[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.

Pathogenic changes of dispersion and contrast of coherent images of biotissues

NASA Astrophysics Data System (ADS)

Pishak, Olga V.

2002-02-01

The paper presents the results of polarization-correlation investigation of multifractal collagen structure of physiologically normal and pathologically changed tissues of women's reproductive sphere and of skin. The technique of polarization selection of coherent biotissues' images with the following determination of their autocorrelation functions and spectral densities is suggested. The correlation-optical criteria of early diagnostics of pathological changes' appearance of myometry (forming of the germ of fibromyoma) and of skin(psoriasis) are determined. The suggested paper is directed to investigation of the possibilities of pathological changes of biotissues' morphological structure by means of determining the polarizationally filtered autocorrelation functions (ACF) and corresponding spectral densities of their coherent images.

Ego-pathology, body experience, and body psychotherapy in chronic schizophrenia.

PubMed

Röhricht, Frank; Papadopoulos, Nina; Suzuki, Iris; Priebe, Stefan

2009-03-01

In a recent pilot RCT, looking at the efficacy of body oriented psychological therapy (BPT) in patients with chronic schizophrenia, a marked improvement in negative symptoms was found in the treatment group. To date, there have been no studies to evaluate the therapeutic processes, correlates and predictors of change in-patients receiving BPT. The aims of this study are to address three specific questions, namely how: (1) Ego-pathology and (2) Body experiences, may change during the treatment (BPT). We also looked at: (3) If these pathologies, and/or changes in them, or other characteristics are associated with specific clinical outcomes. Analysis of data obtained within a pilot randomized controlled trial. In a sample of patients with a diagnosis of chronic schizophrenia, allocated to receive a course of body oriented group psychotherapy, certain parameters were assessed pre- and post-treatment: (1) Ego-pathology, using the ego-pathology inventory (EPI); (2) Body experiences, (size perception/image marking procedure - IMP, body image/body distortion questionnaire - BDQ, and body cathexis/visual-analogue-scales - VAS); and (3) Common symptom factors, using the Positive And Negative Symptom Scale (PANSS). Subjective experiences were also recorded. Four out of six ego-pathology symptom scores improved over the course of therapy (t=2.9-3.5, p<.05-.01). Amongst the measures of body experiences, only the body perception indices of the lower extremities changed significantly from underestimation pre-therapy (BPI median 92.3), becoming accurate estimates post therapy (BPI median 101.1). Contrary to the hypothesis a reduction of negative symptoms in chronic schizophrenia patients was not associated with systematic improvements of ego-pathology or body experiences. The strongest predictor of change was a high score of ego-demarcation pre-treatment (beta=0.89, p<.001). In patients with chronic schizophrenia, body oriented psychological interventions may be effective for both positive therapeutic changes in ego-pathology and negative symptoms, even though these effects are not necessarily related. High scores of ego-pathology at baseline predicted a poor treatment outcome. This finding deserves more systematic studies, as it could potentially identify patients with poorer prognosis and underpin the development of new intervention strategies. Further studies are required to clarify more precisely the exact nature of the processes in BPT.

Agents Which Mediate Pulmonary Edema

DTIC Science & Technology

1990-12-01

described in this report has focused on delineating various approach s to understanding mechanisms of pathological changes leading to pulmonary edema... pathological changes leading to pulmonary edema. Baseline parameters including hemodynamics, gas exchange and lymph flow were determined for the sheep...mediastinal lymph node is catheterized permitting frequent sampling of lung lymph. This model permits the monitoring of changes in pulmonary vascular

The Added Value of Pathology Review in Vulvar Cancer: Results From a Population-based Cohort Study.

PubMed

Barbera, Lisa; Gien, Lilian T; Sutradhar, Rinku; Thomas, Gillian; Covens, Al; Elit, Laurie; Fyles, Anthony; Rakovitch, Eileen; Liu, Ying; Khalifa, Mahmoud

2017-03-01

We conducted a population-based patterns of care study of vulvar carcinoma. This paper describes the changes in reporting based on pathology review. This is a retrospective population-based cohort study. We obtained all pathology records available from the provincial cancer registry for primary invasive squamous cell carcinoma of the vulva diagnosed between 1998 and 2007. Pathology reviews were conducted centrally by a group of gynecologic pathologists and were identified during abstraction. Corresponding original reports were matched to pathology review reports based on accession numbers. We compared the reported value for presence/absence of invasion, grade, depth, thickness, size, lymphovascular space invasion, peripheral margin status, and deep margin status in the original and review report. A total of 1011 vulvar resection reports were identified. From these, we identified 316 pairs of original/review reports. Missing data were common but improved in the reviews. In total, 55 (17%) reports had at least 1 change from the original to the review based on presence of invasion, depth, lymphovascular space invasion, or margin. When we included reports where a variable was missing in the original but then completed in the review, there were clinically relevant changes in 210 reports (66%). Vulvar carcinoma is a rare diagnosis and pathology reviews resulted in potentially important clinical changes in a significant proportion of cases. Referral pathologists play an important role in contributing to high-quality clinical decisions.

Changes in eating pathology and associated symptoms among chronically ill adults attending a brief psychoeducational group.

PubMed

von Ranson, Kristin M; Stevenson, Andrea S; Cannon, Colleen K; Shah, Wendy

2010-08-01

Two quasi-experimental pilot studies examined eating pathology, eating self-efficacy, shame, guilt, and pride in adults with chronic illness before and after participating in brief cognitive-behavioral psychoeducational groups addressing eating concerns. In Study 1, 60 adults completed assessments before and after a series of two groups; in Study 2, 21 adults also completed an assessment five weeks prior to the first group to identify time-related changes in symptoms. Study 1 participants improved across domains, whereas Study 2 analyses also examining time-related changes showed improvements in eating self-efficacy, shame, guilt, and pride, but not in eating pathology. Psychoeducational groups may help improve symptoms including eating pathology, eating self-efficacy, shame, guilt, and pride among chronically-ill adults with eating concerns. 2009 Elsevier Ltd. All rights reserved.

[Morphological structure of suprarenal glands in experimental vibration-induced pathology].

PubMed

Kapanadze, N A; Abzianidze, E N; Sumbadze, Ts M; Korkiia, I I; Amiranidze, M V

2009-01-01

Technical progress has caused development of vibration-induced pathology, which is determined by harmful factors or environmental effects. The harmful factors include physical factors--noise, mechanical vibrations, low temperature, high humidity of the air and incorrect lighting. The aim of our study was the investigation of morphological changes in suprarenal glands under condition of vibration-induced pathology. The experiment was conducted on 20 grown-up white male rats weighting 180-200 g. The animals were daily under an hour vibration during 2 months. The vibration frequency was modulated by means of a general vibration. After an experiment, animals were decapitated in condition of general anesthesia. The experiment revealed important changes in the morphological structure of suprarenal glands. The vibration pathology causes following changes: vessels' and sinusoid capillaries' uneven widening, develop the infiltrate cells, bleeding areas, necrosis and other changes. Based on above-stated it is supposed that technical progress and introduction of new technologies is one of the risk factors, which can cause neurohumoral disorders.

The Social Pathologies of Self-Realization: A Diagnosis of the Consequences of the Shift in Individualization

ERIC Educational Resources Information Center

Hammershoj, Lars Geer

2009-01-01

The aim of this article is to inquire into today's social pathologies, i.e. the negative consequences of the developmental processes of society. In a dialogue with Axel Honneth, the article asserts that a shift has occurred in individualization, a shift that implies a fundamental change in social pathologies: Social pathologies no longer derive…

Confounders in interpreting pathology for safety and risk assessment

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

Wolf, Douglas C.; Mann, Peter C.

2005-02-01

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

Polarization-correlation study of biotissue multifractal structure

NASA Astrophysics Data System (ADS)

Olar, O. I.; Ushenko, A. G.

2003-09-01

This paper presents the results of polarization-correlation study of multifractal collagen structure of physiologically normal and pathologically changed tissues of women"s reproductive sphere and skin. The technique of polarization selection of coherent images of biotissues with further determination of their autocorrelation functions and spectral densities is suggested. The correlation-optical criteria of early diagnostics of appearance of pathological changes in the cases of myometry (forming the germ of fibromyoma) and skin (psoriasis) are determined. This study is directed to investigate the possibilities of recognition of pathological changes of biotissue morphological structure by determining the polarization-dependent autocorrelation functions (ACF) and corresponding spectral densities of tissue coherent images.

Tocopherol And Tocotrienol: Therapeutic Potential In Animal Models of Stress.

