molecular tumor classification.The dual pathogenesis of molecular pathology is reflected by the WHO 2004 classification by the differentiation into low and high grade malignancy, but diluted by the use of PUNLMP (papillary urothelial neoplasia of low malignant potential). The new concept of frequent oligoclonality should induce investigations about the mechanism of propagation of these migrating or metastasizing cells and whether they possess stem cell characteristics. The role of flat urothelial lesions must be revised from a molecular pathological view point, but the histological diagnosis does not gain profit till now. The expression signatures of stromal invasive tumors compared with non-invasive ones points to the major importance of an exact histopathological diagnosis in this area.

  16. Interactions of Pathological Hallmark Proteins

    PubMed Central

    Oláh, Judit; Vincze, Orsolya; Virók, Dezső; Simon, Dóra; Bozsó, Zsolt; Tőkési, Natália; Horváth, István; Hlavanda, Emma; Kovács, János; Magyar, Anna; Szűcs, Mária; Orosz, Ferenc; Penke, Botond; Ovádi, Judit

    2011-01-01

    The disordered tubulin polymerization promoting protein (TPPP/p25) was found to be co-enriched in neuronal and glial inclusions with α-synuclein in Parkinson disease and multiple system atrophy, respectively; however, co-occurrence of α-synuclein with β-amyloid (Aβ) in human brain inclusions has been recently reported, suggesting the existence of mixed type pathologies that could result in obstacles in the correct diagnosis and treatment. Here we identified TPPP/p25 as an interacting partner of the soluble Aβ oligomers as major risk factors for Alzheimer disease using ProtoArray human protein microarray. The interactions of oligomeric Aβ with proteins involved in the etiology of neurological disorders were characterized by ELISA, surface plasmon resonance, pelleting experiments, and tubulin polymerization assay. We showed that the Aβ42 tightly bound to TPPP/p25 (Kd = 85 nm) and caused aberrant protein aggregation by inhibiting the physiologically relevant TPPP/p25-derived microtubule assembly. The pair-wise interactions of Aβ42, α-synuclein, and tubulin were found to be relatively weak; however, these three components formed soluble ternary complex exclusively in the absence of TPPP/p25. The aggregation-facilitating activity of TPPP/p25 and its interaction with Aβ was monitored by electron microscopy with purified proteins by pelleting experiments with cell-free extracts as well as by confocal microscopy with CHO cells expressing TPPP/p25 or amyloid. The finding that the interaction of TPPP/p25 with Aβ can produce pathological-like aggregates is tightly coupled with unusual pathology of the Alzheimer disease revealed previously; that is, partial co-localization of Aβ and TPPP/p25 in the case of diffuse Lewy body disease with Alzheimer disease. PMID:21832049

  17. Expanding the spectrum of neuronal pathology in multiple system atrophy

    PubMed Central

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

    2015-01-01

    Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients

  18. Pathological gambling and criminal responsibility.

    PubMed

    Rachlin, S; Halpern, A L; Portnow, S L

    1986-01-01

    There exists significant interdisciplinary support for eliminating the volitional component of the insanity defense. Somewhat in contrast to this trend is the presentation of pathological gambling as a potentially exculpatory condition in criminal trials. The authors discuss three federal appellate court decisions on this attempted inappropriate usage of psychiatric diagnostic nomenclature. All have upheld convictions, and thereby rejected contentions that such an impulse disorder can form the basis for a valid plea of lack of criminal responsibility. It is suggested that the public interest will be served by statutorily making disturbances of behavioral control insufficient to raise a defense of insanity.

  19. Pathological buying and partnership status.

    PubMed

    Müller, Astrid; de Zwaan, Martina; Mitchell, James E; Zimmermann, Tanja

    2016-05-30

    This pilot study investigated the partnership status and the level of pathological buying (PB) in 157 female patients with PB and 1153 women from a German population-based sample. Slightly more than half of both samples were currently living with a partner. The results suggest a protective effect of being in a couple relationship in the representative sample. In contrast, having a partner was not related to the severity of PB among patients. Future studies should address the question of whether the characteristics and quality of partnership have an impact on the severity and course of PB, and vice versa.

  20. Iliopsoas: Pathology, Diagnosis, and Treatment.

    PubMed

    Anderson, Christian N

    2016-07-01

    Disorders of the iliopsoas can be a significant source of groin pain in the athletic population. Commonly described pathologic conditions include iliopsoas bursitis, tendonitis, impingement, and snapping. The first-line treatment for iliopsoas disorders is typically conservative, including activity modification, physical therapy, nonsteroidal anti-inflammatory drugs, and corticosteroid injections. Surgical treatment can be considered if the patient fails conservative measures and typically involves arthroscopic lengthening of the musculotendinous unit and treatment of concomitant intra-articular abnormality. Tendon release has been described: in the central compartment, in the peripheral compartment, and at the lesser trochanter, with similar outcomes observed between the techniques. PMID:27343394

  1. A comparison of active adverse event surveillance systems worldwide.

    PubMed

    Huang, Yu-Lin; Moon, Jinhee; Segal, Jodi B

    2014-08-01

    Post-marketing drug surveillance for adverse drug events (ADEs) has typically relied on spontaneous reporting. Recently, regulatory agencies have turned their attention to more preemptive approaches that use existing data for surveillance. We conducted an environmental scan to identify active surveillance systems worldwide that use existing data for the detection of ADEs. We extracted data about the systems' structures, data, and functions. We synthesized the information across systems to identify common features of these systems. We identified nine active surveillance systems. Two systems are US based-the FDA Sentinel Initiative (including both the Mini-Sentinel Initiative and the Federal Partner Collaboration) and the Vaccine Safety Datalink (VSD); two are Canadian-the Canadian Network for Observational Drug Effect Studies (CNODES) and the Vaccine and Immunization Surveillance in Ontario (VISION); and two are European-the Exploring and Understanding Adverse Drug Reactions by Integrative Mining of Clinical Records and Biomedical Knowledge (EU-ADR) Alliance and the Vaccine Adverse Event Surveillance and Communication (VAESCO). Additionally, there is the Asian Pharmacoepidemiology Network (AsPEN) and the Shanghai Drug Monitoring and Evaluative System (SDMES). We identified two systems in the UK-the Vigilance and Risk Management of Medicines (VRMM) Division and the Drug Safety Research Unit (DSRU), an independent academic unit. These surveillance systems mostly use administrative claims or electronic medical records; most conduct pharmacovigilance on behalf of a regulatory agency. Either a common data model or a centralized model is used to access existing data. The systems have been built using national data alone or via partnership with other countries. However, active surveillance systems using existing data remain rare. North America and Europe have the most population coverage; with Asian countries making good advances. PMID:25022829

  2. Prenatal Depression and Adverse Birth Outcomes: An Updated Systematic Review

    PubMed Central

    Accortt, Eynav Elgavish; Cheadle, Alyssa C. D.; Schetter, Christine Dunkel

    2015-01-01

    Complications related to preterm birth (PTB) and low birth weight (LBW) are leading causes of infant morbidity and mortality. Prenatal depression is a hypothesized psychosocial risk factor for both birth outcomes. The purpose of this systematic review was to examine evidence published between 1977 and 2013 on prenatal depression and risks of these primary adverse birth outcomes. A systematic search of the PUBMED and PsycINFO databases was conducted to identify studies testing the associations between prenatal depressive symptoms, or diagnoses of depression, and risk of PTB or LBW. We systematically selected 50 published reports on PTB and length of gestation, and 33 reports on LBW and BW. Results were reviewed by two independent reviewers and we evaluated the quality of the evidence with an established systematic review method, the Newcastle Ottawa Scale. We then undertook a narrative synthesis of the results following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Less than a quarter of 50 published reports found that prenatal depression was significantly associated with PTB or gestational age. In contrast, slightly more than half of the 33 reports found that prenatal depression was associated with LBW or BW. When weighing methodological features, we determined that the effects of prenatal depression on LBW are more consistent than effects on length of gestation or PTB. Although the evidence may not be strong enough to support routine depression screening for risk of adverse outcomes, screening to enable detection and timely treatment to reduce risk of postpartum depression is warranted. Further rigorous research on prenatal depression and adverse birth outcomes is needed. PMID:25452215

  3. The Adverse Effects of Air Pollution on the Nervous System

    PubMed Central

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  4. Virtual microscopy in pathology education.

    PubMed

    Dee, Fred R

    2009-08-01

    Technology for acquisition of virtual slides was developed in 1985; however, it was not until the late 1990s that desktop computers had enough processing speed to commercialize virtual microscopy and apply the technology to education. By 2000, the progressive decrease in use of traditional microscopy in medical student education had set the stage for the entry of virtual microscopy into medical schools. Since that time, it has been successfully implemented into many pathology courses in the United States and around the world, with surveys indicating that about 50% of pathology courses already have or expect to implement virtual microscopy. Over the last decade, in addition to an increasing ability to emulate traditional microscopy, virtual microscopy has allowed educators to take advantage of the accessibility, efficiency, and pedagogic versatility of the computer and the Internet. The cost of virtual microscopy in education is now quite reasonable after taking into account replacement cost for microscopes, maintenance of glass slides, and the fact that 1-dimensional microscope space can be converted to multiuse computer laboratories or research. Although the current technology for implementation of virtual microscopy in histopathology education is very good, it could be further improved upon by better low-power screen resolution and depth of field. Nevertheless, virtual microscopy is beginning to play an increasing role in continuing education, house staff education, and evaluation of competency in histopathology. As Z-axis viewing (focusing) becomes more efficient, virtual microscopy will also become integrated into education in cytology, hematology, microbiology, and urinalysis.

  5. The evolution of anatomic pathology.

    PubMed

    Cohen, Stanley; Coffman, Frederick

    2013-01-01

    Science advances both by conceptual leaps and by improved observational and analytic tools. Mechanism and function in biological systems can best be understood in the context of the complex microenvironments in which they occur, and for this purpose morphologic analysis can be critical. Technological advances in cell and tissue imaging are currently finding application in a wide variety of basic, translational, and clinical biomedical studies. "Biophotonics in Pathology" was designed as a multi-authored work to describe the various kinds of imaging strategies that have been developed as computational power keeps increasing. Some of these overlap with radiologic techniques and others do not. The field is continuously evolving, and in this commentary I will touch on additional techniques for morphology-based interrogation of cells and tissues that have recently been described. However, it is important to note that though we are expanding our armamentarium as pathologists, our radiological colleagues have been doing this for many years. Clearly, they have embraced new imaging techniques to a greater extent than have pathologists. This commentary discusses some of the factors responsible for this, and suggests that pathology and radiology are converging towards a more holistic approach to diagnostic imaging.

  6. Dental radiology and oral pathology.

    PubMed

    Halstead, C L; Hoard, B C

    1991-01-01

    This article represents an overview of normal and pathological findings of the oral structures for the practicing radiologist. Some of the disease processes discussed are of dental etiology, whereas others are manifestations of systemic diseases. Normal tooth development is described followed by an overview of radiolucent, radiopaque, and mixed lucent-opaque lesions. In the radiolucent category, normal anatomical landmarks of the jaws include the mental foramen, manidbular canal, incisive canal and maxillary sinuses. Other lucencies that represent normal structures or variations include developing tooth buds and root apices, healing dental extraction sites, prominent submandibular fossae and nutrient canals. In the radiopaque category, normal anatomical landmarks of the jaws include the genial tubercle, mental ridge, external oblique ridge, walls of the submandibular canal, walls of the maxillary sinus, nasal septum, stylohyoid ligament, and zygomatic process. Other opacities that represent normal structures or variations include dental restoration material, dental endodontic material, retained roots, sialoliths, salivary duct calculi, calcified lymph nodes, recent extraction sites, hypercementosis, and foreign bodies. Pathological entities which present radiographically as lucencies, opacities, and mixed lucent-opaque areas include inflammatory lesions, cysts, fibro-osseous disease, benign neoplasms, malignant neoplasms, and lesions secondary to metabolic disorders.

