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Sample records for adverse pathologic features

  1. Pathological features of polyneuropathy in three dogs.

    PubMed

    Tsuboi, Masaya; Uchida, Kazuyuki; Ide, Tetsuya; Ogawa, Mizue; Inagaki, Takehiko; Tamura, Shinji; Saito, Miyoko; Chambers, James K; Nakayama, Hiroyuki

    2013-01-01

    Canine polyneuropathy is a neurological disorder characterized by a dysfunction of multiple peripheral nerves. The etiology of the disease is diverse; it may occur in cases of infectious, immune-mediated, or hereditary conditions or in association with endocrinopathy, neoplasm, or chemical intoxication. It is often difficult to determine the etiology through clinical symptoms. The aim of this study is to investigate pathological differences among three canine polyneuropathy cases with each presumably having a different etiology. Cases included a 13-month-old female border collie (Dog No.1), a 21-month-old male chihuahua (Dog No.2) and an 11-year-old male beagle (Dog No.3). Clinical examinations revealed hindlimb ataxia and sensory loss in Dog No.1, forelimb paralysis and vertebral pain in Dog No.2, and paddling-gait and hypothyroidism in Dog No.3. Histopathologically, axonal swelling and pale myelin were observed in Dog No.1. Giant axons mimicking giant axonal neuropathy were obvious in Dog No.2. Dog No.3 showed atrophic axons and severe interstitial edema. Distributions of peripheral nerve lesions coincided with respective clinical symptoms. According to their clinical and pathological features, Dogs No.1 and No.2 were suspected of hereditary polyneuropathy, while Dog No.3 seemed to have hypothyroidism-associated polyneuropathy. As each case demonstrated unique pathological features, different pathogeneses of peripheral nerve dysfunction were suggested. PMID:23123885

  2. Placental Features of Late-Onset Adverse Pregnancy Outcome

    PubMed Central

    Higgins, Lucy E.; Wareing, Mark; Greenwood, Susan L.; Jones, Rebecca L.; Sibley, Colin P.; Johnstone, Edward D.; Heazell, Alexander E. P.

    2015-01-01

    Objective Currently, no investigations reliably identify placental dysfunction in late pregnancy. To facilitate the development of such investigations we aimed to identify placental features that differ between normal and adverse outcome in late pregnancy in a group of pregnancies with reduced fetal movement. Methods Following third trimester presentation with reduced fetal movement (N = 100), placental structure ex vivo was measured. Placental function was then assessed in terms of (i) chorionic plate artery agonist responses and length-tension characteristics using wire myography and (ii) production and release of placentally derived hormones (by quantitative polymerase chain reaction and enzyme linked immunosorbant assay of villous tissue and explant conditioned culture medium). Results Placentas from pregnancies ending in adverse outcome (N = 23) were ~25% smaller in weight, volume, length, width and disc area (all p<0.0001) compared with those from normal outcome pregnancies. Villous and trophoblast areas were unchanged, but villous vascularity was reduced (median (interquartile range): adverse outcome 10 (10–12) vessels/mm2 vs. normal outcome 13 (12–15), p = 0.002). Adverse outcome pregnancy placental arteries were relatively insensitive to nitric oxide donated by sodium nitroprusside compared to normal outcome pregnancy placental arteries (50% Effective Concentration 30 (19–50) nM vs. 12 (6–24), p = 0.02). Adverse outcome pregnancy placental tissue contained less human chorionic gonadotrophin (20 (11–50) vs. 55 (24–102) mIU/mg, p = 0.007) and human placental lactogen (11 (6–14) vs. 27 (9–50) mg/mg, p = 0.006) and released more soluble fms-like tyrosine kinase-1 (21 (13–29) vs. 5 (2–15) ng/mg, p = 0.01) compared with normal outcome pregnancy placental tissue. Conclusion These data provide a description of the placental phenotype of adverse outcome in late pregnancy. Antenatal tests that accurately reflect elements of this phenotype may

  3. Hyperphosphatemic Familial Tumoral Calcinosis: Odontostomatologic Management and Pathological Features

    PubMed Central

    Favia, Gianfranco; Lacaita, Maria Grazia; Limongelli, Luisa; Tempesta, Angela; Laforgia, Nicola; Cazzolla, Angela Pia; Maiorano, Eugenio

    2014-01-01

    Patient: Male, 9 Final Diagnosis: Hyperphosphatemic familial tumoral calcinosis Symptoms: — Medication: — Clinical Procedure: Ortopantomography Specialty: Dentistry Objective: Rare disease Background: Hyperphosphatemic familial tumoral calcinosis (HFTC) is to a rare autosomal recessive disorder characterized by cutaneous and sub-cutaneous calcified masses, usually adjacent to large joints. The aim of the current study was to report on the clinico-pathological features of a patient with HFCT, with emphasis on alterations in the jawbones and teeth and the subsequent therapeutic interventions. Case Report: A 13-year-old male patient with HFTC diagnosis came to our attention for dental anomalies and maxillary and mandibular hypoplasia. OPT highlighted multiple impacted teeth, short and bulbous teeth, and pulp chamber and canal obliterations. Lateral cephalometric radiograms pointed out retrusion of both jaws, skeletal class II malocclusion, and deep-bite. He underwent orthopedic, orthodontic, conservative, and surgical treatments, allowing the correction of maxillo-facial and dental abnormalities and dysmorphisms without adverse effects. The surgical samples were sent for conventional and confocal laser scanning microscope (CLSM) histopathological examination, which highlighted several metaplastic micro- and macro-calcifications in the soft tissues, and typical islands of homogenous, non-tubular, dentino-osteoid calcified structures in dentinal tissues. Conclusions: The management of maxillo-facial abnormalities in patients affected by HFTC is very difficult and, requires a combined therapeutic approach. To date, very few indications have been published in the literature. PMID:25537063

  4. Pathological features of hypertrophic obstructive cardiomyopathy

    PubMed Central

    Davies, M. J.; Pomerance, Ariela; Teare, R. D.

    1974-01-01

    The macroscopic features of hypertrophic obstructive cardiomyopathy are variable. The most easily recognized picture is of disproportionate and asymmetrical left ventricular hypertrophy with a small ventricular volume. Symmetrical ventricular hypertrophy also occurs and dilatation of the ventricular cavity may lead to a configuration more usually associated with congestive cardiomyopathy. Papillary muscle involvement leads to a bullet shape, often retained even when the ventricle dilates. Eighteen of the hearts showed a distinctive band of fibrous thickening below the aortic valve. This was a mirror image of the free edge of the anterior mitral cusp, had the microscopic features of an endocardial friction lesion, and was clearly the morphological expression of the systolic contact between cusp and septum seen on cineangiography. This band is characteristic of hypertrophic obstructive cardiomyopathy; it was more common in older patients and is of particular diagnostic value in cases with symmetrical hypertrophy, including those with dilated ventricular cavities. Sudden death was the commonest presentation in the younger cases but in several cases over 60 years at death hypertrophic obstructive cardiomyopathy was an incidental necropsy finding. Images PMID:4472994

  5. Consequences of Serotonin Transporter Genotype and Early Adversity on Behavioral Profile – Pathology or Adaptation?

    PubMed Central

    Heiming, Rebecca S.; Sachser, Norbert

    2010-01-01

    This review focuses on how behavioral profile is shaped by early adversity in individuals with varying serotonin transporter (5-HTT) genotype. In a recent study on 5-HTT knockout mice Heiming et al. (2009) simulated a ‘dangerous environment‘ by confronting pregnant and lactating females with odor cues of unfamiliar males, indicating the risk of infant killing. Growing up in a dangerous environment induced increased anxiety-related behavior and decreased exploratory locomotion in the offspring, the effects being most pronounced in mice lacking 5-HTT expression. We argue that these alterations in behavioral profile represent adaptive maternal effects that help the individuals to cope with adversity. In principle, such effects of adversity on behavioral profile should not automatically be regarded as pathological. Rather and in accordance with modern evolutionary theory they may represent adaptations, although individuals with 5-HTT genotype induced susceptibility to adversity may be at risk of developing pathologies. PMID:21151780

  6. Objective Pathological Voice Quality Assessment Based on HOS Features

    NASA Astrophysics Data System (ADS)

    Lee, Ji-Yeoun; Jeong, Sangbae; Choi, Hong-Shik; Hahn, Minsoo

    This work proposes new features to improve the pathological voice quality classification performance. They are the means, the variances, and the perturbations of the higher-order statistics (HOS) such as the skewness and the kurtosis. The HOS-based features show meaningful differences among normal, grade 1, grade 2, and grade 3 voices classified in the GRBAS scale. The jitter, the shimmer, the harmonic-to-noise ratio (HNR), and the variance of the short-time energy are utilized as the conventional features. The performances are measured by the classification and regression tree (CART) method. Specifically, the CART-based method by utilizing both the conventional features and the HOS-based ones shows its effectiveness in the pathological voice quality measurement, with the classification accuracy of 87.8%.

  7. Selecting Disorder-Specific Features for Speech Pathology Fingerprinting.

    PubMed

    Berisha, Visar; Sandoval, Steven; Utianski, Rene; Liss, Julie; Spanias, Andreas

    2013-01-01

    The general aim of this work is to learn a unique statistical signature for the state of a particular speech pathology. We pose this as a speaker identification problem for dysarthric individuals. To that end, we propose a novel algorithm for feature selection that aims to minimize the effects of speaker-specific features (e.g., fundamental frequency) and maximize the effects of pathology-specific features (e.g., vocal tract distortions and speech rhythm). We derive a cost function for optimizing feature selection that simultaneously trades off between these two competing criteria. Furthermore, we develop an efficient algorithm that optimizes this cost function and test the algorithm on a set of 34 dysarthric and 13 healthy speakers. Results show that the proposed method yields a set of features related to the speech disorder and not an individual's speaking style. When compared to other feature-selection algorithms, the proposed approach results in an improvement in a disorder fingerprinting task by selecting features that are specific to the disorder. PMID:25005047

  8. Selecting Disorder-Specific Features for Speech Pathology Fingerprinting

    PubMed Central

    Berisha, Visar; Sandoval, Steven; Utianski, Rene; Liss, Julie; Spanias, Andreas

    2014-01-01

    The general aim of this work is to learn a unique statistical signature for the state of a particular speech pathology. We pose this as a speaker identification problem for dysarthric individuals. To that end, we propose a novel algorithm for feature selection that aims to minimize the effects of speaker-specific features (e.g., fundamental frequency) and maximize the effects of pathology-specific features (e.g., vocal tract distortions and speech rhythm). We derive a cost function for optimizing feature selection that simultaneously trades off between these two competing criteria. Furthermore, we develop an efficient algorithm that optimizes this cost function and test the algorithm on a set of 34 dysarthric and 13 healthy speakers. Results show that the proposed method yields a set of features related to the speech disorder and not an individual's speaking style. When compared to other feature-selection algorithms, the proposed approach results in an improvement in a disorder fingerprinting task by selecting features that are specific to the disorder. PMID:25005047

  9. Clinical and Pathologic Features of Secondary Acute Promyelocytic Leukemia

    PubMed Central

    Duffield, Amy S.; Aoki, Joseph; Levis, Mark; Cowan, Kathleen; Gocke, Christopher D.; Burns, Kathleen H.; Borowitz, Michael J.; Vuica-Ross, Milena

    2013-01-01

    Acute promyelocytic leukemia (APL) is a relatively common form of acute myeloid leukemia (AML) that has an excellent prognosis. In contrast, secondary acute myeloid leukemias, including therapy-related AML and AML with myelodysplasia-related changes, have a relatively poor prognosis. We identified 9 cases of APL at our institution in which there was a history of chemotherapy, radiotherapy, chronic immunosuppression, or antecedent myelodysplastic syndrome. The clinical and pathologic findings in these cases of secondary APL were compared with the clinical and pathologic findings in cases of de novo APL. We found that secondary and de novo APL had abnormal promyelocytes with similar morphologic and immunophenotypic features, comparable cytogenetic findings, comparable rates of FMS-like tyrosine kinase mutations, and similar rates of recurrent disease and death. These data suggest that secondary APL is similar to de novo APL and, thus, should be considered distinct from other secondary acute myeloid neoplasms. PMID:22338051

  10. Retroperitoneal nodular fasciitis: magnetic resonance imaging (MRI) and pathological features.

    PubMed

    Meduri; Zuiani; Del Frate C; Bazzocchi

    1998-07-01

    A case of pelvic nodular fasciitis, with particular reference to its peculiar radiological and pathological features is described. Only a few cases of pelvic nodular fasciitis are reported in the English literature and at the best of our knowledge, this is the first case of retroperitoneal origin. This report discusses the role of MRI in the characterization of soft tissue masses. No specific MRI findings of nodular fasciitis were identified and MRI doesn't add any contribution to the differential diagnosis between benign and malignant lesions. As a consequence, the histopathological examination is necessary for a definitive diagnosis. PMID:10358366

  11. Relationship between childhood adversity and clinical and cognitive features in schizophrenia.

    PubMed

    McCabe, Kathryn L; Maloney, Elizabeth A; Stain, Helen J; Loughland, Carmel M; Carr, Vaughan J

    2012-05-01

    Childhood adversity is associated with elevated risk for a wide range of adult psychiatric disorders, and has significant and sustained negative effects on adult behavioural and social functioning. Elevated rates of childhood adversity have been reported for people with a diagnosis of schizophrenia. The aim of the present study was to assess rates of retrospectively reported childhood adversity among adults with schizophrenia and to examine the relationship between childhood adversity and clinical and cognitive features. Data were available for 408 schizophrenia participants and 267 healthy control participants recruited through the Australian Schizophrenia Research Bank (ASRB). History of childhood adversity was obtained using the Childhood Adversity Questionnaire (CAQ). A five-factor solution was identified from the CAQ. Schizophrenia participants reported experiencing more childhood adversities than controls. In both groups, those reporting childhood adversity were more likely to be female and older. Among participants with schizophrenia, positive symptom severity and fewer years of education were associated with childhood adversity. Lower IQ scores and personality traits were associated with reporting a greater number of childhood adversities and with adversity sub-types of abusive, neglectful and dysfunctional parenting. The rate of childhood adversity reported in this sample was high which suggests greater exposure to adverse childhood events among participants with schizophrenia in comparison with healthy controls. We identified unique groups amongst CAQ items that provided a salient framework from which to investigate the connection between childhood adversity and clinical and cognitive features. PMID:22329951

  12. Pathologic features of pediatric head and neck melanoma.

    PubMed

    Tcheung, Win Janet; Nelson, Kelly; Aldabagh, Bishr; Puja, Puri

    2013-01-01

    Although malignant melanoma is rare in children, its incidence is steadily increasing, and it is potentially lethal. Few studies have examined head and neck melanoma in children, and even fewer have focused on the histopathologic features of melanoma within this anatomic region. To further the understanding of this entity, we examined pathology specimens from nine subjects age 18 years and younger with an original diagnosis of head or neck melanoma. The anatomic locations of these primary melanomas were the face and nose (n = 4), scalp and neck (n = 4), and ear (n = 1). The cases included seven superficial spreading melanomas, one unclassified (possible nodular) melanoma, and one melanoma in situ. No melanomas demonstrating desmoplastic or spindle cell morphologies were noted upon review. Breslow depth ranged from 0 to 2.9 mm (mean 1.3 mm, median 0.6 mm), with Clark level ranging from I to V. Pagetoid scatter was found in eight cases. Other notable features included regression (n = 5), ulceration (n = 1), and associated melanocytic nevus (n = 4). We did not observe any small cell variants; all nine cases had an epithelioid appearance. Nor was any melanoma-associated mortality observed at last follow-up (mean 60.4 mos, median 48 mos, range 2-174 mos). These histopathologic features were consistent with adult-type melanoma, which is in agreement with other histopathologic studies of melanoma in children. PMID:23627731

  13. 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

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

    PubMed

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

    2001-01-01

    The present study was conducted to identify game parameters that would reduce the risk of abuse of video lottery terminals (VLTs) by pathological gamblers, while exerting minimal effects on the behavior of non-pathological gamblers. Three manipulations of standard VLT game features were explored. Participants were exposed to: a counter which displayed a running total of money spent; a VLT spinning reels game where participants could no longer "stop" the reels by touching the screen; and sensory feature manipulations. In control conditions, participants were exposed to standard settings for either a spinning reels or a video poker game. Dependent variables were self-ratings of reactions to each set of parameters. A set of 2(3) x 2 x 2 (game manipulation [experimental condition(s) vs. control condition] x game [spinning reels vs. video poker] x gambler status [pathological vs. non-pathological]) repeated measures ANOVAs were conducted on all dependent variables. The findings suggest that the sensory manipulations (i.e., fast speed/sound or slow speed/no sound manipulations) produced the most robust reaction differences. Before advocating harm reduction policies such as lowering sensory features of VLT games to reduce potential harm to pathological gamblers, it is important to replicate findings in a more naturalistic setting, such as a real bar. PMID:11842526

  15. Genomic Classifier Identifies Men With Adverse Pathology After Radical Prostatectomy Who Benefit From Adjuvant Radiation Therapy

    PubMed Central

    Den, Robert B.; Yousefi, Kasra; Trabulsi, Edouard J.; Abdollah, Firas; Choeurng, Voleak; Feng, Felix Y.; Dicker, Adam P.; Lallas, Costas D.; Gomella, Leonard G.; Davicioni, Elai; Karnes, R. Jeffrey

    2015-01-01

    Purpose The optimal timing of postoperative radiotherapy (RT) after radical prostatectomy (RP) is unclear. We hypothesized that a genomic classifier (GC) would provide prognostic and predictive insight into the development of clinical metastases in men receiving post-RP RT and inform decision making. Patients and Methods GC scores were calculated from 188 patients with pT3 or margin-positive prostate cancer, who received post-RP RT at Thomas Jefferson University and Mayo Clinic between 1990 and 2009. The primary end point was clinical metastasis. Prognostic accuracy of the models was tested using the concordance index for censored data and decision curve analysis. Cox regression analysis tested the relationship between GC and metastasis. Results The cumulative incidence of metastasis at 5 years after RT was 0%, 9%, and 29% for low, average, and high GC scores, respectively (P = .002). In multivariable analysis, GC and pre-RP prostate-specific antigen were independent predictors of metastasis (both P < .01). Within the low GC score (< 0.4), there were no differences in the cumulative incidence of metastasis comparing patients who received adjuvant or salvage RT (P = .79). However, for patients with higher GC scores (≥ 0.4), cumulative incidence of metastasis at 5 years was 6% for patients treated with adjuvant RT compared with 23% for patients treated with salvage RT (P < .01). Conclusion In patients treated with post-RP RT, GC is prognostic for the development of clinical metastasis beyond routine clinical and pathologic features. Although preliminary, patients with low GC scores are best treated with salvage RT, whereas those with high GC scores benefit from adjuvant therapy. These findings provide the first rational selection of timing for post-RP RT. PMID:25667284

  16. A new feature constituting approach to detection of vocal fold pathology

    NASA Astrophysics Data System (ADS)

    Hariharan, M.; Polat, Kemal; Yaacob, Sazali

    2014-08-01

    In the last two decades, non-invasive methods through acoustic analysis of voice signal have been proved to be excellent and reliable tool to diagnose vocal fold pathologies. This paper proposes a new feature vector based on the wavelet packet transform and singular value decomposition for the detection of vocal fold pathology. k-means clustering based feature weighting is proposed to increase the distinguishing performance of the proposed features. In this work, two databases Massachusetts Eye and Ear Infirmary (MEEI) voice disorders database and MAPACI speech pathology database are used. Four different supervised classifiers such as k-nearest neighbour (k-NN), least-square support vector machine, probabilistic neural network and general regression neural network are employed for testing the proposed features. The experimental results uncover that the proposed features give very promising classification accuracy of 100% for both MEEI database and MAPACI speech pathology database.

  17. Clinical and pathological features of an autosomal recessive neuropathy.

    PubMed

    Bouldin, T W; Riley, E; Hall, C D; Swift, M

    1980-06-01

    Two siblings are described, ages 49 and 45 years, having a distinct hereditary motor and sensory neuropathy (HMSN) with severe peroneal nerve involvement. The neuropathic symptoms began in childhood. Both patients have sensorineural deafness. The proband was found to have a cardiac conduction abnormality in the absence of known ischemic heart disease. Electrodiagnostic studies were consistent with a demyelinating peripheral neuropathy. The presence of parental consanguinity and absence of affected individuals in succeeding or preceding generations suggested that the sensorimotor neuropathy in this family is inherited in an autosomal recessive manner. The sural nerve of the proband had significant loss of myelinated fibers and demyelination but few regenerating myelinated fibers and no onion-bulbs. The pathological findings, while nonspecific, are not characteristic of the hypertrophic, neuronal or intermediate types of HMSN. PMID:6247456

  18. Clinical and pathological features of alcohol-related brain damage.

    PubMed

    Zahr, Natalie M; Kaufman, Kimberley L; Harper, Clive G

    2011-05-01

    One of the sequelae of chronic alcohol abuse is malnutrition. Importantly, a deficiency in thiamine (vitamin B(1)) can result in the acute, potentially reversible neurological disorder Wernicke encephalopathy (WE). When WE is recognized, thiamine treatment can elicit a rapid clinical recovery. If WE is left untreated, however, patients can develop Korsakoff syndrome (KS), a severe neurological disorder characterized by anterograde amnesia. Alcohol-related brain damage (ARBD) describes the effects of chronic alcohol consumption on human brain structure and function in the absence of more discrete and well-characterized neurological concomitants of alcoholism such as WE and KS. Through knowledge of both the well-described changes in brain structure and function that are evident in alcohol-related disorders such as WE and KS and the clinical outcomes associated with these changes, researchers have begun to gain a better understanding of ARBD. This Review examines ARBD from the perspective of WE and KS, exploring the clinical presentations, postmortem brain pathology, in vivo MRI findings and potential molecular mechanisms associated with these conditions. An awareness of the consequences of chronic alcohol consumption on human behavior and brain structure can enable clinicians to improve detection and treatment of ARBD. PMID:21487421

  19. Compulsive features in behavioral addictions: the case of pathological gambling

    PubMed Central

    el-Guebaly, Nady; Mudry, Tanya; Zohar, Joseph; Tavares, Hermano; Potenza, Marc N.

    2011-01-01

    Aims To describe, in the context of DSM-V, how a focus on addiction and compulsion is emerging in the consideration of pathological gambling (PG). Methods A systematic literature review of evidence for the proposed re-classification of PG as an addiction. Results Findings include: 1. Phenomenological models of addiction highlighting a motivational shift from impulsivity to compulsivity associated with a protracted withdrawal syndrome and blurring of the ego-syntonic/ego-dystonic dichotomy; 2. Common neurotransmitter (dopamine, serotonin) contributions to PG and substance use disorders (SUDs); 3. Neuroimaging support for shared neurocircuitries between “behavioral” and substance addictions and differences between obsessive-compulsive disorder (OCD), impulse control disorders (ICDs) and SUDs; 4. Genetic findings more closely related to endophenotypic constructs like compulsivity and impulsivity than to psychiatric disorders; 5. Psychological measures such as harm avoidance identifying a closer association between SUDs and PG than with OCD; 6. Community and pharmaco-therapeutic trials data supporting a closer association between SUDs and PG than with OCD. Adapted behavioral therapies, such as exposure therapy appear applicable to OCD, PG, or SUDs, suggesting some commonalities across disorders. Conclusions PG shares more similarities with SUDs than with OCD. Similar to the investigation of impulsivity, studies of compulsivity hold promising insights concerning the course, differential diagnosis and treatment of PG, SUDs, and OCD. PMID:21985690

  20. Pathologic Features of Colorectal Inflammatory Polyps in Miniature Dachshunds.

    PubMed

    Uchida, E; Chambers, J K; Nakashima, K; Saito, T; Ohno, K; Tsujimoto, H; Nakayama, H; Uchida, K

    2016-07-01

    The histopathologic characteristics of colorectal inflammatory polyps that formed in Miniature Dachshunds were compared with those of other colorectal proliferative lesions, including adenomas and adenocarcinomas. Fifty-three colorectal polypoid lesions were histopathologically classified into inflammatory polyps (26 cases), adenoma (18 cases), and adenocarcinoma (9 cases). All 26 dogs that were diagnosed with inflammatory polyps were Miniature Dachshunds, indicating that colorectal inflammatory polyps exhibit a marked predilection for this breed. The inflammatory polyps had complex histopathologic features and were classified into 3 stages based on their epithelial composition. In early stage (stage 1), the polyps tended to exhibit a thickened mucosa containing hyperplastic goblet cells, dilated crypts filled with a large amount of mucus, and mild lymphocyte and macrophage infiltration. In later stages (stages 2 and 3), more severe neutrophil infiltration, interstitial mucus accumulation, granulation tissue, and occasional osteoid tissue were seen. Also, a few small foci of dysplastic epithelial cells were detected. The hyperplastic goblet cells, which were a major component of the epithelium of the inflammatory polyps, were positive for cytokeratin 20 (CK20), while the dysplastic epithelial cells found in inflammatory polyps (stage 3) and the tumor cells of the adenomas and adenocarcinomas were negative for CK20. These CK20-negative epithelial cells exhibited cytoplasmic and nuclear immunoreactivity for beta-catenin. In addition, the epithelial cells in the inflammatory polyps demonstrated significantly higher cyclooxygenase 2 and fibroblast growth factor 2 expression than did those of the adenomas and adenocarcinomas, suggesting that the arachidonate cascade is involved in the development of colorectal inflammatory polyps in miniature dachshunds. PMID:26792840

  1. 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

  2. Representation of fluctuation features in pathological knee joint vibroarthrographic signals using kernel density modeling method.

    PubMed

    Yang, Shanshan; Cai, Suxian; Zheng, Fang; Wu, Yunfeng; Liu, Kaizhi; Wu, Meihong; Zou, Quan; Chen, Jian

    2014-10-01

    This article applies advanced signal processing and computational methods to study the subtle fluctuations in knee joint vibroarthrographic (VAG) signals. Two new features are extracted to characterize the fluctuations of VAG signals. The fractal scaling index parameter is computed using the detrended fluctuation analysis algorithm to describe the fluctuations associated with intrinsic correlations in the VAG signal. The averaged envelope amplitude feature measures the difference between the upper and lower envelopes averaged over an entire VAG signal. Statistical analysis with the Kolmogorov-Smirnov test indicates that both of the fractal scaling index (p=0.0001) and averaged envelope amplitude (p=0.0001) features are significantly different between the normal and pathological signal groups. The bivariate Gaussian kernels are utilized for modeling the densities of normal and pathological signals in the two-dimensional feature space. Based on the feature densities estimated, the Bayesian decision rule makes better signal classifications than the least-squares support vector machine, with the overall classification accuracy of 88% and the area of 0.957 under the receiver operating characteristic (ROC) curve. Such VAG signal classification results are better than those reported in the state-of-the-art literature. The fluctuation features of VAG signals developed in the present study can provide useful information on the pathological conditions of degenerative knee joints. Classification results demonstrate the effectiveness of the kernel feature density modeling method for computer-aided VAG signal analysis. PMID:25096412

  3. 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

  4. 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

  5. Review for carrageenan-based pharmaceutical biomaterials: favourable physical features versus adverse biological effects.

    PubMed

    Liu, Jingjing; Zhan, Xiudan; Wan, Jianbo; Wang, Yitao; Wang, Chunming

    2015-05-01

    Carrageenan (CRG) is a family of natural polysaccharides derived from seaweeds and has widely been used as food additives. In the past decade, owing to its attractive physicochemical properties, CRG has been developed into versatile biomaterials vehicles for drug delivery. Nevertheless, studies also emerged to reveal its adverse effects on the biological system. In this review, we critically appraise the latest literature (two thirds since 2008) on the development of CRG-based pharmaceutical vehicles and the perspective of using CRG for broader biomedical applications. We focus on how current strategies exploit the unique gelling mechanisms, strong water absorption and abundant functional groups of the three major CRG varieties. Notably, CRG-based matrices are demonstrated to increase drug loading and drug solubility, enabling release of orally administrated drugs in zero-order or in a significantly prolonged period. Other amazing features, such as pH-sensitivity and adhesive property, of CRG-based formulations are also introduced. Finally, we discuss the adverse influence of CRG on the human body and then suggest some future directions for the development of CRG-based biomaterials for broader applications in biomedicine. PMID:25659668

  6. 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

  7. 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. PMID:24821099

  8. Spindle epithelial tumor with thymus-like differentiation (SETTLE): clinical-pathological features, differential pathological diagnosis and therapy.

    PubMed

    Ippolito, Serena; Bellevicine, Claudio; Arpaia, Debora; Peirce, Carmela; Ciancia, Giuseppe; Vigliar, Elena; Troncone, Giancarlo; Biondi, Bernadette

    2016-03-01

    Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the thyroid gland. An algorithm for the diagnosis and treatment of SETTLE has yet to be established. The aim of this study was to identify all case reports of SETTLE and to compare the clinical-pathological features and therapy of the cases identified. We performed a PubMed search for case reports of SETTLE in English published up to November 2014 in which "SETTLE" and "Spindle epithelial tumor with thymus-like differentiation" were keywords. We identified 35 articles for a total of 42 cases. We found that SETTLE usually occurs in children and adolescents as an asymptomatic neck mass. Thyroid function tests and tumor markers are invariably within normal range in all patients, and fine needle aspiration biopsy is rarely diagnostic for SETTLE. All 42 patients had undergone thyroidectomy. After surgical resection, chemotherapy (adjuvant or first/second-line treatment) and/or radiotherapy were administered to control tumor growth in cases with metastatic involvement. Although SETTLE presents a low-grade malignancy, it can metastasize to lymph nodes, the mediastinum, lung, vertebrae, and kidney even many years after the initial diagnosis. SETTLE may have a good prognosis if appropriately treated at initial presentation and if patients undergo long-term monitoring with regular clinical and morphological evaluations. PMID:26289127

  9. An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features

    PubMed Central

    2014-01-01

    Background Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. Methods Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. Results All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema

  10. Ron tyrosine kinase receptor synergises with EGFR to confer adverse features in head and neck squamous cell carcinoma

    PubMed Central

    Keller, J; Nimnual, A S; Shroyer, K R; Joy, C; Ischenko, I; Chandler, C S; Dong, L M; Hayman, M J; Chan, E L

    2013-01-01

    Background: Although EGFR inhibitors have shown some success in the treatment of head and neck squamous cell carcinomas (HNSCCs), the results are not dramatic. Additional molecular targets are urgently needed. We previously showed that the loss of Ron receptor activity significantly slowed squamous tumour growth and progression in a murine model. Based on these data, we hypothesised that Ron expression confers an aggressive phenotype in HNSCCs. Methods: We prospectively collected and evaluated 154 snap-frozen, primary HNSCCs for Ron and EGFR expression/phosphorylation. Biomarker correlation with clinical, pathological and outcome data was performed. The biological responses of HNSCC cell lines to Ron knockdown, its activation and the biochemical interaction between Ron and EGFR were examined. Results: We discovered that 64.3% (99 out of 154) HNSCCs expressed Ron. The carcinomas expressed exclusively mature functional Ron, whereas the adjacent nonmalignant epithelium expressed predominantly nonfunctional Ron precursor. There was no significant association between Ron and sex, tumour differentiation, perineural/vascular invasion or staging. However, patients with Ron+HNSCC were significantly older and more likely to have oropharyngeal tumours. Ron+HNSCC also had significantly higher EGFR expression and correlated strongly with phosphorylated EGFR (pEGFR). Newly diagnosed HNSCC with either Ron/pEGFR or both had lower disease-free survival than those without Ron and pEGFR. Knocking down Ron in SCC9 cells significantly blunted their migratory response to not only the Ron ligand, MSP, but also EGF. Stimulation of Ron in SCC9 cells significantly augmented the growth effect of EGF; the synergistic effect of both growth factors in SCC9 cells was dependent on Ron expression. Activated Ron also interacted with and transactivated EGFR. Conclusion: Ron synergises with EGFR to confer certain adverse features in HNSCCs. PMID:23799848

  11. 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.

  12. Pathological features of localized prostate cancer in China: a contemporary analysis of radical prostatectomy specimens.