PubMed

Azlina, Mohd Fahami Nur; Kamisah, Yusof; Qodriyah, Mohd Saad

2017-11-22

Scientific reports had shown that stress is related to numerous pathological changes in the body. These pathological changes can bring about numerous diseases and can significantly cause negative effects in an individual. These include gastric ulcer, liver pathology and neurobehavioral changes. A common pathogenesis in many diseases related to stress involves oxidative damage. Therefore, the administration of antioxidants such as vitamin E is a reasonable therapeutic approach. However, there is conflicting evidence about antioxidant supplementation. The aim of this work was to summarize documented reports on the effects of tocopherol and tocotrienol on various pathological changes induced by stress. This review will reveal the scientific evidence of enteral supplementation of vitamin E in the forms of tocotrienol and tocopherol in animal models of stress. These models mimic the stress endured by critically ill patients in a clinical setting and psychological stress in individuals. Positive outcomes from enteral feeding of vitamin E in reducing the occurrence of stress-induced pathological changes are discussed in this review. These positive findings include their ability to reduced stress-induced gastric ulcers, elevated liver enzymes and improved locomotors activity. Evidences showing tocotrienol and tocopherol effects are not just related to its ability to reduce oxidative stress but also acting on other mechanism are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pathology annual. Part 2

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

Fechner, R.E.; Rosen, P.P.

1987-01-01

This book contains 11 selections. Some of the titles are: Applications of in situ DNA hybridization technology to diagnostic surgical pathology; Neoplasms associated with immune deficiencies; Chronic gastritis: The pathologists's role; Necrosis in lymph nodes; Pathologic changes of osteochondrodysplasia in infancy: A review; and Immunoglobulin light chain nephropathies.

[On "early pathologic anatomy" and "anatomy of medical structure": continuity or point of epistemological rupture?].

PubMed

Lellouch, Alain

2006-06-01

The aim of this paper is to analyse the technical, conceptual and institutional changes from which, through macroscopic pathology, a new medical science (microscopic pathology) emerged. The "early" pathology was mainly implemented by the Ecole de Paris, at the beginning of the 19th century. After 1850, histo-pathology emerged, in German university institutes (which were separate buildings from the wards and from the dissecting rooms of the hospitals). The birth of histo-pathology is also linked with technical improvements in mass manufactured microscopes, with better techniques for fixing and staining histological samples and lastly, in (1848) withVirchow's cellular theory. Among French doctors, only one, the very famous physician Jean-Martin Charcot (1825-1893) was aware of these dramatic changes. Charcot wrote many texts which are testimonies of an epistemological rupture between two very different types of medicine, the old French "médecine d'hôpital" and the new "lab medicine", developed in German speaking countries and based on the microscope.

Improving Anatomic Pathology in Sub-Saharan Africa to Support Cancer Care.

PubMed

Wilson, Michael L; Ayers, Stephanie; Berney, Daniel; Eslan, Alexia; Guarner, Jeannette; Lester, Susan; Masia, Ricard; Moloo, Zahir; Mutuku, Angela; Roberts, Drucilla; Stall, Jennifer; Sayed, Shahin

2018-03-07

Cancer care requires both accurate pathologic diagnosis as well as pathologic cancer staging. We evaluated three approaches to training pathologists in sub-Saharan Africa to perform pathologic cancer staging of breast, cervix, prostate, and colorectal cancers. One of three training methods was used at each workshop: didactic, case-based testing (CBT), or a blended approach. The project involved 52 participants from 16 pathology departments in 11 countries in East, Central, and Southern Africa. Evaluation of each method included pre- and postworkshop knowledge assessments, online pre- and postworkshop surveys of practice changes at the individual and institutional levels, and selected site visits. While CBT resulted in the highest overall average postassessment individual scores, both CBT and blended approaches resulted in 19% increases in average scores from pre- to postworkshop assessments. Institutions that participated in the blended workshop had increased changes in practice as indicated by the institutional survey. Both CBT and a blended approach are effective methods for training pathologists in pathologic cancer staging. Both are superior to traditional lectures alone.

The effect of vitamin E on lung pathology in sulfur mustard-exposed guinea pigs.

PubMed

Gholamnezhad, Zahra; Boskabady, Mohammad Hossein; Amery, Sediqa; Vahedi, Nassim; Tabatabaei, Abass; Boskabady, Morteza; Shahriary, Alireza

2016-12-01

Pulmonary complications of exposure to sulfur mustard (SM) gas range from no effect or mild symptoms to severe bronchial stenosis. In the present study, the protective effect of vitamin E on the lung inflammation of SM-exposed guinea pigs was examined. Guinea pigs (n = 5 for each group) were exposed to ethanol (control group), 40 mg/m 3 inhaled SM (SME group), SME treated with vitamin E (SME + E), SME treated with dexamethasone (SME + D), and SME treated with both treatments (SME + E + D). Pathological evaluation of the lung was done 14 days postexposure. The epithelial desquamation of trachea and other pathologic changes in the lung of the SME group were significantly higher than those in the control group. Furthermore, the pathological changes of trachea and lung in the SME + E and SME + E + D groups were significantly improved compared with those of SME group. In addition, the pathological changes of trachea and lung of SME + E and SME + E + D animals were significantly less than those of SME + D group. © The Author(s) 2015.

Success of digitizing the dept. of pathology: is it just to change the technical platform and go with the slide scanners or do we need a paradigm when it comes to informatics and workflow?

NASA Astrophysics Data System (ADS)

Wintell, M.; Wehlander, E.; Samulesson, B.; Lindsköld, L.

2015-03-01

Can we create values and make success by creating digitized Pathology by only changing the technical platform within the department of pathology? The answer is definitely No. To be able to create values that will pay for the investment of going digital we need to go outside traditional ways of change-management in healthcare. Cooperation before buying the hardware is the key, going there by creating a unique negotiated information-model that spans the whole value chain within the care process in regard of pathology services. This is the core of creating great values throughout the whole healthcare sub process of cancer detection. Region Västra Götaland (VGR), has taken this path and will show that it's possible working/thinking outside the "box."

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

PubMed Central

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

2017-01-01

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

Single Nucleotide Variations of the Human GR Gene Manifested as Pathologic Mutations or Polymorphisms.

PubMed

Kino, Tomoshige

2018-05-11

The human genome contains numerous single nucleotide variations (SNVs), and the human GR gene harbors ∼450 of these genetic changes. Among them, extremely rare non-synonymous variants known as pathologic GR gene mutations develop a characteristic pathologic condition, familial/sporadic generalized glucocorticoid resistance syndrome, by replacing the amino acids critical for GR protein structure and functions, whereas others known as pathologic polymorphisms develop mild manifestations recognized mainly at population bases by changing the GR activities slightly. Recent progress on the structural analysis to the GR protein and subsequent computer-based structural simulation revealed details of the molecular defects caused by such pathologic GR gene mutations, including their impact on the receptor interaction to ligands, nuclear receptor coactivators (NCoAs) or DNA glucocorticoid response elements (GREs). Indeed, those found in the GR ligand-binding domain significantly damage protein structure of the ligand-binding pocket and/or the activation function-2 transactivation domain and change their molecular interaction to glucocorticoids or the LxxLL signature motif of NCoAs. Two mutations found in GR DBD also affect interaction of the mutant receptors to GRE DNA by affecting the critical amino acid for the interaction or changing local hydrophobic circumstance. In this review, we discuss recent findings on the structural simulation of the pathologic GR mutants in connection to their functional and clinical impacts along with brief explanation to recent research achievement on the GR polymorphisms.

Surgical Pathology Resident Rotation Restructuring at a Tertiary Care Academic Center.

PubMed

Mehr, Chelsea R; Obstfeld, Amrom E; Barrett, Amanda C; Montone, Kathleen T; Schwartz, Lauren E

2017-01-01

Changes in the field of pathology and resident education necessitate ongoing evaluation of residency training. Evolutionary change is particularly important for surgical pathology rotations, which form the core of anatomic pathology training programs. In the past, we organized this rotation based on subjective insight. When faced with the recent need to restructure the rotation, we strove for a more evidence-based process. Our approach involved 2 primary sources of data. We quantified the number of cases and blocks submitted per case type to estimate workload and surveyed residents about the time required to gross specimens in all organ systems. A multidisciplinary committee including faculty, residents, and staff evaluated the results and used the data to model how various changes to the rotation would affect resident workload, turnaround time, and other variables. Finally, we identified rotation structures that equally distributed work and created a point-based system that capped grossing time for residents of different experience. Following implementation, we retrospectively compared turnaround time and duty hour violations before and after these changes and surveyed residents about their experiences with both systems. We evaluated the accuracy of the point-based system by examining grossing times and comparing them to the assigned point values. We found overall improvement in the rotation following the implementation. As there is essentially no literature on the subject of surgical pathology rotation organization, we hope that our experience will provide a road map to improve pathology resident education at other institutions.