  7. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  8. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  9. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  10. Glaucoma eye drops adverse skin reactions.

    PubMed

    Cantisani, Carmen; Ambrifi, Marina; Frascani, Federica; Fazia, Gilda; Paolino, Giovanni; Lisi, Roberto; Calvieri, Stefano

    2014-01-01

    The term "Glaucoma" is used to describe a number of diseases of the eye characterized by a particular form of optic nerve damage that is often associated with high intraocular pressure (IOP). The open-angle glaucoma is the most common form that is also referred to as chronic glaucoma. This is described as an optic neuropathy with multifactorial nature in which there is a loss of characteristics of the optic nerve fibers. Therapeutic options for the treatment of this disease are different, you can take advantage of eye drops, laser therapy and conventional surgery or more combined treatments. Medicated eye drops are the most common way to treat glaucoma. Although eye drops are widely used, adverse reactions are not frequently observed and described. In particular, the adverse skin reactions are not frequently described in the literature, but often seen in dermatologic clinic, we reported their skin reactions and possible alternative treatments described in literature and their patent applications. PMID:25487259

  11. Adverse reactions to injectable soft tissue fillers.

    PubMed

    Requena, Luis; Requena, Celia; Christensen, Lise; Zimmermann, Ute S; Kutzner, Heinz; Cerroni, Lorenzo

    2011-01-01

    In recent years, injections with filler agents are often used for wrinkle-treatment and soft tissue augmentation by dermatologists and plastic surgeons. Unfortunately, the ideal filler has not yet been discovered and all of them may induce adverse reactions. Quickly biodegradable or resorbable agents may induce severe complications, but they will normally disappear spontaneously in a few months. Slowly biodegradable or nonresorbable fillers may give rise to severe reactions that show little or no tendency to spontaneous improvement. They may appear several years after the injection, when the patient does not remember which product was injected, and treatment is often insufficient. In this review, we discuss the most commonly used fillers, their most frequent adverse reactions as well as the characteristic histopathologic findings that allow the identification of the injected filler agent. In conclusion, histopathologic study remains as the gold standard technique to identify the responsible filler.

  12. An Ss Model with Adverse Selection.

    ERIC Educational Resources Information Center

    House, Christopher L.; Leahy, John V.

    2004-01-01

    We present a model of the market for a used durable in which agents face fixed costs of adjustment, the magnitude of which depends on the degree of adverse selection in the secondary market. We find that, unlike typical models, the sS bands in our model contract as the variance of the shock increases. We also analyze a dynamic version of the model…

  13. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors.

  14. Major adverse cardiac events during endurance sports.

    PubMed

    Belonje, Anne; Nangrahary, Mary; de Swart, Hans; Umans, Victor

    2007-03-15

    Major adverse cardiac events in endurance exercise are usually due to underlying and unsuspected heart disease. The investigators present an analysis of major adverse cardiac events that occurred during 2 consecutive annual long distance races (a 36-km beach cycling race and a 21-km half marathon) over the past 5 years. All patients with events were transported to the hospital. Most of the 62,862 participants were men (77%; mean age 40 years). Of these, 4 men (3 runners, 1 cyclist; mean age 48 years) collapsed during (n = 2) or shortly after the races, rendering a prevalence of 0.006%. Two patients collapsed after developing chest pain, 1 of whom needed resuscitation at the event site, which was successful. These patients had acute myocardial infarctions and underwent primary angioplasty. The third patient was resuscitated at the site but did not have coronary disease or inducible ventricular tachycardia or ventricular fibrillation and collapsed presumably because of catecholamine-induced ventricular fibrillation. The fourth patient experienced heat stroke and had elevated creatine kinase-MB and troponins in the absence of electrocardiographic changes. In conclusion, the risk for major adverse cardiac events during endurance sports in well-trained athletes is very low.

  15. Aging display's effect on interpretation of digital pathology slide

    NASA Astrophysics Data System (ADS)

    Avanaki, Ali R. N.; Espig, Kathryn S.; Sawhney, Sameer; Pantanowitzc, Liron; Parwani, Anil V.; Xthona, Albert; Kimpe, Tom R. L.

    2015-03-01

    It is our conjecture that the variability of colors in a pathology image effects the interpretation of pathology cases, whether it is diagnostic accuracy, diagnostic confidence, or workflow efficiency. In this paper, digital pathology images are analyzed to quantify the perceived difference in color that occurs due to display aging, in particular a change in the maximum luminance, white point, and color gamut. The digital pathology images studied include diagnostically important features, such as the conspicuity of nuclei. Three different display aging models are applied to images: aging of luminance and chrominance, aging of chrominance only, and a stabilized luminance and chrominance (i.e., no aging). These display models and images are then used to compare conspicuity of nuclei using CIE ΔE2000, a perceptual color difference metric. The effect of display aging using these display models and images is further analyzed through a human reader study designed to quantify the effects from a clinical perspective. Results from our reader study indicate significant impact of aged displays on workflow as well as diagnosis. Comparing original (not aged) images to aged images, aged images were significantly more difficult to read (p-value of 0.0005) and took longer to score (p-value of 0.02). Moreover, luminance and chrominance aging significantly reduced inter-session percent agreement of diagnostic scores (p-value of 0.0418).

  16. Psychiatric adverse effects of pediatric corticosteroid use.

    PubMed

    Drozdowicz, Linda B; Bostwick, J Michael

    2014-06-01

    Corticosteroids, highly effective drugs for myriad disease states, have considerable neuropsychiatric adverse effects that can manifest in cognitive disorders, behavioral changes, and frank psychiatric disease. Recent reviews have summarized these effects in adults, but a comprehensive review on corticosteroid effects in children has not been published since 2005. Here, we systematically review articles published since then that, we find, naturally divide into 3 main areas: (1) chronic effects of acute prenatal and neonatal exposure associated with prematurity and congenital conditions; (2) immediate behavioral effects of acute exposure via oncological protocols; and (3) acute behavioral effects of sporadic use in children and adolescents with other conditions. PsycInfo, MEDLINE, Embase, and Scopus were queried to identify articles reporting psychiatric adverse effects of corticosteroids in pediatric patients. Search terms included corticosteroids, adrenal cortex hormones, steroid psychosis, substance-induced psychoses, glucocorticoids, dexamethasone, hydrocortisone, prednisone, adverse effects, mood disorders, mental disorders, psychosis, psychotic, psychoses, side effect, chemically induced, emotions, affective symptoms, toxicity, behavior, behavioral symptoms, infant, child, adolescent, pediatric, paediatric, neonatal, children, teen, and teenager. Following guidelines for systematic reviews from the Potsdam Consultation on Meta-Analysis, we have found it difficult to draw specific conclusions that are more than general impressions owing to the quality of the available studies. We find a mixed picture with neonates exposed to dexamethasone, with some articles reporting eventual deficits in neuropsychiatric functioning and others reporting no effect. In pediatric patients with acute lymphoblastic leukemia, corticosteroid use appears to correlate with negative psychiatric and behavioral effects. In children treated with corticosteroids for noncancer conditions

  17. The Neuropsychopharmacology of Pathological Gambling

    PubMed Central

    Zakeri, Kourosh; Potenza, Marc N.

    2013-01-01

    Pathological gambling (PG) is an impulse control disorder with prevalence estimates in the range of 0.2–2% in the general population. PG can significantly impact one’s ability to function as it may negatively influence social, financial, and occupational aspects of life. Historically, PG has received relatively little attention from researchers and clinicians, and few treatments, particularly pharmacological, have been both validated and widely employed. Given the clinical relevance of PG, it is important that researchers examine pharmacological and behavioral treatments for their safety and efficacy and that clinicians use empirically validated therapies. Multiple neurochemicals, including serotonin, dopamine, norepinephrine, and opioids, and related neurocircuitry, particularly ventral cortico-striatal pathways, have been implicated in PG. The neurobiological rationale for therapies, particularly pharmacological ones, is reviewed with a perspective on the generation of improved prevention and treatment strategies for PG. PMID:24288522

  18. Diabetes and Alzheimer disease, two overlapping pathologies with the same background: oxidative stress.

    PubMed

    Rosales-Corral, Sergio; Tan, Dun-Xian; Manchester, Lucien; Reiter, Russel J

    2015-01-01

    There are several oxidative stress-related pathways interconnecting Alzheimer's disease and type II diabetes, two public health problems worldwide. Coincidences are so compelling that it is attractive to speculate they are the same disorder. However, some pathological mechanisms as observed in diabetes are not necessarily the same mechanisms related to Alzheimer's or the only ones related to Alzheimer's pathology. Oxidative stress is inherent to Alzheimer's and feeds a vicious cycle with other key pathological features, such as inflammation and Ca(2+) dysregulation. Alzheimer's pathology by itself may lead to insulin resistance in brain, insulin resistance being an intervening variable in the neurodegenerative disorder. Hyperglycemia and insulin resistance from diabetes, overlapping with the Alzheimer's pathology, aggravate the progression of the neurodegenerative processes, indeed. But the same pathophysiological background is behind the consequences, oxidative stress. We emphasize oxidative stress and its detrimental role in some key regulatory enzymes.

  19. Diabetes and Alzheimer Disease, Two Overlapping Pathologies with the Same Background: Oxidative Stress

    PubMed Central

    Rosales-Corral, Sergio; Tan, Dun-Xian; Manchester, Lucien; Reiter, Russel J.

    2015-01-01

    There are several oxidative stress-related pathways interconnecting Alzheimer's disease and type II diabetes, two public health problems worldwide. Coincidences are so compelling that it is attractive to speculate they are the same disorder. However, some pathological mechanisms as observed in diabetes are not necessarily the same mechanisms related to Alzheimer's or the only ones related to Alzheimer's pathology. Oxidative stress is inherent to Alzheimer's and feeds a vicious cycle with other key pathological features, such as inflammation and Ca2+ dysregulation. Alzheimer's pathology by itself may lead to insulin resistance in brain, insulin resistance being an intervening variable in the neurodegenerative disorder. Hyperglycemia and insulin resistance from diabetes, overlapping with the Alzheimer's pathology, aggravate the progression of the neurodegenerative processes, indeed. But the same pathophysiological background is behind the consequences, oxidative stress. We emphasize oxidative stress and its detrimental role in some key regulatory enzymes. PMID:25815110

  20. Sleep physiology and pathology: pertinence to psychiatry.

    PubMed

    Soldatos, Constantin R; Paparrigopoulos, Thomas J

    2005-08-01

    Sleep should not be considered a behavioural state characterized by brain inertia; instead, it is a highly dynamic process involving numerous brainstem areas and all physiological systems of the body. Our understanding of the underlying mechanisms responsible for sleep regulation has considerably advanced since the discovery of rapid eye movement (REM) sleep, about half a century ago. Based on standardized electroencephalographic, electro-oculographic and electromyographic features, two distinct main states periodically alternating throughout the night have been identified: REM and non-REM sleep; the latter is further distinguished into stages 1, 2, 3 and 4. Computerized analysis of sleep recordings yielded more detailed information on sleep physiology and pathology. Although still preliminary, neuroimaging studies promise to elucidate the functional alterations of neuronal substrates during sleep. Regarding sleep disorders, which account for a substantial individual and socio-economic burden, considerable progress has been achieved in terms of their classification, assessment, clinical diagnosis and treatment. Specific sleep disorders within the three major categories, that is, 'dysomnias', 'parasomnias', and 'sleep disorders associated with mental, neurologic, or other medical conditions', exhibit characteristic clinical features; sleep laboratory recordings considerably assist to definitely diagnose several among them. Pertinence of sleep medicine for psychiatrists is obvious, taking into consideration that psychiatric disorders account for the largest diagnostic group of patients with sleep problems. In fact, the basics of this interdisciplinary field should be of special concern both to medical students and clinicians of diverse backgrounds who are interested in acquiring the necessary skills to globally and comprehensively understand and eventually effectively treat their patients.