    PubMed

    Zhu, Yao; Yang, Xiao-Qun; Han, Cheng-Tao; Dai, Bo; Zhang, Hai-Liang; Shi, Guo-Hai; Wang, Chao-Fu; Ye, Ding-Wei

    2015-01-01

    There has been a rapid increase in the incidence of prostate cancer in China, especially in areas with boosted economic development. In this study, we analyzed the pathological features of a contemporary series of radical prostatectomy cases. A total of 230 consecutive, whole-mounted radical prostatectomy specimens collected from 2012 to 2014 were reviewed. The median age of the patients was 68 years, and 64.3% of patients presented with prostate specific antigen alone. Pathological examination indicated that a high proportion (77.4%) of patients had intermediate- or high-risk disease according to the Cancer of the Prostate Risk Assessment Post-Surgical score. After surgery, only 28 patients met the criteria for active surveillance (organ-confined Gleason ≥6 disease). The Prostate Cancer Research International Active Surveillance criteria achieved a sensitivity of 57.1% and a specificity of 98.0% for identifying candidates. The probability of Gleason score upgrading was 24.8% in the entire group and 59.0% in biopsy-confirmed Gleason ≥6 disease. The predominant tumor was located in the transition zone in 14.8% of cases, while only three patients (1.3%) had a predominant tumor located in the anterior region. Patients with transition zone-predominant tumor were likely to have been referred with urinary symptoms and high prostate specific antigen levels. The results of this study highlight the contemporary pathological features of localized prostate cancer in urban China. There was an increased trend towards asymptomatic cases, though most patients had intermediate- or high-risk disease and were suitable for definitive treatment. The low prevalence of dominant cancer in the anterior region may reflect race-based pathological differences. PMID:25799190

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. Acinar Cell Carcinoma of the Pancreas: Overview of Clinicopathologic Features and Insights into the Molecular Pathology

    PubMed Central

    La Rosa, Stefano; Sessa, Fausto; Capella, Carlo

    2015-01-01

    Acinar cell carcinomas (ACCs) of the pancreas are rare pancreatic neoplasms accounting for about 1–2% of pancreatic tumors in adults and about 15% in pediatric subjects. They show different clinical symptoms at presentation, different morphological features, different outcomes, and different molecular alterations. This heterogeneous clinicopathological spectrum may give rise to difficulties in the clinical and pathological diagnosis with consequential therapeutic and prognostic implications. The molecular mechanisms involved in the onset and progression of ACCs are still not completely understood, although in recent years, several attempts have been made to clarify the molecular mechanisms involved in ACC biology. In this paper, we will review the main clinicopathological and molecular features of pancreatic ACCs of both adult and pediatric subjects to give the reader a comprehensive overview of this rare tumor type. PMID:26137463

  19. 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

  20. Using multiparametric data with missing features for learning patterns of pathology

    PubMed Central

    Ingalhalikar, Madhura; Parker, William A.; Bloy, Luke; Roberts, Timothy P.L.; Verma, Ragini

    2014-01-01

    The paper presents a method for learning multimodal classifiers from datasets in which not all subjects have data from all modalities. Usually, subjects with a severe form of pathology are the ones failing to satisfactorily complete the study, especially when it consists of multiple imaging modalities. A classifier capable of handling subjects with unequal numbers of modalities prevents discarding any subjects, as is traditionally done, thereby broadening the scope of the classifier to more severe pathology. It also allows design of the classifier to include as much of the available information as possible and facilitates testing of subjects with missing modalities over the constructed classifier. The presented method employs an ensemble based approach where several subsets of complete data are formed and trained using individual classifiers. The output from these classifiers is fused using a weighted aggregation step giving an optimal probabilistic score for each subject. The method is applied to a spatio-temporal dataset for autism spectrum disorders (ASD)(96 patients with ASD and 42 typically developing controls) that consists of functional features from magnetoencephalography (MEG) and structural connectivity features from diffusion tensor imaging (DTI). A clear distinction between ASD and controls is obtained with an average 5-fold accuracy of 83.3% and testing accuracy of 88.4%. The fusion classifier performance is superior to the classification achieved using single modalities as well as multimodal classifier using only complete data (78.3%). The presented multimodal classifier framework is applicable to all modality combinations. PMID:23286164

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

    PubMed

    Sato, Katsuaki; 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

  2. 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

  3. The Impact of Childhood Adversity on the Clinical Features of Schizophrenia.

    PubMed

    Rajkumar, Ravi Philip

    2015-01-01

    Introduction. Recent research has drawn attention to the link between childhood maltreatment and schizophrenia. Child abuse and neglect may have an impact on symptoms and physical health in these patients. This association has not been studied to date in India. Materials and Methods. Clinically stable patients with schizophrenia (n = 62) were assessed for childhood adversity using the Childhood Trauma Questionnaire. The association of specific forms of adversity with symptomatology and associated variables was examined. Results. Emotional abuse was reported by 56.5% patients and physical abuse by 33.9%; scores for childhood neglect were also high. Persecutory delusions were linked to physical abuse, while anxiety was linked to emotional neglect and depression to emotional abuse and childhood neglect. Physical abuse was linked to elevated systolic blood pressure, while emotional abuse and neglect in women were linked to being overweight. Conclusions. Childhood adversity is common in schizophrenia and appears to be associated with a specific symptom profile. Certain components of the metabolic syndrome also appear to be related to childhood adversity. These results are subject to certain limitations as they are derived from remitted patients, and no control group was used for measures of childhood adversity. PMID:26345291

  4. The Impact of Childhood Adversity on the Clinical Features of Schizophrenia

    PubMed Central

    Rajkumar, Ravi Philip

    2015-01-01

    Introduction. Recent research has drawn attention to the link between childhood maltreatment and schizophrenia. Child abuse and neglect may have an impact on symptoms and physical health in these patients. This association has not been studied to date in India. Materials and Methods. Clinically stable patients with schizophrenia (n = 62) were assessed for childhood adversity using the Childhood Trauma Questionnaire. The association of specific forms of adversity with symptomatology and associated variables was examined. Results. Emotional abuse was reported by 56.5% patients and physical abuse by 33.9%; scores for childhood neglect were also high. Persecutory delusions were linked to physical abuse, while anxiety was linked to emotional neglect and depression to emotional abuse and childhood neglect. Physical abuse was linked to elevated systolic blood pressure, while emotional abuse and neglect in women were linked to being overweight. Conclusions. Childhood adversity is common in schizophrenia and appears to be associated with a specific symptom profile. Certain components of the metabolic syndrome also appear to be related to childhood adversity. These results are subject to certain limitations as they are derived from remitted patients, and no control group was used for measures of childhood adversity. PMID:26345291

  5. 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

  6. 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

  7. 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

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

    PubMed

    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

  9. Hepatolithiasis and the syndrome of recurrent pyogenic cholangitis: clinical, radiologic, and pathologic features.

    PubMed

    Tsui, Wilson Man-shan; Chan, Yiu-kay; Wong, Chi-tat; Lo, Yan-fai; Yeung, Yat-wah; Lee, Yat-wing

    2011-02-01

    Primary hepatothiasis (HL) and recurrent pyogenic cholangitis (RPC) are two terms describing the different aspects of the same disease, with HL emphasizing the pathologic changes and RPC emphasizing the clinical presentation and suppurative inflammation. It is predominantly a disease of the Far East. In the 1960s, it was the third most common cause of emergency abdominal surgery at a university hospital in Hong Kong. Thereafter, its incidence has decreased considerably, possibly due to improved standards of living and Westernized diet. Clinically, patients may present acutely with recurrent bacterial cholangitis and its possible complications, such as liver abscess and septicemic shock, or with chronic complications, such as cholangiocarcinoma. Pathologically, it is characterized by pigmented calcium bilirubinate stones within dilated intrahepatic bile ducts featuring chronic inflammation, mural fibrosis, and proliferation of peribiliary glands, without extrahepatic biliary obstruction. Episodes of suppurative inflammation cumulate in sclerosing cholangitis of peripheral ducts and parenchymal fibrosis resulting from collapse and scarring. Mass-forming inflammatory pseudotumor and neoplasms like intraductal papillary neoplasms and cholangiocarcinoma are increasingly recognized complications. Modern imaging techniques allow definitive diagnosis, accurate assessment for treatment planning, and detection of complications. A multidisciplinary team approach (interventional endoscopist, interventional radiologist, hepatobiliary surgeon, and intensivists) is important for optimal patient outcome. PMID:21344349

  10. Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer’s disease

    PubMed Central

    Sharoar, Md. Golam; Shi, Qi; Ge, Yingying; He, Wanxia; Hu, Xiangyou; Perry, George; Zhu, Xiongwei; Yan, Riqiang

    2015-01-01

    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 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

  11. 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

  12. BRAF V600 mutations and pathological features in Japanese melanoma patients

    PubMed Central

    Tanaka, Ryota; Tsutsumida, Arata; Namikawa, Kenjiro; Eguchi, Hironobu; Omata, Wataru; Oashi, Kohei; Ogawa, Toru; Hayashi, Amiko; Nakamura, Noriyuki; Tsuta, Koji

    2015-01-01

    Ultraviolet radiation is a risk factor for BRAF V600 mutations frequently found in melanomas that cause constitutive BRAF activation. Primary sites of melanoma and the frequency of BRAF mutations might differ between races. Melanoma is rare in Japan (1500–2000 cases/year compared with 132 000/year worldwide) and the frequency and distribution of BRAF V600 mutations are unknown. We aimed to investigate the frequency of BRAF V600 mutations in a cohort of Japanese patients with melanoma and determine the relationship between mutations and clinical/pathologic features. DNA was extracted from 80 formalin-fixed, paraffin-embedded tumours from individuals diagnosed with melanoma. BRAF V600 mutations were detected using the Cobas 4800 System with z480 Analyzer and Cobas 4800 BRAF V600 Mutation Test reagents. BRAF V600 mutations were detected in 41.8% of tested tumours, with an invalid rate of 1.3%. The mutation rate was more than 60% in patients aged less than 60 years and more than 36% in patients with stage III/IV disease. No sex difference in the mutation rate was observed. BRAF V600 mutations were detected in 18.8% of acral lentiginous melanomas (ALMs), 64.7% of superficial spreading melanomas, 50.0% of lentigo maligna melanomas and 20.0% of nodular melanomas. Although the mutation rate was low in ALMs, 36.4% were mutation positive at stage III/IV compared with 9.5% at stage I/II. This study confirmed associations among BRAF V600 mutations, pathological features and subtypes of melanoma. BRAF V600 mutations were more frequent in late-stage ALMs than in early-stage ALMs. Superficial spreading melanomas had similar mutation rates at all stages. These insights suggest improved treatment predictions for stage III/IV melanoma patients. PMID:25051202

  13. BRAF V600 mutations and pathological features in Japanese melanoma patients.

    PubMed

    Yamazaki, Naoya; Tanaka, Ryota; Tsutsumida, Arata; Namikawa, Kenjiro; Eguchi, Hironobu; Omata, Wataru; Oashi, Kohei; Ogawa, Toru; Hayashi, Amiko; Nakamura, Noriyuki; Tsuta, Koji

    2015-02-01

    Ultraviolet radiation is a risk factor for BRAF V600 mutations frequently found in melanomas that cause constitutive BRAF activation. Primary sites of melanoma and the frequency of BRAF mutations might differ between races. Melanoma is rare in Japan (1500-2000 cases/year compared with 132 000/year worldwide) and the frequency and distribution of BRAF V600 mutations are unknown. We aimed to investigate the frequency of BRAF V600 mutations in a cohort of Japanese patients with melanoma and determine the relationship between mutations and clinical/pathologic features. DNA was extracted from 80 formalin-fixed, paraffin-embedded tumours from individuals diagnosed with melanoma. BRAF V600 mutations were detected using the Cobas 4800 System with z480 Analyzer and Cobas 4800 BRAF V600 Mutation Test reagents. BRAF V600 mutations were detected in 41.8% of tested tumours, with an invalid rate of 1.3%. The mutation rate was more than 60% in patients aged less than 60 years and more than 36% in patients with stage III/IV disease. No sex difference in the mutation rate was observed. BRAF V600 mutations were detected in 18.8% of acral lentiginous melanomas (ALMs), 64.7% of superficial spreading melanomas, 50.0% of lentigo maligna melanomas and 20.0% of nodular melanomas. Although the mutation rate was low in ALMs, 36.4% were mutation positive at stage III/IV compared with 9.5% at stage I/II. This study confirmed associations among BRAF V600 mutations, pathological features and subtypes of melanoma. BRAF V600 mutations were more frequent in late-stage ALMs than in early-stage ALMs. Superficial spreading melanomas had similar mutation rates at all stages. These insights suggest improved treatment predictions for stage III/IV melanoma patients. PMID:25051202

  14. Correlation of CT scanning and pathologic features of ophthalmic Graves' disease.

    PubMed

    Trokel, S L; Jakobiec, F A

    1981-06-01

    Correlating the CT scan features of patients with orbital Graves' disease with histopathologic observations allows one to focus more specifically on the distinguishing features of this disease with future research implications. Both CT scanning and pathologic studies have shown clearly that the extraocular muscles are the primary focus of the disease. Swelling of the extraocular muscles generally occurs within their bellys with sparing of the tendons. This contrast with idiopathic inflammation of the muscles or myositis, which tends to involve the tendon as well. All of the associated findings in orbital Graves' disease probably flow from the enlarged volume of the extraocular muscles: proptosis, bowing of the medial lamina papyracea to accommodate the swollen belly of the medial rectus muscle, venous engorgement from stasis induced by direct compression of the orbital venous drainage, conjunctival and lid swelling, and lacrimal gland enlargement. Both radiographic and pathologic changes in the orbital fat are secondary and comparatively insignificant. While there appears to be no selective inflammation of the optic nerve meninges or the perineural connective tissues, enlargement of the extraocular muscle bellys where they converge at the crowded orbital apex brings about compression of the optic nerve, impairs its function, and causes visual decrease. Lymphocytic and plasmacytic infiltration along with edema within the endomysium of the extraocular muscles leads to the activation of fibroblasts with the production of acid mucopolysaccharides and progressive fibrosis. It is not known what attracts the lymphocytes to the extraocular muscles, why certain extraocular muscles are affected preferentially, why the disease may be asymmetrically unilateral, and whether a defect in T cell or B cell functions (or both) is immunologically at fault. PMID:6894976

  15. Carpet Lesions Detected at CT Colonography: Clinical, Imaging, and Pathologic Features

    PubMed Central

    Lam, Vu P.; Weiss, Jennifer M.; Kennedy, Gregory D.; Kim, David H.

    2014-01-01

    Purpose To describe carpet lesions (laterally spreading tumors ≥ 3 cm) detected at computed tomographic (CT) colonography, including their clinical, imaging, and pathologic features. Materials and Methods The imaging reports for 9152 consecutive adults undergoing initial CT colonography at a tertiary center were reviewed in this HIPAA-compliant, institutional review board–approved retrospective study to identify all potential carpet lesions detected at CT colonography. Carpet lesions were defined as morphologically flat, laterally spreading tumors 3 cm or larger. For those patients with neoplastic carpet lesions, CT colonography studies were analyzed to determine maximal lesion width and height, oral contrast material coating, segmental location, and computer-aided detection (CAD) findings. Demographic data and details of clinical treatment in these patients were reviewed. Results Eighteen carpet lesions in 18 patients (0.2%; mean age, 67.1 years; eight men, 10 women) were identified and were subsequently confirmed at colonoscopy and pathologic examination among 20 potential flat masses (≥3 cm) prospectively identified at CT colonography (there were two nonneoplastic rectal false-positive findings). No additional neoplastic carpet lesions were found in the cohort undergoing colonoscopy after CT colonography and/or surgery (there were no false-negatives). Mean lesion width was 46.5 mm (range, 30–80 mm); mean lesion height was 7.9 mm (range, 4–14 mm). Surface retention of oral contrast material was noted in all 18 cases. All but two lesions were located in the distal rectosigmoid or proximal right colon. At CAD, 17 (94.4%) lesions were detected (mean, 6.2 CAD marks per lesion). Sixteen lesions (88.9%) demonstrated advanced histologic features, including a villous component (n = 11), high-grade dysplasia (n = 4), and invasive cancer (n = 5). Sixteen patients (88.9%) required surgical treatment for complete excision. Conclusion CT colonography can effectively

  16. Features of a reattaching turbulent shear layer subject to an adverse pressure gradient

    NASA Technical Reports Server (NTRS)

    Driver, D. M.; Seegmiller, H. L.

    1982-01-01

    Experimental data have been obtained in an incompressible turbulent flow over a rearward-facing step with superimposed adverse pressure gradient. Mean velocities, Reynolds stresses and triple-products measured by a laser Doppler velocimeter are presented for two cases of adverse pressure gradient. Mixing lengths, eddy viscosities, production, convection, turbulent diffusion, and dissipation terms are extracted from the data. These data are compared with various mixing length and eddy-viscosity turbulence models. Numerical calculations incorporating the k-epsilon and the algebraic-stress turbulence models are compared with the data. When determining quantities of engineering interest, the modified algebraic-stress model (ASM) is a significant improvement over the unmodified ASM and the unmodified k-epsilon model

  17. 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

  18. Does the choice of display system influence perception and visibility of clinically relevant features in digital pathology images?

    NASA Astrophysics Data System (ADS)

    Kimpe, Tom; Rostang, Johan; Avanaki, Ali; Espig, Kathryn; Xthona, Albert; Cocuranu, Ioan; Parwani, Anil V.; Pantanowitz, Liron

    2014-03-01

    Digital pathology systems typically consist of a slide scanner, processing software, visualization software, and finally a workstation with display for visualization of the digital slide images. This paper studies whether digital pathology images can look different when presenting them on different display systems, and whether these visual differences can result in different perceived contrast of clinically relevant features. By analyzing a set of four digital pathology images of different subspecialties on three different display systems, it was concluded that pathology images look different when visualized on different display systems. The importance of these visual differences is elucidated when they are located in areas of the digital slide that contain clinically relevant features. Based on a calculation of dE2000 differences between background and clinically relevant features, it was clear that perceived contrast of clinically relevant features is influenced by the choice of display system. Furthermore, it seems that the specific calibration target chosen for the display system has an important effect on the perceived contrast of clinically relevant features. Preliminary results suggest that calibrating to DICOM GSDF calibration performed slightly worse than sRGB, while a new experimental calibration target CSDF performed better than both DICOM GSDF and sRGB. This result is promising as it suggests that further research work could lead to better definition of an optimized calibration target for digital pathology images resulting in a positive effect on clinical performance.

  19. 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

  20. 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

  1. Pathologic features of renal biopsies based on H & E, immunofluorescence and electron microscopy.

    PubMed

    Zahir, S Taghipour; Hosseini, E

    2014-01-01

    Kidneys are complex organs with multiple vital functions. They are an essential part of the urinary system and also are necessary for regulation of body homeostasis like electrolytes, acid base balance and blood pressure. Diagnosis of renal injuries is based on clinical and histopathologic features. In a descriptive cross-sectional study conducted in Shahid Sadoughi Hospital, Yazd, Iran, pathology reports of all renal biopsies, by light microscopic examination, immunofluorecence and electron microscopy (EM) were perused. Data were registered in a questionnaire with questions on patients' demographic information such as age, sex and also questions on clinical signs and symptoms and pathologic findings such as H & E, Immunofluorescence (IF) and electron microscopy. All data were analyzed by SPSS-15 software with descriptive analysis. A total of 80 patients were included in this study, 42 men (52.5%) and 38 women (47.5%), aged 19-73 years (mean: 40.59 ± 16.36). Based on H & E, IF and electron microscopic findings, it seems that in 26.4% of cases the IFM was necessary and in 67.6% was helpful and in 6% was unnecessary for diagnosis. Between 42 patients, EM was necessary in 12% of patients, while in 71.5% was helpful and in 16.5% was unnecessary. Based on IFM the most common renal disease was FSGS (focal segmental glomerulosclerosis) with mean age of 41.3 years. IFM was necessary in RPGN, chronic glomerulonephritis, mesangial hypercellularity, minimal change disease, IgA nephropathy, and was helpful in FSGS, MPGN, tubulointerstitial nephritis, diffuse sclerosing glomerulonephritis and membranous glomerulopathy but was unnecessary in lupus nephritis. EM was necessary in mesangial hypercellularity, chronic glomerulonephritis and diffuse sclerosing glomerulopathy and was helpful in FSGS, MPGN, lupus nephritis and membranous glomerulopathy while it was unnecessary in minimal change disease and IgA nephropathy. PMID:25726629

  2. 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

  3. 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

  4. 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

  5. Identifying features of 'pathological demand avoidance' using the Diagnostic Interview for Social and Communication Disorders (DISCO).

    PubMed

    O'Nions, Elizabeth; Gould, Judith; Christie, Phil; Gillberg, Christopher; Viding, Essi; Happé, Francesca

    2016-04-01

    The term 'pathological demand avoidance' (PDA) was coined by Elizabeth Newson to describe children within the autism spectrum who exhibit obsessive resistance to everyday demands and requests (Newson et al., Arch Dis Child 88:595-600, 2003). Clinical accounts describe avoidance strategies including apparently strategic use of distraction or socially shocking behaviour, and obsessive need for control, reflected in domineering behaviour to peers and adults. Educational and management approaches effective for PDA reportedly differ from those for 'typical' autism spectrum disorders (ASD), and include novelty, humour and flexibility. Identification of PDA in individuals with ASD may have important implications for management (Eaton and Banting, J Learn Disabil Offending Behav 3:150-157, 2012). Despite increasing interest, no clinician-rated instrument for PDA has been developed. Here, items relevant to PDA were identified from the Diagnostic Interview for Social and Communication Disorder (DISCO) (Wing et al., J Child Psychol Psychiatry 43:307-325, 2002). The most PDA-specific subset of relevant DISCO items was selected, based on low endorsement in general across a sample of 153 individuals assessed for possible ASD using the DISCO. Having selected 11 DISCO PDA items for the measure, a subset of individuals with a high number of these features was identified (N = 27). Consistent with Newson's descriptions, this high scoring group was characterised by lack of co-operation, use of apparently manipulative behaviour, socially shocking behaviour, difficulties with other people, anxiety and sudden behavioural changes from loving to aggression. All but one case met criteria for an ASD. This study brings the field a step closer to a clinician-rated measure of PDA features and highlights the need for further elucidation of the PDA phenotype. PMID:26224583

  6. Computed tomography appearance of inflammatory myofibroblastic tumor in the abdomen: CT features and pathologic correlation

    PubMed Central

    Liu, Bo; Xu, Junlong; Wang, Jiaxin; Fan, Hongguang; Ang, Xuan; Liu, Wenming

    2015-01-01

    Objective: To evaluate CT findings of abdominal inflammatory myofibroblastic tumor (IMT) and the relationship with morphological character. Materials and Methods: CT examinations and pathological findings of ten intra-abdominal IMTs were retrospectively analyzed. The histopathological characteristics of the IMTs were confirmed by two pathologists and two radiologists evaluated CT findings of the lesion, with emphasis on the imaging features compared with the corresponding histopathology. Results: The most common imaging characteristics were presence of heterogeneity, all tumors showed varying degrees of contrast enhancement. Two major different CT patterns were individualized. In type one, the tumor had a distinct boundary without a lobular appearance and displayed hypo-enhanced enhancement after administration of contrast in correlated with the mainly histopathologic findings of spindle cells myxoid and hypocellular fibrous (6/10; 60%). In type two, the lesions exhibited indistinct boundaries or complete capsule, ill-defined growth patterns or low intralesional attenuation with marked heterogeneous or circumferential enhancement, which correlated well with the presence of abundance of micromodule and inflammatory cell infiltration (4/10; 40%). Conclusions: Two major different contrast enhancement CT patterns were individualized can help to determine the relationships with histopathologic findings, while cannot be reliably differentiated from other solid lesions based solely on the CT appearance, combined with diagnostic biopsy may facilitate to achieve a correct diagnosis and treatment. PMID:26629216

  7. [An autopsy case of senile dementia with pathological features of Parkinson's disease].

    PubMed

    Oshima, Kenichi; Tsuchiya, Kuniaki; Iritani, Shuji; Niizato, Kazuhiro; Akiyama, Haruhiko; Ikeda, Kenji; Arai, Heii

    2004-07-01

    We report an autopsy case of Parkinson's disease mimicking senile dementia of the Alzheimer type. A Japanese man developed memory disturbance and visual hallucination at age 70. Although he died from pneumonia at age of 74, he had no neurological signs throughout the clinical course. The weight of his brain was 1,420 g. Macroscopic examination of the brain revealed prominent depigmentation of the substantia nigra and locus ceruleus. Histological examination disclosed neuronal loss with astrocytosis and the appearance of the Lewy bodies in the nucleus basalis of Meynert, substantia nigra, locus ceruleus, and dorsal vagal nucleus. There were widespread senile plaques in the brain, including the precentral gyrus, which was compatible with Braak stage C. A small number of neurofibrillary changes were present in the limbic areas, consistent with Braak stage III. This case is consistent with brain stem dominance with the pathological diagnosis of the Consortium on Dementia with Lewy Bodies International Workshop. That is, it is compatible with Parkinson's disease. We postulate that the clinical features of Parkinson's disease are more widespread than previously considered. PMID:15379289

  8. Emerinopathy and Laminopathy Clinical, pathological and molecular features of muscular dystrophy with nuclear envelopathy in Japan

    PubMed Central

    Astejada, MN; Goto, K; Nagano, A; Ura, S; Noguchi, S; Nonaka, I; Nishino, I; Hayashi, YK

    2007-01-01

    Summary Mutations in the genes for nuclear envelope proteins of emerin (EMD) and lamin A/C (LMNA) are known to cause Emery-Dreifuss muscular dystrophy (EDMD) and limb girdle muscular dystrophy (LGMD). We compared clinical features of the muscular dystrophy patients associated with mutations in EMD (emerinopathy) and LMNA (laminopathy) in our series. The incidence of laminopathy was slightly higher than that of emerinopathy. The age at onset of the disease in emerinopathy was variable and significantly older than in laminopathy. The initial symptom of emerinopathy was also variable, whereas nearly all laminopathy patients presented initially with muscle weakness. Calf hypertrophy was often seen in laminopathy, underscoring the importance of mutation screening for LMNA in childhood muscular dystrophy with calf hypertrophy. The clinical spectrum of emerinopathy is actually wider than previously known including EDMD, LGMD, conduction defects with minimal muscle/joint involvement, and their intermittent forms. Pathologically, no marked difference was observed between emerinopathy and laminopathy. Increased number and variation in size of myonuclei were detected. More precise observations using electron microscopy is warranted to characterize the detailed nuclear changes in nuclear envelopathy. PMID:18646565

  9. Cavernous Sinus: A Comprehensive Review of its Anatomy, Pathologic Conditions, and Imaging Features.

    PubMed

    Bakan, A A; Alkan, A; Kurtcan, S; Aralaşmak, A; Tokdemir, S; Mehdi, E; Özdemir, H

    2015-06-01

    The purpose of this article was to review the anatomy of the cavernous sinus (CS), illustrate numerous lesions that can affect the CS, and emphasize the imaging characteristics for each lesion to further refine the differential diagnoses. The CS, notwithstanding its small size, contains a complicated and crucial network that consists of the carotid artery, the venous plexus, and cranial nerves. The wide-ranging types of pathologies that can involve the CS can be roughly classified as tumoral, congenital, infectious/inflammatory/granulomatous, and vascular. Conditions that affect the CS usually lead to symptoms that are similar to each other; thus, for diagnosis, imaging procedures are required. Radiological evaluations are also required to detect pre- and postoperative CS invasion. Magnetic resonance imaging, which can be supplemented with thin-section contrast-enhanced sequences, is the preferred imaging technique for evaluating the CS. For correct diagnosis of CS lesions and accurate evaluations of CS invasions, it is essential to carefully analyze the anatomical structures within the CS and to acquire precise knowledge about the imaging features of CS lesions, which may frequently overlap. PMID:25410584

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. [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

  16. [CLINICAL FEATURES AND OPTIMIZATION OF THE TREATMENT OF CHILDREN WITH COMBINATION GASTRODUODENAL PATHOLOGY AND PRIMARY HYPERTENSION].

    PubMed

    Marushco, Y V; Zlobynets, A S

    2015-01-01

    The paper present dynamic of clinical picture, daily blood pressure monitoring results and subjective assessment of functional status in children with combination of chronic gastroduodenal pathology and primary hypertension when L-carnitine used with the standard treatment regimen. PMID:26118045

  17. [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

  18. Correlation mapping: rapid method for identification of histological features and pathological classification in mid infrared spectroscopic images of lymph nodes

    NASA Astrophysics Data System (ADS)

    Isabelle, Martin; Rogers, Keith; Stone, Nicholas

    2010-03-01

    In this work, a novel technique for rapid image analysis of Fourier transform infrared (FTIR) data obtained from human lymph nodes is explored. It uses the mathematical principle of orthogonality as a method to quickly and efficiently obtain tissue and pathology information from a spectral image cube. It requires less computational power and time compared to most forms of cluster analysis. The values obtained from different tissue and pathology types allows for discrimination of noncancerous from cancerous lymph nodes. It involves the calculation of the dot product between reference spectra and individual spectra from across the tissue image. These provide a measure of the correlation between individual spectra and the reference spectra, and each spectrum or pixel in the image is given a color representing the reference most closely correlating with it. The correlation maps are validated with the tissue and pathology features identified by an expert pathologist from corresponding hematoxylin and eosin stained tissue sections. Although this novel technique requires further study to properly test and validate this tool, with inclusion of more lymph node hyperspectral datasets (containing a greater variety of tissue states), it demonstrates significant clinical potential for pathology diagnosis.

  19. 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

  20. 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

  1. 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

  2. Clinical and Pathological Features of Generalized Granuloma Annulare with Their Correlation: A Retrospective Multicenter Study in Korea

    PubMed Central

    Yun, Jeong Hyun; Lee, Ji Yeoun; Kim, Mi Kyeong; Seo, Young Joon; Kim, Myung Hwa; Cho, Kwang Hyun; Kim, Moon Bum; Lee, Won Soo; Lee, Kwang Hoon; Kim, You Chan; Lee, Seok Jong; Choi, Gwang Seong; Won, Young Ho; Ihm, Chull Wan

    2009-01-01

    Background Generalized granuloma annulare (GGA) is a benign skin disorder of an unknown etiology. Though some cases of GGA have been reported, few systemic reviews of the clinical and pathological features of GGA have been performed. Objective The purpose of this study is to analyze and correlate the clinical and pathological characteristics of GGA in Korean patients. Methods We conducted a retrospective study that included 54 biopsy specimens of Korean GGA patients, and the clinical and pathological features of GGA were reviewed and analyzed for their correlation. Results The cutaneous lesions could be divided into the annular (24, 44%) and nonannular types (30, 56%), and the lesions were more common in males than in females (29 males and 25 females). The incidence of GGA showed a bimodal age distribution. The number of patients who presented within the first decade was 24 cases (44%), and 24 cases (44%) were over the fifth decade. Eight patients (15%) had systemic diseases. Especially, diabetes mellitus (DM) occurred only in the adult GGA patients over forty years old. The pathological findings showed dermal granulomatous lesions that consisted of either a palisading pattern (28, 52%) or an interstitial pattern (26, 48%). Conclusion In contrast to the previously reported studies, the age of GGA onset showed a bimodal distribution, and GGA was observed more often in males. The prevalence of DM in the GGA affected individuals was higher than that found in the general Korean population. Therefore, it is recommended to perform a work-up for DM in the GGA affected patients who are over forty years old. PMID:20523767

  3. 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.

  4. Overexpression of Ku80 correlates with aggressive clinicopathological features and adverse prognosis in esophageal squamous cell carcinoma

    PubMed Central

    WANG, SHUAI; WANG, ZHOU; YANG, YU; SHI, MO; SUN, ZHENGUO

    2015-01-01

    Ku80, a subunit of the heterodymeric Ku protein, is clearly implicated in nonhomologous end joining DNA repair, chemoresistance and radioresistance in malignant tumors. In the present study, the clinicopathological significance of Ku80 in esophageal squamous cell carcinoma (ESCC) was investigated. The expression levels of Ku80 were determined by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry in ESCC specimens and normal esophageal mucosa. The mRNA and protein levels of Ku80 were significantly higher in ESCC tissues than in normal esophageal mucosa, and were significantly associated with tumor differentiation, local invasion, lymph node metastasis and tumor-node-metastasis (TNM) stage. However, overexpression of Ku80 mRNA and protein levels were not significantly correlated with age, gender, tumor site or tumor size. Cox proportional hazards regression model demonstrated that tumor local invasion, lymph node metastasis, TNM stage and Ku80 mRNA and protein levels were independent risk factors indicating the overall survival of patients with ESCC. The present study demonstrated that aberrant Ku80 overexpression is observed in ESCC. In addition, high expression levels of Ku80 are associated with adverse clinicopathological features and unfavorable prognosis in ESCC patients. PMID:26722230

  5. 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

  6. 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. PMID:23811814

  7. 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

  8. 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

  9. Root of the small-bowel mesentery: correlative anatomy and CT features of pathologic conditions.

    PubMed

    Okino, Y; Kiyosue, H; Mori, H; Komatsu, E; Matsumoto, S; Yamada, Y; Suzuki, K; Tomonari, K

    2001-01-01

    The root of the small-bowel mesentery (SBM) is an important peritoneal fold that is contiguous to other peritoneal ligaments and mesocolons. Several pathologic conditions can occur in the SBM itself, and diseases that spread through the connections from adjacent organs frequently involve it. The root of the SBM is contiguous to the hepatoduodenal ligament around the superior mesenteric vein (SMV) and contiguous to the right side of the transverse mesocolon around the gastrocolic trunk. The inferior mesenteric vein, which is a landmark of the descending mesocolon, runs along the left side of the root of the SBM. Malignant neoplasms can spread to the SBM by means of direct extension, extension along the neural plexus, extension along neighboring ligaments, or extension along lymphatic vessels. Inflammatory conditions such as pancreatitis and perforation of a jejunal diverticulum can also spread to the SBM. Anomalies that can occur in the SBM include rotation anomalies and internal hernia. Vascular lesions of the SBM include thrombosis of the superior mesenteric artery (SMA), acute SMV thrombosis, SMA dissection, arterioportal fistula, and portal venous gas. Other pathologic conditions that can occur in the SBM are edema or congestion, mesenteric tear, mesenteric panniculitis, and tumors or tumorlike lesions. PMID:11706218

  10. The radiological features of phylloides tumour of the breast with clinico-pathological correlation.

    PubMed

    Page, J E; Williams, J E

    1991-07-01

    The mammograms of 13 patients with phylloides tumour of the breast are reviewed and the results correlated with clinical and histological features. Three patients had recurrent tumours. There is a strong association between phylloides tumour and fibroadenoma. Many of the tumours are radiologically indistinguishable from fibroadenomata and it is not possible to predict tumour behaviour on the basis of clinical and radiological features alone. PMID:1651822

  11. 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

  12. Primary hepatic cancers with multiple pathologic features in a patient with hepatitis C: report of a case.

    PubMed

    Oshima, Go; Shinoda, Masahiro; Tanabe, Minoru; Masugi, Yohei; Ueno, Akihisa; Takano, Kiminori; Kitago, Minoru; Itano, Osamu; Kawachi, Shigeyuki; Ohara, Kentaro; Oda, Masaya; Tanimoto, Akihiro; Sakamaoto, Michiie; Kitagawa, Yuko

    2012-01-01

    We report a case of multiple primary hepatic cancers exhibiting different pathologic features coexisting in a patient with chronic hepatitis C. Computed tomography showed 2 tumors in segment 8, 20 mm (S8-A) and 5 mm (S8-B) in diameter, and a 10-mm tumor in segment 6 (S6). Based on the images, the S8-A lesion was diagnosed as cholangiocellular carcinoma or combined hepatocellular carcinoma and cholangiocarcinoma (combined HCC-CC). The other 2 tumors were diagnosed as HCC. The patient underwent partial resections of segments 6 and 8. We found 2 more tumors (S8-C was 6 mm in diameter and S8-D was 4 mm) in the resected segment 8 specimen. Histopathologic examination revealed that the S8-A and S8-C tumors were combined HCC-CC, the S8-B and S6 lesions were scirrhous HCC, and the S8-D tumor was an early HCC. This is a very rare case in which different hepatic cancers with multiple pathologic features coexisted. PMID:23101996

  13. 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

  14. Epidemiologic Profile, Sexual History, Pathologic Features, and Human Papillomavirus Status of 103 Patients with Penile Carcinoma

    PubMed Central

    Chaux, Alcides; Netto, George J.; Rodríguez, Ingrid M.; Barreto, José E.; Oertell, Judith; Ocampos, Sandra; Boggino, Hugo; Codas, Ricardo; Bosch, F. Xavier; de Sanjose, Silvia; Muñoz, Nubia; Hildesheim, Allan; Cubilla, Antonio L.