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

PubMed

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

2018-05-30

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

Retaining Pathological Gamblers in Cognitive Behavior Therapy through Motivational Enhancement

ERIC Educational Resources Information Center

Wulfert, Edelgard; Blanchard, Edward B.; Freidenberg, Brian M.; Martell, Rebecca S.

2006-01-01

Treatment for pathological gambling is in its infancy. Several cognitive and behavioral interventions have shown promise, but high attrition and relapse rates suggest that gamblers requesting treatment are not uniformly committed to change. This article describes an exploratory study with 9 severe pathological gamblers--in their majority horse…

[The clinical and pathologic features of Charcot-Marie-Tooth disease].

PubMed

Xiao, Bo; Xie, Jusheng; Yang, Xiaosu; Wu, Zhiguo; Xiao, Jianfeng; Li, Jing

2002-11-01

To study the clinical and pathological features of Charcot-Marie-Tooth disease (CMT). The general clinical data, the changes of neuroelectrophysiology and the pathological features of neural and muscular biopsy of 20 CMT patients were comprehensively analyzed. The clinical manifestations in the two types of CMT were nearly the same, but the changes of neuroelectrophysiology and the pathological characteristics of the neural and muscular biopsy in the two types were obviously different. 16 cases of CMT type 1 were characterized by decreased sensory nerve conduction velocity (SNCV < 30 m/s) and are associated with demyelinating hypertrophic neuropathy. 4 cases of CMT tylpe 2 were characterized by normal SNCV and associated with axonopathy. Neuroelectrophysiology and neural and muscular biopsy are important for the diagnosis of CMT.

The use of thermovision camera to observe physiological and pathological conditions of oral cavity mucous membrane

NASA Astrophysics Data System (ADS)

Dąbrowski, M.; Dulski, R.; Żmuda, S.; Zaborowski, P.; Pogorzelski, C.

2002-06-01

This article presents initial results of investigations of the temperature distribution changes in oral cavity mucous membrane. The investigations aimed to prepare a model of temperature changes existing within mucosal membrane in physiological conditions and to compare those changes with those under pathological conditions. Our investigations were carried out using an infrared imaging system. A representative group of patients was tested.

Dynamic of Change in Pathological Personality Trait Dimensions: A Latent Change Analysis Among at-Risk Women

PubMed Central

Barbot, Baptiste; Hunter, Scott R.; Grigorenko, Elena L.; Luthar, Suniya S.

2012-01-01

This study explores longitudinally a four-factor structure of pathological personality trait dimensions (PPTDs) to examine both its structural stability and intra-individual changes among PPTDs over time. Personality Disorder (PD) scales of the Millon Clinical Multiaxial Inventory-III were administered to 361 low-income women with various psychiatric conditions (drug dependence, depression), who were followed in a two-wave study over 5-years. Cross-sectional and longitudinal factor analyses outlined a robust factorial structure of PPTDs, extrinsically invariant over time, representing Negative Emotionality, Introversion, Antagonism and Impulsivity. Despite moderate rank-order stability in the PPTDs, results also indicated substantial intra-individual variability in the degree and direction of change, consistent with trajectories of change in participants’ clinical diagnoses. Results are discussed in light of current debates on the structure and dynamic of pathological personality. PMID:23710108

The Pathologist 2.0: An Update on Digital Pathology in Veterinary Medicine.

PubMed

Bertram, Christof A; Klopfleisch, Robert

2017-09-01

Using light microscopy to describe the microarchitecture of normal and diseased tissues has changed very little since the middle of the 19th century. While the premise of histologic analysis remains intact, our relationship with the microscope is changing dramatically. Digital pathology offers new forms of visualization, and delivery of images is facilitated in unprecedented ways. This new technology can untether us entirely from our light microscopes, with many pathologists already performing their jobs using virtual microscopy. Several veterinary colleges have integrated virtual microscopy in their curriculum, and some diagnostic histopathology labs are switching to virtual microscopy as their main tool for the assessment of histologic specimens. Considering recent technical advancements of slide scanner and viewing software, digital pathology should now be considered a serious alternative to traditional light microscopy. This review therefore intends to give an overview of the current digital pathology technologies and their potential in all fields of veterinary pathology (ie, research, diagnostic service, and education). A future integration of digital pathology in the veterinary pathologist's workflow seems to be inevitable, and therefore it is proposed that trainees should be taught in digital pathology to keep up with the unavoidable digitization of the profession.

Comparison of cross-sectional anatomy and computed tomography of the tarsus in horses.

PubMed

Raes, Els V; Bergman, Eric H J; van der Veen, Henk; Vanderperren, Katrien; Van der Vekens, Elke; Saunders, Jimmy H

2011-09-01

To compare computed tomography (CT) images of equine tarsi with cross-sectional anatomic slices and evaluate the potential of CT for imaging pathological tarsal changes in horses. 6 anatomically normal equine cadaveric hind limbs and 4 tarsi with pathological changes. Precontrast CT was performed on 3 equine tarsi; sagittal and dorsal reconstructions were made. In all limbs, postcontrast CT was performed after intra-articular contrast medium injection of the tarsocrural, centrodistal, and tarsometatarsal joints. Images were matched with corresponding anatomic slices. Four tarsi with pathological changes underwent CT examination. The tibia, talus, calcaneus, and central, fused first and second, third, and fourth tarsal bones were clearly visualized as well as the long digital extensor, superficial digital flexor, lateral digital flexor (with tarsal flexor retinaculum), gastrocnemius, peroneus tertius, and tibialis cranialis tendons and the long plantar ligament. The lateral digital extensor, medial digital flexor, split peroneus tertius, and tibialis cranialis tendons and collateral ligaments could be located but not always clearly identified. Some small tarsal ligaments were identifiable, including plantar, medial, interosseus, and lateral talocalcaneal ligaments; interosseus talocentral, centrodistal, and tarsometatarsal ligaments; proximal and distal plantar ligaments; and talometatarsal ligament. Parts of the articular cartilage could be assessed on postcontrast images. Lesions were detected in the 4 tarsi with pathological changes. CT of the tarsus is recommended when radiography and ultrasonography are inconclusive and during preoperative planning for treatment of complex fractures. Images from this study can serve as a CT reference, and CT of pathological changes was useful.

Periodontal disease burden and pathological changes in organs of dogs.

PubMed

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

2008-06-01

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

Pathologic changes of wound tissue in rats with stage III pressure ulcers treated by transplantation of human amniotic epithelial cells.

PubMed

Zheng, Xilan; Jiang, Zhixia; Zhou, Aiting; Yu, Limei; Quan, Mingtao; Cheng, Huagang

2015-01-01

This study aims to determine the impact of orthotopic transplantation of human amniotic epithelial cells (hAECs) on the pathologic changes of wound tissues in a self-prepared rat stage III pressure ulcer model. Ninety-six SD rats were randomly divided into the model group (group M), hAEC transplantation group (group H), traditional treatment group (group T), and the control group (group C), with 24 rats in each group. The wound healing time was observed in 6 rats from each group, and 6 rats of each group were selected for post-modeling on day(s) (D) 1, 3, and 7 for HE staining to compare the pathological changes. The healing time of group H was significantly shorter than the other three groups. Moreover, pathological observations revealed that group H exhibited significant proliferation of fibrous tissues and vessels in the dermal layer, and the appearance time and degree of skin appendages were significantly greater than that observed in the other three groups. Pathological observations showed that hAEC transplantation could significantly speed up the healing of stage III pressure ulcer.

Co-Occurrence of Language and Behavioural Change in Frontotemporal Lobar Degeneration.

PubMed

Harris, Jennifer M; Jones, Matthew; Gall, Claire; Richardson, Anna M T; Neary, David; du Plessis, Daniel; Pal, Piyali; Mann, David M A; Snowden, Julie S; Thompson, Jennifer C

2016-01-01

We aimed to evaluate the co-occurrence of language and behavioural impairment in patients with frontotemporal lobar degeneration (FTLD) spectrum pathology. Eighty-one dementia patients with pathological confirmation of FTLD were identified. Anonymized clinical records from patients' first assessment were rated for language and behavioural features from frontotemporal dementia consensus criteria, primary progressive aphasia (PPA) criteria and 1998 FTLD criteria. Over 90% of patients with FTLD pathology exhibited a combination of at least one behavioural and one language feature. Changes in language, in particular, were commonly accompanied by behavioural change. Notably, the majority of patients who displayed language features characteristic of semantic variant PPA exhibited 'early perseverative, stereotyped or compulsive/ritualistic behaviour'. Moreover, 'executive/generation deficits with relative sparing of memory and visuospatial functions' occurred in most patients with core features of non-fluent variant PPA. Behavioural and language symptoms frequently co-occur in patients with FTLD pathology. Current classifications, which separate behavioural and language syndromes, do not reflect this co-occurrence.