  1. Pathology of primary and metastatic mucinous ovarian neoplasms.

    PubMed

    Leen, Sarah Lam Shang; Singh, Naveena

    2012-07-01

    Recent years have seen a dramatic change in the pathological approach to ovarian mucinous neoplasms. A substantial proportion of tumours previously considered to be ovarian primaries actually represent secondary ovarian involvement by tumours elsewhere in the body. Two major categories of tumour have completely disappeared from the diagnostic spectrum: ovarian 'borderline' mucinous tumour associated with pseudomyxoma peritonei, and widely disseminated mucinous carcinomas. The emergent picture of true ovarian primary carcinoma of pure mucinous morphology is that this is a rare malignancy that is low grade and low stage at presentation in the vast majority of cases, with a very low likelihood of aggressive clinical behaviour. A large volume of literature has appeared concerning the pathological distinction of primary from metastatic ovarian mucinous neoplasms in view of the dramatically different prognosis and treacherously similar morphology. Clinicopathological parameters useful in the distinction of primary from metastatic mucinous ovarian carcinomas are reviewed. Major features favouring metastases are bilaterality, size <10 cm, surface involvement, extensive intra-abdominal spread and an extensive infiltrative pattern with desmoplasia. Two morphological patterns essentially exclude ovarian origin: colloid and signet ring carcinomas. Features favouring primary ovarian origin are unilaterality, large size >12 cm, smooth external surface and association with other ovarian pathology. An admixture of benign, borderline and malignant patterns in the same tumour favour primary origin, but can be misleading as a 'maturation' pattern in metastases can result in the same appearance.

  2. Update in large cell lymphoma: understanding the pathology report.

    PubMed

    Hsi, Eric D

    2015-01-01

    The diffuse aggressive large B-cell lymphomas are a heterogeneous group of B-cell malignancies. Although many are readily recognized due to characteristic clinical and pathologic features, several problematic areas still exist in diagnosis of these lymphomas due to a variety of reasons that include imprecise or difficult-to-apply diagnostic criteria, gaps in our understanding of lymphoma biology, and limitations in technologies available in the clinical laboratory compared to the research laboratory. This may result in some degree of confusion in the pathology report, particularly if the issues are not clearly explained, leading to frustration or misinterpretation on the part of the reader. In this review, I will discuss the pathologic features of a subset of the WHO 2008 classification diffuse aggressive large B-cell lymphomas, focusing on areas in which difficulties exist in diagnosis and/or biomarker marker assessment. A deeper understanding of the issues and areas of uncertainty due to limitations in our knowledge about the biology of these diseases should lead to better communication between pathologists and clinicians.

  3. Combinational feature optimization for classification of lung tissue images

    NASA Astrophysics Data System (ADS)

    Samala, Ravi K.; Zhukov, Tatyana; Zhang, Jianying; Tockman, Melvyn; Qian, Wei

    2010-03-01

    A novel approach to feature optimization for classification of lung carcinoma using tissue images is presented. The methodology uses a combination of three characteristics of computational features: F-measure, which is a representation of each feature towards classification, inter-correlation between features and pathology based information. The metadata provided from pathological parameters is used for mapping between computational features and biological information. Multiple regression analysis maps each category of features based on how pathology information is correlated with the size and location of cancer. Relatively the computational features represented the tumor size better than the location of the cancer. Based on the three criteria associated with the features, three sets of feature subsets with individual validation are evaluated to select the optimum feature subset. Based on the results from the three stages, the knowledgebase produces the best subset of features. An improvement of 5.5% was observed for normal Vs all abnormal cases with Az value of 0.731 and 74/114 correctly classified. The best Az value of 0.804 with 66/84 correct classification and improvement of 21.6% was observed for normal Vs adenocarcinoma.

  4. Subvalvular apparatus and adverse outcome of balloon valvotomy in rheumatic mitral stenosis☆

    PubMed Central

    Bhalgat, Parag; Karlekar, Shrivallabh; Modani, Santosh; Agrawal, Ashish; Lanjewar, Charan; Nabar, Ashish; Kerkar, Prafulla; Agrawal, Nandu; Vaideeswar, Pradeep

    2015-01-01

    Background Balloon mitral valvotomy (BMV) is a well-established therapeutic modality for rheumatic mitral stenosis (RMS). However, there are chances of procedural failure and the more ominous post-procedural severe mitral regurgitation. There are only a few prospective studies, which have evaluated the pathogenic mechanisms for these major complications of BMV, especially in relation to the subvalvular apparatus (SVA) pathology. Methods All symptomatic patients of RMS suitable for BMV by echocardiographic criteria in a span of 1 year were selected. In addition to the standard echocardiographic assessment of RMS (Wilkins score and score by Padial et al.), a separate grading and scoring system was assigned to evaluate the severity of the SVA pathology. The SVA score was ‘I’, when none of the two SVAs had severe disease, ‘II’ when one of the two SVAs has severe disease, and ‘III’ when both SVAs had severe disease. With these scoring systems, the outcomes of BMV (successful procedure, failure, and post-procedural mitral regurgitation) were analyzed. Emergency valve replacement was performed depending on clinical situation, and in cases of replacement, the pathology of the excised mitral valves were compared with echocardiographic findings. Results Of the 356 BMVs performed in a year, 43 patients had adverse outcomes in the form of failed procedure (14 patients) and mitral regurgitation (29 patients). Forty-one among these had a SVA score of III. The sensitivity and specificity of the MR score was lesser than the SVA score (sensitivity 0.34 vs. 1.00, specificity 0.92 vs. 0.99, respectively). The mitral valvular morphology in 39 patients who underwent post-procedural valve replacements correlated well with echocardiography findings. Conclusion It is important to assess the degree of SVA pathology in the conventional echocardiographic assessment for RMS, as BMV would have adverse events when both SVAs were severely diseased. PMID:26432729

  5. Clinical features of sporadic fatal insomnia.

    PubMed

    Barash, Jed A

    2009-01-01

    Recent advances in neuropathology, genotyping, and physiochemical characterization of proteins have allowed for the classification and verification of MM2-thalamic Creutzfeldt-Jakob disease (CJD). CJD is a fatal neurodegenerative illness belonging to the transmissible spongiform encephalopathies, also known as prion diseases. Sporadic CJD is generally classified by the genotype at codon 129 of the prion protein gene and the distinct physiochemical features of the pathologic prion protein (PrP(sc)). The entity is characterized by methionine homozygosity at codon 129, type 2 PrP(sc), and, primarily, thalamic pathology (MM2-thalamic CJD). It shares clinical and pathologic similarities with the genetic prion disorder fatal familial insomnia; the MM2-thalamic phenotype has therefore been called sporadic fatal insomnia (SFI). SFI may also present like other neurodegenerative diseases, and common diagnostic findings that are seen in other forms of sporadic CJD may be absent.

  6. Utilising temporal signal features in adverse noise conditions: Detection, estimation, and the reassigned spectrogram.

    PubMed

    Mill, Robert W; Brown, Guy J

    2016-02-01

    Visual displays in passive sonar based on the Fourier spectrogram are underpinned by detection models that rely on signal and noise power statistics. Time-frequency representations specialised for sparse signals achieve a sharper signal representation, either by reassigning signal energy based on temporal structure or by conveying temporal structure directly. However, temporal representations involve nonlinear transformations that make it difficult to reason about how they respond to additive noise. This article analyses the effect of noise on temporal fine structure measurements such as zero crossings and instantaneous frequency. Detectors that rely on zero crossing intervals, intervals and peak amplitudes, and instantaneous frequency measurements are developed, and evaluated for the detection of a sinusoid in Gaussian noise, using the power detector as a baseline. Detectors that rely on fine structure outperform the power detector under certain circumstances; and detectors that rely on both fine structure and power measurements are superior. Reassigned spectrograms assume that the statistics used to reassign energy are reliable, but the derivation of the fine structure detectors indicates the opposite. The article closes by proposing and demonstrating the concept of a doubly reassigned spectrogram, wherein temporal measurements are reassigned according to a statistical model of the noise background. PMID:26936571

  7. Utilising temporal signal features in adverse noise conditions: Detection, estimation, and the reassigned spectrogram.

    PubMed

    Mill, Robert W; Brown, Guy J

    2016-02-01

    Visual displays in passive sonar based on the Fourier spectrogram are underpinned by detection models that rely on signal and noise power statistics. Time-frequency representations specialised for sparse signals achieve a sharper signal representation, either by reassigning signal energy based on temporal structure or by conveying temporal structure directly. However, temporal representations involve nonlinear transformations that make it difficult to reason about how they respond to additive noise. This article analyses the effect of noise on temporal fine structure measurements such as zero crossings and instantaneous frequency. Detectors that rely on zero crossing intervals, intervals and peak amplitudes, and instantaneous frequency measurements are developed, and evaluated for the detection of a sinusoid in Gaussian noise, using the power detector as a baseline. Detectors that rely on fine structure outperform the power detector under certain circumstances; and detectors that rely on both fine structure and power measurements are superior. Reassigned spectrograms assume that the statistics used to reassign energy are reliable, but the derivation of the fine structure detectors indicates the opposite. The article closes by proposing and demonstrating the concept of a doubly reassigned spectrogram, wherein temporal measurements are reassigned according to a statistical model of the noise background.

  8. A tour of the thymus: a review of thymic lesions with radiologic and pathologic correlation.

    PubMed

    Goldstein, Alan J; Oliva, Isabel; Honarpisheh, Hedieh; Rubinowitz, Ami

    2015-02-01

    The thymus is routinely encountered on cross-sectional imaging studies of the chest. It has a variable appearance, undergoes dynamic changes during periods of stress, and demonstrates numerous different pathologic lesions. Understanding the imaging characteristics of these different lesions facilitates accurate radiographic diagnosis and can prevent unnecessary follow-up imaging and intervention. This article will review normal thymic anatomy and development, thymic hyperplasia and associated medical conditions, and the imaging and pathologic features of various benign and malignant thymic lesions.