    2011-01-01

    PURPOSE The incidence of penile cancer is four times higher in Paraguay than in the United States or Europe. There are no adequate scientific explanations for this geographical variation. The goal of this study was to evaluate the interplay among risk factors, morphology of the primary tumor, and HPV status. METHODS Information on socioeconomic status, education level, habits, and sexual history was obtained in 103 Paraguayan patients with penile cancer. All patients were then treated by surgery and specimens were evaluated histopathologically. RESULTS Patients usually dwelled in rural/suburban areas (82%), lived in poverty (75%), had a low education level (91%), and were heavy smokers (76%). Phimosis (57%), moderate/poor hygienic habits (90%), and history of sexually-transmitted diseases (74%) were frequently found. Patients with >10 lifetime female partners had an odds ratio of 3.8 (95% CI 1.1, 12.6; P-trend = .03) for presenting HPV positive tumors when compared to patients with <6 partners. However, this trend was not significant when the number of sexual partners was adjusted for age of first coitus and antecedents of sexually-transmitted diseases. HPV-related tumors (found in 36% of the samples) were characterized by a warty and/or basaloid morphology and high histological grade in most cases. CONCLUSIONS In our series, patients with penile cancer presented a distinctive epidemiological and pathological profile. These data might help explaining the geographical differences in incidence and aid in the design of strategies for cancer control in Paraguay. PMID:22116602

  15. Pathological features in dead on arrival broilers with special reference to heart disorders.

    PubMed

    Nijdam, E; Zailan, A R M; van Eck, J H H; Decuypere, E; Stegeman, J A

    2006-07-01

    A gross postmortem investigation was done on 302 broilers that died between catching and slaughter to establish predisposing factors for dying in this period. Special attention was paid to heart disorders, which were established by determining the ratio of the right ventricle mass to the total ventricle mass (RV:TV) and to postmortem changes in hearts and lungs of broilers that were dead on arrival (DOA). Macroscopic pathologic lesions were found in 89.4% of DOA broilers. Signs of infectious diseases appeared to be most frequent (64.9%), followed by heart and circulation disorders (42.4%), and trauma (29.5%). The RV:TV was significantly higher for DOA broilers in comparison with slaughtered broilers. The prevalence of hearts with an abnormal RV:TV in DOA broilers was 34.4 vs. 4.1% in slaughtered broilers. The DOA broilers with an abnormal heart ratio more frequently showed ascites and hydropericardium. Postmortem changes in lungs depend on the position of the carcass the first several hours after death. Broilers, which remain in dorsal recumbency for several hours after death, develop engorged lungs. A good health status as well as more attention for the catching and crating process is crucial in decreasing the percentage of DOA broilers. Prevention of an increased heart ratio and of ascites will improve the livability in the broiler house and also decrease the DOA rate enormously. PMID:16830873

  16. Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis

    PubMed Central

    2010-01-01

    Background It has been suggested that columnar cell lesions indicate an alteration of the human mammary gland involved in the development of breast cancer. They have not previously been described in canine mammary gland. The aim of this paper is describe the morphologic spectrum of columnar cell lesions in canine mammary gland specimens and their association with other breast lesions. Methods A total of 126 lesions were subjected to a comprehensive morphological review based upon the human breast classification system for columnar cell lesions. The presence of preinvasive (epithelial hyperplasia and in situ carcinoma) and invasive lesions was determined and immunophenotypic analysis (estrogen receptor (ER), progesterone receptor (PgR), high molecular weight cytokeratin (34βE-12), E-cadherin, Ki-67, HER-2 and P53) was perfomed. Results Columnar cell lesions were identified in 67 (53.1%) of the 126 canine mammary glands with intraepithelial alterations. They were observed in the terminal duct lobular units and characterized at dilated acini may be lined by several layers of columnar epithelial cells with elongated nuclei. Of the columnar cell lesions identified, 41 (61.2%) were without and 26 (38.8%) with atypia. Association with ductal hyperplasia was observed in 45/67 (67.1%). Sixty (89.5%) of the columnar cell lesions coexisted with neoplastic lesions (20 in situ carcinomas, 19 invasive carcinomas and 21 benign tumors). The columnar cells were ER, PgR and E-cadherin positive but negative for cytokeratin 34βE-12, HER-2 and P53. The proliferation rate as measured by Ki-67 appeared higher in the lesions analyzed than in normal TDLUs. Conclusions Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions. PMID:20178635

  17. 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

  18. 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

  19. Pathology accessioning and retrieval system with encoding by computer (PARSEC). A microcomputer-based system for anatomic pathology featuring automated SNOP coding and multiple administrative functions.

    PubMed

    Foulis, P R; Norbut, A M; Mendelow, H; Kessler, G F

    1980-06-01

    A pathology accessioning and retrieval system with encoding by computer (PARSEC) has been developed, employing a relatively inexpensive microcomputer. PARSEC performs a variety of administrative functions for anatomic pathology, including accessioning of surgical specimens, storage of patient demographic information, editing, retrieval, and archiving of patient data, as well as CAP (college of American Pathologists) workload units, billing, and inventory functions for histopathology. In addition, appropriate gross and microscopic descriptions and pathologic diagnoses can be entered into the system by a text editor. Automatic assignment of SNOP (Systematized Nomenclature of Pathology) codes, is accomplished via an online SNOP lexicon, allowing the ultimate generation of completed surgical pathology reports. The data base management system employed makes optimum use of disk storage space, while permitting rapid data retrieval. Data file maintenance is automatically accomplished by the system, requiring no user intervention. PMID:7395803

  20. 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

  1. Pathological and immunohistochemical features of subdural histiocytic sarcomas in 15 dogs.

    PubMed

    Ide, Tetsuya; Uchida, Kazuyuki; Kagawa, Yumiko; Suzuki, Kazuhiko; Nakayama, Hiroyuki

    2011-01-01

    Subdural histiocytic sarcomas from 15 dogs (mean age 7.8 years) were histopathologically examined. Among the 15 dogs, there was a marked breed predominance (toward Pembroke Welsh Corgi dogs, 47%), but no gender predilection. Focal solitary subdural masses were detected in the cerebrum (12 cases) and spinal cord (1 case), whereas diffuse infiltrative lesions were observed in the cerebral leptomeninges in 2 cases. All neoplastic lesions had common histological features characterized by the proliferation of pleomorphic histiocytic cells combined with various inflammatory reactions. Multinucleated giant cells, phagocytosis, and atypical mitotic figures in the neoplastic cells were commonly observed. Most of the pleomorphic neoplastic cells in the present cases were immunopositive for monocytic, histiocytic, or both markers, such as human leukocyte antigen (HLA)-DR, ionized calcium-binding adaptor molecule 1 (Iba1), cluster of differentiation (CD)163, and CD204, except for the neoplastic cells in 2 focal and 2 diffuse histiocytic sarcomas. The findings suggest that differences in cell origin, molecular expression, or both patterns are responsible for the distribution patterns of canine subdural histiocytic sarcomas. PMID:21217043

  2. 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

  3. Adaptive multiple feature method (AMFM) for early detecton of parenchymal pathology in a smoking population

    NASA Astrophysics Data System (ADS)

    Uppaluri, Renuka; McLennan, Geoffrey; Enright, Paul; Standen, James; Boyer-Pfersdorf, Pamela; Hoffman, Eric A.

    1998-07-01

    Application of the Adaptive Multiple Feature Method (AMFM) to identify early changes in a smoking population is discussed. This method was specifically applied to determine if differences in CT images of smokers (with normal lung function) and non-smokers (with normal lung function) could be found through computerized texture analysis. Results demonstrated that these groups could be differentiated with over 80.0% accuracy. Further, differences on CT images between normal appearing lung from non-smokers (with normal lung function) and normal appearing lung from smokers (with abnormal lung function) were also investigated. These groups were differentiated with over 89.5% accuracy. In analyzing the whole lung region by region, the AMFM characterized 38.6% of a smoker lung (with normal lung function) as mild emphysema. We can conclude that the AMFM detects parenchymal patterns in the lungs of smokers which are different from normal patterns occurring in healthy non-smokers. These patterns could perhaps indicate early smoking-related changes.

  4. The thyroid: review of imaging features and biopsy techniques with radiologic-pathologic correlation.

    PubMed

    Nachiappan, Arun C; Metwalli, Zeyad A; Hailey, Brian S; Patel, Rishi A; Ostrowski, Mary L; Wynne, David M

    2014-01-01

    Knowledge of the normal and abnormal imaging appearances of the thyroid gland is essential for appropriate identification and diagnosis of thyroid lesions. Thyroid nodules are often detected incidentally at computed tomography, magnetic resonance imaging, and positron emission tomography; however, ultrasonography (US) is the most commonly used imaging modality for characterization of these nodules. US characteristics that increase the likelihood of malignancy in a thyroid nodule include microcalcifications, solid composition, and central vascularity. Nuclear scintigraphy is commonly used for evaluation of physiologic thyroid function and for identification of metabolically active and inactive nodules. When fine-needle aspiration biopsy (FNAB) of a lesion is indicated based on clinical and radiologic features, appropriate US-guided biopsy technique and careful cytologic analysis are crucial for making the diagnosis. FNAB and core biopsy are the two percutaneous techniques used to obtain a specimen, with the latter technique being indicated following nondiagnostic or indeterminate FNAB. Specimen adequacy and diagnostic accuracy vary due to several factors, including location of aspiration and biopsy technique used. The radiologist must have a basic knowledge of thyroid disease, be familiar with specimen processing, and recognize the cytologic and radiologic appearances of thyroid lesions, all of which will facilitate the management of these lesions. Online supplemental material is available for this article. PMID:24617678

  5. 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

  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. 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

  8. Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p

    PubMed Central

    Hsiung, Ging-Yuek R.; DeJesus-Hernandez, Mariely; Feldman, Howard H.; Sengdy, Pheth; Bouchard-Kerr, Phoenix; Dwosh, Emily; Butler, Rachel; Leung, Bonnie; Fok, Alice; Rutherford, Nicola J.; Baker, Matt; Rademakers, Rosa

    2012-01-01

    Frontotemporal dementia and amyotrophic lateral sclerosis are closely related clinical syndromes with overlapping molecular pathogenesis. Several families have been reported with members affected by frontotemporal dementia, amyotrophic lateral sclerosis or both, which show genetic linkage to a region on chromosome 9p21. Recently, two studies identified the FTD/ALS gene defect on chromosome 9p as an expanded GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 gene (C9ORF72). In the present study, we provide detailed analysis of the clinical features and neuropathology for 16 unrelated families with frontotemporal dementia caused by the C9ORF72 mutation. All had an autosomal dominant pattern of inheritance. Eight families had a combination of frontotemporal dementia and amyotrophic lateral sclerosis while the other eight had a pure frontotemporal dementia phenotype. Clinical information was available for 30 affected members of the 16 families. There was wide variation in age of onset (mean = 54.3, range = 34–74 years) and disease duration (mean = 5.3, range = 1–16 years). Early diagnoses included behavioural variant frontotemporal dementia (n = 15), progressive non-fluent aphasia (n = 5), amyotrophic lateral sclerosis (n = 9) and progressive non-fluent aphasia–amyotrophic lateral sclerosis (n = 1). Heterogeneity in clinical presentation was also common within families. However, there was a tendency for the phenotypes to converge with disease progression; seven subjects had final clinical diagnoses of both frontotemporal dementia and amyotrophic lateral sclerosis and all of those with an initial progressive non-fluent aphasia diagnosis subsequently developed significant behavioural abnormalities. Twenty-one affected family members came to autopsy and all were found to have transactive response DNA binding protein with Mr 43 kD (TDP-43) pathology in a wide neuroanatomical distribution. All

  9. Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p.

    PubMed

    Hsiung, Ging-Yuek R; DeJesus-Hernandez, Mariely; Feldman, Howard H; Sengdy, Pheth; Bouchard-Kerr, Phoenix; Dwosh, Emily; Butler, Rachel; Leung, Bonnie; Fok, Alice; Rutherford, Nicola J; Baker, Matt; Rademakers, Rosa; Mackenzie, Ian R A

    2012-03-01

    Frontotemporal dementia and amyotrophic lateral sclerosis are closely related clinical syndromes with overlapping molecular pathogenesis. Several families have been reported with members affected by frontotemporal dementia, amyotrophic lateral sclerosis or both, which show genetic linkage to a region on chromosome 9p21. Recently, two studies identified the FTD/ALS gene defect on chromosome 9p as an expanded GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 gene (C9ORF72). In the present study, we provide detailed analysis of the clinical features and neuropathology for 16 unrelated families with frontotemporal dementia caused by the C9ORF72 mutation. All had an autosomal dominant pattern of inheritance. Eight families had a combination of frontotemporal dementia and amyotrophic lateral sclerosis while the other eight had a pure frontotemporal dementia phenotype. Clinical information was available for 30 affected members of the 16 families. There was wide variation in age of onset (mean = 54.3, range = 34-74 years) and disease duration (mean = 5.3, range = 1-16 years). Early diagnoses included behavioural variant frontotemporal dementia (n = 15), progressive non-fluent aphasia (n = 5), amyotrophic lateral sclerosis (n = 9) and progressive non-fluent aphasia-amyotrophic lateral sclerosis (n = 1). Heterogeneity in clinical presentation was also common within families. However, there was a tendency for the phenotypes to converge with disease progression; seven subjects had final clinical diagnoses of both frontotemporal dementia and amyotrophic lateral sclerosis and all of those with an initial progressive non-fluent aphasia diagnosis subsequently developed significant behavioural abnormalities. Twenty-one affected family members came to autopsy and all were found to have transactive response DNA binding protein with M(r) 43 kD (TDP-43) pathology in a wide neuroanatomical distribution. All had involvement of the extramotor

  10. Optimal selection of wavelet-packet-based features using genetic algorithm in pathological assessment of patients' speech signal with unilateral vocal fold paralysis.

    PubMed

    Behroozmand, Roozbeh; Almasganj, Farshad

    2007-04-01

    Unilateral vocal fold paralysis (UVFP) is one of the most severe types of neurogenic laryngeal disorder in which the patients, due to their vocal cords malfunction, are confronted by some serious problems. As the effect of such pathologies would be significantly evident in the reduced quality and feature variation of dysphonic voices, this study is designed to scrutinize the piecewise variation of some specific types of these features, known as energy and entropy, all over the frequency range of pathological speech signals. In order to do so, the wavelet-packet coefficients, in five consecutive levels of decomposition, are used to extract the energy and entropy measures at different spectral sub-bands. As the decomposition procedure leads to a set of high-dimensional feature vectors, genetic algorithm is invoked to search for a group of optimal sub-band indexes for which the extracted features result in the highest recognition rate for pathological and normal subjects' classification. The results of our simulations, using support vector machine classifier, show that the highest recognition rate, for both optimized energy and entropy measures, is achieved at the fifth level of wavelet-packet decomposition. It is also found that entropy feature, with the highest recognition rate of 100% vs. 93.62% for energy, is more prominent in discriminating patients with UVFP from normal subjects. Therefore, entropy feature, in comparison with energy, demonstrates a more efficient description of such pathological voices and provides us a valuable tool for clinical diagnosis of unilateral laryngeal paralysis. PMID:17034780

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features.

    PubMed Central

    Palacios, J.; Benito, N.; Pizarro, A.; Suárez, A.; Espada, J.; Cano, A.; Gamallo, C.

    1995-01-01

    Previous studies on the cell-cell adhesion molecules P- and E-cadherin have shown that P-cadherin is not expressed in breast cancer. In contrast, the expression of E-cadherin is a normal event in these tumors, but a reduction in the levels of this molecule in neoplastic cells is associated with the histological type, high histological grade, greater tumor size, and metastasis. The expression pattern of P- and E-cadherin were immunohistochemically studied in tissue sections from normal breast tissue, benign breast lesions, and 57 infiltrating breast carcinomas. Cadherin expression was analyzed in parallel with pathological features and the immunohistochemical expression of estrogen and progesterone receptors in breast carcinomas. P-cadherin was detected in the myoepithelial cells and E-cadherin in luminal epithelial cells from normal breast and benign breast lesions. P-cadherin expression was detected in 9 of 45 cases (20%) of infiltrating ductal carcinomas of no special type; none of the special histological types that were analyzed (7 infiltrating lobular carcinomas, 3 colloid carcinomas, and 2 infiltrating papillary carcinomas) expressed P-cadherin. In infiltrating ductal carcinomas, P-cadherin expression correlated significantly with a reduction in E-cadherin expression, histological grade (all cases were grade III tumors), and hormone receptor content (8 of 9 cases were estrogen and progesterone receptor negative). Although E-cadherin was not found in the 7 infiltrating lobular carcinomas, it was present in the remaining histological types and was preserved in 15 infiltrating ductal and 3 colloid and 2 papillary carcinomas and was reduced in 30 infiltrating ductal carcinomas. In addition, a reduction in E-cadherin expression was significantly associated with high histological grade and a lack of steroid hormone receptors in infiltrating ductal carcinomas. No apparent relationship was found between P- and E-cadherin expression and tumor size and axillary lymph

  16. The use of pathologic features in selecting the extent of surgical resection necessary for breast cancer patients treated by primary radiation therapy.

    PubMed

    Harris, J R; Connolly, J L; Schnitt, S J; Cady, B; Love, S; Osteen, R T; Patterson, W B; Shirley, R; Hellman, S; Cohen, R B

    1985-02-01

    The extent of the surgical resection necessary for breast cancer patients treated by primary radiation therapy is unknown. A simple gross excision of the tumor provides the best cosmetic result, but a wide local resection may be important to prevent local recurrence in some patients. In order to identify patients who are not adequately treated by gross excision of the tumor and radiation therapy, we performed a retrospective clinical-pathologic review of 221 treated women with infiltrating duct carcinoma. There were 53 cases in which the excision specimen showed a constellation of three pathologic features: prominent intraductal carcinoma in the tumor, intraductal carcinoma in the grossly-normal adjacent tissue, and poorly-differentiated nuclei. These cases had a 37% risk of a local recurrence at 6 years compared to eight per cent for all other cases (p less than 0.0001). In cases with all three features, the use of a supplemental dose of radiation to the primary site did not significantly reduce the risk of a local recurrence. Local recurrence at 6 years was 34% in cases with all three features, who received supplemental local radiation, compared to 49% in cases not receiving a supplemental dose (p = 0.28). Survival was also worse for patients with all three features compared to other cases (69% vs. 90% at 6 years, p = 0.002). These results indicate that patients with all three pathologic features have a high risk of local recurrence following gross excision of the tumor and radiation therapy. If primary radiation therapy is selected for these patients, they should first undergo a re-excision of the tumor site in order to be certain that areas of extensive intraductal carcinoma have been adequately resected. Patients whose tumors do not show all three features are adequately treated by gross excision of the tumor prior to radiation therapy. PMID:2982337

  17. Ultrasonographic features of the persistence of superior left vena cava and pathological cardiac associations in fetus. Case series.

    PubMed

    Mărginean, Claudiu; Mărginean, Cristina Oana; Muntean, Iolanda; Togănel, Rodica; Meliț, Lorena Elena; Mărginean, Maria Oana; Gozar, Liliana

    2016-06-01

    The persistence of superior left vena cava (PLSVC) is a pathological condition in fetus with risk of association with abnormalities like heterotaxy, cardiac abnormalities - atrioventricular septum defect, and conotruncal anomalies. In this paper we report 23 cases of fetuses with PLSVCs, reviewing their diagnosis, co-morbidities, and evolution in the newborns. PMID:27239657

  18. 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.

  19. [Formation and structural features of morbidity in miners with professional pathology of the peripheral nervous system and the musculoskeletal system].

    PubMed

    Shpagina, L N

    2014-01-01

    There were studied polypathy rates, their relationship with the professional pathology in Kuzbass miners. There was performed the analysis of an array of more than 2000 patients with occupational pathology and also 1800 records from for the coal miners hospitals for patients with no signs of occupational diseases. The rise in morbidity rate of polypathies was turned out to be associated with a very low proportion (less than 20%) of patients' preventive visits. It is advisable to introduce the financial incentives for doctors share for the rise of the number of healthy individuals in the enterprise, for detection rate of chronic general and occupational diseases at the early stages of the disease and for reducing of incidence of polypathies. PMID:25306698

  20. 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

  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. A new approach to the pathology, clinical features and treatment of stress tendinopathy of the Achilles tendon.

    PubMed

    Perugia, L; Ippolitio, E; Postacchini, F

    1976-04-01

    On the basis of clinical, anatomical, surgical, histological and pathological investigations, the authors propose a classification of the tendinopathies of the Achilles tendon associated with stress. These are particularly common in the field of sport. Three syndromes are identified: a) pure peritendinitis; b) peritendinitis associated with tendinosis; c) pure tendinosis. The symptoms and possible complications are described and the problem of treatment is discussed. In pure peritendinitis tenolysis is recommended, but in peritendinitis associated with tendinosis it should be combined with extensive scarification of the tendon in order to promote revitalisation. PMID:977317

  3. 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

  4. 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

  5. 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

  6. 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

  7. Denosumab-associated osteonecrosis of the jaw affects osteoclast formation and differentiation: Pathological features of two cases

    PubMed Central

    MATSUSHITA, YUKI; HAYASHIDA, SAKI; MORISHITA, KOTA; SAKAMOTO, HIROSHI; NARUSE, TOMOFUMI; SAKAMOTO, YUKI; YAMADA, SHIN-ICHI; YANAMOTO, SOUICHI; FUJITA, SHUICHI; IKEDA, TOHRU; UMEDA, MASAHIRO

    2016-01-01

    Medication-related osteonecrosis of the jaw (ONJ) is caused by antiresorptive (bisphosphonates and denosumab) and antiangiogenic agents, with the first report of denosumab-related ONJ emerging in 2010. To date, although certain case reports on denosumab-related ONJ have been published, those of ONJ caused by a single application of the drug are scarce. In addition, only one report described the histopathological features of this condition, although not completely; only the sequestrum resected by conservative surgery was evaluated. Although conservative treatment is recommended, the effectiveness of extensive surgery in the early stages of bisphosphonate-related ONJ has been described in recent years. Here we report the clinical and histopathological features of denosumab-related ONJ caused by single application of the drug, which was treated by extensive surgery in two patients. Histopathological analysis revealed a decreased number of osteoclasts in viable bone around the sequestrum, and these appeared morphologically immature, as indicated by the presence of very few nuclei. These findings are different from those for bisphosphonate-related ONJ and may assist in elucidating the mechanism underlying denosumab-related ONJ. Furthermore, extensive surgery may be effective for the management of this condition. PMID:26893859

  8. 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. PMID:26296628

  9. 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

  10. Primary and Secondary T-cell Lymphomas of the Breast: Clinico-pathologic Features of 11 Cases

    PubMed Central

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

    2009-01-01

    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 nonotherwise specified type. Breast T-cell lymphomas are very infrequent and are morphologically and clinically heterogeneous. PMID:19318917

  11. Middle ear meningiomas: a case series reviewing the clinical presentation, radiologic features, and contemporary management of a rare temporal bone pathology.

    PubMed

    Stevens, Kristin L; Carlson, Matthew L; Pelosi, Stanley; Haynes, David S

    2014-01-01

    Meningiomas are the most common extra-axial intracranial neoplasm and frequently develop in the parasagittal region. Rarely, meningiomas may involve the middle ear and mastoid, resulting from contiguous spread of adjacent intracranial tumor, or less commonly as an isolated primary tumor of the middle ear. Patients with primary middle ear meningiomas (MEMs) often present with non-specific otologic complaints including hearing loss, otorrhea and otalgia thereby mimicking common chronic otitis media, while secondary lesions more frequently manifest sensorineural hearing loss, cranial neuropathy and other neurologic symptoms from the associated intracranial component. The radiological appearance of MEMs often overlaps with other tumors of the temporal bone. Therefore, a correct diagnosis cannot always be made prior to surgical biopsy. While gross total resection with preservation of existing neurological function is possible with smaller lesions, complete tumor removal may be extremely morbid with more extensive or adherent MEMs. In such cases, aggressive subtotal resection with close radiologic follow-up should be considered. Given the rarity of the studied condition, the literature addressing MEMs is sparse. The current study reviews ten additional cases of MEMs, highlighting the clinicopathologic and radiological features that distinguish meningiomas from other middle ear and mastoid pathology. PMID:24650749

  12. 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

  13. 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 Central

    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.

    2014-01-01

    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

  14. 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

  15. Prevalence and Role of a Low-Lying Peroneus Brevis Muscle Belly in Patients With Peroneal Tendon Pathologic Features: A Potential Source of Tendon Subluxation.

    PubMed

    Mirmiran, Roya; Squire, Chad; Wassell, Daniel

    2015-01-01

    A peroneus brevis low-lying muscle belly (LLMB) is a rare anomaly. A few published studies have supported the presence of this anomaly as an etiology for a peroneal tendon tear. However, the association between a peroneus brevis LLMB and tendon subluxation has not been well explored. In the present retrospective study, the magnetic resonance imaging (MRI) and intraoperative findings of 50 consecutive patients undergoing primary peroneal tendon surgery during a 5-year period were assessed. The sensitivity and specificity of MRI compared with the intraoperative findings for identifying peroneal tendon disease were investigated. The presence of associated peroneal tendon pathologic features in patients with and without a peroneus brevis LLMB was also compared. The sensitivity of MRI was high for identifying peroneal tenosynovitis (81.58%) and tear (85.71%). Although the sensitivity of MRI for detecting a peroneus brevis LLMB (3.23%) and tendon subluxation (10.00%) was low, MRI had high specificity at 94.74% and 100%, respectively. Intraoperatively, a peroneus brevis LLMB was seen in 62.00% of the patients with chronic lateral ankle pain and was associated with 64.52% of the patients with tenosynovitis, 29.03% of those with tendon subluxation, and 80.65% of those with a peroneus brevis tendon tear. Although the presence of a peroneus brevis LLMB did not show any statistically significant association with peroneus brevis tendon subluxation, of the 10 patients with intraoperatively observed tendon subluxation, 9 had a concomitant peroneus brevis LLMB. More studies with larger patient populations are needed to better investigate the role of a peroneus brevis LLMB as a mass-occupying lesion resulting in peroneal tendon subluxation. PMID:25998478

  16. 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

  17. 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

  18. Toxic epidermal necrolysis caused by acetaminophen featuring almost 100% skin detachment: Acetaminophen is associated with a risk of severe cutaneous adverse reactions.

    PubMed

    Watanabe, Hideaki; Kamiyama, Taisuke; Sasaki, Shun; Kobayashi, Kae; Fukuda, Kenichiro; Miyake, Yasufumi; Aruga, Tohru; Sueki, Hirohiko

    2016-03-01

    Toxic epidermal necrolysis (TEN) is an adverse reaction that can be induced by various drugs; the associated mortality rate is 20-25%. A previous report showed a weak association between TEN and acetaminophen. Recently, the US Food and Drug Administration declared that acetaminophen is associated with a risk of serious skin reactions, including TEN. Here, we describe the case of a 43-year-old Japanese woman with TEN caused by acetaminophen. She had poorly controlled ulcerative colitis and was treated with high doses of prednisolone, infliximab, acetaminophen and lansoprazole. Nine days after administrating acetaminophen, targetoid erythematous and bullous lesions appeared on the patient's trunk, palms and the soles of her feet. The skin lesions expanded rapidly; within 3 weeks, skin detachment was detected across nearly 100% of the patient's body. However, no mucosal involvement of the eyes, oral cavity or genitalia was found. We performed lymphocyte transformation tests using various drugs; however, a high stimulation index was obtained only with acetaminophen. The patient recovered following treatment with plasmapheresis, i.v. immunoglobulin therapy, topical medication and supportive therapy. Acetaminophen is included in many prescription and over-the-counter products; thus, clinicians should monitor their patients for severe drug reactions, including TEN. PMID:26362011

  19. Pathological gambling.

    PubMed

    Hollander, E; Buchalter, A J; DeCaria, C M

    2000-09-01

    With increasing access to gambling facilities through casinos, the Internet, and other venues, PG is a rapidly emerging mental health concern. This impulse-control disorder tends to be comorbid with a wide range of other disorders and is reportedly associated with a high rate of suicide. For most gamblers, gambling is a form of entertainment, but for many individuals, the activity leads to far-reaching disruption of family and work. The personal and societal financial ramifications are severe, and many individuals with PG end up in the criminal justice system. An understanding of the neurobiology of PG is beginning to surface. 5-HT is linked to behavioral initiation and disinhibition, which are important in the onset of the gambling cycle and the difficulty in ceasing the behavior. Norepinephrine is associated with the arousal and risk taking in patients with PG. Dopamine is linked to positive and negative reward, the addictive component of this disorder. Effective treatment strategies for pathological gamblers are emerging. Potentially useful pharmacologic agents include SRIs (clomipramine and fluvoxamine), mood stabilizers for pathological gamblers with comorbid bipolar disorders (lithium), and naltrexone. Cognitive-behavioral psychotherapies offer promising results in the treatment of patients with this disorder. To devise prevention and early-intervention programs, research is needed to identify specific features of the individuals at risk for gambling problems. Education targeting vulnerable youth that show early signs of gambling behavior may be worthwhile and should be investigated further. Funding is necessary to support these endeavors, so perhaps a portion of tax revenues generated from the gambling industry should go toward specialized treatment facilities, educational efforts, and research into the neurobiology and treatment of PG. PMID:10986732

  20. Cutaneous adverse reactions of imatinib therapy in patients with chronic myeloid leukemia: A six-year follow up.

    PubMed

    Dervis, Emine; Ayer, Mesut; Akin Belli, Asli; Barut, Saime Gul

    2016-04-01

    Imatinib is a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML). Cutaneous adverse reactions of imatinib therapy have been reported in 7%-88.9% patients. We sought to evaluate the prevalence rates of cutaneous adverse reactions of imatinib therapy and to investigate the clinical and pathological characteristics of these reactions. Sixty-six patients (36 men, 30 women; age range 19-83 years) with CML treated with imatinib between 2008 and 2014 were included in the study. Clinical and pathological features of the adverse reactions were investigated. Cutaneous adverse reactions were the most common adverse effects of imatinib therapy and were seen in nine patients with a prevalence rate of 13.6%. The second most common adverse effect was musculoskeletal pain (12.1%). The following cutaneous reactions were observed in patients: edema, rash, pigmentary changes, aphthous stomatitis, alopecia, cutaneous dryness, hyperhidrosis and cheilitis. Imatinib therapy was discontinued in four patients because of various adverse effects. Although the prevalence rate of cutaneous adverse reactions in our study was lower than that in several other studies, cutaneous reactions were common in our study. The relatively low prevalence rate of adverse reactions may be related to the low dosage of imatinib (400 mg/day) used to treat our patients and may have been affected by pharmacogenetic characteristics of our population. PMID:26679005

  1. 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

  2. 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

  3. 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. PMID:26065794

  4. 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

  5. Clinical and pathologic features of Aicardi-Goutières syndrome due to an IFIH1 mutation: A pediatric case report.

    PubMed

    Marguet, Florent; Laquerrière, Annie; Goldenberg, Alice; Guerrot, Anne-Marie; Quenez, Olivier; Flahaut, Philippe; Vanhulle, Catherine; Dumant-Forest, Clémentine; Charbonnier, Françoise; Vezain, Myriam; Bekri, Soumeya; Tournier, Isabelle; Frébourg, Thierry; Nicolas, Gaël

    2016-05-01

    We describe the case of a young patient with calcifying encephalopathy, born to asymptomatic parents. An extensive hypothesis-driven etiological assessment was performed and failed to detect the precise etiology during many years. We therefore decided to perform whole exome sequencing of the child-unaffected parents trio. A de novo pathogenic variant in the IFIH1 gene which has recently been shown to cause autosomal dominant forms of Aicardi-Goutières syndrome was identified. This child presented with a severe form with neonatal thrombocytopenia and hepatomegaly, the latter having been detected during late gestation. Although first milestones were uneventful, he progressively lost motor skills from the age of 12 months and developed severe spastic paraplegia. Brain imaging revealed white matter abnormalities and extensive calcifications. He also presented atypical skin lesions, different from chilblains. His medical history was marked by two episodes of acute pancreatitis. We provide herein the results of pathological examination including detailed description of the neuropathological hallmarks. To our knowledge, this the first detailed clinico-pathological description of a patient with an IFIH1 pathogenic variant. © 2016 Wiley Periodicals, Inc. PMID:26833990

  6. 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

  7. The relationship between the preoperative plasma level of HIF-1α and clinic pathological features, prognosis in non-small cell lung cancer

    PubMed Central

    He, Jiabei; Hu, Ying; Hu, Mingming; Zhang, Siyi; Li, Baolan

    2016-01-01

    Studies have found that hypoxia is the most common feature in all of solid tumor progression, thus it has become a central issue in tumor physiology and cancer treatment. Hypoxia-inducible factor-1α (HIF-1α) could make the tumor produce adaptive biological response to hypoxia and become more aggressive. In this paper, we used enzyme linked immune sorbent assay to detect the plasma level of HIF-1α in patients with NSCLC and healthy volunteers. The results indicated that the 5-year survival rate of patients with squamous cell carcinomas is negatively correlated with the plasma level of HIF-1α and the 5-year survival rate of patients with low level of HIF-1α is higher than those with high level of HIF-1α. The plasma level of HIF-1α in patients with NSCLC is significantly higher than healthy volunteers. There is no significant correlation between the plasma level of HIF-1α and clinical features of NSCLC patients. In a word, there is no connection between the plasma level of HIF-1α and the clinical features of NSCLC patients as well as their prognosis. In stratified analysis, the plasma level of HIF-1α in patients with squamous cell carcinoma is associated with regional lymph node status. PMID:26853843

  8. 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

  9. OAE: The Ontology of Adverse Events

    PubMed Central

    2014-01-01

    Background A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. Description The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term ‘adverse event’ denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. Conclusion OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of

  10. The expression of Epstein-Barr virus latent proteins is related to the pathological features of post-transplant lymphoproliferative disorders.

    PubMed Central

    Delecluse, H. J.; Kremmer, E.; Rouault, J. P.; Cour, C.; Bornkamm, G.; Berger, F.

    1995-01-01

    Transplant recipients are at increased risk for the development of post-transplant lymphoproliferative disorders (PTLDs). PTLDs harbor genomes of the Epstein-Barr virus, a herpesvirus that immortalizes B cells in vitro. At least five viral proteins are required for immortalization. Two of them are particularly important. Latent membrane protein (LMP) has transforming activity in fibroblasts, and Epstein-Barr antigen (EBNA)2 transactivates the expression of numerous cellular and viral genes. To determine whether the expression of EBNA2 and LMP is related to the histological and clinical presentation of PTLD, we tested their expression in 14 Epstein-Barr virus-positive cases. Using monoclonal antibodies to EBNA2 and LMP on paraffin sections, we found an expression of both proteins in 2 of 3 polymorphic PTLD and in 7 of 8 cases of monomorphic, large cell PTLD, without plasmacytic differentiation. One polymorphic and one large cell PTLD expressed LMP only. LMP and EBNA2 were found particularly in immunoblasts. The number of positive cells was extremely variable in the different cases as well as within the same biopsy. Three cases of PTLD had morphological and phenotypical features of plasmacytomas and did not stain for EBNA2 or LMP. This suggests that the expression of EBNA2 and LMP is related to the differentiation stage of the infected cells and that other viral or cellular proteins may contribute to tumor growth. Images Figure 1 Figure 2 PMID:7747805

  11. 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

  12. 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 ...