Goals and objectives for molecular pathology education in residency programs. The Association for Molecular Pathology Training and Education Committee.

PubMed

1999-11-01

Increasing knowledge of the molecular basis of disease and advances in technology for analyzing nucleic acids and gene products are changing pathology practice. The explosion of information regarding inherited susceptibility to disease is an important aspect of this transformation. Pathology residency programs are incorporating molecular pathology education into their curricula to prepare newly trained pathologists for the future, yet little guidance has been available regarding the important components of molecular pathology training. We present general goals for pathology training programs for molecular pathology education. These include recommendations to pathology residents for the acquisition of both basic knowledge in human genetics and molecular biology and specific skills relevant to microbiology, molecular oncology, genetics, histocompatibility, and identity determination. The importance of residents gaining facility in integrating data gained via nucleic acid based-technology with other laboratory and clinical information available in the care of patients is emphasized.

Pathologic features of early inflammatory bowel disease.

PubMed

Finkelstein, Sydney D; Sasatomi, Eizaburo; Regueiro, Miguel

2002-03-01

Often the pathologic changes of IBD are subtle and may not be present in a proportion of biopsy specimens. In cases of early disease, the changes may be missed, and additional specimens should be taken after a period of time. Modifying factors, such as prebiopsy treatment and coexisting disease, should be considered. A forum to review cases and allow for communication between gastroenterologists and pathologists is especially useful for clinicopathologic correlation and assignment of a working diagnosis to each case. Careful attention to the pathologic features of early UC and CD would be most useful when evaluating new therapies for IBD.

Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

NASA Astrophysics Data System (ADS)

VanNasdale, Dean Allan, Jr.

2011-12-01

The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology was present. We found that normal aging changes could be distinguished from pathology associated with AMD and that polarization sensitive imaging can be used to delineate large extents of retinal damage. We found that various types of AMD pathology can also be differentiated based on scattering and polarization altering properties. Our findings demonstrate that polarization sensitive imaging is a useful modality in the evaluation of changes occurring in the normal human macula as well as changes associated with serious macular disease.

[Image reconstruction of conductivity on magnetoacoustic tomography with magnetic induction].

PubMed

Li, Jingyu; Yin, Tao; Liu, Zhipeng; Xu, Guohui

2010-04-01

The electric characteristics such as impedance and conductivity of the organization will change in the case where pathological changes occurred in the biological tissue. The change in electric characteristics usually took place before the change in the density of tissues, and also, the difference in electric characteristics such as conductivity between normal tissue and pathological tissue is obvious. The method of magneto-acoustic tomography with magnetic induction is based on the theory of magnetic eddy current induction, the principle of vibration generation and acoustic transmission to get the boundary of the pathological tissue. The pathological change could be inspected by electricity characteristic imaging which is invasive to the tissue. In this study, a two-layer concentric spherical model is established to simulate the malignant tumor tissue surrounded by normal tissue mutual relations of the magneto-sound coupling effect and the coupling equations in the magnetic field are used to get the algorithms for reconstructing the conductivity. Simulation study is conducted to test the proposed model and validate the performance of the reconstructed algorithms. The result indicates that the use of signal processing method in this paper can image the conductivity boundaries of the sample in the scanning cross section. The computer simulating results validate the feasibility of applying the method of magneto-acoustic tomography with magnetic induction for malignant tumor imaging.

Review at a multidisciplinary tumor board impacts critical management decisions of pediatric patients with cancer.

PubMed

Thenappan, Arun; Halaweish, Ihab; Mody, Rajen J; Smith, Ethan A; Geiger, James D; Ehrlich, Peter F; Jasty Rao, Rama; Hutchinson, Raymond; Yanik, Gregory; Rabah, Raja M; Heider, Amer; Stoll, Tammy; Newman, Erika A

2017-02-01

Optimal cancer care requires a multidisciplinary approach. The purpose of the current study was to evaluate the impact of a multidisciplinary tumor board on the treatment plans of children with solid tumors. The records of 158 consecutive patients discussed at a formal multidisciplinary pediatric tumor board between July 2012 and April 2014 were reviewed. Treatment plans were based on clinical practice guidelines and on current Children's Oncology Group protocols. Alterations in radiologic, pathologic, surgical, and medical interpretations were analyzed to determine the impact on changes in recommendations for clinical management. Overall, 55 of 158 children (35%) had alterations in radiologic, pathologic, medical, or surgical interpretation of clinical data following multidisciplinary discussion. Of these, 64% had changes to the initial recommendation for clinical management. Review of imaging studies resulted in interpretation changes in 30 of 158 patients studied (19%), with 12 clinical management changes. Six of 158 patients (3.9%) had changes in pathologic interpretation, with four patients (2.5%) requiring treatment changes. In eight patients (5%), a change in medical management was recommended, while in 11 patients (7%) there were changes in surgical management that were based solely on discussion and not on interpretation of imaging or pathology. Formal multidisciplinary review led to alterations in interpretation of clinical data in 35% of patients, and the majority led to changes in recommendations for treatment. Comprehensive multidisciplinary tumor board incorporated into the care of children with cancer provides additional perspectives for families and care providers when delineating optimal treatment plans. © 2016 Wiley Periodicals, Inc.

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

PubMed

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

2016-07-01

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

Insular Alzheimer disease pathology and the psychometric correlates of mortality.

PubMed

Royall, Donald R

2008-03-01

Right hemisphere dysfunction is associated with mortality in Alzheimer's disease (AD) and other neurologic conditions. These associations may be mediated by insular pathology, as insular lesions result in demonstrable changes in cardiovascular and autonomic control. AD affects the insulae at a preclinical stage, and insular AD pathology may be present in up to 40% of nondemented septuagenarians and octogenarians. This pathology can affect in vivo cardiac conduction and thereby dispose to cardiac arrhythmias and sudden death. Thus, AD pathology should be considered as a possible explanation for autonomic morbidity and mortality in nondemented elderly persons.

Modeling 4D Pathological Changes by Leveraging Normative Models

PubMed Central

Wang, Bo; Prastawa, Marcel; Irimia, Andrei; Saha, Avishek; Liu, Wei; Goh, S.Y. Matthew; Vespa, Paul M.; Van Horn, John D.; Gerig, Guido

2016-01-01

With the increasing use of efficient multimodal 3D imaging, clinicians are able to access longitudinal imaging to stage pathological diseases, to monitor the efficacy of therapeutic interventions, or to assess and quantify rehabilitation efforts. Analysis of such four-dimensional (4D) image data presenting pathologies, including disappearing and newly appearing lesions, represents a significant challenge due to the presence of complex spatio-temporal changes. Image analysis methods for such 4D image data have to include not only a concept for joint segmentation of 3D datasets to account for inherent correlations of subject-specific repeated scans but also a mechanism to account for large deformations and the destruction and formation of lesions (e.g., edema, bleeding) due to underlying physiological processes associated with damage, intervention, and recovery. In this paper, we propose a novel framework that provides a joint segmentation-registration framework to tackle the inherent problem of image registration in the presence of objects not present in all images of the time series. Our methodology models 4D changes in pathological anatomy across time and and also provides an explicit mapping of a healthy normative template to a subject’s image data with pathologies. Since atlas-moderated segmentation methods cannot explain appearance and locality pathological structures that are not represented in the template atlas, the new framework provides different options for initialization via a supervised learning approach, iterative semisupervised active learning, and also transfer learning, which results in a fully automatic 4D segmentation method. We demonstrate the effectiveness of our novel approach with synthetic experiments and a 4D multimodal MRI dataset of severe traumatic brain injury (TBI), including validation via comparison to expert segmentations. However, the proposed methodology is generic in regard to different clinical applications requiring quantitative analysis of 4D imaging representing spatio-temporal changes of pathologies. PMID:27818606

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

PubMed

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

2017-01-01

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

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

PubMed

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

2016-10-11

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

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

PubMed

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

2014-01-01

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

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

PubMed

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

2009-10-29

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

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

PubMed

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

2016-11-22

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

Classification of Normal and Pathological Gait in Young Children Based on Foot Pressure Data.