  9. The Role of Decidual Macrophages During Normal and Pathological Pregnancy.

    PubMed

    Ning, Fen; Liu, Huishu; Lash, Gendie E

    2016-03-01

    Macrophages perform many specific functions including host defense, homeostasis, angiogenesis, and tissue development. Macrophages are the second most abundant leukocyte population in the non-pregnant endometrium and pregnant decidua and likely play a central role in the establishment and maintenance of normal pregnancy. Importantly, aberrantly activated uterine macrophages can affect trophoblast function and placental development, which may result in various adverse pregnancy outcomes ranging from pre-eclampsia to fetal growth restriction or demise. Only by fully understanding the roles of macrophage in pregnancy will we be able to develop interventions for the treatment of these various pregnancy complications. This review discusses the general origin and classification of monocytes and macrophages and focuses on the phenotype and functional roles of decidual macrophage at the maternal-fetal interface in normal pregnancy, as well as discussing the potential contribution of the abnormal state of these cells to various aspects of pregnancy pathologies. PMID:26750089

  10. Tau protein is essential for stress-induced brain pathology.

    PubMed

    Lopes, Sofia; Vaz-Silva, João; Pinto, Vitor; Dalla, Christina; Kokras, Nikolaos; Bedenk, Benedikt; Mack, Natalie; Czisch, Michael; Almeida, Osborne F X; Sousa, Nuno; Sotiropoulos, Ioannis

    2016-06-28

    Exposure to chronic stress is frequently accompanied by cognitive and affective disorders in association with neurostructural adaptations. Chronic stress was previously shown to trigger Alzheimer's-like neuropathology, which is characterized by Tau hyperphosphorylation and missorting into dendritic spines followed by memory deficits. Here, we demonstrate that stress-driven hippocampal deficits in wild-type mice are accompanied by synaptic missorting of Tau and enhanced Fyn/GluN2B-driven synaptic signaling. In contrast, mice lacking Tau [Tau knockout (Tau-KO) mice] do not exhibit stress-induced pathological behaviors and atrophy of hippocampal dendrites or deficits of hippocampal connectivity. These findings implicate Tau as an essential mediator of the adverse effects of stress on brain structure and function. PMID:27274066

  11. Update in Pathological Diagnosis of Orbital Infections and Inflammations

    PubMed Central

    Lam Choi, Vincent B.; Yuen, Hunter K. L.; Biswas, Jyotirmay; Yanoff, Myron

    2011-01-01

    Orbital infections and inflammations include a broad spectrum of orbital diseases that can be idiopathic, infectious, from primary or secondary inflammatory processes. Being able to properly diagnose and manage these orbital diseases in a timely manner can avoid permanent vision loss and possibly save a patient's life. When clinicians are faced with such patients, quite often the exact diagnosis cannot be made just based on clinical examination, various laboratory tests and imaging are needed. Moreover, orbital biopsies with histopathological analyses are often required, especially for the atypical cases. Thus, it is important for the clinicians to be familiar with the pathological features and characteristics of these orbital diseases. This review provides a comprehensive update on the clinical and pathological diagnosis of these orbital infections and inflammations. PMID:22224014

  12. Degenerative spine disease : pathologic findings in 985 surgical specimens.

    PubMed

    Pytel, Peter; Wollmann, Robert L; Fessler, Richard G; Krausz, Thomas N; Montag, Anthony G

    2006-02-01

    A number of pathologic changes have been reported in spinal surgery specimens. The frequency of many of these is not well defined. We retrospectively reviewed the histologic features of 985 extradural spinal surgery specimens. Of the cases, 1.6% were identified clinically as synovial cysts. In addition, synovial tissue was seen in another 5.3% of cases, often embedded within disk material. Neovascularization of disk tissue was present in 8.1% of cases, chondrocyte clusters in 18.3%, and calcium pyrophosphate crystals in 2.8%, predominantly within disk material. With the exception of crystal deposits, all of these changes were significantly more common in the lumbar spine. A better understanding of cell-based degenerative changes will become essential with increasing research into cell-based therapies for spinal disk disease. We report data on the frequency of different pathologic changes and describe synovial metaplasia as a reactive change not previously reported.

  13. 7 Tesla MRI demonstrates vascular pathology in Balo's concentric sclerosis.

    PubMed

    Berghoff, M; Schlamann, M U; Maderwald, S; Grams, A E; Kaps, M; Ladd, M E; Gizewski, E R

    2013-01-01

    Baló's concentric sclerosis (BCS) is an inflammatory demyelinating disease related to multiple sclerosis; its underlying pathology remains unclear. At 7 T MRI in a 19-year-old female BCS patient, microhaemorrhages and ectatic veins were found in T2 hyperintense regions, features which have not been previously reported in conjunction with BCS, and these findings may support the view that vascular pathology plays a role in BCS. MRS data suggest that neuron loss and lipid turnover still took place months after a remission. Plasma exchange was effective in treating a relapse with severe motor deficits, and the off-label use of natalizumab was successful in maintaining remission in this patient.

  14. Anticoagulation-associated adverse drug events

    PubMed Central

    Piazza, Gregory; Nguyen, Thanh Nha; Cios, Deborah; Labreche, Matthew; Hohlfelder, Benjamin; Fanikos, John; Fiumara, Karen; Goldhaber, Samuel Z.

    2011-01-01

    Purpose Anticoagulant drugs are among the most common medications that cause adverse drug events (ADEs) in hospitalized patients. We performed a five-year retrospective study at Brigham and Women’s Hospital to determine clinical characteristics, types, root causes, and outcomes of anticoagulant-associated adverse drug events (ADEs). Methods We reviewed all inpatient anticoagulant-associated ADEs, including adverse drug reactions (ADRs) and medication errors, reported at Brigham and Women’s Hospital through the Safety Reporting System from May 2004 to May 2009. We also collected data regarding the cost associated with hospitalizations in which ADRs occurred. Results Of 463 anticoagulant-associated ADEs, 226 were MEs (48.8%), 141 were ADRs (30.5%), and 96 (20.7%) involved both a medication error and ADR. Seventy percent of anticoagulant-associated ADEs were potentially preventable. Transcription errors (48%) were the most frequent root cause of anticoagulant-associated medication errors, while medication errors (40%) were a common root cause of anticoagulant-associated ADRs. Death within 30 days of anticoagulant-associated ADEs occurred in 11% of patients. After an anticoagulant-associated ADR, most hospitalization expenditures were attributable to nursing costs (mean $33,189 per ADR) followed by pharmacy costs (mean $7,451 per ADR). Conclusion Most anticoagulant-associated ADEs among inpatients result from medication errors and are therefore potentially preventable. We observed an elevated 30-day mortality rate among patients who suffered an anticoagulant-associated ADE and high hospitalization costs following ADRs. Further Quality Improvement efforts to reduce anticoagulant-associated medication errors are warranted to improve patient safety and decrease health care expenditures. PMID:22114827

  15. ORAL ADVERSE DRUG REACTIONS TO CARDIOVASCULAR DRUGS.

    PubMed

    Torpet, Lis Andersen; Kragelund, Camilla; Reibel, Jesper; Nauntofte, Birgitte

    2004-01-01

    A great many cardiovascular drugs (CVDs) have the potential to induce adverse reactions in the mouth. The prevalence of such reactions is not known, however, since many are asymptomatic and therefore are believed to go unreported. As more drugs are marketed and the population includes an increasing number of elderly, the number of drug prescriptions is also expected to increase. Accordingly, it can be predicted that the occurrence of adverse drug reactions (ADRs), including the oral ones (ODRs), will continue to increase. ODRs affect the oral mucous membrane, saliva production, and taste. The pathogenesis of these reactions, especially the mucosal ones, is largely unknown and appears to involve complex interactions among the drug in question, other medications, the patient's underlying disease, genetics, and life-style factors. Along this line, there is a growing interest in the association between pharmacogenetic polymorphism and ADRs. Research focusing on polymorphism of the cytochrome P450 system (CYPs) has become increasingly important and has highlighted the intra- and inter-individual responses to drug exposure. This system has recently been suggested to be an underlying candidate regarding the pathogenesis of ADRs in the oral mucous membrane. This review focuses on those CVDs reported to induce ODRs. In addition, it will provide data on specific drugs or drug classes, and outline and discuss recent research on possible mechanisms linking ADRs to drug metabolism patterns. Abbreviations used will be as follows: ACEI, ACE inhibitor; ADR, adverse drug reaction; ANA, antinuclear antigen; ARB, angiotensin II receptor blocker; BAB, beta-adrenergic blocker; CCB, calcium-channel blocker; CDR, cutaneous drug reaction; CVD, cardiovascular drug; CYP, cytochrome P450 enzyme; EM, erythema multiforme; FDE, fixed drug eruption; I, inhibitor of CYP isoform activity; HMG-CoA, hydroxymethyl-glutaryl coenzyme A; NAT, N-acetyltransferase; ODR, oral drug reaction; RDM, reactive

  16. [Pathology in Russia: where are we going?].

    PubMed

    Permiakov, N K

    1998-01-01

    The history of Russian pathologic anatomy from the postwar time to nowadays is briefly reviewed. Negative effects of some legislative acts of the all levels of public health, profound financial crisis are shown. Particularly negative were consequences of a narrow specialization of medicine which affected also pathologic anatomy. Insufficient classical education that includes theoretical and prosecutor training of the general profile results in the fall of interest to general pathology this having a negative effect on the prestige of this profession. PMID:9582980

  17. Reducing medical errors and adverse events.

    PubMed

    Pham, Julius Cuong; Aswani, Monica S; Rosen, Michael; Lee, HeeWon; Huddle, Matthew; Weeks, Kristina; Pronovost, Peter J

    2012-01-01

    Medical errors account for ∼98,000 deaths per year in the United States. They increase disability and costs and decrease confidence in the health care system. We review several important types of medical errors and adverse events. We discuss medication errors, healthcare-acquired infections, falls, handoff errors, diagnostic errors, and surgical errors. We describe the impact of these errors, review causes and contributing factors, and provide an overview of strategies to reduce these events. We also discuss teamwork/safety culture, an important aspect in reducing medical errors.

  18. Environmental Perchlorate Exposure: Potential Adverse Thyroid Effects

    PubMed Central

    Leung, Angela M.; Pearce, Elizabeth N.; Braverman, Lewis E.

    2014-01-01

    Purpose of review This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Recent findings Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant IQ in groups who would be particularly susceptible to perchlorate effects. An update regarding the recent proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. Summary The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants. PMID:25106002

  19. Adverse effects of equine rabies immune gobulin.

    PubMed

    Wilde, H; Chomchey, P; Prakongsri, S; Puyaratabandhu, P; Chutivongse, S

    1989-02-01

    Following a recently published prospective study of 485 recipients of equine rabies immune globulin (ERIG) manufactured by Pasteur Vaccins (Paris), this paper reports a study of 323 postexposure rabies patients receiving ERIG manufactured by the Swiss Vaccine and Serum Institute (Berna). It is concluded that there may be significant differences in adverse reaction rates, reflecting differing manufacturing or purification processes and protein content. Further studies of different ERIG products and of different lots of the same product are needed while ERIG remains an essential component of postexposure rabies treatment in developing countries.

  20. Agomelatine: a review of adverse effects.

    PubMed

    2013-03-01

    More pharmacovigilance data on agomelatine became available in 2012. The main sources of information were surveillance data from the French national monitoring system, EU periodic safety update reports (PSURs), and the European pharmacovigilance database. The principal adverse effects of agomelatine consist of hepatic, pancreatic, neuropsychiatric, muscular and cutaneous disorders. The harms associated with agomelatine, which has no proven efficacy in depression, clearly outweigh the benefits. Until regulatory agencies decide to withdraw agomelatine from the market, it is up to healthcare professionals to protect patients from this unnecessarily dangerous drug.

  1. Adverse Effects of Psychotropic Medications: A Call to Action.

    PubMed

    Mago, Rajnish

    2016-09-01

    Adverse effects are common, bothersome, and a leading cause of discontinuation of treatment. The methodology for evaluating adverse effects of medications has been greatly neglected, however, especially in comparison to the methodology for assessment of efficacy of medications. Existing methods for assessment and reporting of adverse effects have important limitations leading to lack of much-needed data related to adverse effects. Lastly, there is little systematic research into management of most adverse effects. A series of recommendations are made in this article about how to improve identification, assessment, reporting, and management of adverse effects. PMID:27514294

  2. Imaging of cerebrovascular pathology in animal models of Alzheimer's disease

    PubMed Central

    Klohs, Jan; Rudin, Markus; Shimshek, Derya R.; Beckmann, Nicolau

    2014-01-01

    In Alzheimer's disease (AD), vascular pathology may interact with neurodegeneration and thus aggravate cognitive decline. As the relationship between these two processes is poorly understood, research has been increasingly focused on understanding the link between cerebrovascular alterations and AD. This has at last been spurred by the engineering of transgenic animals, which display pathological features of AD and develop cerebral amyloid angiopathy to various degrees. Transgenic models are versatile for investigating the role of amyloid deposition and vascular dysfunction, and for evaluating novel therapeutic concepts. In addition, research has benefited from the development of novel imaging techniques, which are capable of characterizing vascular pathology in vivo. They provide vascular structural read-outs and have the ability to assess the functional consequences of vascular dysfunction as well as to visualize and monitor the molecular processes underlying these pathological alterations. This article focusses on recent in vivo small animal imaging studies addressing vascular aspects related to AD. With the technical advances of imaging modalities such as magnetic resonance, nuclear and microscopic imaging, molecular, functional and structural information related to vascular pathology can now be visualized in vivo in small rodents. Imaging vascular and parenchymal amyloid-β (Aβ) deposition as well as Aβ transport pathways have been shown to be useful to characterize their dynamics and to elucidate their role in the development of cerebral amyloid angiopathy and AD. Structural and functional imaging read-outs have been employed to describe the deleterious affects of Aβ on vessel morphology, hemodynamics and vascular integrity. More recent imaging studies have also addressed how inflammatory processes partake in the pathogenesis of the disease. Moreover, imaging can be pivotal in the search for novel therapies targeting the vasculature. PMID:24659966

  3. Parsing (malicious) pleasures: schadenfreude and gloating at others’ adversity

    PubMed Central

    Leach, Colin Wayne; Spears, Russell; Manstead, Antony S. R.