  13. Clinico-pathological features and somatic gene alterations in refractory ceramic fibre-induced murine mesothelioma reveal mineral fibre-induced mesothelioma identities

    PubMed Central

    Andujar, Pascal; Lecomte, Céline; Renier, Annie; Fleury-Feith, Jocelyne; Kheuang, Laurence; Daubriac, Julien; Janin, Anne; Jaurand, Marie-Claude

    2007-01-01

    Although human malignant mesothelioma (HMM) is mainly caused by asbestos exposure, refractory ceramic fibres (RCFs) have been classified as possibly carcinogenic to humans on the basis of their biological effects in rodents’ lung and pleura and in cultured cells. Hence, further investigations are needed to clarify the mechanism of fibre-induced carcinogenicity and to prevent use of harmful particles. In a previous study, mesotheliomas were found in hemizygous Nf2 (Nf2+/−) mice exposed to asbestos fibres, and showed similar alterations in genes at the Ink4 locus and in Trp53 as described in HMM. Here we found that Nf2+/− mice developed mesotheliomas after intra-peritoneal inoculation of a RCF sample (RCF1). Clinical features in exposed mice were similar to those observed in HMM, showing association between ascite and mesothelioma. Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2+/− mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations. Nf2 gene was inactivated in all cultures. In most cases, co-inactivation of genes at the Ink4 locus and Nf2 was found and, at a lower rate, of Trp53 and Nf2. These results are the first to identify mutations in RCF-induced mesothelioma. They suggest that nf2 mutation is complementary of p15Ink4b, p16Ink4a and p19Arf or p53 mutations and show similar profile of gene alterations resulting from exposure to ceramic or asbestos fibres in Nf2+/− mice, also consistent with the one found in HMM. These somatic genetic changes define different pathways of mesothelial cell transformation. PMID:17272307

  14. [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

  15. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions. PMID:25458866

  16. 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

  17. Punctate follicular porokeratosis: clinical and pathologic features.

    PubMed

    Trikha, Ritika; Wile, Anna; King, Joy; Ward, Kimberley H M; Brodell, Robert T

    2015-11-01

    Porokeratosis is a disorder of keratinization characterized by an abnormal cornoid lamella surrounding an annular, scaly plaque with an atrophic center. A histologic variant of this condition has been proposed, termed follicular porokeratosis, in cases where follicular involvement was contiguous with an annular cornoid lamella. There has been only 1 report of punctate follicular porokeratosis, in which cornoid lamellae originated exclusively from hair follicles with no associated annular plaque. The authors present the second case of punctate follicular porokeratosis, further supporting the contention that this entity is a unique form of porokeratosis rather than a histologic variant. A 56-year-old African American female presented to the dermatology clinic with a 3-month history of keratotic lesions localized on the right posterior shoulder. Examination revealed an area of perifollicular keratotic papules, each surrounded by an erythematous rim. Histopathology revealed a cornoid lamella originating within a hair follicle, with the parakeratotic column protruding through the follicular orifice. The static nature of the condition along with exclusive involvement of hair follicles supports the notion of punctate follicular porokeratosis as a distinct clinical entity. The diagnosis of this condition relies heavily on proper histopathologic sampling revealing punctate follicular cornoid lamellae. PMID:26485244

  18. 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

  19. Masochism and pathological gambling.

    PubMed

    Rosenthal, Richard J

    2015-03-01

    That all pathological gamblers have an "unconscious wish to lose," an idea first expressed by Freud and Bergler, is neither true nor useful; wrong as well, however, are the reasons for neglecting masochism in relation to gambling. There is a small but clinically significant subgroup of pathological gamblers who are masochistic. I present clinical vignettes and a more extended treatment account to illustrate its importance. Masochism has been a confusing concept. As used here it refers to the deliberate seeking of pain, loss, suffering, or humiliation. There may be pleasure in pain, or an obligatory combining of pleasure and pain. A sense of power and control may be achieved through suffering. The case material illustrates clinically useful types (sexual masochism, masochistic personality disorder, moral masochism, relational masochism) as well as some common masochistic dynamics encountered in the treatment of pathological gamblers. These masochistic patterns are often identifiable during the initial evaluation. Distinguishing features may include a reversal of normal attitudes about winning and losing, the absence of an early winning phase, sometimes a memorable early loss. Gamblers may sabotage opportunities for success or create unnecessary obstacles for themselves. Losing may be more comfortable than winning or may be overtly sexualized. PMID:25734872

  20. 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

  1. 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

  2. Curriculum Guidelines for Pathology and Oral Pathology.

    ERIC Educational Resources Information Center

    Journal of Dental Education, 1985

    1985-01-01

    Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

  3. Adverse reactions to sulfites

    PubMed Central

    Yang, William H.; Purchase, Emerson C.R.

    1985-01-01

    Sulfites are widely used as preservatives in the food and pharmaceutical industries. In the United States more than 250 cases of sulfite-related adverse reactions, including anaphylactic shock, asthmatic attacks, urticaria and angioedema, nausea, abdominal pain and diarrhea, seizures and death, have been reported, including 6 deaths allegedly associated with restaurant food containing sulfites. In Canada 10 sulfite-related adverse reactions have been documented, and 1 death suspected to be sulfite-related has occurred. The exact mechanism of sulfite-induced reactions is unknown. Practising physicians should be aware of the clinical manifestations of sulfite-related adverse reactions as well as which foods and pharmaceuticals contain sulfites. Cases should be reported to health officials and proper advice given to the victims to prevent further exposure to sulfites. The food industry, including beer and wine manufacturers, and the pharmaceutical industry should consider using alternative preservatives. In the interim, they should list any sulfites in their products. PMID:4052897

  4. 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…

  5. [Adverse reaction of pseudoephedrine].

    PubMed

    López Lois, G; Gómez Carrasco, J A; García de Frías, E

    2005-04-01

    We present a case of a 7 years old girl who developed an episode of myoclonic movements and tremors after being medicated with a not well quantified amount of a pseudoephedrine/antihistamine combination. We want to highlight the potential toxicity of pseudoephedrine, usually administered as part of cold-syrup preparations which are used for symptomatic treatment of upper respiratory tract cough and congestion associated with the common cold and allergic rhinitis. Although these products are generally considered to be safe either by physicians and parents, we can't underestimate the potential adverse events and toxic effects that can occur when administering these medications. PMID:15826569

  6. 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

  7. 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

  8. Pathological gambling and treatment outcomes for adults age 50 or older in methadone maintenance treatment.

    PubMed

    Engel, Rafael J; Rosen, Daniel

    2015-01-01

    This study examined the relationship of pathological gambling to negative treatment outcomes for methadone maintenance patients aged 50 or older. The study included 130 methadone maintenance patients. Pathological gambling was determined using the Lie-Bet, a screen for pathological gambling; the outcomes were remaining in treatment and negative urine screens for drug use. Twenty percent of the sample identified as pathological gamblers. Pathological gambling was unrelated to remaining in treatment or negative urine screens. Although pathological gambling had no adverse influence on these treatment outcomes, the prevalence of pathological gambling suggests that screening for it may provide insights about other concerns. PMID:25202832

  9. Pathology of Perineural Spread.

    PubMed

    Brown, Ian S

    2016-04-01

    The perineural space is a compartment located between the nerve axons, supporting cells and tissues, and the epineural fibrous sheath. Tumor cells invade this space in response to a complex interplay of trophic factors in the local microenviroment. This attraction of tumor cells to nerves is referred to as neurotropism. The perineural space provides a conduit for tumor spread beyond the primary site of tumor occurrence. Perineural tumor growth is of two types: perineural invasion, affecting small unnamed nerves; and perineural spread, affecting larger, named nerves and presenting with clinical symptoms related to the involved nerve. Both forms of perineural tumor growth represent an adverse prognostic feature and are an essential element of the histopathologic reporting of malignancies of the head and neck region. Perineural spread is associated with decreased overall survival. Endoneurial invasion frequently accompanies perineural spread. The epineurium is more resistant to invasion and represents an important barrier to tumor spread. Immunohistochemical stains such as broad-spectrum keratin can aid in defining the proximal extent of perineural tumor spread. PMID:27123388

  10. 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

  11. Adverse antibiotic drug interactions.

    PubMed

    Bint, A J; Burtt, I

    1980-07-01

    There is enormous potential for drug interactions in patients who, today, often receive many drugs. Antibiotics are prominent amongst the groups of drugs commonly prescribed. Many interactions take place at the absorption stage. Antacids and antidiarrhoeal preparations, in particular, can delay and reduce the absorption of antibiotics such as tetracyclines and clindamycin, by combining with them in the gastrointestinal tract to form chelates or complexes. Other drugs can affect gastric motility, which in turn often controls the rate at which antibiotics are absorbed. Some broad spectrum antibiotics can alter the bacterial flora of the gut which may be related to malabsorption states. The potentiation of toxic side effects of one drug by another is a common type of interaction. Antibiotics which are implicated in this type of interaction are those which themselves possess some toxicity such as aminoglycosides, some cephalosporins, tetracyclines and colistin. Some of the most important adverse interactions with antibiotics are those which involve other drugs which have a low toxicity/efficacy ratio. These include anticoagulants such as warfarin, anticonvulsants such as phenytoin and phenobarbitone and oral antidiabetic drugs like tolbutamide. Risk of interaction arises when the metabolism of these drugs is inhibited by liver microsomal enzyme inhibitors such as some sulphonamides and chloramphenicol, or is enhanced by enzyme inducers such as rifampicin. PMID:6995091

  12. ADVERSE CUTANEOUS DRUG REACTION

    PubMed Central

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR. PMID:19967009

  13. 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.

  14. 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…

  15. Voice data mining for laryngeal pathology assessment.

    PubMed

    Hemmerling, Daria; Skalski, Andrzej; Gajda, Janusz

    2016-02-01

    The aim of this study was to evaluate the usefulness of different methods of speech signal analysis in the detection of voice pathologies. Firstly, an initial vector was created consisting of 28 parameters extracted from time, frequency and cepstral domain describing the human voice signal based on the analysis of sustained vowels /a/, /i/ and /u/ all at high, low and normal pitch. Afterwards we used a linear feature extraction technique (principal component analysis), which enabled a reduction in the number of parameters and choose the most effective acoustic features describing the speech signal. We have also performed non-linear data transformation which was calculated using kernel principal components. The results of the presented methods for normal and pathological cases will be revealed and discussed in this paper. The initial and extracted feature vectors were classified using the k-means clustering and the random forest classifier. We found that reasonably good classification accuracies could be achieved by selecting appropriate features. We obtained accuracies of up to 100% for classification of healthy versus pathology voice using random forest classification for female and male recordings. These results may assist in the feature development of automated detection systems for diagnosis of patients with symptoms of pathological voice. PMID:26471193

  16. 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…

  17. Clinical governance and pathology

    PubMed Central

    Crook, M

    2002-01-01

    This article looks at clinical governance and pathology. Clinical governance should be an important tool in seeking quality improvement within the Natinal Health Service. But how as pathologists should we go about it? PMID:11896066

  18. Gastrointestinal Lymphoma: Radiologic-Pathologic Correlation.

    PubMed

    Manning, Maria A; Somwaru, Alexander S; Mehrotra, Anupamjit K; Levine, Marc S

    2016-07-01

    Extranodal lymphoma is a heterogeneous group of hematologic neoplasms that can affect every abdominal organ, with distinctive pathologic, radiologic, and clinical features. The radiologic findings are closely related to the underlying pathophysiology, and an understanding of these characteristic features should facilitate recognition of extranodal lymphoma and its various subtypes. Within the abdomen, lymphoma is found most commonly in the gastrointestinal tract, especially the stomach. This article presents the findings in gastrointestinal tract lymphoma. PMID:27265607

  19. The Pathology of Alcoholic Liver Disease.

    PubMed

    Alpert, Lindsay; Hart, John

    2016-08-01

    The term "alcoholic liver disease" encompasses a spectrum of pathologic conditions ranging from isolated steatosis to established cirrhosis. Within this spectrum, varying degrees of inflammation, hepatocellular ballooning degeneration, hepatocyte necrosis, cholestasis, and fibrosis may be encountered. This article reviews the characteristic histologic features of the many forms of alcoholic liver disease. Histologic scoring systems are described, and diseases with overlapping morphologic features and comorbid conditions are also discussed. PMID:27373610

  20. 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

  1. Clinical and pathological correlations in endometrial pathology

    PubMed Central

    Bohîlțea, RE; Sajin, M; Furtunescu, F; Bohîlțea, LC; Mihart, A; Baros, A; Anca, AF

    2015-01-01

    The incidence and mortality rate of endometrial cancer has been registering an increasing trend both in Romania and in the whole world. The paper’s aim is to analyze the diagnostic approach of endometrial pathology in the University Emergency Hospital Bucharest, on a four years period. The medium age of the patients was of 50.51 ± 10.924 years, and the median age was of 48 years. The youngest patient suffering from endometrial cancer was of 30 years. Dilation and uterine curettage represent the main method used in the performance of endometrial biopsy, based on which the certitude etiologic histopathologic diagnosis was established in 68.4% of the patients with endometrial pathology. Hyperplasias represented half of the pathology (54.9%), most of them being without atypias. Endometrial carcinoma was identified in 19% of the patients. The diagnosis of the disease in IA stage represents 5.5% of the total endometrial cases and the diagnosis of the disease in the stage of its limitation to the uterus (stage IA, IB and IC) was of 64.2%. The endometrioid adenocarcinoma represents the most encountered histopathological form and the degree of tumor differentiation established for 68,15% of the cases was predominantly 1 and 2 (88%). The main symptom, which determines the patients’ decision to go to the physician, is the abnormal uterine bleeding. 66% of the cases of endometrial cancer in the stage of the disease limited to the uterus are diagnosed in Romania based on the abnormal uterine bleeding. However, 34% of the cases are diagnosed in advanced stages, presenting a significantly low life expectancy. PMID:26664489

  2. Pathological Gambling and Substance Use Disorders

    PubMed Central

    Wareham, Justin D.; Potenza, Marc N.

    2013-01-01

    Pathological gambling (PG) has been considered as a behavioral addiction having similarities with substance use disorders (SUDs). Shared features exist in diagnostic, clinical, physiological, and behavioral domains. Current conceptualizations of addiction, as well as experimental studies of PG and SUDs, are reviewed in order to provide a perspective on the areas of convergence between addictive behaviors in PG and SUDs. PMID:20575651

  3. Adverse possession of subsurface minerals

    SciTech Connect

    Bowles, P.N.

    1983-01-01

    Concepts applicable to adverse possession of subsurface minerals are generally the same as those that apply to adverse possession of all real estate. However, special requirements must be satisfied in order to perfect title to subsurface minerals by adverse possession, particularly when there has been a severance of the true title between surface and subsurface minerals. In those jurisdictions where senior and junior grants came from the state or commonwealth covering the same or some of the same land and in those areas where descriptions of land were vague or not carefully drawn, adverse possession serves to solidify land and mineral ownership. There may be some public, social, and economic justification in rewarding, with good title, those who take possession and use real estate for its intended use, including the extraction of subsurface minerals. 96 refernces.

  4. 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

  5. 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

  6. Pathological conditions re-shape physiological Tregs into pathological Tregs

    PubMed Central

    Yang, William Y.; Shao, Ying; Lopez-Pastrana, Jahaira; Mai, Jietang; Wang, Hong; Yang, Xiao-feng

    2015-01-01

    CD4+FOXP3+ regulatory T cells (Tregs) are a subset of CD4 T cells that play an essential role in maintaining peripheral immune tolerance, controlling acute and chronic inflammation, allergy, autoimmune diseases, and anti-cancer immune responses. Over the past 20 years, significant progress has been made since Tregs were first characterized in 1995. Many concepts and principles regarding Tregs generation, phenotypic features, subsets (tTregs, pTregs, iTregs, and iTreg35), tissue specificity (central Tregs, effector Tregs, and tissue resident Tregs), homeostasis (highly dynamic and apoptotic), regulation of Tregs by receptors for PAMPs and DAMPs, Treg plasticity (re-differentiation to other CD4 T helper cell subsets, Th1, Th2, Tfh and Th17), and epigenetic regulation of Tregs phenotypes and functions have been innovated. In this concise review, we want to briefly analyze these eight new progresses in the study of Tregs. We have also proposed for the first time a novel concept that “physiological Tregs” have been re-shaped into “pathological Tregs” in various pathological environments. Continuing of the improvement in our understanding on this important cellular component about the immune tolerance and immune suppression, would lead to the future development of novel therapeutics approaches for acute and chronic inflammatory diseases, allergy, allogeneic transplantation-related immunity, sepsis, autoimmune diseases, and cancers. PMID:26623425

  7. 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

  8. Molecular systems evaluation of oligomerogenic APP(E693Q) and fibrillogenic APP(KM670/671NL)/PSEN1(Δexon9) mouse models identifies shared features with human Alzheimer's brain molecular pathology.

    PubMed

    Readhead, B; Haure-Mirande, J-V; Zhang, B; Haroutunian, V; Gandy, S; Schadt, E E; Dudley, J T; Ehrlich, M E

    2016-08-01

    , including ECM 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

  9. 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. PMID:26372537

  10. 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

  11. Complications of Pathologic Myopia.

    PubMed

    Cho, Bum-Joo; Shin, Joo Young; Yu, Hyeong Gon

    2016-01-01

    Pathologic myopia (PM) is one of the leading causes of visual impairment worldwide. The pathophysiology of PM is not fully understood, but the axial elongation of the eye followed by chorioretinal thinning is suggested as a key mechanism. Pathologic myopia may lead to many complications such as chorioretinal atrophy, foveoschisis, choroidal neovascularization, rhegmatogenous retinal detachment, cataract, and glaucoma. Some complications affect visual acuity significantly, showing poor visual prognosis. This article aims to review the types, pathophysiology, treatment, and visual outcome of the complications of PM. PMID:26649982

  12. Fetal Programming and Cardiovascular Pathology

    PubMed Central

    Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

    2016-01-01

    Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

  13. [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

  14. Training pathologists in mouse pathology.

    PubMed

    Sundberg, J P; Ward, J M; HogenEsch, H; Nikitin, A Yu; Treuting, P M; Macauley, J B; Schofield, P N

    2012-03-01

    Expertise in the pathology of mice has expanded from traditional regulatory and drug safety screening (toxicologic pathology) primarily performed by veterinary pathologists to the highly specialized area of mouse research pathobiology performed by veterinary and medical pathologists encompassing phenotyping of mutant mice and analysis of research experiments exploiting inbred mouse strains and genetically engineered lines. With increasing use of genetically modified mice in research, mouse pathobiology and, by extension, expert mouse research-oriented pathologists have become integral to the success of basic and translational biomedical research. Training for today's research-oriented mouse pathologist must go beyond knowledge of anatomic features of mice and strain-specific background diseases to the specialized genetic nomenclature, husbandry, and genetics, including the methodology of genetic engineering and complex trait analysis. While training can be accomplished through apprenticeships in formal programs, these are often heavily service related and do not provide the necessary comprehensive training. Specialty courses and short-term mentoring with expert specialists are opportunities that, when combined with active practice and publication, will lead to acquisition of the skills required for cutting-edge mouse-based experimental science. PMID:20817889

  15. Biologics in dermatology: adverse effects.

    PubMed

    Sehgal, Virendra N; Pandhi, Deepika; Khurana, Ananta

    2015-12-01

    Biologics are a group of drugs that precisely affect certain specific steps in the immune response and are an extremely useful group when used in an appropriate setting. However, their use can often be a double-edged sword. Careful patient selection and thorough knowledge of adverse effects is a key to their successful use in various disorders. The initial enthusiasm has gradually given way to a more cautious approach wherein a balance is sought between clinical usefulness and expected side effects. The adverse effects of the biologics most commonly used in dermatology have been carefully listed for ready reference. The plausible causes of the adverse reactions are succinctly outlined along with their incriminating factor(s). Besides, in brief, the attention has been focused on their management. The content should provide an essential didactic content for educating the practitioner. PMID:26147909

  16. 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

  17. Is Psychometrics Pathological Science?

    ERIC Educational Resources Information Center

    Michell, Joel

    2008-01-01

    Pathology of science occurs when the normal processes of scientific investigation break down and a hypothesis is accepted as true within the mainstream of a discipline without a serious attempt being made to test it and without any recognition that this is happening. It is argued that this has happened in psychometrics: The hypothesis upon which…

  18. 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…

  19. 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…

  20. Pathology of Extranodal Lymphoma.

    PubMed

    Heckendorn, Emily; Auerbach, Aaron

    2016-07-01

    An overview of the pathology of extranodal lymphoma is presented. The emphasis of this presentation is on the classification system of extranodal lymphomas, including both B-cell and T-cell lymphomas, based on their morphology, phenotype, and molecular alterations. PMID:27265600

  1. 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

  2. Automatically Recognizing Medication and Adverse Event Information From Food and Drug Administration’s Adverse Event Reporting System Narratives

    PubMed Central

    Polepalli Ramesh, Balaji; Belknap, Steven M; Li, Zuofeng; Frid, Nadya; West, Dennis P

    2014-01-01

    Background The Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) is a repository of spontaneously-reported adverse drug events (ADEs) for FDA-approved prescription drugs. FAERS reports include both structured reports and unstructured narratives. The narratives often include essential information for evaluation of the severity, causality, and description of ADEs that are not present in the structured data. The timely identification of unknown toxicities of prescription drugs is an important, unsolved problem. Objective The objective of this study was to develop an annotated corpus of FAERS narratives and biomedical named entity tagger to automatically identify ADE related information in the FAERS narratives. Methods We developed an annotation guideline and annotate medication information and adverse event related entities on 122 FAERS narratives comprising approximately 23,000 word tokens. A named entity tagger using supervised machine learning approaches was built for detecting medication information and adverse event entities using various categories of features. Results The annotated corpus had an agreement of over .9 Cohen’s kappa for medication and adverse event entities. The best performing tagger achieves an overall performance of 0.73 F1 score for detection of medication, adverse event and other named entities. Conclusions In this study, we developed an annotated corpus of FAERS narratives and machine learning based models for automatically extracting medication and adverse event information from the FAERS narratives. Our study is an important step towards enriching the FAERS data for postmarketing pharmacovigilance. PMID:25600332

  3. Adversity and advancing nursing knowledge.

    PubMed

    Reed, Pamela G

    2008-04-01

    This column reports the theme of adversity addressed in reference to theoretical and metatheoretical considerations for advancing nursing knowledge. The development and content of three classic nursing theories are presented by Neuman representatives, and by theorists King and Roy. Topics for continued dialogue are identified as derived from the interface between philosophy of science issues and these theories. PMID:18378823

  4. 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…

  5. 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

  6. 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

  7. 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

  8. Digital imaging applications in anatomic pathology.

    PubMed

    Leong, F Joel W-M; Leong, Anthony S-Y

    2003-03-01

    Digital imaging has progressed at a rapid rate and is likely to eventually replace chemical photography in most areas of professional and amateur digital image acquisition. In pathology, digital microscopy has implications beyond that of taking a photograph. The arguments for adopting this new medium are compelling, and given similar developments in other areas of pathology and radiologic imaging, acceptance of the digital medium should be viewed as a component of the technological evolution of the laboratory. A digital image may be stored, replicated, catalogued, employed for educational purposes, transmitted for further interpretation (telepathology), analyzed for salient features (medical vision/image analysis), or form part of a wider digital healthcare strategy. Despite advances in digital camera technology, good image acquisition still requires good microscope optics and the correct calibration of all system components, something which many neglect. The future of digital imaging in pathology is very promising and new applications in the fields of automated quantification and interpretation are likely to have profound long-term influence on the practice of anatomic pathology. This paper discusses the state of the art of digital imaging in anatomic pathology. PMID:12605090

  9. [Tropical climate pathology].

    PubMed

    Besancenot, J P

    1997-01-01

    In addition to being a determinant factor for the development of infectious and parasitic diseases, tropical weather conditions can have harmful effects for the human organism different from those of temperate climates. Adverse effects can result from aggressive environmental factors such as ultraviolet radiation, extreme heat, abrupt changes in temperature, and tropical storms. In weather-sensitive subjects, exposure to tropical conditions increases the risk of acute reactions including ischemic heart disease, asthma attacks, and kidney stones. Adverse effects can be enhanced by suddenness of change in climate as underlined by the stress experienced by air travelers. In practice it is important to recognize that different tropical climates have different effects on health. Intertropical climates range from dry and rainy areas to plains and mountain areas. Knowledge of the concepts of climatopathology is necessary to advise patients on the choice of destination and the most favorable period for travel. PMID:9612744

  10. 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. PMID:26914914

  11. In situ follicular lymphoma: pathologic characteristics and diagnostic features.

    PubMed

    Carbone, Antonino; Gloghini, Annunziata; Santoro, Armando

    2012-03-01

    The diagnosis of in situ follicular lymphoma (FL) is feasible when immunohistochemical characterization is carried out and genetic abnormalities are assessed. We usually use a selected diagnostic panel of antibodies (CD10, CD20, CD23, BCL2, BCL6, and Ki67) in lymph nodes with follicular hyperplasia only when we analyze an unexplained lymphadenopathy. Molecular studies, for example, fluorescence in situ hybridization analysis for t(14;18), are restricted to doubtful cases in which immunohistochemistry data are ambiguous. Immunohistochemically, the involved follicles show strongly positive staining for BCL2 and CD10. The BCL2+ cells are confined only to germinal centers and are not seen in the interfollicular region or elsewhere in the lymph node. The BCL2 staining in the abnormal follicles is notable for its high-level and uniform intensity. In situ FL may be associated with overt FL or with lymphomas other than FL or with other malignancies. The crucial point relies on distinguishing in situ FL arising in asymptomatic patients from cases with presence of lymphoma at the same or other sites. Other open questions remain on the frequency with which in situ FLs occur and the frequency of concomitant systemic disease. PMID:21560142

  12. 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

  13. Otic artery: a review of normal and pathological features.

    PubMed

    Vasović, Ljiljana; Arsić, Stojanka; Vlajković, Slobodan; Jovanović, Ivan; Jovanović, Predrag; Ugrenović, Sladjana; Andjelković, Zlatibor

    2010-05-01

    Three primitive arteries - the trigeminal, otic and hypoglossal take the names according to their close relation with the V, VIII and XII cranial nerves, while at the cervical level, the first segmental artery is named the primitive proatlantal intersegmental artery. When the human embryo is 4 mm long, these arteries serve as transitory anastomoses between primitive internal carotid arteries and bilateral longitudinal neural arterial plexus, which is the precursor of future basilar artery. Normal and/or abnormal morphofunctional aspects of the prenatal and postnatal forms of the otic artery are described according to the personal and literature data. Many (ab) normal arteries are also noted in differential diagnosis of the otic artery. Postnatally, individual incidence rates of the carotid-vertebrobasilar anastomoses have been found to be inversely related to their order of disappearance. The persistent trigeminal artery has a reported incidence from 0.06-0.6%, whereas the persistent primitive otic artery has been convincingly documented only in minor rates. Persistent carotid-vertebrobasilar anastomoses between the anterior and posterior cranial circulation are important to recognize during angiography for endovascular and surgical planning. Most frequently, the otic artery was an incidental finding. PMID:20424561

  14. American Society for Clinical Pathology

    MedlinePlus

    ... With the National Cancer Institute for Inaugural Global Pathology Conference March 2016 OneLab Memo ASCP Action Alert - ... 2016 Copyright © 2016 by American Society for Clinical Pathology. All Rights Reserved. Terms of Use About ASCP ...

  15. American Society for Clinical Pathology

    MedlinePlus

    ... Science Letter to Council of Deans: State of Pathology Training in Medical School Help Chart the Future ... Need Copyright © 2016 by American Society for Clinical Pathology. All Rights Reserved. Terms of Use About ASCP ...

  16. Adverse reactions to injectable aesthetic microimplants.

    PubMed

    Requena, C; Izquierdo, M J; Navarro, M; Martínez, A; Vilata, J J; Botella, R; Amorrortu, J; Sabater, V; Aliaga, A; Requena, L

    2001-06-01

    New inert materials such as polymerized silicones, Bioplastique, Artecoll, and Dermalive are now being used as injectable aesthetic microimplants. These substances are better than the old ones because they tend not to migrate and do not usually produce much of a host immune response. Adverse reactions after injection of these materials are rare, although there are a few reported cases as a result of bad technique or anomalous granulomatous reactions. We report on four patients with unsightly results after cosmetic microimplants, including one of Artecoll, one of Dermalive (to the best of our knowledge, the latter is the first such case reported), and two of silicone. This report describes the histopathologic features of cutaneous reactions to these injectable aesthetic materials. PMID:11391099

  17. Cardiovascular adverse effects of phenytoin.

    PubMed

    Guldiken, B; Rémi, J; Noachtar, Soheyl

    2016-05-01

    Phenytoin is an established drug in the treatment of acute repetitive seizures and status epilepticus. One of its main advantages over benzodiazepines is the less sedative effect. However, the possibility of cardiovascular adverse effects with the intravenous use of phenytoin cause a reluctance to its usage, and this has lead to a search for safer anticonvulsant drugs. In this study, we aimed to review the studies which evaluated the safety of phenytoin with respect to cardiovascular adverse effects. The original clinical trials and case reports listed in PUBMED in English language between the years of 1946-2014 were evaluated. As the key words, "phenytoin, diphenylhydantoin, epilepsy, seizure, cardiac toxicity, asystole, arrhythmia, respiratory arrest, hypotension, death" were used. Thirty-two clinical trials and ten case reports were identified. In the case reports, a rapid infusion rate (>50 mg/min) of phenytoin appeared as the major cause of increased mortality. In contrast, no serious cardiovascular adverse effects leading to death were met in the clinical trials which applied the recommended infusion rate and dosages. An infusion rate of 50 mg/min was reported to be safe for young patients. For old patients and patients with a cardiovascular co-morbidity, a slower infusion rate was recommended with a careful follow-up of heart rhythm and blood pressure. No cardiovascular adverse effect was reported in oral phenytoin overdoses except one case with a very high serum phenytoin level and hypoalbuminemia. Phenytoin is an effective and well tolerated drug in the treatment of epilepsy. Intravenous phenytoin is safe when given at recommended infusion rates and doses. PMID:26645393

  18. From telepathology to virtual pathology institution: the new world of digital pathology.

    PubMed

    Kayser, K; Kayser, G; Radziszowski, D; Oehmann, A

    Telepathology has left its childhood. Its technical development is mature, and its use for primary (frozen section) and secondary (expert consultation) diagnosis has been expanded to a great amount. This is in contrast to a virtual pathology laboratory, which is still under technical constraints. Similar to telepathology, which can also be used for e-learning and e-training in pathology, as exemplarily is demonstrated on Digital Lung Pathology (Klaus.Kayser@charite.de) at least two kinds of virtual pathology laboratories will be implemented in the near future: a) those with distributed pathologists and distributed (> or = 1) laboratories associated to individual biopsy stations/surgical theatres, and b) distributed pathologists (usually situated in one institution) and a centralized laboratory, which digitizes complete histological slides. Both scenarios are under intensive technical investigations. The features of virtual pathology comprise a virtual pathology institution (mode a) that accepts a complete case with the patient's history, clinical findings, and (pre-selected) images for first diagnosis. The diagnostic responsibility is that of a conventional institution. The Internet serves as platform for information transfer, and an open server such as the iPATH (http://telepath.patho.unibas.ch) for coordination and performance of the diagnostic procedure. The size and number of transferred images have to be limited, and usual different magnifications have to be used. The sender needs to possess experiences in image sampling techniques, which present with the most significant information. A group of pathologists is "on duty", or selects one member for a predefined duty period. The diagnostic statement of the pathologist(s) on duty is retransmitted to the sender with full responsibility. The first experiences of a virtual pathology institution group working with the iPATH server working with a small hospital of the Salomon islands are promising. A centralized

  19. [Adverse events of psychotropic drugs].

    PubMed

    Watanabe, Koichiro; Kikuchi, Toshiaki

    2014-01-01

    The authors discuss adverse events which are often missed but clinicians should pay attention to in order to preserve patients'quality of life(QOL). Among mood stabilizers, lithium may cause a urinary volume increase, hyperparathyroidism, and serum calcium elevation; sodium valproate possibly increases androgenic hormone levels and the risk of polycystic ovary syndrome (PCOS) as well as hypothyroidism. Moreover, in addition to teratogenesis, it has been reported that fetal exposure to a higher dose of valproate is associated with a lower intelligence quotient and higher incidence of autism spectrum disorders in children. Antidepressants with a higher affinity for serotonin transporters might induce gastrointestinal bleeding, and some antidepressants cause sexual dysfunction more frequently than others. Activation syndrome is still a key side effect which should be noted. Regarding the adverse events of antipsychotics, subjective side effects unpleasant to patients such as dysphoria and a lower subjective well-being should not be overlooked. We clinicians have to cope with adverse events worsening the QOL of patients with psychiatric disorders and, therefore, we need to adopt appropriate counter-measures. PMID:24864567

  20. An Exploratory Study of Clinical Measures Associated with Subsyndromal Pathological Gambling in Patients with Binge Eating Disorder

    PubMed Central

    White, Marney A.; Grilo, Carlos M.; Potenza, Marc N.

    2013-01-01

    Both binge eating disorder (BED) and pathological gambling (PG) are characterized by impairments in impulse control. Subsyndromal levels of PG have been associated with measures of adverse health. The nature and significance of PG features in individuals with BED is unknown. Ninety-four patients with BED (28 men and 66 women) were classified by gambling group based on inclusionary criteria for Diagnostic and Statistical Manual-IV (DSM-IV) PG and compared on a range of behavioral, psychological and eating disorder (ED) psychopathology variables. One individual (1.1% of the sample) met criteria for PG, although 18.7% of patients with BED displayed one or more DSM-IV criteria for PG, hereafter referred to as problem gambling features. Men were more likely than women to have problem gambling features. BED patients with problem gambling features were distinguished by lower self-esteem and greater substance problem use. After controlling for gender, findings of reduced self-esteem and increased substance problem use among patients with problem gambling features remained significant. In patients with BED, problem gambling features are associated with a number of heightened clinical problems. PMID:20577790

  1. 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.

  2. 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

  3. Adverse Pregnancy Outcomes Following Motor Vehicle Crashes

    PubMed Central

    Vladutiu, Catherine J.; Marshall, Stephen W.; Poole, Charles; Casteel, Carri; Menard, M. Kathryn; Weiss, Harold B.