PubMed

Guo, Guodong; Guffey, Keegan; Chen, Wenbin; Pergami, Paola

2017-01-01

Human gait recognition, an active research topic in computer vision, is generally based on data obtained from images/videos. We applied computer vision technology to classify pathology-related changes in gait in young children using a foot-pressure database collected using the GAITRite walkway system. As foot positioning changes with children's development, we also investigated the possibility of age estimation based on this data. Our results demonstrate that the data collected by the GAITRite system can be used for normal/pathological gait classification. Combining age information and normal/pathological gait classification increases the accuracy of the classifier. This novel approach could support the development of an accurate, real-time, and economic measure of gait abnormalities in children, able to provide important feedback to clinicians regarding the effect of rehabilitation interventions, and to support targeted treatment modifications.

Brain Pathology Contributes to Simultaneous Change in Physical Frailty and Cognition in Old Age

PubMed Central

Yu, Lei; Wilson, Robert S.; Boyle, Patricia A.; Schneider, Julie A.; Bennett, David. A.

2014-01-01

Objective. First, we tested the hypothesis that the rate of change of physical frailty and cognitive function in older adults are correlated. Next, we examined if their rates of change are associated with the same brain pathologies. Methods. About 2,167 older adults participating in the Religious Orders Study and the Rush Memory and Aging Project had annual clinical evaluations. Bivariate random coefficient models were used to estimate simultaneously the rates of change in both frailty and cognition, and the correlation of change was characterized by a joint distribution of the random effects. Then, we examined whether postmortem indices from deceased were associated with the rate of change of frailty and cognition. Results. During an average follow-up of 6 years, frailty worsened by 0.09 unit/y and cognition declined by 0.08 unit/y. Most individuals showed worsening frailty and cognition (82.8%); 17% showed progressive frailty alone and <1% showed only cognitive decline. The rates of change of frailty and cognition were strongly correlated (ρ = −0.73, p < .001). Among deceased (N = 828), Alzheimer’s disease pathology, macroinfarcts, and nigral neuronal loss showed independent associations with the rate of change in both frailty and cognition (all ps < .001). In these models, demographics explained about 9% of the variation in individual rate of change in frailty, and neuropathologies explained about 8%. In contrast, demographics and neuropathologies accounted for 2% and 30%, respectively, of the variance in the cognitive decline. Conclusion. The rates of change in frailty and cognition are strongly correlated and this may be due in part because they share a common pathologic basis. PMID:25136002

Goals and Objectives for Molecular Pathology Education in Residency Programs

PubMed Central

1999-01-01

Increasing knowledge of the molecular basis of disease and advances in technology for analyzing nucleic acids and gene products are changing pathology practice. The explosion of information regarding inherited susceptibility to disease is an important aspect of this transformation. Pathology residency programs are incorporating molecular pathology education into their curricula to prepare newly trained pathologists for the future, yet little guidance has been available regarding the important components of molecular pathology training. We present general goals for pathology training programs for molecular pathology education. These include recommendations to pathology residents for the acquisition of both basic knowledge in human genetics and molecular biology and specific skills relevant to microbiology, molecular oncology, genetics, histocompatibility, and identity determination. The importance of residents gaining facility in integrating data gained via nucleic acid based-technology with other laboratory and clinical information available in the care of patients is emphasized. PMID:11272908

[Epidemiology of refractive errors].

PubMed

Wolfram, C

2017-07-01

Refractive errors are very common and can lead to severe pathological changes in the eye. This article analyzes the epidemiology of refractive errors in the general population in Germany and worldwide and describes common definitions for refractive errors and clinical characteristics for pathologicaal changes. Refractive errors differ between age groups due to refractive changes during the life time and also due to generation-specific factors. Current research about the etiology of refractive errors has strengthened the influence of environmental factors, which led to new strategies for the prevention of refractive pathologies.

Radiographic, computed tomographic, gross pathological and histological findings with suspected apical infection in 32 equine maxillary cheek teeth (2012-2015).

PubMed

Liuti, T; Smith, S; Dixon, P M

2018-01-01

Equine maxillary cheek teeth apical infections are a significant disorder because of frequent spread of infection to the supporting bones. The accuracy of computed tomographic imaging (CT) of this disorder has not been fully assessed. To compare the radiographic and CT findings in horses diagnosed with maxillary cheek teeth apical infections with pathological findings in the extracted teeth to assess the accuracy of these imaging techniques. Observational clinical study. Thirty-two maxillary cheek teeth (in 29 horses) diagnosed with apical infections by clinical, radiographic and principally by CT examinations, were extracted orally. The extracted teeth were subjected to further CT, gross pathological and histological examinations. Four normal teeth extracted from a cadaver served as controls. Pulpar and apical changes highly indicative of maxillary cheek teeth apical infection were present in all 32 teeth on CT, but in just 17/32 teeth (53%) radiographically. Gross pulpar/apical abnormalities and histological pulpar/periapical changes were present in 31/32 (97%) extracted teeth. On CT, one tooth contained small gas pockets in the apical aspect of one pulp and adjacent periodontal space, however no pathological changes were found following its extraction. The study is descriptive and is confined to a small number of cases. This study showed a 97% agreement between CT diagnosis of maxillary cheek teeth apical infection and the presence of pathological changes in the extracted teeth, confirming the diagnostic accuracy of CT compared with radiography for this disorder. © 2017 EVJ Ltd.

Preferred Names, Preferred Pronouns, and Gender Identity in the Electronic Medical Record and Laboratory Information System: Is Pathology Ready?

PubMed

Imborek, Katherine L; Nisly, Nicole L; Hesseltine, Michael J; Grienke, Jana; Zikmund, Todd A; Dreyer, Nicholas R; Blau, John L; Hightower, Maia; Humble, Robert M; Krasowski, Matthew D

2017-01-01

Electronic medical records (EMRs) and laboratory information systems (LISs) commonly utilize patient identifiers such as legal name, sex, medical record number, and date of birth. There have been recommendations from some EMR working groups (e.g., the World Professional Association for Transgender Health) to include preferred name, pronoun preference, assigned sex at birth, and gender identity in the EMR. These practices are currently uncommon in the United States. There has been little published on the potential impact of these changes on pathology and LISs. We review the available literature and guidelines on the use of preferred name and gender identity on pathology, including data on changes in laboratory testing following gender transition treatments. We also describe pathology and clinical laboratory challenges in the implementation of preferred name at our institution. Preferred name, pronoun preference, and gender identity have the most immediate impact on the areas of pathology with direct patient contact such as phlebotomy and transfusion medicine, both in terms of interaction with patients and policies for patient identification. Gender identity affects the regulation and policies within transfusion medicine including blood donor risk assessment and eligibility. There are limited studies on the impact of gender transition treatments on laboratory tests, but multiple studies have demonstrated complex changes in chemistry and hematology tests. A broader challenge is that, even as EMRs add functionality, pathology computer systems (e.g., LIS, middleware, reference laboratory, and outreach interfaces) may not have functionality to store or display preferred name and gender identity. Implementation of preferred name, pronoun preference, and gender identity presents multiple challenges and opportunities for pathology.

Preferred Names, Preferred Pronouns, and Gender Identity in the Electronic Medical Record and Laboratory Information System: Is Pathology Ready?

PubMed Central

Imborek, Katherine L.; Nisly, Nicole L.; Hesseltine, Michael J.; Grienke, Jana; Zikmund, Todd A.; Dreyer, Nicholas R.; Blau, John L.; Hightower, Maia; Humble, Robert M.; Krasowski, Matthew D.

2017-01-01

Background: Electronic medical records (EMRs) and laboratory information systems (LISs) commonly utilize patient identifiers such as legal name, sex, medical record number, and date of birth. There have been recommendations from some EMR working groups (e.g., the World Professional Association for Transgender Health) to include preferred name, pronoun preference, assigned sex at birth, and gender identity in the EMR. These practices are currently uncommon in the United States. There has been little published on the potential impact of these changes on pathology and LISs. Methods: We review the available literature and guidelines on the use of preferred name and gender identity on pathology, including data on changes in laboratory testing following gender transition treatments. We also describe pathology and clinical laboratory challenges in the implementation of preferred name at our institution. Results: Preferred name, pronoun preference, and gender identity have the most immediate impact on the areas of pathology with direct patient contact such as phlebotomy and transfusion medicine, both in terms of interaction with patients and policies for patient identification. Gender identity affects the regulation and policies within transfusion medicine including blood donor risk assessment and eligibility. There are limited studies on the impact of gender transition treatments on laboratory tests, but multiple studies have demonstrated complex changes in chemistry and hematology tests. A broader challenge is that, even as EMRs add functionality, pathology computer systems (e.g., LIS, middleware, reference laboratory, and outreach interfaces) may not have functionality to store or display preferred name and gender identity. Conclusions: Implementation of preferred name, pronoun preference, and gender identity presents multiple challenges and opportunities for pathology. PMID:29114436

Electron microscopic examination of the myelinated axons of corpus callosum in perfused young and old rats.