    2015-01-01

    We offer the first empirical comparison of the pleasure in seeing (i.e., schadenfreude) and in causing (i.e., gloating) others’ adversity. In Study 1, we asked participants to recall and report on an (individual or group) episode of pleasure that conformed to our formal definition of schadenfreude, gloating, pride, or joy, without reference to an emotion word. Schadenfreude and gloating were distinct in the situational features of the episode, participants’ appraisals of it, and their expressions of pleasure (e.g., smiling, boasting). In Study 2, we had participants imagine being in an (individual or group) emotion episode designed to fit our conceptualization of schadenfreude or gloating. Individual and group versions of the emotions did not differ much in either study. However, the two pleasures differed greatly in their situational features, appraisals, experience, and expression. This parsing of the particular pleasures of schadenfreude and gloating brings nuance to the study of (malicious) pleasure, which tends to be less finely conceptualized and examined than displeasure despite its importance to social relations. PMID:25767455

  4. Parsing (malicious) pleasures: schadenfreude and gloating at others' adversity.

    PubMed

    Leach, Colin Wayne; Spears, Russell; Manstead, Antony S R

    2015-01-01

    We offer the first empirical comparison of the pleasure in seeing (i.e., schadenfreude) and in causing (i.e., gloating) others' adversity. In Study 1, we asked participants to recall and report on an (individual or group) episode of pleasure that conformed to our formal definition of schadenfreude, gloating, pride, or joy, without reference to an emotion word. Schadenfreude and gloating were distinct in the situational features of the episode, participants' appraisals of it, and their expressions of pleasure (e.g., smiling, boasting). In Study 2, we had participants imagine being in an (individual or group) emotion episode designed to fit our conceptualization of schadenfreude or gloating. Individual and group versions of the emotions did not differ much in either study. However, the two pleasures differed greatly in their situational features, appraisals, experience, and expression. This parsing of the particular pleasures of schadenfreude and gloating brings nuance to the study of (malicious) pleasure, which tends to be less finely conceptualized and examined than displeasure despite its importance to social relations. PMID:25767455

  5. Adverse reaction to lupine-fortified pasta.

    PubMed

    Hefle, S L; Lemanske, R F; Bush, R K

    1994-08-01

    A 5-year-old girl with peanut sensitivity experienced urticaria and angioedema after ingesting a spaghetti-like pasta fortified with sweet lupine seed flour. The pasta was extracted and used in immunologic studies in patients with peanut sensitivity to determine whether such individuals are at similar risk. Results of skin prick tests with the lupine pasta extract were positive in five of seven subjects; these patients also reported a history of adverse reactions to green peas. In direct RAST studies IgE binding from pooled sera from patients with peanut sensitivity to the lupine pasta extract was 7 times that of a nonallergic control serum, and individual serum samples demonstrated binding from 1 to 6 times that of the negative control. Direct RAST studies of lupine seed flour with serum samples from patients with peanut allergy demonstrated IgE binding 1 to 11 times that of the negative control. Immunoblotting studies of electrophoretically separated pasta extract and lupine seed flour proteins showed IgE-binding protein bands at approximately 21 kd and in the range of 35 to 55 kd molecular weight. We conclude that some peanut-sensitive patients may be at risk for adverse reactions to lupine.

  6. Early adversity, immunity and infectious disease.

    PubMed

    Avitsur, Ronit; Levy, Sigal; Goren, Naama; Grinshpahet, Rachel

    2015-01-01

    Complex interactions between biological, behavioral and environmental factors are involved in mediating individual differences in health and disease. In this review, we present evidence suggesting that increased vulnerability to infectious disease may be at least, in part, due to long-lasting effects of early life psychosocial adversities. Studies have shown that maternal psychosocial stress during pregnancy is associated with long lasting changes in immune function and disease resistance in the offspring. Studies further indicated that harsh environmental conditions during the neonatal period may also cause lasting changes in host response to infectious disease. Although the mechanisms involved in these effects have not been fully examined, several potential mediators have been described, including changes in the development of the offspring hypothalamic-pituitary-adrenal axis, alterations in epigenetic pathways, stress-related maternal health risk behavior and infection during pregnancy. Although there are ample literature indicating that perinatal psychosocial stress increases vulnerability to disease, other reports suggest that mild predictable stressors may benefit the organism and allow better coping with future stressors. Thus, understanding the possible consequences of perinatal adversities and the mechanisms that are involved in immune regulation is important for increasing awareness to the potential outcomes of early negative life events and providing insight into potential therapies to combat infection in vulnerable individuals.

  7. Adverse reactions to food: allergies and intolerances.

    PubMed

    Montalto, Massimo; Santoro, Luca; D'Onofrio, Ferruccio; Curigliano, Valentina; Gallo, Antonella; Visca, Dina; Cammarota, Giovanni; Gasbarrini, Antonio; Gasbarrini, Giovanni

    2008-01-01

    All the anomalous reactions secondary to food ingestion are defined as 'adverse reactions to food'. In 1995 the European Academy of Allergology and Clinical Immunology suggested a classification on the basis of the responsible pathogenetic mechanism; according to this classification, non-toxic reactions can be divided into 'food allergies' when they recognize immunological mechanisms, and 'food intolerances' when there are no immunological implications. The diagnostic approach to adverse reactions to food is based on accurate clinical history and objective examination, and further execution of specific tests when allergy or intolerance is suspected. The therapy for food allergies is the elimination of the food to which hypersensibility has been found; this strategy can lead, especially in pediatric age, to tolerance. If elimination diets cannot be completely performed, or if it is not possible to identify the food to eliminate, some drugs (e.g. antihistaminics, steroids, etc.) can be administered. Specific allergen immunotherapy has been recently introduced. Fundamental is food allergy prevention, especially in high-risk subjects. The therapeutic approach to secondary food intolerances is based principally on primitive disease resolution; on the other hand, some specific treatments (e.g. beta-galactosidases in lactose malabsorption) are available in case of primary intolerance. PMID:18431058

  8. Consumer reporting of adverse events following immunization

    PubMed Central

    Clothier, Hazel J; Selvaraj, Gowri; Easton, Mee Lee; Lewis, Georgina; Crawford, Nigel W; Buttery, Jim P

    2014-01-01

    Surveillance of adverse events following immunisation (AEFI) is an essential component of vaccine safety monitoring. The most commonly utilized passive surveillance systems rely predominantly on reporting by health care providers (HCP). We reviewed adverse event reports received in Victoria, Australia since surveillance commencement in July 2007, to June 2013 (6 years) to ascertain the contribution of consumer (vaccinee or their parent/guardian) reporting to vaccine safety monitoring and to inform future surveillance system development directions. Categorical data included were: reporter type; serious and non-serious AEFI category; and, vaccinee age group. Chi-square test and 2-sample test of proportions were used to compare categories; trend changes were assessed using linear regression. Consumer reporting increased over the 6 years, reaching 21% of reports received in 2013 (P <0.001), most commonly for children aged less than 7 years. Consumer reports were 5% more likely to describe serious AEFI than HCP (P = 0.018) and 10% more likely to result in specialist clinic attendance (P <0.001). Although online reporting increased to 32% of all report since its introduction in 2010, 85% of consumers continued to report by phone. Consumer reporting of AEFI is a valuable component of vaccine safety surveillance in addition to HCP reporting. Changes are required to AEFI reporting systems to implement efficient consumer AEFI reporting, but may be justified for their potential impact on signal detection sensitivity. PMID:25483686

  9. Ranking Adverse Drug Reactions With Crowdsourcing

    PubMed Central

    Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel

    2015-01-01

    Background There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. Objective The intent of the study was to rank ADRs according to severity. Methods We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. Results There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. Conclusions ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making. PMID:25800813

  10. Adverse outcome pathway development II: best practices.

    PubMed

    Villeneuve, Daniel L; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H; LaLone, Carlie A; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-12-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of "functional equivalence" can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach. PMID:25466379

  11. Immunomodulatory drugs: Oral and systemic adverse effects

    PubMed Central

    Mattila, Riikka; Gomez-Font, Rafael; Meurman, Jukka H.

    2014-01-01

    Objectives: The main objectives are to present the different adverses effects of the immunomodulatory drugs that can impair the quality of life of the immunosupressed patients and study the impact of immunomodualtion on oral diseases. Immunomodulatory drugs have changed the treatment protocols of many diseases where immune functions play a central role, such as rheumatic diseases. Their effect on oral health has not been systematically investigated, however. Study Design: We review current data on the new immunomodulatory drugs from the oral health perspective based on open literature search of the topic. Results: These target specific drugs appear to have less drug interactions than earlier immunomodulating medicines but have nevertheless potential side effects such as activating latent infections. There are some data showing that the new immunomodulatory drugs may also have a role in the treatment of certain oral diseases such as lichen planus or ameliorating symptoms in Sjögren´s syndrome, but the results have not been overly promising. Conclusions: In general, data are sparse of the effect of these new drugs vs. oral diseases and there are no properly powered randomized controlled trials published on this topic. Key words:Immunomodulatory drugs, oral diseases, adverse effects, therapeutic action. PMID:23986016

  12. Adverse outcome pathway development II: best practices.

    PubMed

    Villeneuve, Daniel L; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H; LaLone, Carlie A; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-12-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of "functional equivalence" can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach.

  13. Adverse Outcome Pathway Development II: Best Practices

    PubMed Central

    Villeneuve, Daniel L.; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H.; LaLone, Carlie A.; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-01-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of “functional equivalence” can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach. PMID:25466379

  14. [Adverse drug reactions in pregnant women].

    PubMed

    Lacroix, Isabelle; Cabou, Cendrine; Montastruc, Jean-Louis; Damase-Michel, Christine

    2007-01-01

    A Prospective pharmacovigilance survey of adverse drug reactions (ADRs) in pregnant women was performed in collaboration with gynaecologists and obstetricians of Midi-Pyrenees area (south west of france). The aim of the study was to evaluate the incidence of adverse drug reactions in pregnant women. The incidence of ADRs in pregnant women was low: 0.3%. Moreover, a retrospective pharmacoepidemiological study was conducted to characterize ADRs in pregnant women. Reports of ADRs collected in the Midi-Pyrenees pharmacovigilance centre from 1982 to 2002 were used: type of ADRs, drugs involved and potential risk factors were compared for pregnant women and for age-matched non pregnant women. Forty seven and 94 reports of ADRs were collected in pregnant and non-pregnant women respectively. Anaphylactic reactions were only observed in pregnant women (3 cases, p = 0.04). We observed 1 ADR related stillbirth (due to anaphylactic reaction) in pregnant women. Drugs for gynaecological and cardiovascular systems were more frequently involved in ADRs in pregnant women than in controls. ADRs mainly occurred during the third trimester of pregnancy. The incidence of ADRs is very low in pregnant women. However, one must pay attention on the risk of anaphylactic reactions in pregnant women. PMID:18206108

  15. A history of pituitary pathology.

    PubMed

    Asa, Sylvia L; Mete, Ozgur

    2014-03-01

    The history of pituitary pathology is a long one that dates back to biblical times, but the last 25 years have represented an era of "coming of age." The role of the pituitary in health and disease was the subject of many studies over the last century. With the development of electron microscopy, immunoassays, and immunohistochemistry, the functional alterations associated with pituitary disease have been clarified. The additional information provided by molecular genetic studies has allowed progress in understanding the pathogenesis of pituitary disorders. Nevertheless, many questions remain to be answered. For example, pathologists cannot morphologically distinguish locally aggressive adenomas from carcinomas when tumor is confined to the sella. Sadly, basal cell carcinoma, the most common carcinoma of skin, usually causes less morbidity than pituitary adenomas, which occur in almost 20 % of the general population, can cause significant illness and even death, and yet are still classified as benign. The opportunity to increase awareness of the impact of these common lesions on quality of life is the current challenge for physicians and patients. We anticipate that ongoing multidisciplinary approaches to pituitary disease research will offer new insights into diseases arising from this fascinating organ.