    2013-01-01

    Background Motor vehicle crashes are a leading cause of serious trauma during pregnancy, but little is known about their relationships with pregnancy outcomes. Purpose To estimate the association between motor vehicle crashes and adverse pregnancy outcomes. Methods A retrospective cohort study of 878,546 pregnant women, aged 16–46 years, who delivered a singleton infant in North Carolina (NC) from 2001 to 2008. Pregnant drivers in crashes were identified by probabilistic linkage of vital records and crash reports. Poisson regression modeled the association among crashes, vehicle safety features, and adverse pregnancy outcomes. Analyses were conducted in 2012. Results In 2001–2008, 2.9% of pregnant NC women were drivers in one or more crashes. After a single crash, compared to not being in a crash, pregnant drivers had slightly elevated rates of preterm birth (adjusted rate ratio, aRR=1.23, 95% CI=1.19, 1.28); placental abruption (aRR=1.34, 95% CI=1.15, 1.56); and premature rupture of the membranes (PROM; aRR=1.32, 95% CI=1.21, 1.43). Following a second or subsequent crash, pregnant drivers had more highly elevated rates of preterm birth (aRR=1.54, 95% CI=1.24, 1.90); stillbirth (aRR=4.82, 95% CI=2.85, 8.14); placental abruption (aRR=2.97, 95% CI=1.60, 5.53); and PROM (aRR=1.95, 95% CI=1.27, 2.99). Stillbirth rates were elevated following crashes involving unbelted pregnant drivers (aRR=2.77, 95% CI=1.22, 6.28) compared to belted pregnant drivers. Conclusions Crashes while driving during pregnancy were associated with elevated rates of adverse pregnancy outcomes, and multiple crashes were associated with even higher rates of adverse pregnancy outcomes. Crashes were especially harmful if drivers were unbelted. PMID:24139777

  4. 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

  5. Pathology of melanoma.

    PubMed

    Elder, David E

    2015-04-01

    The pathology of melanoma is discussed in relation to surgical diagnosis and management. Pitfalls that may result in problems of clinicopathologic communication are emphasized. A compelling vision for the future is that all tumors will be characterized by their driving oncogenes, suppressor genes, and other genomic factors. The success of targeted therapy directed against individual oncogenes, despite its limitations, suggests that a repertoire of targeted agents will be developed that can be used against a variety of different tumors, depending on the results of genetic testing. Nevertheless, histopathologic diagnosis and surgical therapy will remain mainstays of management for melanoma. PMID:25769708

  6. 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. PMID:7625911

  7. Detecting Adverse Events Using Information Technology

    PubMed Central

    Bates, David W.; Evans, R. Scott; Murff, Harvey; Stetson, Peter D.; Pizziferri, Lisa; Hripcsak, George

    2003-01-01

    Context: Although patient safety is a major problem, most health care organizations rely on spontaneous reporting, which detects only a small minority of adverse events. As a result, problems with safety have remained hidden. Chart review can detect adverse events in research settings, but it is too expensive for routine use. Information technology techniques can detect some adverse events in a timely and cost-effective way, in some cases early enough to prevent patient harm. Objective: To review methodologies of detecting adverse events using information technology, reports of studies that used these techniques to detect adverse events, and study results for specific types of adverse events. Design: Structured review. Methodology: English-language studies that reported using information technology to detect adverse events were identified using standard techniques. Only studies that contained original data were included. Main Outcome Measures: Adverse events, with specific focus on nosocomial infections, adverse drug events, and injurious falls. Results: Tools such as event monitoring and natural language processing can inexpensively detect certain types of adverse events in clinical databases. These approaches already work well for some types of adverse events, including adverse drug events and nosocomial infections, and are in routine use in a few hospitals. In addition, it appears likely that these techniques will be adaptable in ways that allow detection of a broad array of adverse events, especially as more medical information becomes computerized. Conclusion: Computerized detection of adverse events will soon be practical on a widespread basis. PMID:12595401

  8. 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. PMID:24590540

  9. Exosomes in liver pathology.

    PubMed

    Sato, Keisaku; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco

    2016-07-01

    Exosomes are small (∼100nm) membrane-bound extracellular vesicles released by various types of cells into biological fluids. They contain proteins, mRNAs and miRNAs as cargo. Different cell types can take up exosomes by endocytosis and the cargo contained within them can be transferred horizontally to these recipient cells. Exosomal proteins and miRNAs can be functional and regulate physiological cell events modifying the microenvironment in target cells, a key event of liver pathology. Exosome-mediated cell-cell communication can alter tumor growth, cell migration, antiviral infection and hepatocyte regeneration, indicating that exosomes have great potential for development as diagnostic or therapeutic tools. Analyses of circulating total or exosomal miRNAs have identified a large number of candidate miRNAs that are regulated in liver diseases, and the diagnostic testing using single or multiple miRNAs shows good sensitivity and specificity. Some candidate miRNAs have been identified to play an important role in various liver disorders. This review summarizes recent findings on the role of extracellular vesicles in liver diseases and their diagnostic and therapeutic potential, mainly focusing on exosomes but also includes microvesicles in liver pathology. PMID:26988731

  10. Tracking in anatomic pathology.

    PubMed

    Pantanowitz, Liron; Mackinnon, Alexander C; Sinard, John H

    2013-12-01

    Bar code-based tracking solutions, long present in clinical pathology laboratories, have recently made an appearance in anatomic pathology (AP) laboratories. Tracking of AP "assets" (specimens, blocks, slides) can enhance laboratory efficiency, promote patient safety, and improve patient care. Routing of excess clinical material into research laboratories and biorepositories are other avenues that can benefit from tracking of AP assets. Implementing tracking is not as simple as installing software and turning it on. Not all tracking solutions are alike. Careful analysis of laboratory workflow is needed before implementing tracking to assure that this solution will meet the needs of the laboratory. Such analysis will likely uncover practices that may need to be modified before a tracking system can be deployed. Costs that go beyond simply that of purchasing software will be incurred and need to be considered in the budgeting process. Finally, people, not technology, are the key to assuring quality. Tracking will require significant changes in workflow and an overall change in the culture of the laboratory. Preparation, training, buy-in, and accountability of the people involved are crucial to the success of this process. This article reviews the benefits, available technology, underlying principles, and implementation of tracking solutions for the AP and research laboratory. PMID:23634908

  11. [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

  12. 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

  13. 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

  14. Skeletal muscle pathology in Huntington's disease

    PubMed Central

    Zielonka, Daniel; Piotrowska, Izabela; Marcinkowski, Jerzy T.; Mielcarek, Michal

    2014-01-01

    Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by the expansion of a polyglutamine stretch within the huntingtin protein (HTT). The neurological symptoms, that involve motor, cognitive and psychiatric disturbances, are caused by neurodegeneration that is particularly widespread in the basal ganglia and cereberal cortex. HTT is ubiquitously expressed and in recent years it has become apparent that HD patients experience a wide array of peripheral organ dysfunction including severe metabolic phenotype, weight loss, HD-related cardiomyopathy and skeletal muscle wasting. Although skeletal muscles pathology became a hallmark of HD, the mechanisms underlying muscular atrophy in this disorder are unknown. Skeletal muscles account for approximately 40% of body mass and are highly adaptive to physiological and pathological conditions that may result in muscle hypertrophy (due to increased mechanical load) or atrophy (inactivity, chronic disease states). The atrophy is caused by degeneration of myofibers and their replacement by fibrotic tissue is the major pathological feature in many genetic muscle disorders. Under normal physiological conditions the muscle function is orchestrated by a network of intrinsic hypertrophic and atrophic signals linked to the functional properties of the motor units that are likely to be imbalanced in HD. In this article, we highlight the emerging field of research with particular focus on the recent studies of the skeletal muscle pathology and the identification of new disease-modifying treatments. PMID:25339908

  15. Adverse drug reactions in dermatology.

    PubMed

    Ferner, R E

    2015-03-01

    Adverse drug reactions (ADRs) - that is, unintended and harmful responses to medicines - are important to dermatologists because many present with cutaneous signs and because dermatological treatments can cause serious ADRs. The detection of ADRs to new drugs is often delayed because they have a long latency or are rare or unexpected. This means that ADRs to newer agents emerge only slowly after marketing. ADRs are part of the differential diagnosis of unusual rashes. A good drug history that includes details of drug dose, time-course of the reaction and factors that may make the patient more susceptible, will help. For example, Stevens-Johnson syndrome with abacavir is much commoner in patients with HLA-B*5701, and has a characteristic time course. Newer agents have brought newer reactions; for example, acneiform rashes associated with epidermal growth factor receptor inhibitors such as erlotinib. Older systemic agents used to treat skin disease, including corticosteroids and methotrexate, cause important ADRs. The adverse effects of newer biological agents used in dermatology are becoming clearer; for example, hypersensitivity reactions or loss of efficacy from antibody formation and progressive multifocal leucoencephalopathy due to reactivation of latent JC (John Cunningham) virus infections during efalizumab treatment. Unusual or serious harm from medicines, including ADRs, medication errors and overdose, should be reported. The UK Yellow Card scheme is online, and patients can report their own ADRs. PMID:25622648

  16. [Recipients adverse reactions: guidance supports].

    PubMed

    Bazin, A

    2010-12-01

    Since 1994, adverse effects of transfusion transmitted to the French haemovigilance network are registered on "e-fit", the database of the French agency for the safety of health products (Afssaps). In order to improve their analysis, guidance supports have been made by Afssaps working groups. Each support deals with a blood transfusion side effect and is composed of five parts including pathophysiological mechanisms, diagnostic criteria, management recommendations, etiologic investigations and rules of filing the notification form on e-fit. The major characteristics of sheets published or soon-to-be published are presented: transfusion-related acute lung injury, transfusion-transmitted bacterial infection, non-haemolytic febrile reaction, allergic reaction, transfusion-associated circulatory overload, hypotensive transfusion reaction, alloimmunization, erythrocyte incompatibility reaction and hemosiderosis. These new supports give relevant guidelines allowing a better analysis and evaluation of recipients' adverse reactions, particularly their diagnosis, gravity and accountability. They could also initiate studies in European and international haemovigilance and transfusion networks. PMID:21051267

  17. Adverse effects of plasma transfusion.

    PubMed

    Pandey, Suchitra; Vyas, Girish N

    2012-05-01

    Plasma utilization has increased over the past two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions after infusion of fresh-frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: 1) transfusion-related acute lung injury, 2) transfusion-associated circulatory overload, and 3) allergic and/or anaphylactic reactions. Other less common risks include 1) transmission of infections, 2) febrile nonhemolytic transfusion reactions, 3) red blood cell alloimmunization, and 4) hemolytic transfusion reactions. The effects of pathogen inactivation or reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice. PMID:22578374

  18. [Cystic renal pathology].

    PubMed

    Rosi, P; Cesaroni, M; Bracarda, S; Rociola, W; Virgili, G

    1993-08-01

    Ultrasonography has a great interest in diagnosis of cystic kidney disorders for typical eco-pattern of this pathology. In this work we show the eco-pattern of the most common cystic kidney disorders. Particularly we examine simple cysts (typical, atypical, complicated), multicystic kidney dysplasia, autosomal recessive polycystic kidney disease (infantile) autosomal dominant polycystic kidney disease (adult age). The so-called neoplastic cysts (multiloculated cysts, multiloculated cysts nephroma, cystic nephroblastoma), medullar cysts (medullary sponge kidney, medullary cystic disease), parapyelic cysts, acquired cystic kidney disease in renal failure patients, parasitic cysts, epidermoid cysts. About this disorders we present the more typical and expressive ultrasonographic appearance and we define the role and the opportunity of diagnostic setting by echography, moreover ultrasonography allows us to make a differential diagnosis between cystic kidney disorders and other kidney disease. PMID:8353538

  19. [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. PMID:26764296

  20. [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

  1. "Adversative Conjunction": The Poetics of Linguistic Opposition.

    ERIC Educational Resources Information Center

    Wallerstein, Nicholas

    1992-01-01

    The general use of adversative conjunction in (primarily) English and U.S. poetry is outlined. The contention is that the adversative is not merely a grammatical convenience but sometimes a highly functional tool of rhetorical strategy. (36 references) (LB)

  2. Intrapelvic chronic expanding hematoma: magnetic resonance imaging findings with pathological correlation.

    PubMed

    Sakurai, Jun; Akaki, Shiro; Yonezawa, Masaru; Horiguchi, Ikuyo; Nakamura, Satoko; Kanazawa, Susumu

    2010-01-01

    Chronic expanding hematoma is rare and occasionally misdiagnosed as malignant neoplasm. We describe a case in the female pelvis and correlate findings from pathology and magnetic resonance imaging. On diffusion-weighted images (DWI), our patient's hematoma showed 2 different signal intensities, which corresponded to pathological features of fresh and altered blood components. DWI can distinguish between such pathological features of a chronic expanding hematoma. PMID:20585198

  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. Physiotherapy assessment of patients with rotator cuff pathology

    PubMed Central

    2014-01-01

    Pathology of the rotator cuff and sub-acromial bursa are considered to be the main cause of shoulder pain and dysfunction. In the absence of trauma, conservative care, including physiotherapy is the primary treatment. This paper aims to present the key features of a physiotherapy assessment, excluding diagnostic tests for rotator cuff pathology. It describes and explores how assessment can be used to direct management options and develop a treatment plan.

  5. Public hospital pathology--at what cost?

    PubMed

    White, G H; Pascoe, P J

    1994-01-01

    Public hospital laboratories have in the past fended off financial scrutiny and accountability on the grounds of their complexity and lack of compelling need. However, the cost of providing diagnostic laboratory services has now come under intense scrutiny because of budget reductions and options for private sector competition. Costing of pathology services is not difficult, but their organisation and outputs do have unique features that need to be understood and defined to ensure that the costing model used provides robust data that accurately reflects how resources are consumed. The cost data generated for diagnostic services can then be compared to the various benchmarks widely used for activity-based funding, such as the Commonwealth Medical Benefits Schedule and the pathology component of the AN-DRG Service Weights System, while the requirement and funding for other activities can be rationally determined. PMID:10140592

  6. Fiber optics in adverse environments

    SciTech Connect

    Lyous, P.B.

    1982-01-01

    Radiation effects in optical fibers are considered, taking into account recent progress in the investigation of radiation resistant optical fibers, radiation damage in optical fibers, radiation-induced transient absorption in optical fibers, X-ray-induced transient attenuation at low temperatures in polymer clad silica (PCS) fibers, optical fiber composition and radiation hardness, the response of irradiated optical waveguides at low temperatures, and the effect of ionizing radiation on fiber-optic waveguides. Other topics explored are related to environmental effects on components of fiber optic systems, and radiation detection systems using optical fibers. Fiber optic systems in adverse environments are also discussed, giving attention to the survivability of Army fiber optics systems, space application of fiber optics systems, fiber optic wavelength multiplexing for civil aviation applications, a new fiber optic data bus topology, fiber optics for aircraft engine/inlet control, and application of fiber optics in high voltage substations.

  7. Recommendations for pathology peer review.

    PubMed

    Morton, Daniel; Sellers, Rani S; Barale-Thomas, Erio; Bolon, Brad; George, Catherine; Hardisty, Jerry F; Irizarry, Armando; McKay, Jennifer S; Odin, Marielle; Teranishi, Munehiro

    2010-12-01

    Pathology peer review verifies and improves the accuracy and quality of pathology diagnoses and interpretations. Pathology peer review is recommended when important risk assessment or business decisions are based on nonclinical studies. For pathology peer review conducted before study completion, the peer-review pathologist reviews sufficient slides and pathology data to assist the study pathologist in refining pathology diagnoses and interpretations. Materials to be reviewed are selected by the peer-review pathologist. Consultations with additional experts or a formal (documented) pathology working group may be used to resolve discrepancies. The study pathologist is solely responsible for the content of the final pathology data and report, makes changes resulting from peer-review discussions, initiates the audit trail for microscopic observations after all changes resulting from peer-review have been made, and signs the final pathologist's report. The peer-review pathologist creates a signed peer-review memo describing the peer-review process and confirming that the study pathologist's report accurately and appropriately reflects the pathology data. The study pathologist also may sign a statement of consensus. It is not necessary to archive working notes created during the peer-review process. PMID:20924082

  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. PMID:3302664

  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. Macrophage polarization in pathology.

    PubMed

    Sica, Antonio; Erreni, Marco; Allavena, Paola; Porta, Chiara

    2015-11-01

    Macrophages are cells of the innate immunity constituting the mononuclear phagocyte system and endowed with remarkable different roles essential for defense mechanisms, development of tissues, and homeostasis. They derive from hematopoietic precursors and since the early steps of fetal life populate peripheral tissues, a process continuing throughout adult life. Although present essentially in every organ/tissue, macrophages are more abundant in the gastro-intestinal tract, liver, spleen, upper airways, and brain. They have phagocytic and bactericidal activity and produce inflammatory cytokines that are important to drive adaptive immune responses. Macrophage functions are settled in response to microenvironmental signals, which drive the acquisition of polarized programs, whose extremes are simplified in the M1 and M2 dichotomy. Functional skewing of monocyte/macrophage polarization occurs in physiological conditions (e.g., ontogenesis and pregnancy), as well as in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer) and is now considered a key determinant of disease development and/or regression. Here, we will review evidence supporting a dynamic skewing of macrophage functions in disease, which may provide a basis for macrophage-centered therapeutic strategies. PMID:26210152

  11. 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.

  12. 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. PMID:25078411

  13. Speech Pathology Assistant. Trainee Manual.

    ERIC Educational Resources Information Center

    National Association for Hearing and Speech Action, Silver Spring, MD.

    Part of an instructional set which includes an instructor's guide, this trainee manual is designed to provide speech pathology students with some basic and essential knowledge about the communication process. The manual contains nine modules: (1) speech pathology assistant, (2) the bases of speech (structure and function of the speech mechanism,…

  14. 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

  15. 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

  16. 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

  17. Pathology of congenital syphilis in rabbits.

    PubMed Central

    Froberg, M K; Fitzgerald, T J; Hamilton, T R; Hamilton, B; Zarabi, M

    1993-01-01

    We have developed a model for congenital syphilis in the rabbit. This report provides additional information on newborn tissue pathology in animals that were infected in utero. A total of 35 pregnancies were evaluated, each containing 6 to 12 newborns. In the infected group, the mortality was approximately 50%; of the live newborns, half appeared normal and half were hyperreflexic, weak, and runty. Gross pathology in the sickly newborns was quite prevalent and involved enlarged spleens with isolated spots of necrosis; enlarged livers that were overtly congested and hemorrhagic and had numerous granular, white spots; and brains with hemorrhage in the occipital area. Histopathology was apparent in different tissues. Lymphocytes, plasma cells, and vacuolated macrophages were prominent in livers, spleens, brains, and bones. A few actively motile treponemes were visualized by dark-field microscopy within extracts of spleen and within cerebrospinal fluid. Low numbers of treponemes were also demonstrated in sections of brain and liver by using the Warthin-Starry silver stain technique. Blood hematocrits were decreased, and extramedullary hematopoiesis was prominent within spleens and livers; this is consistent with anemia. This rabbit model exhibits many of the same pathologic features commonly found in human congenital syphilis. Images PMID:8406873

  18. Pathologic Outcomes following Urethral Diverticulectomy in Women

    PubMed Central

    Laudano, Melissa A.; Jamzadeh, Asha E.; Lee, Richard K.; Robinson, Brian D.; Tyagi, Renuka; Kaplan, Steven A.; Te, Alexis E.

    2014-01-01

    Purpose. Although most urethral diverticula in women are benign, there is a subset of patients who develop malignant changes. Limited studies report the pathologic findings associated with this relatively rare entity. We describe the clinicopathologic findings of women who underwent urethral diverticulectomy. Methods. A consecutive series of 29 women who underwent surgical resection of a urethral diverticulum were identified between 1992 and 2013. Clinical and radiographic data was collected by retrospective review of patient medical records. All pathological slides were rereviewed by a single urologic pathologist. Results. Of the 14 women with clinical data, 9 (64%) presented with urgency, 7 (50%) with urinary frequency, 3 (21%) with urinary incontinence, and 3 (21%) with dysuria. Mean diverticular size was 2.3 (±1.4) cm. Although one patient (3%) had invasive adenocarcinoma on final pathology, the remaining 28 cases (97%) demonstrated benign features. The most common findings were inflammation (55%) and nephrogenic adenoma (21%). Conclusions. Although most urethral diverticula in women are benign, there is a subset of patients who develop malignancy in association with the diverticulum. In this series, 97% of cases had a benign histology. These findings are important when counseling patients regarding treatment options. PMID:24860605

  19. 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

  20. Translational pathology of neoplasia

    PubMed Central

    Grizzle, William E.; Srivastava, Sudhir; Manne, Upender

    2012-01-01

    With the increasing use of individualized medical care (personalized medicine) in treating and managing patients with cancer, the utilization of biomarkers in selecting and tailoring such medical approaches also is increasing and becoming more important. Specifically, many therapies are effective against only a subgroup of a specific type of tumors and exposing patients with different non-responsive subgroups of the same tumor to ineffective therapies, not only exposes these patients needlessly to acute and chronic side effects of the therapy, but also adds to the costs of medical care. For example, the Oncotype Dx test for estrogen receptor positive tumors that are node negative has been used to identify low risk tumors for which surgery alone is an adequate therapy. Biomarkers may be used to aid in multiple aspects of medical care related to cancer, including early detection, diagnosis, risk assessment, as well as in predicting the aggressiveness of cancers (i.e., prognosis) and predicting the therapeutic efficacy of treatments (i.e., prediction). Biomarkers may be also used as surrogate endpoints to aid in evaluating therapies and preventive approaches. Types of biomarkers vary greatly and include histopathologic appearance, stage of the lesion, quantitative morphologic features, size of the lesion, metastatic pattern and extent of metastasis, as well as imaging and molecular features. The types of measurements of biomarkers also vary; for example, molecular features can be measured at the DNA, mRNA or protein levels as well as at regulatory levels (e.g., microRNA). The usefulness of each biomarker is limited by its sensitivity and specificity in fulfilling its role (e.g., in early detection) and the requirements of sensitivity and specificity to accomplish specific tasks are affected by multiple variables. For example, both very high specificity and sensitivity of a test are required to screen a population with a low prevalence of a specific tumor. The goal of

  1. Translational pathology of neoplasia.

    PubMed

    Grizzle, William E; Srivastava, Sudhir; Manne, Upender

    2010-01-01

    With the increasing use of individualized medical care (personalized medicine) in treating and managing patients with cancer, the utilization of biomarkers in selecting and tailoring such medical approaches also is increasing and becoming more important. Specifically, many therapies are effective against only a subgroup of a specific type of tumors and exposing patients with different non-responsive subgroups of the same tumor to ineffective therapies, not only exposes these patients needlessly to acute and chronic side effects of the therapy, but also adds to the costs of medical care. For example, the Oncotype Dx test for estrogen receptor positive tumors that are node negative has been used to identify low risk tumors for which surgery alone is an adequate therapy. Biomarkers may be used to aid in multiple aspects of medical care related to cancer, including early detection, diagnosis, risk assessment, as well as in predicting the aggressiveness of cancers (i.e., prognosis) and predicting the therapeutic efficacy of treatments (i.e., prediction). Biomarkers may be also used as surrogate endpoints to aid in evaluating therapies and preventive approaches. Types of biomarkers vary greatly and include histopathologic appearance, stage of the lesion, quantitative morphologic features, size of the lesion, metastatic pattern and extent of metastasis, as well as imaging and molecular features. The types of measurements of biomarkers also vary; for example, molecular features can be measured at the DNA, mRNA or protein levels as well as at regulatory levels (e.g., microRNA). The usefulness of each biomarker is limited by its sensitivity and specificity in fulfilling its role (e.g., in early detection) and the requirements of sensitivity and specificity to accomplish specific tasks are affected by multiple variables. For example, both very high specificity and sensitivity of a test are required to screen a population with a low prevalence of a specific tumor. The goal of

  2. 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

  3. Severe cutaneous adverse drug reactions.

    PubMed

    Chung, Wen-Hung; Wang, Chuang-Wei; Dao, Ro-Lan

    2016-07-01

    The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCAR), including drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which are rare but occasionally fatal. Some pathogens may induce skin reactions mimicking SCAR. There are several models to explain the interaction of human leukocyte antigen (HLA), drug and T-cell receptor (TCR): (i) the "hapten/prohapten" theory; (ii) the "p-i concept"; (iii) the "altered peptide repertoire"; and (iv) the "altered TCR repertoire". The checkpoints of molecular mechanisms of SCAR include specific drug antigens interacting with the specific HLA loci (e.g. HLA-B*15:02 for carbamazepine-induced SJS/TEN and HLA-B*58:01 for allopurinol-induced SCAR), involvement of specific TCR, induction of T-cell-mediated responses (e.g. granulysin, Fas ligand, perforin/granzyme B and T-helper 1/2-associated cytokines) and cell death mechanism (e.g. miR-18a-5p-induced apoptosis; annexin A1 and formyl peptide receptor 1-induced necroptosis in keratinocytes). In addition to immune mechanism, metabolism has been found to play a role in the pathogenesis of SCAR, such as recent findings of strong association of CYP2C9*3 with phenytoin-induced SCAR and impaired renal function with allopurinol SCAR. With a better understanding of the mechanisms, effective therapeutics and prevention for SCAR can be improved. PMID:27154258

  4. Myosinopathies: pathology and mechanisms.

    PubMed

    Tajsharghi, Homa; Oldfors, Anders

    2013-01-01

    The myosin heavy chain (MyHC) is the molecular motor of muscle and forms the backbone of the sarcomere thick filaments. Different MyHC isoforms are of importance for the physiological properties of different muscle fiber types. Hereditary myosin myopathies have emerged as an important group of diseases with variable clinical and morphological expression depending on the mutated isoform and type and location of the mutation. Dominant mutations in developmental MyHC isoform genes (MYH3 and MYH8) are associated with distal arthrogryposis syndromes. Dominant or recessive mutations affecting the type IIa MyHC (MYH2) are associated with early-onset myopathies with variable muscle weakness and ophthalmoplegia as a consistent finding. Myopathies with scapuloperoneal, distal or limb-girdle muscle weakness including entities, such as myosin storage myopathy and Laing distal myopathy are the result of usually dominant mutations in the gene for slow/β cardiac MyHC (MYH7). Protein aggregation is part of the features in some of these myopathies. In myosin storage myopathy protein aggregates are formed by accumulation of myosin beneath the sarcolemma and between myofibrils. In vitro studies on the effects of different mutations associated with myosin storage myopathy and Laing distal myopathy indicate altered biochemical and biophysical properties of the light meromyosin, which is essential for thick filament assembly. Protein aggregates in the form of tubulofilamentous inclusions in association with vacuolated muscle fibers are present at late stage of dominant myosin IIa myopathy and sometimes in Laing distal myopathy. These protein aggregates exhibit features indicating defective degradation of misfolded proteins. In addition to protein aggregation and muscle fiber degeneration some of the myosin mutations cause functional impairment of the molecular motor adding to the pathogenesis of myosinopathies. PMID:22918376

  5. 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

  6. Clinico-Pathological Correlations of the Most Common Neurodegenerative Dementias

    PubMed Central

    Taipa, Ricardo; Pinho, João; Melo-Pires, Manuel

    2012-01-01

    Neurodegenerative dementias are a group of neurological disorders characterized by deterioration in several cognitive domains in which there is selective and progressive loss of specific populations of neurons. The precise neurobiological basis for the different neurodegenerative dementias remains unknown. It is expected that different pathologies reflect different mechanisms, at least early in the neurodegeneration process. The next decades promise treatments directed to causes and mechanisms, bringing an outstanding challenge to clinicians due to heterogeneous clinical presentations with the same molecular pathology. The purpose of this brief review is to describe the key neuropathological features of the most common neurodegenerative dementias (Alzheimer disease, dementia with Lewy bodies and Parkinson’s disease dementia, and frontotemporal lobar degeneration) and the relationship with the clinical syndromes described in clinico-pathological studies. We expect this overview contributes for the understanding of this broad topic integrating the two ends of the spectrum: clinical and pathological. PMID:22557993

  7. 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

  8. 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

  9. Emotion Dysregulation Mediates the Relationship between Lifetime Cumulative Adversity and Depressive Symptomatology

    PubMed Central

    Abravanel, Benjamin T.; Sinha, Rajita

    2014-01-01

    Repeated exposure to stressful events across the lifespan, referred to as cumulative adversity, is a potent risk factor for depression. Research indicates that cumulative adversity detrimentally affects emotion regulation processes, which may represent a pathway linking cumulative adversity to vulnerability to depression. However, empirical evidence that emotion dysregulation mediates the relationship between cumulative adversity and depression is limited, particularly in adult populations. We examined the direct and indirect effects of cumulative adversity on depressive symptomatology in a large community sample of adults (n = 745) who were further characterized by risk status: never-depressed (n = 638) and “at-risk” remitted mood-disordered (n = 107). All participants completed the Cumulative Adversity Inventory (CAI), the Difficulties in Emotion Regulation Scale (DERS), and the Center for Epidemiologic Studies Depression Scale (CES-D). Bootstrapped confidence intervals were computed to estimate the indirect effect of emotion dysregulation on the relationship between cumulative adversity and depressive symptomatology and to test whether this indirect effect was moderated by risk status. Emotion dysregulation partially and significantly mediated the relationship between cumulative adversity and depressive symptomatology independent of risk status. Overall, cumulative adversity and emotion dysregulation accounted for 50% of the variance in depressive symptomatology. These findings support the hypothesis that disruption of adaptive emotion regulation processes associated with repeated exposure to stressful life events represents an intrapersonal mechanism linking the experience of adverse events to depression. Our results support the utility of interventions that simultaneously emphasize stress reduction and emotion regulation to treat and prevent depressive vulnerability and pathology. PMID:25528603

  10. 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

  11. 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.

  12. 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.

  13. [Acute adverse effects of dialysis].

    PubMed

    Opatrný, K

    2003-02-01

    Adverse reactions to dialyzers are a not very frequent, but because of the serious, sometimes fatal course, a dreaded complication of haemodialysis treatment. Most important among these reactions are hypersensitive reactions (anaphylactoid, reaction type A to dialyzer), which develop as a rule within the 10th minute of the procedure, and the reaction caused by the action of perfluorohydrocarbon which develop hours after onset or even completion of haemodialysis. Explanation of the development of hypersensitive reactions (HSR) by complement activation and formation of anaphylatoxins C3a and C5a during contact of blood with the bioincompatible dialysis membrane has been abandoned. Evidence of the etiological role of ethylene oxide (ETO) in the development of HSR influenced the selection of materials for the production of dialyzers and sterilization during manufacture, it emphasized the importance of rinsing of the dialyzer in the dialysis centre and led to the wide application of alternative methods of sterilization by gamma radiation and steam. HSR may be also caused by overproduction of bradykinin and inhibition of its degradation or degradation of its metabolites. Excessive bradykinin production caused by dialysis membranes with a negative charge is potentiated e.g. by a lower pH and increased plasma dilution in the initial stage of haemodialysis. Inhibition of bradykinin degradation develops during treatment with angiotensin converting enzyme inhibitors (ACEI). In prevention of HSR associated with bradykinin in addition to elimination of a combination of a negatively charged dialysis membrane and ACEI treatment a part is played also by rinsing of the dialyzer before haemodialysis with a bicarbonate solution and the modification of the membrane surface (implemented by the manufacturer) which reduces its negative charge. The first reaction to the dialyzer in conjunction with perfluorohydrocarbon (PF-5070), used in production of some dialyzers for testing the

  14. 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

  15. 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)

  16. 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...

  17. Adverse Drug Reactions in Dental Practice

    PubMed Central

    Becker, Daniel E.

    2014-01-01

    Adverse reactions may occur with any of the medications prescribed or administered in dental practice. Most of these reactions are somewhat predictable based on the pharmacodynamic properties of the drug. Others, such as allergic and pseudoallergic reactions, are less common and unrelated to normal drug action. This article will review the most common adverse reactions that are unrelated to drug allergy. PMID:24697823

  18. Nurses must report adverse drug reactions.

    PubMed

    Griffith, Richard

    There is renewed determination throughout the European Union (EU) to reduce the economic cost and high death rate associated with adverse drug reactions through better pharmacovigilance. Timely reporting and sharing of information concerning adverse drug reactions is vital to the success of this initiative. In the UK, the reporting of serious adverse drug reactions is facilitated by the Yellow Card Scheme, yet despite being well placed to monitor the effect of medicines on patients, nurses do not make full use of the scheme. This article sets out the impact of adverse drug reactions in the EU and argues that it is essential that nurses must be at the vanguard of adverse reaction reporting if the EU's pharmacovigilance initiative is to be a success. PMID:23905231

  19. 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

  20. Immune-Related Adverse Events From Immune Checkpoint Inhibitors.

    PubMed

    Marrone, K A; Ying, W; Naidoo, J

    2016-09-01

    Immunotherapy for cancer treatment has come of age, specifically with the use of immune checkpoint antibodies directed against molecules such as CTLA-4, PD-1, and PD-L1. Single-agent and combinatorial approaches utilizing these agents and other immunotherapies that may enhance antitumor effects are under investigation. With increasing clinical use of these agents, an appreciation for their toxicities comes to the fore. Adverse events that occur as a result of the immunologic effects of these therapies are termed "immune-related adverse events" (irAEs), and range in both frequency and severity in reported single-agent and combination studies. Improvements in our understanding of how and why irAEs develop and how to effectively manage them are needed. Herein we provide a state-of-the-art synopsis of the incidence, clinical features, mechanisms, and management of selected irAEs with immune checkpoint inhibitors currently in use. PMID:27170616

  1. 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

  2. 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

  3. 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. PMID:26690743

  4. Controversies in the pathological assessment of colorectal cancer

    PubMed Central

    Maguire, Aoife; Sheahan, Kieran

    2014-01-01

    Pathologic assessment of colorectal cancer specimens plays an essential role in patient management, informing prognosis and contributing to therapeutic decision making. The tumor-node-metastasis (TNM) staging system is a key component of the colorectal cancer pathology report and provides important prognostic information. However there is significant variation in outcome of patients within the same tumor stage. Many other histological features such as tumor budding, vascular invasion, perineural invasion, tumor grade and rectal tumor regression grade that may be of prognostic value are not part of TNM staging. Assessment of extramural tumor deposits and peritoneal involvement contributes to TNM staging but there are some difficulties with the definition of both of these features. Controversies in colorectal cancer pathology reporting include the subjective nature of some of the elements assessed, poor reporting rates and reproducibility and the need for standardized examination protocols and reporting. Molecular pathology is becoming increasingly important in prognostication and prediction of response to targeted therapies but accurate morphology still has a key role to play in colorectal cancer pathology reporting. PMID:25110416

  5. 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

  6. Adverse event recording post hip fracture surgery.

    PubMed

    Doody, K; Mohamed, K M S; Butler, A; Street, J; Lenehan, B

    2013-01-01

    Accurate recording of adverse events post hip fracture surgery is vital for planning and allocating resources. The purpose of this study was to compare adverse events recorded prospectively at point of care with adverse recorded by the Hospital In-Patient Enquiry (HIPE) System. The study examined a two month period from August to September 2011 at University Hospital Limerick. Out of a sample size of 39, there were 7 males (17.9%) and 32 females (82.1%) with an age range of between 53 and 98 years. The mean age was 80.5 years. 55 adverse events were recorded, in contrast to the HIPE record of 13 (23.6%) adverse events. The most common complications included constipation 10 (18.2%), anaemia 8 (14.5%), urinary retention 8 (14.50%), pneumonia 5 (9.1%) and delirium 5 (9.1%). Of the female cohort, 24 (68.8%) suffered an adverse event, while only 4 (57%) males suffered an adverse event. PMID:24579408

  7. 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.