PubMed

Sargon, Mustafa F; Denk, C Cem; Celik, H Hamdi; Surucu, H Selcuk; Aldur, M Mustafa

2007-07-01

In this study, the myelinated axons of parts of the corpus callosums of young and old rats were examined under the electron microscope and a grading system was performed for quantitating the ultrastructural pathological changes of these axons. Except the old splenium group, the only ultrastructural pathological change, observed in the myelinated axons was the separation in myelin configuration. In addition to this finding, in the old splenium group, in some of the myelinated axons, an interruption was observed in the myelin configuration. Additionally, these ultrastructural pathological findings were present in the larger sized myelinated axons of the corpus callosum.

Wavelet analysis in two-dimensional tomography

NASA Astrophysics Data System (ADS)

Burkovets, Dimitry N.

2002-02-01

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

Mitochondria and Mitochondrial Cascades in Alzheimer’s Disease

PubMed Central

Swerdlow, Russell H.

2017-01-01

Decades of research indicate mitochondria from Alzheimer’s disease (AD) patients differ from those of non-AD individuals. Initial studies revealed structural differences, and subsequent studies showed functional deficits. Observations of structure and function changes prompted investigators to consider the consequences, significance, and causes of AD-related mitochondrial dysfunction. Currently, extensive research argues mitochondria may mediate, drive, or contribute to a variety of AD pathologies. The perceived significance of these mitochondrial changes continues to grow, and many currently believe AD mitochondrial dysfunction represents a reasonable therapeutic target. Debate continues over the origin of AD mitochondrial changes. Some argue amyloid-β (Aβ) induces AD mitochondrial dysfunction, a view that does not challenge the amyloid cascade hypothesis and that may in fact help explain that hypothesis. Alternatively, data indicate mitochondrial dysfunction exists independent of Aβ, potentially lies upstream of Aβ deposition, and suggest a primary mitochondrial cascade hypothesis that assumes mitochondrial pathology hierarchically supersedes Aβ pathology. Mitochondria, therefore, appear at least to mediate or possibly even initiate pathologic molecular cascades in AD. This review considers studies and data that inform this area of AD research. PMID:29036828

Diagnostic Discrepancies in Mandatory Slide Review of Extradepartmental Head and Neck Cases: Experience at a Large Academic Center.

PubMed

Mehrad, Mitra; Chernock, Rebecca D; El-Mofty, Samir K; Lewis, James S

2015-12-01

Medical error is a significant problem in the United States, and pathologic diagnoses are a significant source of errors. Prior studies have shown that second-opinion pathology review results in clinically major diagnosis changes in approximately 0.6% to 5.8% of patients. The few studies specifically on head and neck pathology have suggested rates of changed diagnoses that are even higher. Objectives .- To evaluate the diagnostic discrepancy rates in patients referred to our institution, where all such cases are reviewed by a head and neck subspecialty service, and to identify specific areas with more susceptibility to errors. Five hundred consecutive, scanned head and neck pathology reports from patients referred to our institution were compared for discrepancies between the outside and in-house diagnoses. Major discrepancies were defined as those resulting in a significant change in patient clinical management and/or prognosis. Major discrepancies occurred in 20 cases (4% overall). Informative follow-up material was available on 11 of the 20 patients (55.0%), among whom, the second opinion was supported in 11 of 11 cases (100%). Dysplasia versus invasive squamous cell carcinoma was the most common (7 of 20; 35%) area of discrepancy, and by anatomic subsite, the sinonasal tract (4 of 21; 19.0%) had the highest rate of discrepant diagnoses. Of the major discrepant diagnoses, 12 (12 of 20; 60%) involved a change from benign to malignant, one a change from malignant to benign (1 of 20; 5%), and 6 involved tumor classification (6 of 20; 30%). Head and neck pathology is a relatively high-risk area, prone to erroneous diagnoses in a small fraction of patients. This study supports the importance of second-opinion review by subspecialized pathologists for the best care of patients.

Common Postmortem Computed Tomography Findings Following Atraumatic Death: Differentiation between Normal Postmortem Changes and Pathologic Lesions

PubMed Central

Gonoi, Wataru; Okuma, Hidemi; Shirota, Go; Shintani, Yukako; Abe, Hiroyuki; Takazawa, Yutaka; Fukayama, Masashi; Ohtomo, Kuni

2015-01-01

Computed tomography (CT) is widely used in postmortem investigations as an adjunct to the traditional autopsy in forensic medicine. To date, several studies have described postmortem CT findings as being caused by normal postmortem changes. However, on interpretation, postmortem CT findings that are seemingly due to normal postmortem changes initially, may not have been mere postmortem artifacts. In this pictorial essay, we describe the common postmortem CT findings in cases of atraumatic in-hospital death and describe the diagnostic pitfalls of normal postmortem changes that can mimic real pathologic lesions. PMID:26175579

Prevention of Blast-Related Injuries

DTIC Science & Technology

2015-07-14

pathology of traumatic axonal injury involves distinct injury processes, neurofilament compaction (NFC) and impaired axoplasmic transport (IAT)1. In rat...assessments and may render diagnosis of blast related pathology even more difficult. These neuronal injury changes in the grey matter that appeared...were from blast studies using rodents16,17 and impulse noise18. A putative pathological implication for microglia comes from studies by Kane et al

Digital pathology and image analysis for robust high-throughput quantitative assessment of Alzheimer disease neuropathologic changes.

PubMed

Neltner, Janna Hackett; Abner, Erin Lynn; Schmitt, Frederick A; Denison, Stephanie Kay; Anderson, Sonya; Patel, Ela; Nelson, Peter T

2012-12-01

Quantitative neuropathologic methods provide information that is important for both research and clinical applications. The technologic advancement of digital pathology and image analysis offers new solutions to enable valid quantification of pathologic severity that is reproducible between raters regardless of experience. Using an Aperio ScanScope XT and its accompanying image analysis software, we designed algorithms for quantitation of amyloid and tau pathologies on 65 β-amyloid (6F/3D antibody) and 48 phospho-tau (PHF-1)-immunostained sections of human temporal neocortex. Quantitative digital pathologic data were compared with manual pathology counts. There were excellent correlations between manually counted and digitally analyzed neuropathologic parameters (R² = 0.56-0.72). Data were highly reproducible among 3 participants with varying degrees of expertise in neuropathology (intraclass correlation coefficient values, >0.910). Digital quantification also provided additional parameters, including average plaque area, which shows statistically significant differences when samples are stratified according to apolipoprotein E allele status (average plaque area, 380.9 μm² in apolipoprotein E [Latin Small Letter Open E]4 carriers vs 274.4 μm² for noncarriers; p < 0.001). Thus, digital pathology offers a rigorous and reproducible method for quantifying Alzheimer disease neuropathologic changes and may provide additional insights into morphologic characteristics that were previously more challenging to assess because of technical limitations.

Treatment of pathological gambling - integrative systemic model.

PubMed

Mladenović, Ivica; Lažetić, Goran; Lečić-Toševski, Dušica; Dimitrijević, Ivan

2015-03-01

Pathological gambling was classified under impulse control disorders within the International Classification of Diseases (ICD-10) (WHO 1992), but the most recent Diagnostic and Statistical Manual, 5th edition (DSM-V), (APA 2013), has recognized pathological gambling as a first disorder within a new diagnostic category of behavioral addictions - Gambling disorder. Pathological gambling is a disorder in progression, and we hope that our experience in the treatment of pathological gambling in the Daily Hospital for Addictions at The Institute of Mental Health, through the original "Integrative - systemic model" would be of use to colleagues, dealing with this pathology. This model of treatment of pathological gambling is based on multi-systemic approach and it primarily represents an integration of family and cognitive-behavioral therapy, with traces of psychodynamic, existential and pharmacotherapy. The model is based on the book "Pathological gambling - with self-help manual" by Dr Mladenovic and Dr Lazetic, and has been designed in the form of a program that lasts 10 weeks in the intensive phase, and then continues for two years in the form of "extended treatment" ("After care"). The intensive phase is divided into three segments: educational, insight with initial changes and analysis of the achieved changes with the definition of plans and areas that need to be addressed in the extended treatment. "Extended treatment" lasts for two years in the form of group therapy, during which there is a second order change of the identified patient, but also of other family members. Pathological gambling has been treated in the form of systemic-family therapy for more than 10 years at the Institute of Mental Health (IMH), in Belgrade. For second year in a row the treatment is carried out by the modern "Integrative-systemic model". If abstinence from gambling witihin the period of one year after completion of the intensive phase of treatment is taken as the main criterion of the effectiveness of our model, at this time it exceeds 90%. Given the relatively short period of application, it is necessary to continue to monitor and evaluate the model after 5 years.