  16. Pathological Gambling: Neuropsychopharmacology and Treatment

    PubMed Central

    Bullock, Scott A.; Potenza, Marc N.

    2013-01-01

    Pathological gambling (PG) affects about 0.2–2% of adults and the impact extends to family members, employers and society as a whole. Recent research has identified similarities in the pathophysiologies of PG and substance use disorders (SUDs). As such, findings regarding SUDs provide a framework for investigating PG. The aims of the manuscript are two-fold. First, we will briefly revivew neural systems implicated in PG. Cortico-limbic circuitry involving the ventral striatum, ventromedial prefrontal cortex, anterior cingulate cortex, and dorsolateral prefrontal cortex are discussed as are the neurotransmitters norepinephrine, serotonin, dopamine, opioids, glutamate, and gamma-aminobutyric acid (GABA). This background will provide a framework for reviewing the psychopharmacological treatments that have been tested for efficacy and safety in treating PG. Of medications, the strongest data suggest the efficacy and tolerability of opioid antagonists in the treatment of PG, and other agents have varying degree of empirical support. As behavioral therapies have also shown efficacy, they will be briefly considered as well. Future research is needed to understand how treatments work in PG and for whom specific treatments might work best. PMID:24349964

  17. Practical pathology of aging mice.

    PubMed

    Pettan-Brewer, Christina; Treuting, Piper M

    2011-01-01

    Old mice will have a subset of lesions as part of the progressive decline in organ function that defines aging. External and palpable lesions will be noted by the research, husbandry, or veterinary staff during testing, cage changing, or physical exams. While these readily observable lesions may cause alarm, not all cause undue distress or are life-threatening. In aging research, mice are maintained until near end of life that, depending on strain and genetic manipulation, can be upwards of 33 months. Aging research has unique welfare issues related to age-related decline, debilitation, fragility, and associated pain of chronic diseases. An effective aging research program includes the collaboration and education of the research, husbandry, and veterinary staff, and of the members of the institution animal care and use committee. This collaborative effort is critical to humanely maintaining older mice and preventing excessive censorship due to non-lethal diseases. Part of the educational process is becoming familiar with how old mice appear clinically, at necropsy and histopathologically. This baseline knowledge is important in making the determination of humane end points, defining health span, contributing causes of death and effects of interventions. The goal of this paper is to introduce investigators to age-associated diseases and lesion patterns in mice from clinical presentation to pathologic assessment. To do so, we present and illustrate the common clinical appearances, necropsy and histopathological lesions seen in subsets of the aging colonies maintained at the University of Washington. PMID:22953032

  18. Bone Remodeling Under Pathological Conditions.

    PubMed

    Xiao, Wenmei; Li, Shuai; Pacios, Sandra; Wang, Yu; Graves, Dana T

    2016-01-01

    Bone is masterfully programmed to repair itself through the coupling of bone formation following bone resorption, a process referred to as coupling. In inflammatory or other conditions, the balance between bone resorption and bone formation shifts so that a net bone loss results. This review focuses on four pathologic conditions in which remodeling leads to net loss of bone, postmenopausal osteoporosis, arthritis, periodontal disease, and disuse bone loss, which is similar to bone loss associated with microgravity. In most of these there is an acceleration of the resorptive process due to increased formation of bone metabolic units. This initially leads to a net bone loss since the time period of resorption is much faster than the time needed for bone formation that follows. In addition, each of these processes is characterized by an uncoupling that leads to net bone loss. Mechanisms responsible for increased rates of bone resorption, i.e. the formation of more bone metabolic units, involve enhanced expression of inflammatory cytokines and increased expression of RANKL. Moreover, the reasons for uncoupling are discussed which range from a decrease in expression of growth factors and bone morphogenetic proteins to increased expression of factors that inhibit Wnt signaling. PMID:26599114

  19. Pathologizing sexual deviance: a history.

    PubMed

    De Block, Andreas; Adriaens, Pieter R

    2013-01-01

    This article provides a historical perspective on how both American and European psychiatrists have conceptualized and categorized sexual deviance throughout the past 150 years. During this time, quite a number of sexual preferences, desires, and behaviors have been pathologized and depathologized at will, thus revealing psychiatry's constant struggle to distinguish mental disorder--in other words, the "perversions," "sexual deviations," or "paraphilias"--from immoral, unethical, or illegal behavior. This struggle is apparent in the works of 19th- and early-20th-century psychiatrists and sexologists, but it is also present in the more recent psychiatric textbooks and diagnostic manuals, such as the consecutive editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM). While much of the historical literature revolves around the controversy over homosexuality, this article also reviews the recent medicohistorical and sociohistorical work on other forms of sexual deviance, including the diagnostic categories listed in the latest edition, the DSM-IV-TR: exhibitionism, voyeurism, fetishism, frotteurism, pedophilia, sexual masochism, sexual sadism, and transvestic fetishism. PMID:23480073

  20. Hodgkin lymphoma: Pathology and biology.

    PubMed

    Mathas, Stephan; Hartmann, Sylvia; Küppers, Ralf

    2016-07-01

    The Hodgkin and Reed-Sternberg (HRS) tumor cells of classical Hodgkin lymphoma (HL), as well as the lymphocyte predominant (LP) cells of nodular lymphocyte predominant HL (NLPHL), are derived from mature B cells. However, HRS cells have largely lost their B-cell phenotype and show a very unusual expression of many markers of other hematopoietic cell lineages, which aids in the differential diagnosis between classical HL (cHL) and NLPHL and distinguishes cHL from all other hematopoietic malignancies. The bi- or multinucleated Reed-Sternberg cells most likely derive from the mononuclear Hodgkin cells through a process of incomplete cytokinesis. HRS cells show a deregulated activation of numerous signaling pathways, which is partly mediated by cellular interactions in the lymphoma microenvironment and partly by genetic lesions. In a fraction of cases, Epstein-Barr virus contributes to the pathogenesis of cHL. Recurrent genetic lesions in HRS cells identified so far often involve members of the nuclear factor-κB (NF-κB) and JAK/STAT pathways and genes involved in major histocompatibility complex expression. However, further lead transforming events likely remain to be identified. We here discuss the current knowledge on HL pathology and biology. PMID:27496304

  1. Practical pathology of aging mice

    PubMed Central

    Pettan-Brewer, Christina; Treuting, Piper M.

    2011-01-01

    Old mice will have a subset of lesions as part of the progressive decline in organ function that defines aging. External and palpable lesions will be noted by the research, husbandry, or veterinary staff during testing, cage changing, or physical exams. While these readily observable lesions may cause alarm, not all cause undue distress or are life-threatening. In aging research, mice are maintained until near end of life that, depending on strain and genetic manipulation, can be upwards of 33 months. Aging research has unique welfare issues related to age-related decline, debilitation, fragility, and associated pain of chronic diseases. An effective aging research program includes the collaboration and education of the research, husbandry, and veterinary staff, and of the members of the institution animal care and use committee. This collaborative effort is critical to humanely maintaining older mice and preventing excessive censorship due to non-lethal diseases. Part of the educational process is becoming familiar with how old mice appear clinically, at necropsy and histopathologically. This baseline knowledge is important in making the determination of humane end points, defining health span, contributing causes of death and effects of interventions. The goal of this paper is to introduce investigators to age-associated diseases and lesion patterns in mice from clinical presentation to pathologic assessment. To do so, we present and illustrate the common clinical appearances, necropsy and histopathological lesions seen in subsets of the aging colonies maintained at the University of Washington. PMID:22953032

  2. Heterogeneity of cerebral TDP-43 pathology in sporadic amyotrophic lateral sclerosis: Evidence for clinico-pathologic subtypes.

    PubMed

    Takeuchi, Ryoko; Tada, Mari; Shiga, Atsushi; Toyoshima, Yasuko; Konno, Takuya; Sato, Tomoe; Nozaki, Hiroaki; Kato, Taisuke; Horie, Masao; Shimizu, Hiroshi; Takebayashi, Hirohide; Onodera, Osamu; Nishizawa, Masatoyo; Kakita, Akiyoshi; Takahashi, Hitoshi

    2016-06-23

    Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are types of major TDP-43 (43-kDa TAR DNA-binding protein) proteinopathy. Cortical TDP-43 pathology has been analyzed in detail in cases of FTLD-TDP, but is still unclear in cases of ALS. We attempted to clarify the cortical and subcortical TDP-43 pathology in Japanese cases of sporadic ALS (n = 96) using an antibody specific to phosphorylated TDP-43 (pTDP-43). The cases were divided into two groups: those without pTDP-43-positive neuronal cytoplasmic inclusions in the hippocampal dentate granule cells (Type 1, n = 63), and those with such inclusions (Type 2, n = 33). Furthermore, the Type 2 cases were divided into two subgroups based on semi-quantitative estimation of pTDP-43-positive dystrophic neurites (DNs) in the temporal neocortex: Type 2a (accompanied by no or few DNs, n = 22) and Type 2b (accompanied by abundant DNs, n = 11). Clinico-pathologic analysis revealed that cognitive impairment was a feature in patients with Type 2a and Type 2b, but not in those with Type 1, and that importantly, Type 2b is a distinct subtype characterized by a poor prognosis despite the less severe loss of lower motor neurons, the unusual subcortical dendrospinal pTDP-43 pathology, and more prominent glial involvement in cortical pTDP-43 pathology than other two groups. Considering the patient survival time and severity of motor neuron loss in each group, transition from Type 1 to Type 2, or from Type 2a to Type 2b during the disease course appeared unlikely. Therefore, each of these three groups was regarded as an independent subtype.

  3. Heterogeneity of cerebral TDP-43 pathology in sporadic amyotrophic lateral sclerosis: Evidence for clinico-pathologic subtypes.