  8. Learning from adverse incidents involving medical devices.

    PubMed

    Amoore, John; Ingram, Paula

    While an adverse event involving a medical device is often ascribed to either user error or device failure, the causes are typically multifactorial. A number of incidents involving medical devices are explored using this approach to investigate the various causes of the incident and the protective barriers that minimised or prevented adverse consequences. User factors, including mistakes, omissions and lack of training, conspired with background factors--device controls and device design, storage conditions, hidden device damage and physical layout of equipment when in use--to cause the adverse events. Protective barriers that prevented or minimised the consequences included staff vigilance, operating procedures and alarms. PMID:12715578

  9. 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

  10. 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

  11. [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. PMID:25300121

  12. Lupus Nephritis: Animal Modeling of a Complex Disease Syndrome Pathology

    PubMed Central

    McGaha, Tracy L; Madaio, Michael P.

    2014-01-01

    Nephritis as a result of autoimmunity is a common morbidity associated with Systemic Lupus Erythematosus (SLE). There is substantial clinical and industry interest in medicinal intervention in the SLE nephritic process; however, clinical trials to specifically treat lupus nephritis have not resulted in complete and sustained remission in all patients. Multiple mouse models have been used to investigate the pathologic interactions between autoimmune reactivity and SLE pathology. While several models bear a remarkable similarity to SLE-driven nephritis, there are limitations for each that can make the task of choosing the appropriate model for a particular aspect of SLE pathology challenging. This is not surprising given the variable and diverse nature of human disease. In many respects, features among murine strains mimic some (but never all) of the autoimmune and pathologic features of lupus patients. Although the diversity often limits universal conclusions relevant to pathogenesis, they provide insights into the complex process that result in phenotypic manifestations of nephritis. Thus nephritis represents a microcosm of systemic disease, with variable lesions and clinical features. In this review, we discuss some of the most commonly used models of lupus nephritis (LN) and immune-mediated glomerular damage examining their relative strengths and weaknesses, which may provide insight in the human condition. PMID:25722732

  13. 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

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

    PubMed

    Ganguly, Prabarna; Brenhouse, Heather C

    2015-02-01

    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

  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. 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...

  17. Adverse cutaneous drug eruptions: current understanding.

    PubMed

    Hoetzenecker, W; Nägeli, M; Mehra, E T; Jensen, A N; Saulite, I; Schmid-Grendelmeier, P; Guenova, E; Cozzio, A; French, L E

    2016-01-01

    Adverse cutaneous drug reactions are recognized as being major health problems worldwide causing considerable costs for health care systems. Most adverse cutaneous drug reactions follow a benign course; however, up to 2% of all adverse cutaneous drug eruptions are severe and life-threatening. These include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Physicians should be aware of specific red flags to rapidly identify these severe cutaneous drug eruptions and initiate appropriate treatment. Besides significant progress in clinical classification and treatment, recent studies have greatly enhanced our understanding in the pathophysiology of adverse cutaneous drug reactions. Genetic susceptibilities to certain drugs have been identified in SJS/TEN patients, viral reactivation in DRESS has been elucidated, and the discovery of tissue resident memory T cells helps to better understand the recurrent site-specific inflammation in patients with fixed drug eruption. PMID:26553194

  18. 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

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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

  6. Ovarian masses revisited: radiologic and pathologic correlation.

    PubMed

    Sutton, C L; McKinney, C D; Jones, J E; Gay, S B

    1992-09-01

    Diagnosis of ovarian masses can be difficult because many pathologic conditions can affect the ovary and have similar clinical and radiologic manifestations. Knowledge of pathologic, age-specific characteristics can help refine the differential diagnosis. Ovarian masses are nonneoplastic (ovarian functional cysts, polycystic ovary disease, and ovarian torsion) or neoplastic (surface epithelial, sex cord-stromal, germ cell, and metastatic tumors). Functional cysts, if complicated by hemorrhage, can have a confusing ultrasonographic (US) appearance. Polycystic disease and torsion are easily diagnosed with US. Benign and malignant forms of serous and mucinous surface epithelial tumors can usually be differentiated with US. Imaging features of surface epithelial tumors of low malignant potential are nonspecific, resembling those of benign serous and mucinous tumors. Mature (benign) teratomas are usually cystic, with components of fat, soft tissue, and calcium, and are sonographically distinct from immature (malignant) teratomas, which are mostly solid. Sex cord-stromal tumors occur more often in menopausal or postmenopausal women and are typically solid. Metastatic disease is less common than other ovarian tumors; however, its radiologic appearance may resemble those of other masses. PMID:1529129

  7. Cranial Pathologies in a Specimen of Pachycephalosaurus

    PubMed Central

    Peterson, Joseph E.; Vittore, Christopher P.

    2012-01-01

    Background A frontoparietal dome of a large pachycephalosaurid collected from the Upper Cretaceous Hell Creek Formation in 2001 is identified as Pachycephalosaurus wyomingensis. The specimen features two large oval depressions on the dorsal surface, accompanied by numerous circular pits on the margin and inner surface of the larger depressions. Methodology/Principal Findings In order to identify the origin of these structures, computed tomography (CT) data and morphological characteristics of the specimen are analyzed and compared with similar osteological structures in fossil and extant archosaurs caused by taphonomic processes, non-pathologic bone resorption, and traumatic infection/inflammatory origins. The results of these analyses suggest that the structures are pathologic lesions likely resulting from a traumatic injury and followed by secondary infection at the site. Conclusions/Significance The presence of lesions on a frontoparietal dome, and the exclusivity of their distribution along the dorsal dome surface, offers further insight into frontoparietal dome function and supports previously hypothesized agonistic behavior in pachycephalosaurids. PMID:22558394

  8. Intrahepatic cholangiocarcinoma: radiologic-pathologic correlation.

    PubMed

    Ros, P R; Buck, J L; Goodman, Z D; Ros, A M; Olmsted, W W

    1988-06-01

    Seventeen proved cases of intrahepatic cholangiocarcinoma (ICAC) were reviewed to establish a radiologic-pathologic correlation. The most common appearance of ICAC at computed tomography (CT) is that of a single, homogeneous low-attenuation mass. Multiple low-attenuation lesions were present in four cases. Calcification was depicted by CT in three cases. At angiography, ICAC has a variable appearance with avascular, hypovascular, and hypervascular patterns possible. Portal obstruction was seen in only one case. The most common appearance of ICAC at sonography is that of a homogeneously hyperechoic mass, either single or multiple. In only one case was ICAC hypoechoic. Plain abdominal radiography demonstrated calcification in three patients and evidence of Thorotrast (thorium dioxide) deposition in one. Upper gastrointestinal series demonstrated abnormal gastric folds in two cases, corresponding to gastric invasion by ICAC. There were no characteristic radiographic findings, but the following features may be helpful in differentiating ICAC from other primary intrahepatic tumors, particularly typical hepatocellular carcinoma: a homogeneously echogenic or high-attenuation appearance on images that reflects the uniform nature observed at pathologic examination, the presence of calcification, and the uncommon invasion of portal or hepatic veins. Conversely, the presence of satellite lesions may blur the the distinction between ICAC and metastatic liver disease. PMID:2834769

  9. 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

  10. [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

  11. Forensic Pathology of Traumatic Brain Injury.

    PubMed

    Finnie, J W

    2016-09-01

    Traumatic brain injury constitutes a significant proportion of cases requiring forensic examination, and it encompasses (1) blunt, nonmissile head injury, especially involving motor vehicle accidents, and (2) penetrating, missile injury produced by a range of high- and lower-velocity projectiles. This review examines the complex pathophysiology and biomechanics of both types of neurotrauma and assesses the macroscopic and histologic features of component lesions, which may be used to determine the cause and manner of death resulting from an intentional assault or accident. Estimation of the survival time postinjury by pathologic examination is also important where malicious head injury is suspected, in an attempt to ascertain a time at which the traumatic event might have been committed, thereby evaluating the authenticity of statements made by the alleged perpetrator. PMID:26578643

  12. Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration

    PubMed Central

    Rohrer, Jonathan D.; Lashley, Tammaryn; Schott, Jonathan M.; Warren, Jane E.; Mead, Simon; Isaacs, Adrian M.; Beck, Jonathan; Hardy, John; de Silva, Rohan; Warrington, Elizabeth; Troakes, Claire; Al-Sarraj, Safa; King, Andrew; Borroni, Barbara; Clarkson, Matthew J.; Ourselin, Sebastien; Holton, Janice L.; Fox, Nick C.; Revesz, Tamas; Rossor, Martin N.

    2011-01-01

    Relating clinical symptoms to neuroanatomical profiles of brain damage and ultimately to tissue pathology is a key challenge in the field of neurodegenerative disease and particularly relevant to the heterogeneous disorders that comprise the frontotemporal lobar degeneration spectrum. Here we present a retrospective analysis of clinical, neuropsychological and neuroimaging (volumetric and voxel-based morphometric) features in a pathologically ascertained cohort of 95 cases of frontotemporal lobar degeneration classified according to contemporary neuropathological criteria. Forty-eight cases (51%) had TDP-43 pathology, 42 (44%) had tau pathology and five (5%) had fused-in-sarcoma pathology. Certain relatively specific clinicopathological associations were identified. Semantic dementia was predominantly associated with TDP-43 type C pathology; frontotemporal dementia and motoneuron disease with TDP-43 type B pathology; young-onset behavioural variant frontotemporal dementia with FUS pathology; and the progressive supranuclear palsy syndrome with progressive supranuclear palsy pathology. Progressive non-fluent aphasia was most commonly associated with tau pathology. However, the most common clinical syndrome (behavioural variant frontotemporal dementia) was pathologically heterogeneous; while pathologically proven Pick's disease and corticobasal degeneration were clinically heterogeneous, and TDP-43 type A pathology was associated with similar clinical features in cases with and without progranulin mutations. Volumetric magnetic resonance imaging, voxel-based morphometry and cluster analyses of the pathological groups here suggested a neuroanatomical framework underpinning this clinical and pathological diversity. Frontotemporal lobar degeneration-associated pathologies segregated based on their cerebral atrophy profiles, according to the following scheme: asymmetric, relatively localized (predominantly temporal lobe) atrophy (TDP-43 type C); relatively symmetric

  13. 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.

  14. 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)…

  15. Physiological and pathological cardiac hypertrophy.

    PubMed

    Shimizu, Ippei; Minamino, Tohru

    2016-08-01

    The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy. PMID:27262674

  16. 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…

  17. 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

  18. 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

  19. Automatic classification for pathological prostate images based on fractal analysis.

    PubMed

    Huang, Po-Whei; Lee, Cheng-Hsiung

    2009-07-01

    Accurate grading for prostatic carcinoma in pathological images is important to prognosis and treatment planning. Since human grading is always time-consuming and subjective, this paper presents a computer-aided system to automatically grade pathological images according to Gleason grading system which is the most widespread method for histological grading of prostate tissues. We proposed two feature extraction methods based on fractal dimension to analyze variations of intensity and texture complexity in regions of interest. Each image can be classified into an appropriate grade by using Bayesian, k-NN, and support vector machine (SVM) classifiers, respectively. Leave-one-out and k-fold cross-validation procedures were used to estimate the correct classification rates (CCR). Experimental results show that 91.2%, 93.7%, and 93.7% CCR can be achieved by Bayesian, k-NN, and SVM classifiers, respectively, for a set of 205 pathological prostate images. If our fractal-based feature set is optimized by the sequential floating forward selection method, the CCR can be promoted up to 94.6%, 94.2%, and 94.6%, respectively, using each of the above three classifiers. Experimental results also show that our feature set is better than the feature sets extracted from multiwavelets, Gabor filters, and gray-level co-occurrence matrix methods because it has a much smaller size and still keeps the most powerful discriminating capability in grading prostate images. PMID:19164082

  20. 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.

  1. Adverse events temporally associated with meningococcal vaccines.

    PubMed Central

    Yergeau, A; Alain, L; Pless, R; Robert, Y

    1996-01-01

    OBJECTIVE: To determine the incidence of severe adverse events temporally associated with meningococcal vaccines administered as part of a mass vaccination program. DESIGN: Retrospective descriptive study of events reported to a passive provincial surveillance system. SETTING: The province of Quebec. PARTICIPANTS: The 1,198,751 individuals aged 6 months to 20 years who were vaccinated against meningococcal disease between Dec. 27, 1992, and Mar. 31, 1993. OUTCOME MEASURES: Total numbers and rates of severe adverse events, including allergic reactions, anaphylactic reactions, neurological events (other than abnormal crying and screaming) and other serious or unusual events. RESULTS: A total of 118 reports of severe adverse events were selected from the surveillance system. The most frequent were allergic reactions (9.2 per 100,000 doses). Few anaphylactic or neurologic reactions were reported (0.1 and 0.5 per 100,000 doses respectively). There were no reports of sequelae or of encephalopathy, meningitis or encephalitis. CONCLUSION: Meningococcal vaccines seem to be associated with fewer adverse events than have previously been reported. Existing surveillance programs are useful for determining the incidence of adverse events temporally associated with vaccines. PMID:8630839

  2. 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. PMID:25802092

  3. Histopathological Features of Brain Arteriovenous Malformations in Japanese Patients.

    PubMed

    Hermanto, Yulius; Takagi, Yasushi; Yoshida, Kazumichi; Ishii, Akira; Kikuchi, Takayuki; Funaki, Takeshi; Mineharu, Yohei; Miyamoto, Susumu

    2016-06-15

    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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Digital photography in anatomical pathology.

    PubMed

    Leong, F J; Leong, A S

    2004-01-01

    Digital imaging has made major inroads into the routine practice of anatomical pathology and replaces photographic prints and Kodachromes for reporting and conference purposes. More advanced systems coupled to computers allow greater versatility and speed of turnaround as well as lower costs of incorporating macroscopic and microscopic pictures into pathology reports and publications. Digital images allow transmission to remote sites via the Internet for consultation, quality assurance and educational purposes, and can be stored on and disseminated by CD-ROM. Total slide digitisation is now a reality and will replace glass slides to a large extent. Three-dimensional images of gross specimens can be assembled and posted on websites for interactive educational programmes. There are also applications in research, allowing more objective and automated quantitation of a variety of morphological and immunohistological parameters. Early reports indicate that medical vision systems are a reality and can provide for automated computer-generated histopathological diagnosis and quality assurance. PMID:15048004

  10. Identifying Adverse Drug Events by Relational Learning

    PubMed Central

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

    2013-01-01

    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

  11. Standardizing drug adverse event reporting data.

    PubMed

    Wang, Liwei; Jiang, Guoqian; Li, Dingcheng; Liu, Hongfang

    2013-01-01

    Normalizing data in the Adverse Event Reporting System (AERS), an FDA database, would improve the mining capacity of AERS for drug safety signal detection. In this study, we aim to normalize AERS and build a publicly available normalized Adverse drug events (ADE) data source.he drug information in AERS is normalized to RxNorm, a standard terminology source for medication. Drug class information is then obtained from the National Drug File - Reference Terminology (NDF-RT). Adverse drug events (ADE) are aggregated through mapping with the PT (Preferred Term) and SOC (System Organ Class) codes of MedDRA. Our study yields an aggregated knowledge-enhanced AERS data mining set (AERS-DM). The AERS-DM could provide more perspectives to mine AERS database for drug safety signal detection and could be used by research community in the data mining field. PMID:23920875

  12. A revised inventory of Adverse Childhood Experiences.

    PubMed

    Finkelhor, David; Shattuck, Anne; Turner, Heather; Hamby, Sherry

    2015-10-01

    This study examines whether the items from the original Adverse Childhood Experiences (ACE) scale can be improved in their prediction of health outcomes by adding some additional widely recognized childhood adversities. The analyses come from the National Survey of Children's Exposure to Violence 2014, a telephone survey conducted from August 2013 through April 2014 with a nationally representative sample of 1,949 children and adolescents aged 10-17 and their caregivers who were asked about adversities, physical health conditions and mental health symptoms. The addition of measures of peer victimization, peer isolation/rejection, and community violence exposure added significantly to the prediction of mental health symptoms, and the addition of a measure of low socioeconomic status (SES) added significantly to the prediction of physical health problems. A revised version of the ACES scale is proposed. PMID:26259971

  13. 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. PMID:23499043

  14. 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

  15. Tumors of the Testis: Morphologic Features and Molecular Alterations.

    PubMed

    Howitt, Brooke E; Berney, Daniel M

    2015-12-01

    This article reviews the most frequently encountered tumor of the testis; pure and mixed malignant testicular germ cell tumors (TGCT), with emphasis on adult (postpubertal) TGCTs and their differential diagnoses. We additionally review TGCT in the postchemotherapy setting, and findings to be integrated into the surgical pathology report, including staging of testicular tumors and other problematic issues. The clinical features, gross pathologic findings, key histologic features, common differential diagnoses, the use of immunohistochemistry, and molecular alterations in TGCTs are discussed. PMID:26612222

  16. Medical discourse in pathological anatomy.

    PubMed

    Moskalenko, R; Tatsenko, N; Romanyuk, A; Perelomova, O; Moskalenko, Yu

    2012-05-01

    The paper is devoted to the peculiarities of medical discourse in pathological anatomy as coherent speech and as a linguistic correlate of medical practice taking into account the analysis of its strategies and tactics. The purpose of the paper is to provide a multifaceted analysis of the speech strategies and tactics of pathological anatomy discourse and ways of their implementation. The main strategies of medical discourse in pathological anatomy are an anticipating strategy, a diagnosing strategy and an explaining one. The supporting strategies are pragmatic, conversational and a rhetorical one. The pragmatic strategy is implemented through contact establishing tactics, the conversational one - with the help of control tactics, the rhetorical one - with the help of attention correction tactics. The above mentioned tactics and strategies are used in the distinguishing of major, closely interrelated strategies: "the contact strategy" (to establish contact with a patient's relatives - phatic replicas of greeting and addressing) and "the strategy of explanation" (used in the practice of a pathologist for a detailed explanation of the reasons of a patient's death). The ethic aspect of speech conduct of a doctor-pathologist is analyzed. PMID:22870841

  17. Digital imaging in anatomic pathology.

    PubMed

    O'Brien, M J; Sotnikov, A V

    1996-10-01

    Advances in computer technology continue to bring new innovations to departments of anatomic pathology. This article briefly reviews the present status of digital optical imaging, and explores the directions that this technology may lead over the next several years. Technical requirements for digital microscopic and gross imaging, and the available options for image archival and retrieval are summarized. The advantages of digital images over conventional photography in the conference room, and the usefulness of digital imaging in the frozen section suite and gross room, as an adjunct to surgical signout and as a resource for training and education, are discussed. An approach to the future construction of digital histologic sections and the computer as microscope is described. The digital technologic applications that are now available as components of the surgical pathologist's workstation are enumerated. These include laboratory information systems, computerized voice recognition, and on-line or CD-based literature searching, texts and atlases and, in some departments, on-line image databases. The authors suggest that, in addition to these resources that are already available, tomorrow's surgical pathology workstation will include network-linked digital histologic databases, on-line software for image analysis and 3-D image enhancement, expert systems, and ultimately, advanced pattern recognition capabilities. In conclusion, the authors submit that digital optical imaging is likely to have a significant and positive impact on the future development of anatomic pathology. PMID:8853053

  18. Adverse Drug Reactions of the Lower Extremities.

    PubMed

    Adigun, Chris G

    2016-07-01

    Adverse drug reactions (ADRs) are a common cause of dermatologic consultation, involving 2 to 3 per 100 medical inpatients in the United States. Female patients are 1.3 to 1.5 times more likely to develop ADRs, except in children less than 3 years of age, among whom boys are more often affected. Certain drugs are more frequent causes, including aminopenicillins, trimethoprim-sulfamethoxazole, and nonsteroidal antiinflammatory drugs. Chemotherapeutic agents commonly cause adverse reactions to the skin and nails, with certain agents causing particular patterns of reactions. ADRs can involve any area of the skin; the appendages, including hair and nails; as well as mucosa. PMID:27215159

  19. [Update of pathological diagnosis of pulmonary neuroendocrine tumor].

    PubMed

    Xiaodong, Teng; Ming, Zhao; Maode, Lai

    2016-05-25

    Pulmonary neuroendocrine tumors are common in pathological practice and its pathological classification and histological grading are not exactly the same as that of those in the digestive tract and pancreas. In 2015 edition of World Health Organization classification, pulmonary neuroendocrine tumors are classified as carcinoid tumors (including typical carcinoid and atypical carcinoid), small cell lung carcinoma, large cell neuroendocrine carcinoma, and precursor lesion diffuse idiopathic neuroendocrine cell hyperplasia; each category has distinctive morphological and immunohistochemical features. The morphologic features including growth patterns and cytological appearances are keys for the diagnosis of neuroendocrine tumor, and immunohistochemical findings are also critical for its diagnosis. Furthermore, the diagnostic criteria vary for different types of specimen. In this article, we present a concise review and summary of the update of clinicopathological characterizations of pulmonary neuroendocrine tumor, with an emphasis on its diagnostic criteria and differential diagnosis. PMID:27045239

  20. 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

  1. 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

  2. The spectrum of gastric pathology in portal hypertension-An endoscopic and pathologic study of 550 cases.

    PubMed

    Ma, Changqing; Chen, Chien-Huan; Liu, Ta-Chiang

    2016-08-01

    One of the main tasks for pathologists when evaluating gastric biopsies from patients with portal hypertensive gastropathy (PHG) is to examine whether there is increased mucosal vasculature as suggested by endoscopy. However, the full spectrum of pathology findings in patients with portal hypertension (pHTN) is largely unknown. We systematically characterized the endoscopic and pathologic features in gastric biopsies from pHTN patients (study group) and compared with those from patients without pHTN (control group). The study group consisted of 550 consecutive surveillance esophagogastroduodenoscopic (EGD) biopsies, whereas the control group included 281 consecutive EGD biopsies for a variety of indications. As expected, the endoscopic prevalence of PHG was 28%, among which two-thirds showed corresponding histopathologic evidence of increased vasculature. However, non-Helicobacter pylori gastritis was the most common finding in pHTN patients on histology (40%). In addition, hyperplastic polyp was also more common in pHTN patients than in controls (6% vs 3%; P=0.0314). In contrast, pathology findings of nonspecific reactive changes (29% vs 51%; P<0.0001), proton pump inhibitor-related changes (16% vs 30%; P<0.0001), and malignancy (1% vs 3%; P=0.0138) were less common in pHTN patients. Our results show a spectrum of gastric endoscopic and pathologic findings in pHTN patients. The predominant gastric pathology in pHTN patients may be associated with pHTN-induced gastric microcirculation impairment. PMID:27461830

  3. Metastatic melanoma: Pathologic characterization, current treatment, and complications of therapy.

    PubMed

    Wick, Mark R; Gru, Alejandro A

    2016-07-01

    Metastatic melanoma (MM) has the potential to involve virtually any anatomical site, and it also has a wide spectrum of histological appearances. General clinicopathologic data pertaining to MM are presented in this review, together with a discussion of its differential diagnosis and therapy. "Biological" agents used in the treatment of melanoma are considered, along with the pathological features of the complications that they may cause. PMID:27234321

  4. 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

  5. The impact of asymmetric flows on pathological speech

    NASA Astrophysics Data System (ADS)

    Erath, Byron D.; Peterson, Sean D.; Plesniak, Michael W.

    2010-11-01

    In voiced speech the vocal folds form a divergent glottal passage during the closing phases of the phonatory cycle. Due to the adverse pressure gradient, asymmetric flow develops within the glottis causing the glottal jet to separate from one vocal fold wall, and fully-attach to the opposing wall. The asymmetric pressures that arise from this flow configuration directly influence the vocal fold energy exchange process, and are expected to have the greatest influence on vocal fold motion when pathologies that affect the vocal fold musculature are present. A theoretical flow solution that produces the pressure distributions arising from asymmetric glottal flows is implemented into a two-mass model of speech. The impact of flow asymmetries on pathological vocal fold motion is investigated by modifying the tissue parameters of the speech model to represent unilateral paralysis. The influence of asymmetric flow behavior on pathological vocal fold motion is quantified and compared to the commonly-reported simplified case involving symmetric flow behavior.

  6. 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…

  7. 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...

  8. 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

  9. 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)

  10. 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

  11. 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)

  12. 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

  13. [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. PMID:27040337

  14. 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...

  15. 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…

  16. 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

  17. 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

  18. Genetic-pathologic characterization of myeloproliferative neoplasms.

    PubMed

    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

  19. 42 CFR 493.853 - Condition: Pathology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes...

  20. 42 CFR 493.853 - Condition: Pathology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes...

  1. 42 CFR 493.853 - Condition: Pathology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes...

  2. 42 CFR 493.853 - Condition: Pathology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes...

  3. 42 CFR 493.853 - Condition: Pathology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes...

  4. 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

  5. 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

  6. Hyperthyroidism Presenting With Pathologic Fractures

    PubMed Central

    Sarezky, Margaret D.; Corwin, Daniel J.; Harrison, Victor S.; Jacobstein, Cynthia

    2016-01-01

    Previous studies have shown that thyroid hormone directly stimulates bone resorption in in vitro organ culture, and in adults excess thyroid hormone is associated with decreased bone mineral density. There are limited data in children regarding the effect of hyperthyroidism on bone metabolism and even fewer instances in the literature of hyperthyroidism presenting with bone demineralization and fracture. We report a case of an 11-year-old boy with undiagnosed hyperthyroidism presenting with fractures and osteoporosis. This case emphasizes the importance of maintaining a broad differential diagnosis when a patient presents with a pathologic fracture. PMID:26746406

  7. 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. PMID:3944564

  8. Automated Classification of Pathology Reports.

    PubMed

    Oleynik, Michel; Finger, Marcelo; Patrão, Diogo F C

    2015-01-01

    This work develops an automated classifier of pathology reports which infers the topography and the morphology classes of a tumor using codes from the International Classification of Diseases for Oncology (ICD-O). Data from 94,980 patients of the A.C. Camargo Cancer Center was used for training and validation of Naive Bayes classifiers, evaluated by the F1-score. Measures greater than 74% in the topographic group and 61% in the morphologic group are reported. Our work provides a successful baseline for future research for the classification of medical documents written in Portuguese and in other domains. PMID:26262339

  9. 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

  10. Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

    SciTech Connect

    Lin, Charles; Tripcony, Lee; Keller, Jacqui; Poulsen, Michael; Martin, Jarad; Jackson, James; Dickie, Graeme

    2012-01-01

    Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis. Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

  11. 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

  12. 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...

  13. 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...

  14. 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...

  15. 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

  16. An Investigation of Vocal Tract Characteristics for Acoustic Discrimination of Pathological Voices

    PubMed Central

    Lee, Jung-Won; Kang, Hong-Goo; Choi, Jeung-Yoon; Son, Young-Ik

    2013-01-01

    This paper investigates the effectiveness of measures related to vocal tract characteristics in classifying normal and pathological speech. Unlike conventional approaches that mainly focus on features related to the vocal source, vocal tract characteristics are examined to determine if interaction effects between vocal folds and the vocal tract can be used to detect pathological speech. Especially, this paper examines features related to formant frequencies to see if vocal tract characteristics are affected by the nature of the vocal fold-related pathology. To test this hypothesis, stationary fragments of vowel /aa/ produced by 223 normal subjects, 472 vocal fold polyp subjects, and 195 unilateral vocal cord paralysis subjects are analyzed. Based on the acoustic-articulatory relationships, phonation for pathological subjects is found to be associated with measures correlated with a raised tongue body or an advanced tongue root. Vocal tract-related features are also found to be statistically significant from the Kruskal-Wallis test in distinguishing normal and pathological speech. Classification results demonstrate that combining the formant measurements with vocal fold-related features results in improved performance in differentiating vocal pathologies including vocal polyps and unilateral vocal cord paralysis, which suggests that measures related to vocal tract characteristics may provide additional information in diagnosing vocal disorders. PMID:24288686

  17. 100 years of Lewy pathology.

    PubMed

    Goedert, Michel; Spillantini, Maria Grazia; Del Tredici, Kelly; Braak, Heiko

    2013-01-01

    In 1817, James Parkinson described the symptoms of the shaking palsy, a disease that was subsequently defined in greater detail, and named after Parkinson, by Jean-Martin Charcot. Parkinson expected that the publication of his monograph would lead to a rapid elucidation of the anatomical substrate of the shaking palsy; in the event, this process took almost a century. In 1912, Fritz Heinrich Lewy identified the protein aggregates that define Parkinson disease (PD) in some brain regions outside the substantia nigra. In 1919, Konstantin Nikolaevich Tretiakoff found similar aggregates in the substantia nigra and named them after Lewy. In the 1990s, α-synuclein was identified as the main constituent of the Lewy pathology, and its aggregation was shown to be central to PD, dementia with Lewy bodies, and multiple system atrophy. In 2003, a staging scheme for idiopathic PD was introduced, according to which α-synuclein pathology originates in the dorsal motor nucleus of the vagal nerve and progresses from there to other brain regions, including the substantia nigra. In this article, we review the relevance of Lewy's discovery 100 years ago for the current understanding of PD and related disorders. PMID:23183883

  18. Clinical and electrodiagnostic features of sciatic neuropathies.

    PubMed

    Distad, B Jane; Weiss, Michael D

    2013-02-01

    Sciatic neuropathy is the second most common neuropathy of the lower extremity and a common cause of foot drop. This article reviews the anatomy, clinical features, pathophysiology, and electrodiagnostic assessment of sciatic neuropathies. There are multiple potential sites of pathology, determined in part by the mechanism of insult, including trauma, compression, masses, inflammation, and vascular lesions. Diagnosis is augmented by careful electrodiagnostic studies and imaging to help distinguish sciatic neuropathy from other sources of pathology. Electrodiagnostic studies may also help in assessing for early recovery and in determining prognosis. PMID:23177034

  19. Paternal employment in solvent related occupations and adverse pregnancy outcomes.

    PubMed

    Daniell, W E; Vaughan, T L

    1988-03-01

    Washington State birth certificates were examined for associations between adverse pregnancy outcomes and paternal employment in solvent exposed occupations. Four cohorts defined by live, singleton births to fathers usually employed as auto body shop workers, painters (construction and maintenance), printers, or fibreglass workers were compared retrospectively with both a systematically selected control cohort and a low solvent exposed, occupationally defined control cohort (paternal electricians). The effects of maternal race and medical illness were controlled by sample restriction; maternal age and gravidity by stratified analysis. There was evidence of increased risk of low birth weight for infants born to fathers employed as body shop workers (relative risk = 1.6; 95% confidence interval = 1.1-2.4) or painters (RR = 1.4; CI = 0.9-2.1) when compared with the systematically selected controls but not with the electrician controls. The excess risk appeared stronger when only term infants were analysed suggesting a mechanism of growth retardation rather than prematurity. There was no evidence of increased risk among the other exposed cohorts or for other adverse pregnancy outcomes. Several design features limit the interpretation of the findings and confirmation by other studies is needed. PMID:3348995

  20. Anatomical pathology is dead? Long live anatomical pathology.

    PubMed

    Nicholls, John M; Francis, Glenn D

    2011-10-01

    The standard diagnostic instrument used for over 150 years by anatomical pathologists has been the optical microscope and glass slide. The advent of immunohistochemistry in the routine laboratory in the 1980s, followed by in situ hybridisation in the 1990s, has increased the armamentaria available to the diagnostic pathologist, and this technology has led to changed patient management in a limited number of neoplastic diseases. The first decade of the 21 century has seen an increasing number of publications using proteomic technologies that promise to change disease diagnosis and management, the traditional role of an anatomical pathologist. Despite the plethora of publications on proteomics and pathology, to date there are actually limited data where proteomic technologies do appear to be of greater diagnostic value than the standard histological slide. Though proteomic techniques will become more prevalent in the future, it will need the expertise of an anatomical pathologist to dissect out and validate this added information. PMID:21876472

  1. 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

  2. Automatic adverse drug events detection using letters to the editor.

    PubMed

    Yang, Chao; Srinivasan, Padmini; Polgreen, Philip M

    2012-01-01

    We present and test the intuition that letters to the editor in journals carry early signals of adverse drug events (ADEs). Surprisingly these letters have not yet been exploited for automatic ADE detection unlike for example, clinical records and PubMed. Part of the challenge is that it is not easy to access the full-text of letters (for the most part these do not appear in PubMed). Also letters are likely underrated in comparison with full articles. Besides demonstrating that this intuition holds we contribute techniques for post market drug surveillance. Specifically, we test an automatic approach for ADE detection from letters using off-the-shelf machine learning tools. We also involve natural language processing for feature definitions. Overall we achieve high accuracy in our experiments and our method also works well on a second new test set. Our results encourage us to further pursue this line of research. PMID:23304379

  3. Automatic Adverse Drug Events Detection Using Letters to the Editor

    PubMed Central

    Yang, Chao; Srinivasan, Padmini; Polgreen, Philip M.