Lessons from a non-domestic canid: joint disease in captive raccoon dogs (Nyctereutes procyonoides).

PubMed

Lawler, Dennis F; Evans, Richard H; Nieminen, Petteri; Mustonen, Anne-Mari; Smith, Gail K

2012-01-01

The purpose of this study was to describe pathological changes of the shoulder, elbow, hip and stifle joints of 16 museum skeletons of the raccoon dog (Nyctereutes procyonoides). The subjects had been held in long-term captivity and were probably used for fur farming or research, thus allowing sufficient longevity for joint disease to become recognisable. The prevalence of disorders that include osteochondrosis, osteoarthritis and changes compatible with hip dysplasia, was surprisingly high. Other changes that reflect near-normal or mild pathological conditions, including prominent articular margins and mild bony periarticular rim, were also prevalent. Our data form a basis for comparing joint pathology of captive raccoon dogs with other mammals and also suggest that contributing roles of captivity and genetic predisposition should be explored further in non-domestic canids.

A classification of the mechanisms producing pathological tissue changes.

PubMed

Grippo, John O; Oh, Daniel S

2013-05-01

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

Prevalence of Trypanosoma cruzi and organ alterations in Virginia opossums (Didelphis virginiana) from western Mexico - short communication.

PubMed

Carnevali, Vincenzo; Nogueda-Torres, Benjamín; Villagrán-Herrera, María E; De Diego-Cabrera, José A; Rocha-Chávez, Gonzalo; Martínez-Ibarra, José A

2017-12-01

Small populations of Virginia opossum (Didelphis virginiana) in western Mexico are endangered by hunting and natural predators as well as by different kinds of diseases. After two serological analyses using Serodia® latex particle agglutination and indirect haemagglutination (IHA) tests, 35 (53.03%) of 66 collected opossums in two small towns in western Mexico were positive for the presence of Trypanosoma cruzi. Twenty-eight of the 35 seropositive opossums had pathological lesions: 11 had changes in only one organ, 13 in two organs, and four had pathological changes in three organs. Splenomegaly was the most common finding in the examined opossums, followed by hepatomegaly. These potentially fatal pathological changes could contribute to the scarcity of the opossum population, even leading to the extinction of this species in western Mexico.

Trouble shooting in toxicopathology

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

Rousseaux, C.G.

2005-09-01

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

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

PubMed

Berg, Kyra; Wright, Joanne L

2016-12-01

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

Pathological conformations involving the amino terminus of tau occur early in Alzheimer’s disease and are differentially detected by monoclonal antibodies

PubMed Central

Combs, Benjamin; Hamel, Chelsey; Kanaan, Nicholas M.

2016-01-01

Conformational changes involving the amino terminus of the tau protein are among the earliest alterations associated with tau pathology in Alzheimer’s disease and other tauopathies. This region of tau contains a phosphatase-activating domain (PAD) that is aberrantly exposed in pathological forms of the protein, an event that is associated with disruptions in anterograde fast axonal transport. We utilized four antibodies that recognize the amino terminus of tau, TNT1, TNT2 (a novel antibody), Tau12, and Tau13, to further study this important region. Using scanning alanine mutations in recombinant tau proteins, we refined the epitopes of each antibody. We examined the antibodies’ relative abilities to specifically label pathological tau in non-denaturing and denaturing assays to gain insight into some of the mechanistic details of PAD exposure. We then determined the pattern of tau pathology labeled by each antibody in human hippocampal sections at various disease stages in order to characterize PAD exposure in the context of disease progression. The characteristics of reactivity for the antibodies fell into two groups. TNT1 and TNT2 recognized epitopes within amino acids 7–12 and specifically identified recombinant tau aggregates and pathological tau from Alzheimer’s disease brains in a conformation-dependent manner. These antibodies labeled early pre-tangle pathology from neurons in early Braak stages and colocalized with thiazine red, a marker of fibrillar pathology, in classic neurofibrillary tangles. However, late tangles were negative for TNT1 and TNT2 indicating a loss of the epitope in later stages of tangle evolution. In contrast, Tau12 and Tau13 both identified discontinuous epitopes in the amino terminus and were unable to differentiate between normal and pathological tau in biochemical and tissue immunohistological assays. Despite the close proximity of these epitopes, the antibodies demonstrated remarkably different abilities to identify pathological changes in tau indicating that detection of conformational alterations involving PAD exposure is not achieved by all N-terminal tau antibodies and that a relatively discrete region of the N-terminus (i.e., amino acids 7–12, the TNT1 and TNT2 epitope) is central to the differences between normal and pathological tau. The appearance of PAD in early tau pathology and its disappearance in late-stage tangles suggest that toxic forms of tau are associated with the earliest forms of tau deposits. Collectively, these findings demonstrate that the TNT antibodies are useful markers for early conformational display of PAD and provide information regarding conformational changes that have potential implications in the toxic mechanisms of tau pathology. PMID:27260838

Magnetic Resonance Imaging to Detect Early Molecular and Cellular Changes in Alzheimer's Disease.

PubMed

Knight, Michael J; McCann, Bryony; Kauppinen, Risto A; Coulthard, Elizabeth J

2016-01-01

Recent pharmaceutical trials have demonstrated that slowing or reversing pathology in Alzheimer's disease is likely to be possible only in the earliest stages of disease, perhaps even before significant symptoms develop. Pathology in Alzheimer's disease accumulates for well over a decade before symptoms are detected giving a large potential window of opportunity for intervention. It is therefore important that imaging techniques detect subtle changes in brain tissue before significant macroscopic brain atrophy. Current diagnostic techniques often do not permit early diagnosis or are too expensive for routine clinical use. Magnetic Resonance Imaging (MRI) is the most versatile, affordable, and powerful imaging modality currently available, being able to deliver detailed analyses of anatomy, tissue volumes, and tissue state. In this mini-review, we consider how MRI might detect patients at risk of future dementia in the early stages of pathological change when symptoms are mild. We consider the contributions made by the various modalities of MRI (structural, diffusion, perfusion, relaxometry) in identifying not just atrophy (a late-stage AD symptom) but more subtle changes reflective of early dementia pathology. The sensitivity of MRI not just to gross anatomy but to the underlying "health" at the cellular (and even molecular) scales, makes it very well suited to this task.

The changing role of the pathologist in the management of Barrett's oesophagus.

PubMed

Hopcroft, Suzanne A; Shepherd, Neil A

2014-10-01

Pathological specimens from columnar-lined oesophagus (CLO) comprise a considerable proportion of the workload of gastrointestinal pathologists in Western countries. There remain controversies concerning the diagnostic role of pathology. More recently, in the UK at least, the diagnosis has been regarded as primarily an endoscopic endeavour, with pathology being corroborative and only diagnostic when endoscopic features are equivocal or when there are additional features that make the endoscopic diagnosis unclear. There is also recognition that demonstration of intestinalisation or 'goblet cells' is not paramount, and should not be required for the diagnosis. There have been notable changes in the management of CLO neoplasia: pathologists are centrally involved in its management. Pathological assessment of endoscopic mucosal resection (EMR) specimens provides the most useful means of determining the management of early neoplasia and of determining indications for surgery. This represents an extraordinarily rapid change in management, in that, <10 years ago, laborious Seattle-type biopsy protocols were recommended, and high grade dysplasia was an indication for resectional surgery. Now, individual patient management is paramount: multi-professional meetings determine management after biopsy and EMR assessment. One significant change is that major resections are undertaken less often, in Western countries, for CLO neoplasia. © 2014 John Wiley & Sons Ltd.

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

PubMed

Gu, Jiang; Taylor, Clive R

2014-01-01

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

Practicing Pathology in the Era of Big Data and Personalized Medicine

PubMed Central

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

2014-01-01

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

Specific features of cytological and colposcopical pattern in pregnant women with benign cervix uteri pathology in anamnesis.