    PubMed

    Takeuchi, Ryoko; Tada, Mari; Shiga, Atsushi; Toyoshima, Yasuko; Konno, Takuya; Sato, Tomoe; Nozaki, Hiroaki; Kato, Taisuke; Horie, Masao; Shimizu, Hiroshi; Takebayashi, Hirohide; Onodera, Osamu; Nishizawa, Masatoyo; Kakita, Akiyoshi; Takahashi, Hitoshi

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are types of major TDP-43 (43-kDa TAR DNA-binding protein) proteinopathy. Cortical TDP-43 pathology has been analyzed in detail in cases of FTLD-TDP, but is still unclear in cases of ALS. We attempted to clarify the cortical and subcortical TDP-43 pathology in Japanese cases of sporadic ALS (n = 96) using an antibody specific to phosphorylated TDP-43 (pTDP-43). The cases were divided into two groups: those without pTDP-43-positive neuronal cytoplasmic inclusions in the hippocampal dentate granule cells (Type 1, n = 63), and those with such inclusions (Type 2, n = 33). Furthermore, the Type 2 cases were divided into two subgroups based on semi-quantitative estimation of pTDP-43-positive dystrophic neurites (DNs) in the temporal neocortex: Type 2a (accompanied by no or few DNs, n = 22) and Type 2b (accompanied by abundant DNs, n = 11). Clinico-pathologic analysis revealed that cognitive impairment was a feature in patients with Type 2a and Type 2b, but not in those with Type 1, and that importantly, Type 2b is a distinct subtype characterized by a poor prognosis despite the less severe loss of lower motor neurons, the unusual subcortical dendrospinal pTDP-43 pathology, and more prominent glial involvement in cortical pTDP-43 pathology than other two groups. Considering the patient survival time and severity of motor neuron loss in each group, transition from Type 1 to Type 2, or from Type 2a to Type 2b during the disease course appeared unlikely. Therefore, each of these three groups was regarded as an independent subtype. PMID:27338935

  4. Imatinib Activates Pathological Hypertrophy by Altering Myocyte Calcium Regulation

    PubMed Central

    Barr, Larry; Makarewich, Catherine A.; Berretta, Remus M.; Gao, Hui; Troupes, Constantine D.; Woitek, Felix; Recchia, Fabio; Kubo, Hajime; Force, Thomas; Houser, Steven R.

    2014-01-01

    Background Imatinib mesylate is a selective tyrosine-kinase inhibitor used in the treatment of multiple cancers, most notably chronic myelogenous leukemia (CML). There is evidence that imatinib can induce cardiotoxicity in cancer patients. Our hypothesis is that imatinib alters calcium regulatory mechanisms and can contribute to development of pathological cardiac hypertrophy. Methods/Results Neonatal rat ventricular myocytes (NRVMs) were treated with clinical doses (Low: 2µM, High: 5µM) of imatinib and assessed for molecular changes. Imatinib increased peak systolic Ca2+ and Ca2+ transient decay rates and Western analysis revealed significant increases in phosphorylation of phospholamban (Thr-17) and the ryanodine receptor (Ser-2814), signifying activation of CaMKII. Imatinib significantly increased NRVM volume as assessed by Coulter counter, myocyte surface area and ANP abundance seen by Western. Imatinib induced cell death, but did not activate the classical apoptotic program as assessed by caspase-3 cleavage, indicating a necrotic mechanism of death in myocytes. We expressed AdNFATc3-GFP in NRVMS and showed imatinib treatment significantly increased NFAT translocation that was inhibited by the calcineurin inhibitor FK506 or CaMKII inhibitors. Conclusion These data show that imatinib can activate pathological hypertrophic signaling pathways by altering intracellular Ca2+ dynamics. This is likely a contributing mechanism for the adverse cardiac effects of imatinib. PMID:24931551

  5. International pediatric liver cancer pathological classification: current trend.

    PubMed

    Tanaka, Yukichi; Inoue, Takeshi; Horie, Hiroshi

    2013-12-01

    This review describes the pathological classification of pediatric liver cancer types and subtypes proposed at the recent international symposium (March 2011, Los Angeles, USA) and meetings involving pathologists serving as central reviewers for the Children's Oncology Group, Société Internationale d'Oncologie Pédiatrique, Gesellschaft für Pädiatrische Onkologie und Hämatologie, or Japanese Study Group for Pediatric Liver Tumors, and pediatric oncologists/surgeons specializing in liver cancers, as well as immunohistochemical panels, recommendations for submission, sampling and evaluation of diagnostic specimens. The pathological classification is intended to be standardized and clinically meaningful, thus improving future patient management and prognosis. The most common pediatric liver cancer is hepatoblastoma (HBL). HBL has two types, the wholly epithelial type and the mixed epithelial and mesenchymal (MEM) type. The wholly epithelial type was subdivided into well-differentiated fetal (pure fetal with low mitotic activity), crowded fetal (mitotically active), embryonal, epithelial mixed, small cell undifferentiated, and cholangioblastic. A macrotrabecular pattern and a pleomorphic epithelial pattern were recognized as supplemental features of epithelial components. The MEM type was subdivided into MEM without teratoid features and MEM with teratoid features. Other liver cancers in children were divided into hepatocellular carcinoma (classic hepatocellular carcinoma and fibrolamellar carcinoma) and hepatocellular malignant tumor not otherwise specified. This classification is basically applied to pretreatment specimens; the evaluation of post-chemotherapy specimens will be the subject of further studies.

  6. Adverse allergic reaction to Technetium-99m methylene diphosphonate

    SciTech Connect

    Spicer, J.A.; Preston, D.F.; Stephens, R.L.

    1985-04-01

    Adverse allergic reactions to radiopharmaceuticals are rare but have been documented in the literature. This report presents data consistent with a definite adverse reaction to the radiopharmaceutical (/sup 99m/Tc)MDP.

  7. Adverse outcome pathway (AOP) development I: Strategies and principles

    EPA Science Inventory

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically-supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organizatio...

  8. Adverse Outcome Pathways – Tailoring Development to Support Use

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) represent an ideal framework for connecting high-throughput screening (HTS) data and other toxicity testing results to adverse outcomes of regulatory importance. The AOP Knowledgebase (AOP-KB) captures AOP information to facilitate the development,...

  9. Adverse Outcome Pathway (AOP) Network Development for Fatty Liver

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk re...

  10. Adverse respiratory effects of outdoor air pollution in the elderly.

    PubMed

    Bentayeb, M; Simoni, M; Baiz, N; Norback, D; Baldacci, S; Maio, S; Viegi, G; Annesi-Maesano, I

    2012-09-01

    Compared to the rest of the population, the elderly are potentially highly susceptible to the effects of outdoor air pollution due to normal and pathological ageing. The purpose of the present review was to gather data on the effects on respiratory health of outdoor air pollution in the elderly, on whom data are scarce. These show statistically significant short-term and chronic adverse effects of various outdoor air pollutants on cardiopulmonary morbidity and mortality in the elderly. When exposed to air pollution, the elderly experience more hospital admissions for asthma and chronic obstructive pulmonary disease (COPD) and higher COPD mortality than others. Previous studies also indicate that research on the health effects of air pollution in the elderly has been affected by methodological problems in terms of exposure and health effect assessments. Few pollutants have been considered, and exposure assessment has been based mostly on background air pollution and more rarely on objective measurements and modelling. Significant progress needs to be made through the development of 'hybrid' models utilising the strengths of information on exposure in various environments to several air pollutants, coupled with daily activity exposure patterns. Investigations of chronic effects of air pollution and of multi-pollutant mixtures are needed to better understand the role of air pollution in the elderly. Lastly, smoking, occupation, comorbidities, treatment and the neighbourhood context should be considered as confounders or modifiers of such a role. In this context, the underlying biological, physiological and toxicological mechanisms need to be explored to better understand the phenomenon through a multidisciplinary approach. PMID:22871325

  11. Patient stratification and identification of adverse event correlations in the space of 1190 drug related adverse events

    PubMed Central

    Roitmann, Eva; Eriksson, Robert; Brunak, Søren

    2014-01-01

    Purpose: New pharmacovigilance methods are needed as a consequence of the morbidity caused by drugs. We exploit fine-grained drug related adverse event information extracted by text mining from electronic medical records (EMRs) to stratify patients based on their adverse events and to determine adverse event co-occurrences. Methods: We analyzed the similarity of adverse event profiles of 2347 patients extracted from EMRs from a mental health center in Denmark. The patients were clustered based on their adverse event profiles and the similarities were presented as a network. The set of adverse events in each main patient cluster was evaluated. Co-occurrences of adverse events in patients (p-value < 0.01) were identified and presented as well. Results: We found that each cluster of patients typically had a most distinguishing adverse event. Examination of the co-occurrences of adverse events in patients led to the identification of potentially interesting adverse event correlations that may be further investigated as well as provide further patient stratification opportunities. Conclusions: We have demonstrated the feasibility of a novel approach in pharmacovigilance to stratify patients based on fine-grained adverse event profiles, which also makes it possible to identify adverse event correlations. Used on larger data sets, this data-driven method has the potential to reveal unknown patterns concerning adverse event occurrences. PMID:25249979

  12. The Family Functioning of Female Pathological Gamblers

    ERIC Educational Resources Information Center

    Dowling, Nicki; Smith, David; Thomas, Trang

    2009-01-01

    The available evidence suggests that pathological gambling significantly disrupts family relationships and has a substantial impact on family members. However, these conclusions are based almost exclusively on male pathological gamblers and their female spouses or partners. The current study, which was a secondary study derived from a treatment…

  13. Pathological Gambling and Related Problems among Adolescents.

    ERIC Educational Resources Information Center

    Ladouceur, Robert; Boudreault, Normand; Jacques, Christian; Vitaro, Frank

    1999-01-01

    Evaluates the prevalence of pathological gambling and related problems among 3,426 students in junior and senior high schools in Quebec City. Results indicate that 77% have gambled in the last twelve months and 13% gamble at least once a week. Results also reveal that pathological gambling is associated with drug and alcohol use, poor grades, and…

  14. [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.

  15. Cognitive-Behavioral Therapy for Pathological Gamblers

    ERIC Educational Resources Information Center

    Petry, Nancy M.; Ammerman, Yola; Bohl, Jaime; Doersch, Anne; Gay, Heather; Kadden, Ronald; Molina, Cheryl; Steinberg, Karen

    2006-01-01

    Few studies have evaluated efficacy of psychotherapies for pathological gambling. Pathological gamblers (N = 231) were randomly assigned to (a) referral to Gamblers Anonymous (GA), (b) GA referral plus a cognitive-behavioral (CB) workbook, or (c) GA referral plus 8 sessions of individual CB therapy. Gambling and related problems were assessed…

  16. Diagnosis and pathology of endocrine diseases

    SciTech Connect

    Shriver, B.D.

    1988-01-01

    This book contains 22 papers under the headings of Diagnosis and Pathology of endocrine diseases. Topics covered include: Laboratory tests in the diagnosis and management of thyroid disorders, Pathology of thyroid diseases, Diagnosis of adrenourtical disease, Radiologic techniques in evaluating endocrine disorders; and the Pituitary and adrenal glands.

  17. 42 CFR 493.853 - Condition: Pathology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Performing Tests of Moderate Complexity (including the Subcategory), High Complexity, Or Any Combination of These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes...

  18. 42 CFR 493.853 - Condition: Pathology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Performing Tests of Moderate Complexity (including the Subcategory), High Complexity, Or Any Combination of These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes...

  19. Pathological Demand Avoidance: Exploring the Behavioural Profile

    ERIC Educational Resources Information Center

    O'Nions, Elizabeth; Viding, Essi; Greven, Corina U; Ronald, Angelica; Happé, Francesca

    2014-01-01

    "Pathological Demand Avoidance" is a term increasingly used by practitioners in the United Kingdom. It was coined to describe a profile of obsessive resistance to everyday demands and requests, with a tendency to resort to "socially manipulative" behaviour, including outrageous or embarrassing acts. Pathological demand…

  20. Adverse weather impacts on arable cropping systems

    NASA Astrophysics Data System (ADS)

    Gobin, Anne

    2016-04-01

    Damages due to extreme or adverse weather strongly depend on crop type, crop stage, soil conditions and management. The impact is largest during the sensitive periods of the farming calendar, and requires a modelling approach to capture the interactions between the crop, its environment and the occurrence of the meteorological event. The hypothesis is that extreme and adverse weather events can be quantified and subsequently incorporated in current crop models. Since crop development is driven by thermal time and photoperiod, a regional crop model was used to examine the likely frequency, magnitude and impacts of frost, drought, heat stress and waterlogging in relation to the cropping season and crop sensitive stages. Risk profiles and associated return levels were obtained by fitting generalized extreme value distributions to block maxima for air humidity, water balance and temperature variables. The risk profiles were subsequently confronted with yields and yield losses for the major arable crops in Belgium, notably winter wheat, winter barley, winter oilseed rape, sugar beet, potato and maize at the field (farm records) to regional scale (statistics). The average daily vapour pressure deficit (VPD) and reference evapotranspiration (ET0) during the growing season is significantly lower (p < 0.001) and has a higher variability before 1988 than after 1988. Distribution patterns of VPD and ET0 have relevant impacts on crop yields. The response to rising temperatures depends on the crop's capability to condition its microenvironment. Crops short of water close their stomata, lose their evaporative cooling potential and ultimately become susceptible to heat stress. Effects of heat stress therefore have to be combined with moisture availability such as the precipitation deficit or the soil water balance. Risks of combined heat and moisture deficit stress appear during the summer. These risks are subsequently related to crop damage. The methodology of defining

  1. [Features of neurologic semiotics at chronic obstructive pulmonary disease].