    2012-01-01

    We present and test the intuition that letters to the editor in journals carry early signals of adverse drug events (ADEs). Surprisingly these letters have not yet been exploited for automatic ADE detection unlike for example, clinical records and PubMed. Part of the challenge is that it is not easy to access the full-text of letters (for the most part these do not appear in PubMed). Also letters are likely underrated in comparison with full articles. Besides demonstrating that this intuition holds we contribute techniques for post market drug surveillance. Specifically, we test an automatic approach for ADE detection from letters using off-the-shelf machine learning tools. We also involve natural language processing for feature definitions. Overall we achieve high accuracy in our experiments and our method also works well on a second new test set. Our results encourage us to further pursue this line of research. PMID:23304379

  4. Anaphylactoid and adverse reactions to radiocontrast agents.

    PubMed

    Hagan, John B

    2004-08-01

    Over the past 75 years, radiocontrast agents have provided numerous diagnostic and therapeutic advances. The benefits of these agents must be weighed against the potential risks for each individual undergoing radiologic tests. This summary is intended to be a guide for the allergy and immunology specialist to direct him or her to the current literature regarding adverse reactions to traditional and less commonly used radiologic contrast agents. PMID:15242724

  5. 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…

  6. Adverse effects of human immunoglobulin therapy.

    PubMed

    Stiehm, E Richard

    2013-07-01

    Human immunoglobulin (IG) is used for IgG replacement therapy in primary and secondary immunodeficiency, for prevention and treatment of certain infections, and as an immunomodulatory agent for autoimmune and inflammatory disorders. IG has a wide spectrum of antibodies to microbial and human antigens. Several high-titered IGs are also available enriched in antibodies to specific viruses or bacterial toxins. IG can be given intravenously (IGIV), intramuscularly (IGIM) or by subcutaneous infusions (SCIG). Local adverse reactions such as persistent pain, bruising, swelling and erythema are rare with IGIV infusions but common (75%) with SCIG infusions. By contrast, adverse systemic reactions are rare with SCIG infusions but common with IGIV infusions, occurring as often as 20% to 50% of patients and 5% to 15% of all IGIV infusions. Systemic adverse reactions can be immediate (60% of reactions) occurring within 6 hours of an infusion, delayed (40% of reactions) occurring 6 hours-1 week after an infusion, and late (less than 1% of reactions), occurring weeks and months after an infusion. Immediate systemic reactions such as head and body aches, chills and fever are usually mild and readily treatable. Immediate anaphylactic and anaphylactoid reactions are uncommon. The most common delayed systemic reaction is persistent headache. Less common but more serious delayed reactions include aseptic meningitis, renal failure, thromboembolism, and hemolytic reactions. Late reactions are uncommon but often severe, and include lung disease, enteritis, dermatologic disorders and infectious diseases. The types, incidence, causes, prevention, and management of these reactions are discussed. PMID:23835249

  7. 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. PMID:26070758

  8. Contribution of new technologies to characterization and prediction of adverse effects.

    PubMed

    Rouquié, David; Heneweer, Marjoke; Botham, Jane; Ketelslegers, Hans; Markell, Lauren; Pfister, Thomas; Steiling, Winfried; Strauss, Volker; Hennes, Christa

    2015-02-01

    Identification of the potential hazards of chemicals has traditionally relied on studies in laboratory animals where changes in clinical pathology and histopathology compared to untreated controls defined an adverse effect. In the past decades, increased consistency in the definition of adversity with chemically-induced effects in laboratory animals, as well as in the assessment of human relevance has been reached. More recently, a paradigm shift in toxicity testing has been proposed, mainly driven by concerns over animal welfare but also thanks to the development of new methods. Currently, in vitro approaches, toxicogenomic technologies and computational tools, are available to provide mechanistic insight in toxicological Mode of Action (MOA) of the adverse effects observed in laboratory animals. The vision described as Tox21c (Toxicity Testing in the 21st century) aims at predicting in vivo toxicity using a bottom-up-approach, starting with understanding of MOA based on in vitro data to ultimately predict adverse effects in humans. At present, a practical application of the Tox21c vision is still far away. While moving towards toxicity prediction based on in vitro data, a stepwise reduction of in vivo testing is foreseen by combining in vitro with in vivo tests. Furthermore, newly developed methods will also be increasingly applied, in conjunction with established methods in order to gain trust in these new methods. This confidence is based on a critical scientific prerequisite: the establishment of a causal link between data obtained with new technologies and adverse effects manifested in repeated-dose in vivo toxicity studies. It is proposed to apply the principles described in the WHO/IPCS framework of MOA to obtain this link. Finally, an international database of known MOAs obtained in laboratory animals using data-rich chemicals will facilitate regulatory acceptance and could further help in the validation of the toxicity pathway and adverse outcome pathway

  9. Challenges in disclosure of adverse events and errors in surgery; perspectives from sub-Saharan Africa.

    PubMed

    Ibrahim, Abdulrasheed; Garba, Ekundayo Stephen; Asuku, Malachy Eneye

    2012-01-01

    Surgery in sub-Saharan Africa is widely known to be done against a background of poverty and illiteracy, late presentation with complicated pathologies, and a desperate lack of infrastructure. In addition, patient autonomy and self determination are highly flavored by cultural practices and religious beliefs. Any of these factors can influence the pattern and disclosure of adverse events and errors. The impact of these in the relationships between surgeons and patients, and between health institutions and patients must be considered as it may affect disclosure and response to errors. This article identifies the peculiar socioeconomic and cultural challenges that may hinder disclosure and proposes strategies for instituting disclosure of errors and adverse events services in Sub-Saharan Africa. PMID:23077703

  10. [Basic trends in general human pathology and principles of its teaching in higher medical education].

    PubMed

    Khitrov, N K; Sarkisov, D S; Romadanova, N B

    1994-01-01

    The paper considers the current trends in the development of biological and medical sciences: their subject, tasks, methods, and place of General Human Pathology among other subjects, its value for the clinical discipline. It defines and analyzes the most topical and disputable directions of General Human Pathology, primarily including those which form the bases for the pathology theory. Arguments are advanced for the necessity of introducing the subject General Pathology of Man into the curriculum of higher medical educational establishments at various faculties. Consideration is given to the specific features of this subject teaching at the faculty training researchers and research pedagogical personnel, at the Pharmaceutical and Higher Nurse Training Faculties of the I. M. Sechenov Moscow Medical Academy. A proposal is given to consider and to discuss the most important problems of General Pathology and its teaching, which are listed in the paper. PMID:7524869

  11. Bioactive lipids in pathological retinopathy.

    PubMed

    Ma, Qi; Shen, Jun-Hui; Shen, Sheng-Rong; Das, Undurti N

    2014-01-01

    Diabetic retinopathy is a common condition that occurs in patients with diabetes with long-standing hyperglycemia that is characterized by inappropriate angiogenesis. This pathological angiogenesis could be a sort of physiological proliferative response to injury by the endothelium. Recent studies suggested that reactive oxygen species (ROS) play a significant role in this angiogenesis. Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor that plays a significant role in diabetic retinopathy. The interaction between VEGF and ROS, and theirs in turn with pro- and anti-inflammatory cytokines and anti-inflammatory bioactive lipid molecules such as lipoxins, resolvins, protectins, and maresins is particularly relevant to understand the pathophysiology of diabetic retinopathy and develop future therapeutic interventions. PMID:24188230

  12. [Cellular pathology of neurodegenerative disorders].

    PubMed

    Wakabayashi, Koichi

    2013-01-01

    Common cellular and molecular mechanisms including protein aggregation and inclusion body formation are involved in many neurodegenerative diseases. α-Synuclein is a major component of Lewy bodies in Parkinson's disease (PD) as well as in glial cytoplasmic inclusions in multiple system atrophy (MSA). Tau is a principal component of neurofibrillary and glial tangles in tauopathies. Recently, TDP-43 was identified as a component of ubiquitinated inclusions in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. PD is traditionally considered a movement disorder with hallmark lesions in the brainstem pigmented nuclei. However, pathological changes occur in widespread regions of the central and peripheral nervous systems in this disease. Furthermore, primary glial involvement ("gliodegeneration") can be observed in PD and MSA as well as in tauopathy. The present article reviews abnormal protein accumulation and inclusion body formation inside and outside the central nervous system. PMID:23965852

  13. Cerebral pathology post heart transplantation.

    PubMed

    Peteghem, S Van; Pauw, M De

    2015-04-01

    Cerebral pathology is frequently encountered post heart transplantation with a cumulative incidence of about 80% after 15 years. A broad spectrum of disease entities is reported, from minor abnormalities to life-threatening diseases. Although cerebral infections and malignancies are rare in this patient population, they have a high mortality rate. Since 1991, 171 orthotopic heart transplantations were performed at the Ghent University Hospital with a 10-year survival rate of 75%. Severe cerebral complications occurred in 10 patients, with epilepsy in 2 patients, cerebrovascular accidents in 4 patients, cerebral infections in 3 patients and a cerebral malignancy in 1 patient, resulting in a fatal outcome in 7 patients. We present four of these cases. PMID:25292206

  14. Glomerular disease: looking beyond pathology.

    PubMed

    Wiggins, Roger C; Alpers, Charles E; Holzman, Lawrence B; He, John C; Salant, David J; Chugh, Sumant S; Natarajan, Rama; Trachtman, Howard; Brasile, Lauren; Star, Robert A; Rys-Sikora, Krystyna E; Moxey-Mims, Marva M; Flessner, Michael F

    2014-06-01

    The National Institute of Diabetes and Digestive and Kidney Diseases-supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives aimed at improved understanding of kidney function and disease progression. Over the past 2 years, 1600 participants posted almost 300 ideas covering all areas of kidney disease. An overriding theme that evolved through these discussions is the need to move beyond pathology to take advantage of basic science and clinical research opportunities to improve diagnostic classification and therapeutic options for people with primary glomerular disease. High-priority research areas included focus on therapeutic targets in glomerular endothelium and podocytes, regenerating podocytes through developmental pathways, use of longitudinal phenotypically defined disease cohorts to improve classification schemes, identifying biomarkers, disease-specific therapeutics, autoantibody triggers, and changing the clinical research culture to promote participation in clinical trials. Together, these objectives provide a path forward for improving clinical outcomes of glomerular disease. PMID:24700796

  15. Glomerular Disease: Looking beyond Pathology

    PubMed Central

    Wiggins, Roger C.; Alpers, Charles E.; Holzman, Lawrence B.; He, John C.; Salant, David J.; Chugh, Sumant S.; Natarajan, Rama; Trachtman, Howard; Brasile, Lauren; Star, Robert A.; Rys-Sikora, Krystyna E.; Moxey-Mims, Marva M.

    2014-01-01

    The National Institute of Diabetes and Digestive and Kidney Diseases–supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives aimed at improved understanding of kidney function and disease progression. Over the past 2 years, 1600 participants posted almost 300 ideas covering all areas of kidney disease. An overriding theme that evolved through these discussions is the need to move beyond pathology to take advantage of basic science and clinical research opportunities to improve diagnostic classification and therapeutic options for people with primary glomerular disease. High-priority research areas included focus on therapeutic targets in glomerular endothelium and podocytes, regenerating podocytes through developmental pathways, use of longitudinal phenotypically defined disease cohorts to improve classification schemes, identifying biomarkers, disease-specific therapeutics, autoantibody triggers, and changing the clinical research culture to promote participation in clinical trials. Together, these objectives provide a path forward for improving clinical outcomes of glomerular disease. PMID:24700796

  16. Peripheral nerve and neuromuscular junction pathology in Pompe disease

    PubMed Central

    Falk, Darin J.; Todd, Adrian Gary; Lee, Sooyeon; Soustek, Meghan S.; ElMallah, Mai K.; Fuller, David D.; Notterpek, Lucia; Byrne, Barry J.

    2015-01-01

    Pompe disease is a systemic metabolic disorder characterized by lack of acid-alpha glucosidase (GAA) resulting in ubiquitous lysosomal glycogen accumulation. Respiratory and ambulatory dysfunction are prominent features in patients with Pompe yet the mechanism defining the development of muscle weakness is currently unclear. Transgenic animal models of Pompe disease mirroring the patient phenotype have been invaluable in mechanistic and therapeutic study. Here, we demonstrate significant pathological alterations at neuromuscular junctions (NMJs) of the diaphragm and tibialis anterior muscle as prominent features of disease pathology in Gaa knockout mice. Postsynaptic defects including increased motor endplate area and fragmentation were readily observed in Gaa−/− but not wild-type mice. Presynaptic neuropathic changes were also evident, as demonstrated by significant reduction in the levels of neurofilament proteins, and alterations in axonal fiber diameter and myelin thickness within the sciatic and phrenic nerves. Our data suggest the loss of NMJ integrity is a primary contributor to the decline in respiratory and ambulatory function in Pompe and arises from both pre- and postsynaptic pathology. These observations highlight the importance of systemic phenotype correction, specifically restoration of GAA to skeletal muscle and the nervous system for treatment of Pompe disease. PMID:25217571

  17. Modeling Pathological Speech Perception From Data With Similarity Labels.

    PubMed

    Berisha, Visar; Liss, Julie; Sandoval, Steven; Utianski, Rene; Spanias, Andreas

    2014-05-01

    The current state of the art in judging pathological speech intelligibility is subjective assessment performed by trained speech pathologists (SLP). These tests, however, are inconsistent, costly and, oftentimes suffer from poor intra- and inter-judge reliability. As such, consistent, reliable, and perceptually-relevant objective evaluations of pathological speech are critical. Here, we propose a data-driven approach to this problem. We propose new cost functions for examining data from a series of experiments, whereby we ask certified SLPs to rate pathological speech along the perceptual dimensions that contribute to decreased intelligibility. We consider qualitative feedback from SLPs in the form of comparisons similar to statements "Is Speaker A's rhythm more similar to Speaker B or Speaker C?" Data of this form is common in behavioral research, but is different from the traditional data structures expected in supervised (data matrix + class labels) or unsupervised (data matrix) machine learning. The proposed method identifies relevant acoustic features that correlate with the ordinal data collected during the experiment. Using these features, we show that we are able to develop objective measures of the speech signal degradation that correlate well with SLP responses. PMID:25435817

  18. Modeling Pathological Speech Perception From Data With Similarity Labels

    PubMed Central

    Berisha, Visar; Liss, Julie; Sandoval, Steven; Utianski, Rene; Spanias, Andreas

    2014-01-01

    The current state of the art in judging pathological speech intelligibility is subjective assessment performed by trained speech pathologists (SLP). These tests, however, are inconsistent, costly and, oftentimes suffer from poor intra- and inter-judge reliability. As such, consistent, reliable, and perceptually-relevant objective evaluations of pathological speech are critical. Here, we propose a data-driven approach to this problem. We propose new cost functions for examining data from a series of experiments, whereby we ask certified SLPs to rate pathological speech along the perceptual dimensions that contribute to decreased intelligibility. We consider qualitative feedback from SLPs in the form of comparisons similar to statements “Is Speaker A's rhythm more similar to Speaker B or Speaker C?” Data of this form is common in behavioral research, but is different from the traditional data structures expected in supervised (data matrix + class labels) or unsupervised (data matrix) machine learning. The proposed method identifies relevant acoustic features that correlate with the ordinal data collected during the experiment. Using these features, we show that we are able to develop objective measures of the speech signal degradation that correlate well with SLP responses. PMID:25435817

  19. Image microarrays (IMA): Digital pathology's missing tool

    PubMed Central

    Hipp, Jason; Cheng, Jerome; Pantanowitz, Liron; Hewitt, Stephen; Yagi, Yukako; Monaco, James; Madabhushi, Anant; Rodriguez-canales, Jaime; Hanson, Jeffrey; Roy-Chowdhuri, Sinchita; Filie, Armando C.; Feldman, Michael D.; Tomaszewski, John E.; Shih, Natalie NC.; Brodsky, Victor; Giaccone, Giuseppe; Emmert-Buck, Michael R.; Balis, Ulysses J.

    2011-01-01

    Introduction: The increasing availability of whole slide imaging (WSI) data sets (digital slides) from glass slides offers new opportunities for the development of computer-aided diagnostic (CAD) algorithms. With the all-digital pathology workflow that these data sets will enable in the near future, literally millions of digital slides will be generated and stored. Consequently, the field in general and pathologists, specifically, will need tools to help extract actionable information from this new and vast collective repository. Methods: To address this limitation, we designed and implemented a tool (dCORE) to enable the systematic capture of image tiles with constrained size and resolution that contain desired histopathologic features. Results: In this communication, we describe a user-friendly tool that will enable pathologists to mine digital slides archives to create image microarrays (IMAs). IMAs are to digital slides as tissue microarrays (TMAs) are to cell blocks. Thus, a single digital slide could be transformed into an array of hundreds to thousands of high quality digital images, with each containing key diagnostic morphologies and appropriate controls. Current manual digital image cut-and-paste methods that allow for the creation of a grid of images (such as an IMA) of matching resolutions are tedious. Conclusion: The ability to create IMAs representing hundreds to thousands of vetted morphologic features has numerous applications in education, proficiency testing, consensus case review, and research. Lastly, in a manner analogous to the way conventional TMA technology has significantly accelerated in situ studies of tissue specimens use of IMAs has similar potential to significantly accelerate CAD algorithm development. PMID:22200030

  20. Lung vasculitis and alveolar hemorrhage: pathology.

    PubMed

    Fishbein, Gregory A; Fishbein, Michael C

    2011-06-01

    Pulmonary vasculitides are a diverse group of limited and systemic disorders associated with inflammation of pulmonary vessels and parenchyma. These diseases often have distinctive clinical, serological, and histopathological features-extrapulmonary sites of involvement, circulating autoantibodies, predispositions for small or large vessels, and others. Some have characteristic inflammatory lesions; others are characterized by the absence of such lesions. Frequently pathological findings overlap, rendering classification, and diagnosis a challenge. The anti-neutrophil cytoplasmic antibody (ANCA)-associated small-vessel diseases constitute the major pulmonary vasculitides. These include Wegener granulomatosis (WG), Churg Strauss syndrome (CSS), and microscopic polyangiitis (MPA). Less frequently, diseases such as polyarteritis nodosa, Takayasu arteritis, Behçet syndrome, and connective tissue diseases may involve pulmonary vessels, but these entities are better associated with extrapulmonary disease. Diffuse alveolar hemorrhage (DAH) is a severe manifestation of pulmonary vasculitis. DAH is most commonly seen in small-vessel vasculitides, specifically MPA and WG. Other syndromes associated with DAH include Goodpasture syndrome, Henoch-Schönlein purpura, and systemic lupus erythematosus. Less commonly, DAH may be secondary to infection or drugs/toxins. Furthermore, in the absence of discernable systemic disease, DAH may be idiopathic-referred to as isolated pulmonary capillaritis (IPC) or idiopathic pulmonary hemosiderosis (IPH), depending on the presence of capillaritis. PMID:21674412

  1. 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.

  2. 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

  3. 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

  4. A Suggested Molecular Pathology Curriculum for Residents: A Report of the Association for Molecular Pathology.

    PubMed

    Aisner, Dara L; Berry, Anna; Dawson, D Brian; Hayden, Randall T; Joseph, Loren; Hill, Charles E

    2016-03-01

    Molecular pathology is an essential element of pathology training. As more molecular tests have become available, there is an increasing need for pathology trainees to receive a strong foundation in molecular pathology. Appointed by the Training and Education Committee of the Association for Molecular Pathology, the Molecular Curriculum Task Force has developed a suggested curriculum in molecular pathology for residents. The foundations of molecular pathology are presented as a series of goals and objectives that residency programs can use to develop their educational programs. As pathologists continue to expand their roles to include regular clinical consultations in the realm of molecular testing, a strong foundation in molecular pathology and genomic medicine has become essential to the practice of pathology. PMID:26857063

  5. 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

  6. Microbial imbalance and intestinal pathologies: connections and contributions

    PubMed Central

    Yang, Ye; Jobin, Christian

    2014-01-01

    Microbiome analysis has identified a state of microbial imbalance (dysbiosis) in patients with chronic intestinal inflammation and colorectal cancer. The bacterial phylum Proteobacteria is often overrepresented in these individuals, with Escherichia coli being the most prevalent species. It is clear that a complex interplay between the host, bacteria and bacterial genes is implicated in the development of these intestinal diseases. Understanding the basic elements of these interactions could have important implications for disease detection and management. Recent studies have revealed that E. coli utilizes a complex arsenal of virulence factors to colonize and persist in the intestine. Some of these virulence factors, such as the genotoxin colibactin, were found to promote colorectal cancer in experimental models. In this Review, we summarize key features of the dysbiotic states associated with chronic intestinal inflammation and colorectal cancer, and discuss how the dysregulated interplay between host and bacteria could favor the emergence of E. coli with pathological traits implicated in these pathologies. PMID:25256712

  7. Optical and digital microscopic imaging techniques and applications in pathology.

    PubMed

    Chen, Xiaodong; Zheng, Bin; Liu, Hong

    2011-01-01

    The conventional optical microscope has been the primary tool in assisting pathological examinations. The modern digital pathology combines the power of microscopy, electronic detection, and computerized analysis. It enables cellular-, molecular-, and genetic-imaging at high efficiency and accuracy to facilitate clinical screening and diagnosis. This paper first reviews the fundamental concepts of microscopic imaging and introduces the technical features and associated clinical applications of optical microscopes, electron microscopes, scanning tunnel microscopes, and fluorescence microscopes. The interface of microscopy with digital image acquisition methods is discussed. The recent developments and future perspectives of contemporary microscopic imaging techniques such as three-dimensional and in vivo imaging are analyzed for their clinical potentials. PMID:21483100

  8. Trichodinosis associated with pathology of the reproductive tract in waterfowl.

    PubMed

    Carnaccini, S; Lowenstine, L J; Sentíes-Cué, C G; Nyaoke, A; Bland, M; Bickford, A A; Shivaprasad, H L; Stoute, S T

    2016-08-01

    Trichodinid ciliophorans are opportunistic parasites of many species of fish, amphibians, and molluscs, but yet never reported in association with lesions in birds. Postmortem and histopathological evaluation of a commercial adult Toulouse gander and female goose, and a wild Mallard drake revealed the presence of severe pathological parasitic colonization of their reproductive tracts. Histopathological findings included moderate to severe granulocytic inflammation, acanthosis, accentuation of the rete pegs, and proliferative hyperplastic squamous metaplasia of the mucosa of the ejaculatory ducts and groove, sulcus spermaticus, glandular part of the phallus (cavum penis), and oviduct in association with large numbers of ciliated protozoa anchored to the tissues or free in the lumen. These protozoa had characteristic morphological features analogous to the family of Trichodinidae. The source of this parasitism could not be determined. To our knowledge, this is the first report of trichodinosis associated with pathology in birds. PMID:26926786

  9. Pharmacogenetics of idiosyncratic adverse drug reactions.

    PubMed

    Pirmohamed, Munir

    2010-01-01

    Idiosyncratic adverse drug reactions are unpredictable and thought to have an underlying genetic etiology. With the completion of the human genome and HapMap projects, together with the rapid advances in genotyping technologies, we have unprecedented capabilities in identifying genetic predisposing factors for these relatively rare, but serious, reactions. The main roadblock to this is the lack of sufficient numbers of well-characterized samples from patients with such reactions. This is now beginning to be solved through the formation of international consortia, including developing novel ways of identifying and recruiting patients affected by these reactions, both prospectively and retrospectively. This has been led by the research on abacavir hypersensitivity - its association with HLA-B*5701 forms the gold standard of how we need to identify associations and implement them in clinical practice. Strong genetic predisposing factors have also been identified for hypersensitivity reactions such as are associated with carbamazepine, allopurinol, flucloxacillin, and statin-induced myopathy. However, for most other idiosyncratic adverse drug reactions, the genetic effect sizes have been low to moderate, although this may partly be due to the fact that only small numbers have been investigated and limited genotyping strategies have been utilized. It may also indicate that genetic predisposition will be dependent on multiple genes, with complex interactions with environmental factors. Irrespective of the strength of the genetic associations identified with individual idiosyncratic adverse drug reactions, it is important to undertake functional investigations to provide insights into the mechanism(s) of how the drug interacts with the gene variant to lead to a phenotype, which can take a multitude of clinical forms with variable severity. Such investigations will be essential in preventing the burden caused by idiosyncratic reactions, both in healthcare and in industry

  10. Determinants of Adverse Events in Vascular Surgery

    PubMed Central

    Hernandez-Boussard, Tina; McDonald, Kathryn; Morton, John; Dalman, Ron L; Bech, Fritz R

    2016-01-01

    Background Patient safety is a national priority. Patient Safety Indicators (PSIs) monitor potential adverse events during hospital stays. Surgical specialty PSI benchmarks do not exist, which are needed to account for differences in the range of procedures performed, reasons for the procedure, and differences in patient characteristics. A comprehensive profile of adverse events in vascular surgery was created. Study Design The Nationwide Inpatient Sample was queried for 8 vascular procedures using ICD-9-CM codes from 2005–2009. Factors associated with PSI development were evaluated in univariate and multivariate analyses. Results A total of 1,412,703 patients underwent a vascular procedure and 5.2% developed a PSI. PSIs were more frequent in female, non-white patients with public payers (p<.01). Patients at mid and low volume hospitals had greater odds of developing a PSI (Odds Ratio [OR], 1.17; 95% Confidence Interval [CI], 1.10–1.23 and OR, 1.69; CI, 1.53–1.87). Amputations had highest PSI risk-adjusted rate (RAR) and carotid endarterectomy and endovascular abdominal aortic aneurysm (AAA) repair had lower RAR (p<.0001). PSI RAR increased linearly by severity of patient indication: claudicants (OR, 0.40, CI, 0.35–0.46), rest pain patients (OR, 0.78, CI 0.69–0.90), ulcer (OR: 1.20, CI: 1.07–1.34) and gangrene patients (OR:1.85, CI: 1.66–2.06). Conclusions Patient safety events in vascular surgery were high and varied by procedure, with amputations and open AAA having substantially more potential adverse events. PSIs were associated with black race, public payer, and procedure indication. It is important to note the overall higher rates of PSIs occurring in vascular patients and appropriately adjust benchmarks for this surgical specialty. PMID:22425449

  11. Adverse blood transfusion outcomes: establishing causation.

    PubMed

    Isbister, James P; Shander, Aryeh; Spahn, Donat R; Erhard, Jochen; Farmer, Shannon L; Hofmann, Axel

    2011-04-01

    The transfusion of allogeneic red blood cells (RBCs) and other blood components is ingrained in modern medical practice. The rationale for administering transfusions is based on key assumptions that efficacy is established and risks are acceptable and minimized. Despite the cliché that, "the blood supply is safer than ever," data about risks and lack of efficacy of RBC transfusions in several clinical settings have steadily accumulated. Frequentist statisticians and clinicians demand evidence from randomized clinical trials (RCTs); however, causation for the recognized serious hazards of allogeneic transfusion has never been established in this manner. On the other hand, the preponderance of evidence implicating RBC transfusions in adverse clinical outcomes related to immunomodulation and the storage lesion comes from observational studies, and a broad and critical analysis to evaluate causation is overdue. It is suggested in several circumstances that this cannot wait for the design, execution, and conduct of rigorous RCTs. We begin by examining the nature and definition of causation with relevant examples from transfusion medicine. Deductive deterministic methods may be applied to most of the well-accepted and understood serious hazards of transfusion, with modified Koch's postulates being fulfilled in most circumstances. On the other hand, when several possible interacting risk factors exist and RBC transfusions are associated with adverse clinical outcomes, establishing causation requires inferential probabilistic methodology. In the latter circumstances, the case for RBC transfusions being causal for adverse clinical outcomes can be strengthened by applying modified Bradford Hill criteria to the plethora of existing observational studies. This being the case, a greater precautionary approach to RBC transfusion is necessary and equipoise that justifying RCTs may become problematic. PMID:21345639

  12. Standardizing adverse drug event reporting data

    PubMed Central

    2014-01-01

    Background The Adverse Event Reporting System (AERS) is an FDA database providing rich information on voluntary reports of adverse drug events (ADEs). Normalizing data in the AERS would improve the mining capacity of the AERS for drug safety signal detection and promote semantic interoperability between the AERS and other data sources. In this study, we normalize the AERS and build a publicly available normalized ADE data source. The drug information in the AERS is normalized to RxNorm, a standard terminology source for medication, using a natural language processing medication extraction tool, MedEx. Drug class information is then obtained from the National Drug File-Reference Terminology (NDF-RT) using a greedy algorithm. Adverse events are aggregated through mapping with the Preferred Term (PT) and System Organ Class (SOC) codes of Medical Dictionary for Regulatory Activities (MedDRA). The performance of MedEx-based annotation was evaluated and case studies were performed to demonstrate the usefulness of our approaches. Results Our study yields an aggregated knowledge-enhanced AERS data mining set (AERS-DM). In total, the AERS-DM contains 37,029,228 Drug-ADE records. Seventy-one percent (10,221/14,490) of normalized drug concepts in the AERS were classified to 9 classes in NDF-RT. The number of unique pairs is 4,639,613 between RxNorm concepts and MedDRA Preferred Term (PT) codes and 205,725 between RxNorm concepts and SOC codes after ADE aggregation. Conclusions We have built an open-source Drug-ADE knowledge resource with data being normalized and aggregated using standard biomedical ontologies. The data resource has the potential to assist the mining of ADE from AERS for the data mining research community. PMID:25157320

  13. [Haematological adverse effects caused by psychiatric drugs].

    PubMed

    Mazaira, Silvina

    2008-01-01

    Almost all clases of psychiatric drugs (typical and atypical antipsychotics, antidepressants, mood stabilizers, benzodiazepines) have been reported as possible causes of haematological toxicity. This is a review of the literature in which different clinical situations involving red blood cells, white blood cells, platelets and impaired coagulation are detailed and the drugs more frequently involved are listed. The haematological adverse reactions detailed here include: aplastic anemia, haemolitic anemia, leukopenia, agranulocytosis, leukocytosis, eosinophilia, thrombocytosis, thrombocytopenia, disordered platelet function and impaired coagulation. The haematologic toxicity profile of the drugs more frequently involved: lithium, clozapine, carbamazepine, valproic acid and SSRI antidepressants is mentioned. PMID:19424521

  14. [Adverse drug effects in the community pharmacy].

    PubMed

    Arnet, Isabelle; Seidling, Hanna M; Hersberger, Kurt E

    2015-12-01

    Community pharmacists represent an important pillar for the identification and the reporting of adverse drug effects (ADE}. Thanks to their broad view on the pharmacotherapy, over-the-counter medication included, they contribute greatly to the improvement of drug safety. In principle, the community pharmacy will face three groups of ADE which require specific attention. This article deals with these specific ADE groups and presents some illustrative examples from daily practice. Furthermore, we suggest some solutions to identify potential relevant interactions - including herbal-drug interactions - and give tips for daily practice, along with some often overseen cutaneous ADE. PMID:26654812

  15. [Injectable fillers: adverse reactions and their management].

    PubMed

    Rzany, B; Bachmann, F; Nast, A

    2013-02-01

    Injectable fillers are one of the corner stones of aesthetic medicine. In general they are safe to use. However, adverse reactions may occur. These reactions may be acute, subacute or delayed, e.g. after decades. It is important to know these reactions and to be prepared so that they can be adequately treated, in view of the clinical symptoms, the injected material and if applicable other diseases/treatments that might trigger these reactions. Last but not least, all reactions should be reported either to specialized registries or regulatory agencies. Only then we are able to learn more about these reactions and their best possible treatment. PMID:23407758

  16. 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

  17. Adverse environments and children's creativity development: transforming the notion of "success in adversity" in China.

    PubMed

    Cheng, Li; Tan, Mei; Liu, Zhengkui

    2015-01-01

    China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications for China's future as it brings together one of China's core cultural values-"success in adversity"-the importance of creativity, and very real social and economic needs. "Success in adversity" reflects the strongly held belief that individuals who suffer adverse environments can rise to excellence and success through persistence, effort, and creativity. In this article, we briefly explore the historical sources of this belief and how it is closely related to the Chinese conception of creativity. We then present some studies on the creativity of some of China's migrant children. Findings show that while migrant children as a group may not generally exhibit higher creativity than their urban peers as hypothesized, indications of resilience and creative potential suggest that the notion of success in adversity may contribute to the positive development of China's migrant children more substantially when it is informed by research and augmented by research-supported policy. PMID:25732020

  18. 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

  19. 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

  20. 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

  1. Basic techniques in endoscopic ultrasound-guided fine needle aspiration for solid lesions: Adverse events and avoiding them

    PubMed Central

    Fujii, Larissa L.; Levy, Michael J.

    2014-01-01

    Endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) is often the preferred technique for tissue acquisition in the diagnosis of suspected intrathoracic and intraabdominal pathology. Although EUS FNA is a safe and accurate procedure, it has been associated with a low risk of adverse events. The unique properties of the echoendoscope and its ability to acquire tissue outside of the gastrointestinal lumen impart risks that are not associated with routine endoscopic procedures. In this review, we discuss the risk of perforation related to the echoendoscope itself and adverse events related to FNA of solid masses including infections, bleeding, pancreatitis and pancreatic duct leak, bile duct leak and tumor seeding. We also provide tips on how to avoid the most common adverse events related to EUS-FNA. PMID:24949409

  2. Adverse Effects of Common Drugs: Adults.

    PubMed

    Lewis, Peter R; Karpa, Kelly Dowhower; Felix, Todd Matthew

    2015-09-01

    Although drugs can be an essential and lifesaving component of the care of adult patients, their use frequently is accompanied by adverse effects and life-threatening adverse drug reactions that can result in significant disability and mortality. The potential for drug-related severe morbidity and mortality is compounded during periods of hospitalization, when high-risk drugs such as anticoagulants or insulin are used, and when care in an intensive care unit is required. Patient factors in adults that can increase the risk of drug harms include immunosuppression, cognitive impairment, depression, alcoholism and other substance abuse disorders, chronic kidney disease, hepatic dysfunction, coagulopathies, limited English proficiency, institutional/nursing home care, and underinsurance or lack of insurance. Physician factors that can increase the risk of drug harms include inappropriate prescribing of drugs (including to pregnant and breastfeeding women), failure to appropriately discontinue/deprescribe drugs, insufficient drug reconciliation, failure to coordinate care among multiple prescribing clinicians, and failure to elicit and incorporate into health histories and clinical decision-making the widespread use of nonprescription drugs, herbal products, and dietary supplements. PMID:26375995

  3. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype. PMID:26919895

  4. Fingolimod-Associated Peripheral Vascular Adverse Effects.

    PubMed

    Russo, Margherita; Guarneri, Claudio; Mazzon, Emanuela; Sessa, Edoardo; Bramanti, Placido; Calabrò, Rocco Salvatore

    2015-10-01

    Fingolimod is the first oral disease-modifying drug approved for the treatment of multiple sclerosis. The drug is usually well tolerated, and common adverse effects include bradycardia, headache, influenza, diarrhea, back pain, increased liver enzyme levels, and cough. Fingolimod is thought to provide therapeutic benefit by preventing normal lymphocyte egress from lymphoid tissues, thus reducing the infiltration of autoaggressive lymphocytes into the central nervous system. However, because the drug acts on different sphingosine-1-phosphate receptors, it may induce several biological effects by influencing endothelial cell-cell adhesion, angiogenesis, vascular development, and cardiovascular function. We describe a patient with multiple sclerosis who, after 3 weeks of fingolimod administration, developed purplish blotches over the dorsal surface of the distal phalanges of the second and fifth digits and the middle phalanx of the fourth ray, itching, and edema on his left hand, without other evident clinical manifestations. When fingolimod therapy was discontinued, the clinical picture regressed within a few days but reappeared after a rechallenge test. Physicians should be aware of unexpected peripheral vascular adverse effects due to fingolimod use, and patients with vascular-based acropathies should be carefully screened and monitored when taking this drug. PMID:26349949

  5. Adverse Effects of Common Drugs: General Concepts.

    PubMed

    Karpa, Kelly Dowhower; Lewis, Peter R; Felix, Todd Matthew

    2015-09-01

    Adverse drug reactions (ADRs) contribute to substantial morbidity and mortality and add to rising health care costs. Many ADRs are preventable with appropriate prescribing and monitoring because they often occur as an extension of a drug's mechanism of action or known drug interactions. Patients at higher risk of ADRs include those at the extremes of age, those with multiple comorbidities, those taking multiple drugs, and patients admitted to intensive care units or experiencing transitions of care. Because the risk of ADRs becomes greater as the number of drugs and dietary supplements taken increases, it is imperative that prescribers be vigilant about the prescribing cascade and take steps to discontinue drugs that are likely to be more harmful than helpful. Pharmacists serve as important partners in clinical care environments by conducting comprehensive drug reviews, aiding in drug/dosage selection, and developing therapeutic monitoring plans. Although the potential exists for clinicians to use electronic health record systems to aid in clinical decision making through drug safety decision support tools, computer systems should never replace clinical judgment. Clinicians also are encouraged to report ADRs to the Food and Drug Administration Adverse Event Reporting System. PMID:26375993

  6. Translating Developmental Science to Address Childhood Adversity.

    PubMed

    Garner, Andrew S; Forkey, Heather; Szilagyi, Moira

    2015-01-01

    Demystifying child development is a defining element of pediatric care, and pediatricians have long appreciated the profound influences that families and communities have on both child development and life course trajectories. Dramatic advances in the basic sciences of development are beginning to reveal the biologic mechanisms underlying well-established associations between a spectrum of childhood adversities and less than optimal outcomes in health, education and economic productivity. Pediatricians are well positioned to translate this new knowledge into both practice and policy, but doing so will require unprecedented levels of collaboration with educators, social service providers, and policy makers. Pediatricians might recognize the negative impact of family-level adversities on child development, but developing an effective response will likely require the engagement of community partners. By developing collaborative, innovative ways to promote the safe, stable, and nurturing relationships that are biologic prerequisites for health, academic success, and economic productivity, family-centered pediatric medical homes will remain relevant in an era that increasingly values wellness and population health. PMID:26183002

  7. [The undesirable, psychologically adverse effects of screening].

    PubMed

    Döbrössy, Bence; Kovács, Attila; Budai, András; Cornides, Agnes; Döbrössy, Lajos

    2007-09-01

    The psychological adverse effects might play an important role in the non-compliance with the offered screening examination. The possible sources of them are three-fold: 1. The general human attitude, such as the rejection of health interventions, particularly those aiming at the prevention of eventual future health problems instead of handling existing complaints and symptoms at present; the screening can be seen as a "future-oriented" intervention. 2. The cultural image of cancer and the disbelief of its curability. 3. The subjective experiences in relation to the screening process. The providers have to do their best to eliminate these causes: by means of a) health education addressing people of various ages, social classes and cultural levels, promoting the understanding of the importance of disease prevention, and, changing their negative, defeatist attitude towards cancer; b) minimizing the psychological adverse effects of all kinds. This can be done by proper organisation of the screening process; optimizing the quality of work, and, provision of good quality of information and advice to the screenees before, during and after the screening. PMID:17766222

  8. 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

  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. Managing the adverse effects of radiation therapy.

    PubMed

    Berkey, Franklin J

    2010-08-15

    Nearly two thirds of patients with cancer will undergo radiation therapy as part of their treatment plan. Given the increased use of radiation therapy and the growing number of cancer survivors, family physicians will increasingly care for patients experiencing adverse effects of radiation. Selective serotonin reuptake inhibitors have been shown to significantly improve symptoms of depression in patients undergoing chemotherapy, although they have little effect on cancer-related fatigue. Radiation dermatitis is treated with topical steroids and emollient creams. Skin washing with a mild, unscented soap is acceptable. Cardiovascular disease is a well-established adverse effect in patients receiving radiation therapy, although there are no consensus recommendations for cardiovascular screening in this population. Radiation pneumonitis is treated with oral prednisone and pentoxifylline. Radiation esophagitis is treated with dietary modification, proton pump inhibitors, promotility agents, and viscous lidocaine. Radiation-induced emesis is ameliorated with 5-hydroxytryptamine3 receptor antagonists and steroids. Symptomatic treatments for chronic radiation cystitis include anticholinergic agents and phenazopyridine. Sexual dysfunction from radiation therapy includes erectile dysfunction and vaginal stenosis, which are treated with phosphodiesterase type 5 inhibitors and vaginal dilators, respectively. PMID:20704169

  11. 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

  12. Quinoxalines Potential to Target Pathologies.

    PubMed

    Tristán-Manzano, María; Guirado, Antonio; Martínez-Esparza, María; Gálvez, Jesús; García-Peñarrubia, Pilar; Ruiz-Alcaraz, Antonio J

    2015-01-01

    The study of quinoxalines has increased immeasurably during the last two decades, due firstly to their relatively simple chemical synthesis, which has generated a vast variety of compounds with diverse structural modifications, and secondly, to the wide therapeutic potential and biological activities exhibited by this family of compounds. Quinoxalines constitute a rising biomedical class of low-molecular weight heterocyclic compounds with potential functions as antitumour, anti-inflammatory, antibacterial, antiviral, antifungal, antiparasitic and antidiabetic agents, as well as being of interest for the potential treatment of glaucoma, insomnia, cardiovascular and neurological diseases, among others. However, a deeper knowledge of the molecular targets of quinoxalines that fulfil a key role in certain pathologies is required for the development of new and more specific drugs through a rational design strategy to avoid undesirable side effects. In the present review, we summarize the most important molecular targets of the quinoxaline derivatives discovered to date, thus providing a first reference index for researchers to identify the potential targets of their quinoxalines derived collections, which could facilitate the development of new quinoxaline- based therapies. PMID:26264925

  13. 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

  14. 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

  15. 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

  16. 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

  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. 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

  19. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  20. 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,...

  1. 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...

  2. 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...

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

    PubMed

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

    2015-02-01

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

  4. 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

  5. Dermatologic adverse effects of antiretroviral therapy: recognition and management.

    PubMed

    Luther, Jay; Glesby, Marshall J

    2007-01-01

    Despite the decrease in opportunistic infections associated with HIV in the highly active antiretroviral treatment (HAART) era, a significant number of patients still present with skin pathology, some of which can be attributed directly or indirectly to antiretroviral therapy. The non-nucleoside reverse transcriptase inhibitors exhibit a class effect with regard to skin adverse manifestations, and the spectrum of disease can vary from a mild morbilliform rash to Stevens-Johnson syndrome. Certain protease inhibitors are associated with rash, and indinavir causes retinoid-like manifestations such as paronychia, alopecia, ingrown toe-nails, and curling of straight hair. Abacavir, a nucleoside reverse transcriptase inhibitor, is notorious for causing a hypersensitivity reaction in select patients. The fusion inhibitor enfuvirtide causes injection-site reactions in the overwhelming majority of patients, although a new method of delivery has decreased the rate and severity of these reactions. A syndrome of lipoatrophy with or without lipohypertrophy, often termed lipodystrophy, has been described in patients receiving HAART. Potential management of lipoatrophy includes switching antiretrovirals and surgical treatment with facial fillers. Lastly, skin manifestations of the immune reconstitution inflammatory syndrome, including herpes zoster and warts, must be recognized and treated accordingly. In the evaluation of the individual HIV-infected patient receiving antiretroviral therapy who presents with a skin disorder, clinicians should consider the CD4 cell count as a marker of the degree of immunodeficiency, the specific antiretrovirals used, and the timing of the initiation of antiretroviral therapy in order to formulate a rational differential diagnosis. Management should be individualized based on the specific drug that is implicated and the severity of the reaction. PMID:17645377

  6. Preoperative easily misdiagnosed telangiectatic osteosarcoma: clinical–radiologic–pathologic correlations

    PubMed Central

    Gao, Zhen-Hua; Yin, Jun-Qiang; Liu, Da-Wei; Meng, Quan-Fei

    2013-01-01

    Abstract Purpose: To describe the clinical, imaging, and pathologic characteristics and diagnostic methods of telangiectatic osteosarcoma (TOS) for improving the diagnostic level. Materials and methods: The authors retrospectively reviewed patient demographics, serum alkaline phosphatase (AKP) levels, preoperative biopsy pathologic reports, pathologic materials, imaging findings, and treatment outcomes from 26 patients with TOS. Patient images from radiography (26 cases) and magnetic resonance (MR) imaging (22 cases) were evaluated by 3 authors in consensus for intrinsic characteristics. There were 15 male and 11 female patients in the study, with an age of 9–32 years (mean age 15.9 years). Results: Eighteen of 26 patients died of lung metastases within 5 years of follow-up. The distal femur was affected more commonly (14 cases, 53.8%). Regarding serum AKP, normal (8 cases) or mildly elevated (18 cases) levels were found before preoperative chemotherapy. Radiographs showed geographic bone lysis without sclerotic margin (26 cases), cortical destruction (26 cases), periosteal new bone formation (24 cases), soft-tissue mass (23 cases), and matrix mineralization (4 cases). The aggressive radiographic features of TOS simulated the appearance of conventional high-grade intramedullary osteosarcoma, though different from aneurysmal bone cyst. MR images demonstrated multiple big (16 cases) or small (6 cases) cystic spaces, fluid-fluid levels (14 cases), soft-tissue mass (22 cases), and thick peripheral and septal enhancement (22 cases). Nine of 26 cases were misdiagnosed as aneurysmal bone cysts by preoperative core-needle biopsy, owing to the absence of viable high-grade sarcomatous cells in the small tissue samples. Conclusion: The aggressive growth pattern with occasional matrix mineralization, and multiple big or small fluid-filled cavities with thick peripheral, septal, and nodular tissue surrounding the fluid-filled cavities are characteristic imaging features of

  7. 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.

  8. [Biliary pathology. Key aspects of the problem].

    PubMed

    Il'chenko, A A

    2011-01-01

    Based on the clinical experience gained in the Department of Pathology biliary tract, Central Research Institute of Gastroenterology, were reviewed key aspects of biliary pathology on the issues of classification, diagnosis, treatment, and tactics for management of patients with various diseases of the biliary tract. PMID:21560643

  9. 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…

  10. Abdominal wall herniae and their underlying pathology

    PubMed Central

    Upchurch, Emma; Al-Akash, Musallam

    2016-01-01

    We describe a case of pseudomyxoma peritonei presenting as a strangulated inguinal hernia. We review the current literature regarding the incidence of underlying pathology in patients presenting with abdominal wall herniae and discuss the need for histological assessment of the hernia sac in selected patients. We highlight the importance of assessing for and being aware of significant underlying pathology in certain patients. PMID:26855074

  11. Computer Assisted Learning Systems in Pathology Teaching.

    ERIC Educational Resources Information Center

    Harkin, P. J. R.; And Others

    1986-01-01

    Describes the use of computer assisted instructional systems in the teaching of pathology. Explains the components of a typical computer-based system and compares interactive systems which use visual displays ranging from microfiche projectors to video discs. Discusses computer programs prepared for courses in general pathology and systemic…

  12. 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…

  13. [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. PMID:26027397

  14. 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…

  15. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 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....

  3. 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....

  4. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  5. 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…

  6. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  7. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Postmarketing reporting of adverse experiences. 600.80 Section 600.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Reporting of Adverse Experiences § 600.80 Postmarketing reporting of adverse experiences....

  8. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Postmarketing reporting of adverse experiences. 600.80 Section 600.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Reporting of Adverse Experiences § 600.80 Postmarketing reporting of adverse experiences....

  9. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Postmarketing reporting of adverse experiences. 600.80 Section 600.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Reporting of Adverse Experiences § 600.80 Postmarketing reporting of adverse experiences....

  10. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Postmarketing reporting of adverse experiences. 600.80 Section 600.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Reporting of Adverse Experiences § 600.80 Postmarketing reporting of adverse experiences....

  11. 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

  12. Glial Tau Pathology in Tauopathies: Functional Consequences

    PubMed Central

    Kahlson, Martha A.; Colodner, Kenneth J.

    2015-01-01

    Tauopathies are a class of neurodegenerative diseases characterized by the presence of hyperphosphorylated and aggregated tau pathology in neuronal and glial cells. Though the ratio of neuronal and glial tau aggregates varies across diseases, glial tau aggregates can populate the same degenerating brain regions as neuronal tau aggregates. While much is known about the deleterious consequences of tau pathology in neurons, the relative contribution of glial tau pathology to these diseases is less clear. Recent studies using a number of model systems implicate glial tau pathology in contributing to tauopathy pathogenesis. This review aims to highlight the functional consequences of tau overexpression in glial cells and explore the potential contribution of glial tau pathology in the pathogenesis of neurodegenerative tauopathies. PMID:26884683

  13. Integrating anatomical pathology to the healthcare enterprise.

    PubMed

    Daniel-Le Bozec, Christel; Henin, Dominique; Fabiani, Bettina; Bourquard, Karima; Ouagne, David; Degoulet, Patrice; Jaulent, Marie-Christine

    2006-01-01

    For medical decisions, healthcare professionals need that all required information is both correct and easily available. We address the issue of integrating anatomical pathology department to the healthcare enterprise. The pathology workflow from order to report, including specimen process and image acquisition was modeled. Corresponding integration profiles were addressed by expansion of the IHE (Integrating the Healthcare Enterprise) initiative. Implementation using respectively DICOM Structured Report (SR) and DICOM Slide-Coordinate Microscopy (SM) was tested. The two main integration profiles--pathology general workflow and pathology image workflow--rely on 13 transactions based on HL7 or DICOM standard. We propose a model of the case in anatomical pathology and of other information entities (orders, image folders and reports) and real-world objects (specimen, tissue samples, slides, etc). Cases representation in XML schemas, based on DICOM specification, allows producing DICOM image files and reports to be stored into a PACS (Picture Archiving and Communication System. PMID:17108550

  14. 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.

  15. 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.

  16. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database.

    PubMed

    Soukavong, Mick; Kim, Jungmee; Park, Kyounghoon; Yang, Bo Ram; Lee, Joongyub; Jin, Xue Mei; Park, Byung Joo

    2016-09-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

  17. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database

    PubMed Central

    2016-01-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

  18. Early Childhood Adversity and Pregnancy Outcomes

    PubMed Central

    Smith, Megan V.; Gotman, Nathan; Yonkers, Kimberly A.

    2016-01-01

    Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

  19. Early Childhood Adversity and Pregnancy Outcomes.

    PubMed

    Smith, Megan V; Gotman, Nathan; Yonkers, Kimberly A

    2016-04-01

    Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers' delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

  20. 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

  1. 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. PMID:26084665

  2. Adverse drug reactions: classification, susceptibility and reporting.

    PubMed

    Kaufman, Gerri

    2016-08-10

    Adverse drug reactions (ADRs) are increasingly common and are a significant cause of morbidity and mortality. Historically, ADRs have been classified as type A or type B. Type A reactions are predictable from the known pharmacology of a drug and are associated with high morbidity and low mortality. Type B reactions are idiosyncratic, bizarre or novel responses that cannot be predicted from the known pharmacology of a drug and are associated with low morbidity and high mortality. Not all ADRs fit into type A and type B categories; therefore, additional categories have been developed. These include type C (continuing), type D (delayed use), and type E (end of use) reactions. Susceptibility to ADRs is influenced by age, gender, disease states, pregnancy, ethnicity and polypharmacy. Drug safety is reliant on nurses and other healthcare professionals being alert to the possibility of ADRs, working with patients to optimise medicine use and exercising vigilance in the reporting of ADRs through the Yellow Card Scheme. PMID:27507394

  3. Managing Adverse Events With Immune Checkpoint Agents.

    PubMed

    Dadu, Ramona; Zobniw, Chrystia; Diab, Adi

    2016-01-01

    Immune checkpoint inhibitors (anti-cytotoxic T-lymphocyte antigen 4 and anti programmed cell death 1/programmed cell death 1 ligand antibodies) have shown impressive clinical activity in multiple cancer types. Despite achieving great clinical success, challenges and limitations of these drugs as monotherapy or various combinational strategies include the development of a unique set of immune-related adverse events (irAEs) that can be severe and even fatal. Therefore, identification of patients at risk, prevention, consistent communication between patients and medical team, rapid recognition, and treatment of irAEs are critical in optimizing treatment outcomes. This review focuses on the description of more common irAEs and provides a suggested approach for management of specific irAEs. PMID:27111908

  4. The NAS Perchlorate Review: Adverse Effects?

    SciTech Connect

    Johnston, Richard B.; Corley, Richard; Cowan, Linda; Utiger, Robert D.

    2005-11-01

    To the editor: Drs. Ginsberg and Rice argue that the reference dose for perchlorate of 0.0007 mg/kg per day recommended by the National Academies’ Committee to Assess the Health Implications of Perchlorate Ingestion is not adequately protective. As members of the committee, we disagree. Ginsberg and Rice base their conclusion on three points. The first involves the designation of the point of departure as a NOEL (no-observed-effect level) versus a LOAEL (lowest-observed-adverse- effect level). The committee chose as its point of departure a dose of perchlorate (0.007 mg/kg per day) that when given for 14 days to 7 normal subjects did not cause a significant decrease in the group mean thyroid iodide uptake (Greer et al. 2002). Accordingly, the committee considered it a NOEL. Ginsberg and Rice focus on the fact that only 7 subjects were given that dose, and they 1seem to say that attention should be paid only to the results in those subjects in whom there was a 1fall in thyroid iodide uptake, and that the results in those in whom there was no fall or an increase should be ignored. They consider the dose to be a LOAEL because of the fall in uptake in those few subjects. It is important to note that a statistically significant decrease of, for example, 5% or even 10%, would not be biologically important and, more important, would not be sustained. For example, in another study (Braverman et al. 2004), administration of 0.04 mg/kg per day to normal subjects for 6 months had no effect on thyroid iodide uptake when measured at 3 and 6 months, and no effect on serum thyroid hormone or thyrotropin concentrations measured monthly (inspection of Figure 5A in the paper by Greer et al. suggests that this dose would inhibit thyroid iodide uptake by about 25% if measured at 2 weeks). The second issue involves database uncertainty. In clinical studies, perchlorate has been administered prospectively to 68 normal subjects for 2 weeks to 6 months. In one study (Brabant et al. 1992

  5. Pathological mandibular fracture: A severe complication of periimplantitis

    PubMed Central

    Rodriguez-Campo, Francisco; Naval-Parra, Beatriz; Sastre-Pérez, Jesús

    2015-01-01

    Nowadays, dental implant treatment is a very common option for patients even in medical compromised conditons. Some complications related to them have been described. Periimplantitis (PI) is one of the biggest concerns complications of these kind of treatments, probably has a multifactorial aethiology. Usually the consequences of PI are the loss of the implants and prostheses, expenses of money and time for dentists and patients. Very often PI implies the necesity of repeating the treatment . Pathological mandibular fracture due to PI is a severe but infrequent complication after dental implant treatment, especially after PI. In this study we present three cases of mandibular pathologic fractures among patients with different medical and dental records but similar management: two of them had been treated years ago of oral squamous cell carcinoma with surgery and radiotherapy, the other patient received oral bisphosphonates for osteoporosis some years after implantation. We analized the causes, consequences and posible prevention of these fractures as well as the special features of this kind of mandibular fractures and the different existing treatments. Key words:Periimplantitis, pathological mandibular fracture, mandibular atrophy, bicortical implants. PMID:26155355

  6. Computer-assisted systems for forensic pathology and forensic toxicology.

    PubMed

    Druid, H; Holmgren, P; Löwenhielm, P

    1996-09-01

    A computer software, RättsBASE (RB), was developed for all forensic pathology units in Sweden and introduced in 1992. Simultaneously, a corresponding software, ToxBASE (TB), was developed for the Department of Forensic Toxicology, where all forensic toxicology in Sweden is managed. Both of the databases were created using dBASE IV, and the programming was carried out according to specifications from the staff at the forensic toxicology and forensic pathology units. since the development or RB and TB was coordinated, the systems can run together smoothly. The purpose of both systems was to automate the offices and to enable compilation of detailed statistics. Installation of Novell Netware and ISDN-connections (Integrated Service Digital Network) has enabled rapid communication between the units and easy compilation of nationwide statistics of forensic pathology and forensic toxicology. the systems offer a wide spectrum of reports and include a simple module for evaluation of the importance of the forensic efforts for th whole death investigation. The configuration of the softwares has also enabled processing of a large amount of related toxicological and autopsy data that in turn has yielded a base for compilation of toxicology interpretation lists. This article includes a summary of the features of the software and a discussion of its benefits and limitations. PMID:15637819

  7. Granulovacuolar degeneration: a neurodegenerative change that accompanies tau pathology.

    PubMed

    Köhler, Christoph

    2016-09-01

    Granule-containing vacuoles in the cytoplasm of hippocampal neurons are a neuropathological feature of Alzheimer's disease. Granulovacuolar degeneration (GVD) is not disease-specific and can be observed in other neurodegenerative disorders and even in the brains of non-demented elderly people. However, several studies have reported much higher numbers of neurons undergoing GVD in the hippocampus of Alzheimer's disease cases. Recently, a neuropathological staging system for GVD has facilitated neuropathological assessment. Data obtained by electron microscopy and immunolabeling suggest that GVD inclusions are a special form of autophagic vacuole. GVD frequently occurs together with pathological changes of the microtubule-associated protein tau, but to date, the relationship between the two lesions remains elusive. Originally identified in hematoxylin- and silver-stained sections, immunolabeling has shown that the granules are composed of a variety of proteins, including those related to tau pathology, autophagy, diverse signal transduction pathways, cell stress and apoptosis. Several of these proteins serve as markers of GVD. Most researchers and authors have interpreted the sequestration of proteins into GVD inclusions as either a cellular defense mechanism or one that leads to the impairment of important cellular functions. This review provides a detailed overview of the various aspects of GVD and focuses on the relationship between tau pathology and GVD. PMID:27062260

  8. VEGF-A, cytoskeletal dynamics, and the pathological vascular phenotype

    SciTech Connect

    Nagy, Janice A. . E-mail: jnagy@bidmc.harvard.edu; Senger, Donald R. . E-mail: dsenger@bidmc.harvard.edu

    2006-03-10

    Normal angiogenesis is a complex process involving the organization of proliferating and migrating endothelial cells (ECs) into a well-ordered and highly functional vascular network. In contrast, pathological angiogenesis, which is a conspicuous feature of tumor growth, ischemic diseases, and chronic inflammation, is characterized by vessels with aberrant angioarchitecture and compromised barrier function. Herein we review the subject of pathological angiogenesis, particularly that driven by vascular endothelial growth factor (VEGF-A), from a new perspective. We propose that the serious structural and functional anomalies associated with VEGF-A-elicited neovessels, reflect, at least in part, imbalances in the internal molecular cues that govern the ordered assembly of ECs into three dimensional vascular networks and preserve vessel barrier function. Adopting such a viewpoint widens the focus from solely on specific pro-angiogenic stimuli such as VEGF-A to include a key set of cytoskeletal regulatory molecules, the Rho GTPases, which are known to direct multiple aspects of vascular morphogenesis including EC motility, alignment, multi-cellular organization, as well as intercellular junction integrity. We offer this perspective to draw attention to the importance of endothelial cytoskeletal dynamics for proper neovascularization and to suggest new therapeutic strategies with the potential to improve the pathological vascular phenotype.

  9. Pathology of Podocytopathies Causing Nephrotic Syndrome in Children

    PubMed Central

    Ranganathan, Sarangarajan

    2016-01-01

    Nephrotic syndrome (NS) in children includes a diverse group of diseases that range from genetic diseases without any immunological defects to causes that are primarily due to immunological effects. Recent advances in molecular and genomic studies have resulted in a plethora of genetic defects that have been localized to the podocyte, the basic structure that is instrumental in normal filtration process. Although the disease can manifest from birth and into adulthood, the primary focus of this review would be to describe the novel genes and pathology of primary podocyte defects that cause NS in children. This review will restrict itself to the pathology of congenital NS, minimal change disease (MCD), and its variants and focal segmental glomerulosclerosis (FSGS). The two major types of congenital NS are Finnish type characterized by dilated sausage shaped tubules morphologically and diffuse mesangial sclerosis characterized by glomerulosclerosis. MCD has usually normal appearing biopsy features on light microscopy and needs electron microscopy for diagnosis, whereas FSGS in contrast has classic segmental sclerosing lesions identified in different portions of the glomeruli and tubular atrophy. This review summarizes the pathological characteristics of these conditions and also delves into the various genetic defects that have been described as the cause of these primary podocytopathies. Other secondary causes of NS in children, such as membranoproliferative and membranous glomerulonephritis, will not be covered in this review. PMID:27066465

  10. Pathologic diagnosis of central centrifugal cicatricial alopecia on horizontal sections.

    PubMed

    Miteva, Mariya; Tosti, Antonella

    2014-11-01

    The pathologic findings in Central Centrifugal Cicatricial Alopecia (CCCA) have not been studied systematically in horizontal sections. Our objective was to establish the pathologic features, and their frequency in horizontal sections of scalp biopsies obtained from patients with clinically and histologically proven CCCA. Serial horizontal sections of 51 cases were evaluated retrospectively. All biopsies were assessed at 4 levels and at least on 24 horizontal sections. The most common pathologic findings were follicular miniaturization (81% of the cases); premature desquamation of the inner root sheath (96%), focal preservation of the sebaceous glands (94%), which in most of these cases appeared as surrounding "in a hug" an intact vellus follicle; compound follicular structures with perifollicular fibrosis and/or inflammation (89%), lamellar hyperkeratosis/parakeratosis in the hair canal (79%), absent or mild inflammation (77%), and naked hair shafts (68%). Horizontal sections are useful in CCCA to identify early or focal disease and to provide the clinician with better information on the presence of follicular miniaturization, inflammation, and scarring, which can be used to tailor the treatment to the individual patient. PMID:25222198

  11. Pathological mandibular fracture: A severe complication of periimplantitis.

    PubMed

    Naval-Gías, Luis; Rodriguez-Campo, Francisco; Naval-Parra, Beatriz; Sastre-Pérez, Jesús

    2015-04-01

    Nowadays, dental implant treatment is a very common option for patients even in medical compromised conditons. Some complications related to them have been described. Periimplantitis (PI) is one of the biggest concerns complications of these kind of treatments, probably has a multifactorial aethiology. Usually the consequences of PI are the loss of the implants and prostheses, expenses of money and time for dentists and patients. Very often PI implies the necesity of repeating the treatment . Pathological mandibular fracture due to PI is a severe but infrequent complication after dental implant treatment, especially after PI. In this study we present three cases of mandibular pathologic fractures among patients with different medical and dental records but similar management: two of them had been treated years ago of oral squamous cell carcinoma with surgery and radiotherapy, the other patient received oral bisphosphonates for osteoporosis some years after implantation. We analized the causes, consequences and posible prevention of these fractures as well as the special features of this kind of mandibular fractures and the different existing treatments. Key words:Periimplantitis, pathological mandibular fracture, mandibular atrophy, bicortical implants. PMID:26155355

  12. Review: Axon pathology in age-related neurodegenerative disorders.

    PubMed

    Adalbert, R; Coleman, M P

    2013-02-01

    'Dying back' axon degeneration is a prominent feature of many age-related neurodegenerative disorders and is widespread in normal ageing. Although the mechanisms of disease- and age-related losses may differ, both contribute to symptoms. Here, we review recent advances in understanding axon pathology in age-related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and glaucoma. In particular, we highlight the importance of axonal transport, autophagy, traumatic brain injury and mitochondrial quality control. We then place these disease mechanisms in the context of changes to axons and dendrites that occur during normal ageing. We discuss what makes ageing such an important risk factor for many neurodegenerative disorders and conclude that the processes of normal ageing and disease combine at the molecular, cellular or systems levels in a range of disorders to produce symptoms. Pathology identical to disease also occurs at the cellular level in most elderly individuals. Thus, normal ageing and age-related disease are inextricably linked and the term 'healthy ageing' downplays the important contributions of cellular pathology. For a full understanding of normal ageing or age-related disease we must study both processes. PMID:23046254

  13. Prediction of pathological complete response of breast cancer patients undergoing neoadjuvant chemotherapy: usefulness of breast MRI computer-aided detection

    PubMed Central

    Kim, H; Park, J S; Shin, H J; Cha, J H; Chae, E Y; Choi, W J

    2014-01-01

    Objective: To evaluate the usefulness of MR computer-aided detection (CAD) in patients undergoing neoadjuvant chemotherapy for prediction of the pathological complete response of tumours. Methods: 148 patients with breast cancer (mean age, 47.3 years; range, 29–72 years) who underwent neoadjuvant chemotherapy were included in our study. They underwent MRI before and after neoadjuvant chemotherapy, and we reviewed the pathological result as the gold standard. The computer-generated kinetic features for each lesion were recorded, and the features analysed included “threshold enhancement” at 50% and 100% minimum thresholds; degree of initial peak enhancement; and enhancement profiles comprising lesion percentages of washout, plateau and persistent enhancement. The final pathological size and character of tumours were correlated with post-chemotherapy mammography, ultrasonography and MR CAD findings. Kruskal–Wallis test and intraclass correlation coefficient were used to analyse the findings. Results: We divided the 148 patients into complete pathological response and non-complete pathological response groups. A complete pathological response was defined as no histopathological evidence of any residual invasive cancer cells in the breast or axillary lymph nodes. 39 patients showed complete pathological response, and 109 patients showed non-complete pathological response. Between enhancement profiles of MR CAD, plateau proportion of tumours was significantly correlated with the pathological response of tumours (mean proportion of plateau on complete pathological response group was 27%, p = 0.007). Conclusion: When plateau proportion of tumours is high, we can predict non-complete pathological response of neoadjuvant chemotherapy. Advances in knowledge: MR CAD can be a useful tool for the assessment of response to neoadjuvant chemotherapy and prediction of pathological results. PMID:25162970

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

    PubMed

    Madabhushi, Anant; Lee, George

    2016-10-01

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

  15. Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly

    PubMed Central

    Lesnick, Timothy G.; Przybelski, Scott A.; Knopman, David S.; Preboske, Greg M.; Kantarci, Kejal; Raman, Mekala R.; Machulda, Mary M.; Mielke, Michelle M.; Lowe, Val J.; Senjem, Matthew L.; Gunter, Jeffrey L.; Rocca, Walter A.; Roberts, Rosebud O.; Petersen, Ronald C.; Jack, Clifford R.

    2015-01-01

    both vascular and amyloid pathologies, the effect of both pathologies on cognition was additive and not synergistic. For a 79-year-old subject, the predicted annual rate of global z-score decline was −0.02 if on neither pathway, −0.07 if on the vascular pathway, −0.08 if on the amyloid pathway and −0.13 if on both pathways. The main conclusions of this study were: (i) amyloid and vascular pathologies seem to be at least partly independent processes that both affect longitudinal cognitive trajectories adversely and are major drivers of cognitive decline in the elderly; and (ii) cognitive reserve seems to offset the deleterious effect of both pathologies on the cognitive trajectories. PMID:25595145

  16. Activation of the endothelin system mediates pathological angiogenesis during ischemic retinopathy.

    PubMed

    Patel, Chintan; Narayanan, S Priya; Zhang, Wenbo; Xu, Zhimin; Sukumari-Ramesh, Sangeetha; Dhandapani, Krishnan M; Caldwell, R William; Caldwell, Ruth B

    2014-11-01

    Retinopathy of prematurity adversely affects premature infants because of oxygen-induced damage of the immature retinal vasculature, resulting in pathological neovascularization (NV). Our pilot studies using the mouse model of oxygen-induced retinopathy (OIR) showed marked increases in angiogenic mediators, including endothelins and endothelin receptor (EDNR) A. We hypothesized that activation of the endothelin system via EDNRA plays a causal role in pathological angiogenesis and up-regulation of angiogenic mediators, including vascular endothelial growth factor A (VEGFA) in OIR. Mice were exposed to 75% oxygen from post-natal day P7 to P12, treated with either vehicle or EDNRA antagonist BQ-123 or EDNRB antagonist BQ-788 on P12, and kept at room air from P12 to P17 (ischemic phase). RT-PCR analysis revealed increased levels of EDN2 and EDNRA mRNA, and Western blot analysis revealed increased EDN2 expression during the ischemic phase. EDNRA inhibition significantly increased vessel sprouting, resulting in enhanced physiological angiogenesis and decreased pathological NV, whereas EDNRB inhibition modestly improved vascular repair. OIR triggered significant increases in VEGFA protein and mRNA for delta-like ligand 4, apelin, angiopoietin-2, and monocyte chemoattractant protein-1. BQ-123 treatment significantly reduced these alterations. EDN2 expression was localized to retinal glia and pathological NV tufts of the OIR retinas. EDN2 also induced VEGFA protein expression in cultured astrocytes. In conclusion, inhibition of the EDNRA during OIR suppresses pathological NV and promotes physiological angiogenesis. PMID:25203536

  17. Cumulative early life adversity predicts longevity in wild baboons

    PubMed Central

    Tung, Jenny; Archie, Elizabeth A.; Altmann, Jeanne; Alberts, Susan C.

    2016-01-01

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302

  18. Cumulative early life adversity predicts longevity in wild baboons.

    PubMed

    Tung, Jenny; Archie, Elizabeth A; Altmann, Jeanne; Alberts, Susan C

    2016-01-01

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302

  19. Impaired Decisional Impulsivity in Pathological Videogamers

    PubMed Central

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

    2013-01-01

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

  20. Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease

    PubMed Central

    Neumann, Juliane; Bras, Jose; Deas, Emma; O'Sullivan, Sean S.; Parkkinen, Laura; Lachmann, Robin H.; Li, Abi; Holton, Janice; Guerreiro, Rita; Paudel, Reema; Segarane, Badmavady; Singleton, Andrew; Lees, Andrew; Hardy, John; Houlden, Henry; Revesz, Tamas; Wood, Nicholas W.

    2009-01-01

    Mutations in the glucocerebrosidase gene (GBA) are associated with Gaucher's disease, the most common lysosomal storage disorder. Parkinsonism is an established feature of Gaucher's disease and an increased frequency of mutations in GBA has been reported in several different ethnic series with sporadic Parkinson's disease. In this study, we evaluated the frequency of GBA mutations in British patients affected by Parkinson's disease. We utilized the DNA of 790 patients and 257 controls, matched for age and ethnicity, to screen for mutations within the GBA gene. Clinical data on all identified GBA mutation carriers was reviewed and analysed. Additionally, in all cases where brain material was available, a neuropathological evaluation was performed and compared to sporadic Parkinson's disease without GBA mutations. The frequency of GBA mutations among the British patients (33/790 = 4.18%) was significantly higher (P = 0.01; odds ratio = 3.7; 95% confidence interval = 1.12–12.14) when compared to the control group (3/257 = 1.17%). Fourteen different GBA mutations were identified, including three previously undescribed mutations, K7E, D443N and G193E. Pathological examination revealed widespread and abundant α-synuclein pathology in all 17 GBA mutation carriers, which were graded as Braak stage of 5–6, and had McKeith's limbic or diffuse neocortical Lewy body-type pathology. Diffuse neocortical Lewy body-type pathology tended to occur more frequently in the group with GBA mutations compared to matched Parkinson's disease controls. Clinical features comprised an early onset of the disease, the presence of hallucinations in 45% (14/31) and symptoms of cognitive decline or dementia in 48% (15/31) of patients. This study demonstrates that GBA mutations are found in British subjects at a higher frequency than any other known Parkinson's disease gene. This is the largest study to date on a non-Jewish patient sample with a detailed genotype/phenotype/pathological analyses