    PubMed

    Litvinenko, I V; Baranov, V L; Kolcheva, Iu A

    2011-01-01

    Chronic obstructive pulmonary disease (COPD) is actual pathology, when it forms the mixed hypoxemia. In the conditions of a chronic hypoxemia structures of organism with high level of metabolic processes, namely brain tissues, suffer. Character of defeat of the central nervous system at that pathology is insufficiently studied. In this article we studied and analysed the presence of such changes as depression, anxiety, cognitive impairment and features of neurologic semiotics at COPD in 50 patients.

  2. Adverse effects of 5α-reductase inhibitors: What do we know, don't know, and need to know?

    PubMed

    Traish, Abdulmaged M; Melcangi, Roberto Cosimo; Bortolato, Marco; Garcia-Segura, Luis M; Zitzmann, Michael

    2015-09-01

    Steroids are important physiological orchestrators of endocrine as well as peripheral and central nervous system functions. One of the key processes for regulation of these molecules lies in their enzymatic processing by a family of 5α-reductase (5α-Rs) isozymes. By catalyzing a key rate-limiting step in steroidogenesis, this family of enzymes exerts a crucial role not only in the physiological control but also in pathological events. Indeed, both 5α-R inhibition and supplementation of 5α-reduced metabolites are currently used or have been proposed as therapeutic strategies for a wide array of pathological conditions. In particular, the potent 5α-R inhibitors finasteride and dutasteride are used in the treatments of benign prostatic hyperplasia (BPH), as well as in male pattern hair loss (MPHL) known as androgenetic alopecia (AGA). Recent preclinical and clinical findings indicate that 5α-R inhibitors evoke not only beneficial, but also adverse effects. Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents. Furthermore, research on the non-sexual adverse effects such as diabetes, psychosis, depression, and cognitive function are needed to better understand the broad spectrum of the effects these drugs may elicit during their use in treatment of AGA or BPH. In this review, we will summarize the state of art on this topic, overview the key unresolved questions that have emerged on the pharmacological targeting of these enzymes and their products, and highlight the need for further studies to ascertain the severity and duration of the adverse effects of 5α-R inhibitors, as well as their biological underpinnings. PMID

  3. Kix domain specific Immunoglobulin A can protect from adverse lung and cerebral pathology induced by Plasmodium berghei ANKA.

    PubMed

    Kumar, Anil; Deore, Sapna; Kumar, Santosh; Bankar, Tanuja; Lotke, Anil; Parab, Pradeep; Krishnasastry, Musti

    2015-08-28

    Plasmodium specific IgA has been detected in serum and breast milk among the endemic population but the role it can play in vivo is not clear. In this report, we demonstrate the utility of Malaria specific IgA, elicited by peptide sequences (referred as Mpep3 and Mpep4) of region VI of EBA-175 (PfrVI). Immunization of mice with KLH tagged or untagged peptides of Mpep3, Mpep4 or with PfrVI have resulted in specific IgA response that inhibits the in vitro invasion of Plasmodium falciparum merozoites. Mice having the IgA specific to Mpep4 have exhibited higher tolerance to Plasmodium berghei ANKA parasitemia, exhibited several fold lesser sequestration of infected RBC, lesser damage to microvasculature with no signs of perivascular haemorrhage and lesser lung inflammation in comparison to unimmunized mice. In addition, the immunized mice have B-cell population that secrete the IgA specific to PfrVI. These results suggest that the IgA specific to these malarial antigens can confer significant advantage to hosts and it may also reduce the severity of malaria infection. PMID:26188504

  4. Physical basis of adverse and therapeutic effects of low intensity microwave radiation.

    PubMed

    Hyland, G J

    2008-05-01

    A physical basis of adverse and therapeutic effects of low intensity microwave radiation is presented based on the concept of oscillatory similitude between the frequency of an external microwave field (together with any lower frequency modulations thereof) and those of certain endogenous dipolar coherent excitations allied to aliveness, which play the role of 'tuned circuits' via which a living organism is electromagnetically sensitised in a non-linear way to external fields too weak to be able to cause heating. From this perspective, an external electromagnetic field affects a living system not as a toxin but rather by perturbing its endogenous electromagnetic activity. The possibility of adverse perturbation is illustrated by reference to the microwave fields used in mobile telecommunications whose signals interfere in a non-thermal way with biofunctionality--in particular, undermining the efficacy of processes that would otherwise afford natural protection against the development of pathology. Therapeutic modalities of microwave exposure, on the other hand, are illustrated using the example of microwave resonance therapy--which can be considered as an electromagnetic version of acupuncture, and as an example of 'quantum medicine'--whose normalising effect on a wide range of pathologies is striking, and which affords a novel alternative to conventional pharmacological interventions.

  5. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Adverse reaction file. 606.170 Section 606.170 Food... reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding... investigation of each reported adverse reaction shall be made. A written report of the investigation of...

  6. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. Link to an amendment published at 77 FR 18, Jan. 3, 2012. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding each unit of blood or blood...

  7. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties....

  8. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  9. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  10. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  11. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  12. Adversity and Resilience: A Synthesis of International Research

    ERIC Educational Resources Information Center

    Noltemeyer, Amity L.; Bush, Kevin R.

    2013-01-01

    Children and adolescents worldwide experience a variety of adversities that have the potential to disrupt typical development. However, some of these individuals exhibit resilience, evidencing normal development in the face of adversity. Here we review research on these constructs of risk, adversity, and resilience; synthesize international…

  13. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CFR part 68) and applicable guidelines, to avoid adverse effects. (c) Consulting party review. If the... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a)...

  14. Pathology in the era of Web 2.0.

    PubMed

    Schreiber, William E; Giustini, Dean M

    2009-12-01

    In the past few years, the term Web 2.0 has become a descriptor for the increased functionality of Web sites, including those with medical content. Most physicians do not know what Web 2.0 means or how it can impact their work lives. This review provides some background on the evolution of Web 2.0 and describes how its features are being incorporated into medical Web sites. Some potential applications of Web 2.0 in pathology and laboratory medicine are discussed, as are the issues that must be considered when adopting this new technology.

  15. Confocal Raman microscopy of pathologic cells in cerebrospinal fluid

    NASA Astrophysics Data System (ADS)

    Gonchukov, S. A.; Lonkina, T. V.; Minaeva, S. A.; Sundukov, A. V.; Migmanov, T. E.; Lademann, J.; Darvin, M. E.; Bagratashvili, V. N.

    2014-01-01

    In this work, the spatial localization of leucocytes, bacteria, and erythrocytes in the crystal pattern of a dried droplet of cerebrospinal fluid (CSF) is established. Characteristic lines are detected and identified in the Raman spectrum of the CSF that point to the presence of pathologic cells therein and can be used in a timely way to diagnose meningitis, the spectroscopic sample preparation procedure being simple enough. A dry CSF sample retains its characteristic spectral features for no less than three days, which is important for its safe keeping and transportation, and also for the computer processing of its spectra.

  16. Pediatric surgical pathology. Second edition

    SciTech Connect

    Dehner, L.P.

    1987-01-01

    The edition provides view of congenital, hereditary, infectious, and inflammatory neoplastic diseases occurring during the first two decades of life, with special reference to clinical, laboratory, and roentgenographic features. Material includes observations from some of the major national studies on Wilms' tumor and rhabdomyosarcomas, the new classification of pediatric malignant lymphomas, a discussion of the role of immunocytochemistry as it applies to the diagnosis of childhood infections and neoplasms, an examination of graft-versus-host disease in the liver and intestinal tract and more.

  17. Monitoring Adverse Drug Reactions: A Preliminary Study

    PubMed Central

    Reynolds, J. L.

    1981-01-01

    The feasibility of family physicians functioning as monitors of adverse drug reactions (ADR) was examined over one month in ten practices. This was done as a preliminary trial, before attempting to use the 200 family physicians of the National Reporting System of the College of Family Physicians of Canada to monitor ADRs on a national basis. Both of these trials were designed to examine the feasibility of family physicians acting as prospective monitors of ADRs in newly marketed drugs and to identify a drug group suitable for monitoring. This study examined the detection of ADRs, prescribing and practice profiles. No firm conclusion could be reached as to the value of family doctors monitoring ADRs. This study supports the evidence that older patients receive more drugs and are at even greater risk of an ADR. Antibiotics, cardiovascular, anti-inflammatory or antidepressant drugs are suggested as those most suitable for prospective monitoring in a family practice setting. PMID:21289786

  18. Adverse reactions to the sulphite additives

    PubMed Central

    Misso, Neil LA

    2012-01-01

    Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. Most studies report a prevalence of sulphite sensitivity of 3 to 10% among asthmatic subjects who ingest these additives. However, the severity of these reactions varies, and steroid-dependent asthmatics, those with marked airway hyperresponsiveness, and children with chronic asthma, appear to be at greater risk. Although a number of potential mechanisms have been proposed, the precise mechanisms underlying sulphite sensitivity remain unclear. PMID:24834193

  19. Adverse skeletal effects of drugs - beyond Glucocorticoids.

    PubMed

    O'Sullivan, Susannah; Grey, Andrew

    2015-01-01

    Osteoporotic fractures are an important public health problem with significant individual and societal costs. In addition to the major risk factors for osteoporotic fracture, low bone mineral density (BMD), age, low body weight and history of fracture or falls, some drugs are now considered to be important secondary risk factor for bone loss and fracture, particularly amongst predisposed individuals. Currently available data are often generated from small observational clinical studies, making risk assessment and development of management guidelines difficult. In many cases, the exposed population has a low baseline risk for fracture and additional assessment and treatment may not be necessary. In this review, we focus on drugs other than glucocorticoids identified as potentially causing adverse skeletal effects, summarizing the existing evidence from preclinical and clinical studies, and suggest recommendations for patient management. PMID:25039381

  20. Management of adverse effects of mood stabilizers.

    PubMed

    Murru, Andrea; Popovic, Dina; Pacchiarotti, Isabella; Hidalgo, Diego; León-Caballero, Jordi; Vieta, Eduard

    2015-08-01

    Mood stabilizers such as lithium and anticonvulsants are still standard-of-care for the acute and long-term treatment of bipolar disorder (BD). This systematic review aimed to assess the prevalence of their adverse effects (AEs) and to provide recommendations on their clinical management. We performed a systematic research for studies reporting the prevalence of AEs with lithium, valproate, lamotrigine, and carbamazepine/oxcarbazepine. Management recommendations were then developed. Mood stabilizers have different tolerability profiles and are eventually associated to cognitive, dermatological, endocrine, gastrointestinal, immunological, metabolic, nephrogenic, neurologic, sexual, and teratogenic AEs. Most of those can be transient or dose-related and can be managed by optimizing drug doses to the lowest effective dose. Some rare AEs can be serious and potentially lethal, and require abrupt discontinuation of medication. Integrated medical attention is warranted for complex somatic AEs. Functional remediation and psychoeducation may help to promote awareness on BD and better medication management.