PubMed

Bysaha, Nataliya Yu

2016-01-01

a tendency of increasing incidence of the cervix uteri precancer and cancer in women of reproductive age is noticed recently being related to the growth of number of the sexually-transmitted infections. The cervix uteri pathology incidence in women of fertile age is 20-25%. to study the specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in the anamnesis and the character of its change post partum. we have examined 195 women during their pregnancy and 3-5 months post partum. All pregnant women, alongside with generally accepted clinical and laboratory examinations, were subjected to the simple and extended colposcopy, cytology of the targeted smears and, according to indications, the histological studies of bioptate. according to the results of the colcoscopical studies and the signs of the cervix uteri pathology found, the patients were divided into several groups. A control group included 49 pregnant women. The clinical and instrumental examination of 146 women with cervix uteri pathology has been carried out both during pregnancy and post partum. the structure of the clinical forms of benign and premalignant changes in the cervix uteri epithelium in pregnant patients has been found. Specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in anamnesis have been studied. The relationship between the parity of pregnancy, delivery, route of delivery and regress of both benign and premalignant changes in the cervix uteri epithelium 3-5 months post partum has been determined.

Overview of the "epigenetic end points in toxicologic pathology and relevance to human health" session of the 2014 Society Of Toxicologic Pathology Annual Symposium.

PubMed

Hoenerhoff, Mark J; Hartke, James

2015-01-01

The theme of the Society of Toxicologic Pathology 2014 Annual Symposium was "Translational Pathology: Relevance of Toxicologic Pathology to Human Health." The 5th session focused on epigenetic end points in biology, toxicity, and carcinogenicity, and how those end points are relevant to human exposures. This overview highlights the various presentations in this session, discussing integration of epigenetics end points in toxicologic pathology studies, investigating the role of epigenetics in product safety assessment, epigenetic changes in cancers, methodologies to detect them, and potential therapies, chromatin remodeling in development and disease, and epigenomics and the microbiome. The purpose of this overview is to discuss the application of epigenetics to toxicologic pathology and its utility in preclinical or mechanistic based safety, efficacy, and carcinogenicity studies. © 2014 by The Author(s).

[Pathological changes in rats with acute Dysosma versipellis poisoning].

PubMed

Xu, Xiang; Xu, Mao-sheng; Zhu, Jian-hua; Huang, Guang-zhao

2013-10-01

To observe the pathological changes of major organs in rats with acute Dysosma versipellis poisoning and investigate the toxic mechanism and the injuries of target tissues and organs. Forty Sprague-Dawley (SD) rats were randomly divided into three experimental groups, which were given the gavage with 0.5, 1.0 and 2.0 LDo doses of Dysosma versipellis decoction, and one control group, which was given the gavage with 1.0 LD0 dose of normal saline. The rats were sacrificed 14 days after Dysosma versipellis poisoning and samples including brain, heart, liver, lung, and kidney were taken. After pathological process, the pathological changes of the major organs and tissues were observed by light microscope and electron microscope. The experimental data were statistical analyzed by chi2 test. The observations of light microscopy: loose cytoplasm of neurons with loss of most Nissl bodies; swelling of myocardial cells with disappearance of intercalated disk and striations; hepatocellular edema with ballooning degeneration; and swelling epithelial cells of renal proximal convoluted tubule with red light coloring protein-like substances in the tube. The observations of electron microscopy: the structures of cell membrane and nuclear membrane of neurons were destroyed; cytoplasm of neurons, obvious edema; and most organelles, destroyed and disappeared. The mortalities of rats after acute poisoning of the four groups increased with doses (P < 0.05). Acute Dysosma versipellis poisoning can cause multi-organ pathological changes. There is a positive correlation between the toxic effect and the dosage. The target tissues and organs are brain (neurons), heart, liver and kidney.

[Viscosity determination of synovial fluids from the canine hip and elbow joint as well as the human knee joint].

PubMed

Helms, Gabriele; Rittmann, Pia; Wefstaedt, Patrick; Windhagen, Henning; Pressel, Thomas; Behrens, Bernd-Arno; Nolte, Ingo

2008-01-01

The development of pathological changes in both human and canine hip joints is mainly caused by a lack of synovial fluid lubrication. This results in an increased joint abrasion. Even after implantation of joint prosthesis, inadequate lubrication can lead to abrasion in the tribological pair. This can finally result in aseptic loosening of the prosthesis. In spite of the enormous number of studies that have been performed on human, only little knowledge about the tribological properties of the joints in dogs is available in the literature. For this reason the viscosities of synovial fluid, derived from physiological and pathologically changed canine elbow joints were measured. The viscosities were determined by the use of a cone-plate viscometer at different temperatures and shear rates. The obtained values were compared with the viscosity values of pathologically changed synovial fluids from human knee joints as well as with pathological samples from the canine hip joint. The results show that the viscosity values vary within a series of measurements and are inversely proportional to the temperature of the sample and the shear rate. The differences between the average viscosities of canine and human synovial fluids taken from pathologically changed joints are below 4% (22.5 s(-1) at theta1 = 25 degrees C). The findings of this study are being implemented in a FE-Model for the computation of actual forces in the hip joint during different movements. This would represent a contribution to an improved prosthetic treatment of canine and human hips.

The Kidney in Aging: Physiological Changes and Pathological Implications.

PubMed

Sobamowo, H; Prabhakar, S S

2017-01-01

Aging is associated with progressive decline in renal function along with concurrent morphological changes that ultimately lead to glomerulosclerosis. The mechanisms leading to such changes in the kidney with age as well as the basis of controversies that surround the physiological basis vs pathological nature of aging kidney are the focus of this in-depth review. In addition, the renal functional defects of acid-base homeostasis and electrolyte disturbances in elderly and the physiological basis of such disorders are also discussed. © 2017 Elsevier Inc. All rights reserved.

[Clinical and pathological features of Alport syndrome in children].

PubMed

Zhu, Chun-Hua; Huang, Song-Ming; Wu, Hong-Mei; Bao, Hua-Ying; Chen, Ying; Han, Yuan; Zhao, Fei; Zhang, Ai-Hua; Zhang, Wei-Zhen

2010-03-01

To study the clinical and pathological features of Alport syndrome in children. The clinical and histopathological data of 10 hospitalized children with Alport syndrome from February 2007 to February 2009 were retrospectively reviewed. There were 7 males and 3 females, with the age ranging from 2 years to 6 years and 7 months (mean 3 years and 2 months). Five of 10 cases had positive family history. X-linked dominant inheritance Alport syndrome was diagnosed in 8 cases, and autosomal recessive inheritance Alport syndrome in 2 cases. Recurrent gross hematuria was found in 5 cases, hematuria and proteinuria in 3 cases, massive proteinuria in 1 case, and nephritic syndrome in 1 case. Under the light microscope, 8 cases presented with mesangial proliferation glomerulonephritis, and 2 cases with focal segmental glomerulosclerosis. Immunofluorescence assay showed that all cases had IgM deposition in glomerulus. Only 1 case showed typical glomerular basement membrane (GBM) pathological changes. All cases showed abnormal alpha-chain distribution in renal collagen IV. The children with Alport syndrome have diverse clinical manifestations. Characteristic histopathological presentations could not be found under a light microscope, mesangial proliferation glomerulonephritis is the dominant pathological change, and IgM deposition in glomerulus is common. The GBM pathological change in children is not common. Immunofluorescence assay of alpha-chain in collagen IV is needed for the diagnosis of Alport syndrome.

Implementing digital technology to enhance student learning of pathology.

PubMed

Farah, C S; Maybury, T

2009-08-01

The introduction of digital technologies into the dental curriculum is an ongoing feature of broader changes going on in tertiary education. This report examines the introduction of digital virtual microscopy technology into the curriculum of the School of Dentistry at the University of Queensland (UQ) in Brisbane, Australia. Sixty students studying a course in pathology in 2005 were introduced to virtual microscopy technology alongside the more traditional light microscope and then asked to evaluate their own learning outcomes from this technology via a structured 5-point LIKART survey. A wide variety of questions dealing the pedagogic implications of the introduction of virtual microscopy into pathology were asked of students with the overall result being that it positively enhanced their learning of pathology via digital microscopic means. The success of virtual microscopy in dentistry at UQ is then discussed in the larger context of changes going on in tertiary education. In particular, the change from the print-literate tradition to the electronic one, that is from 'literacy to electracy'. Virtual microscopy is designated as a component of this transformation to electracy. Whilst traditional microscopic skills may still be valued in dental curricula, the move to virtual microscopy and computer-assisted, student-centred learning of pathology appears to enhance the learning experience in relation to its effectiveness in helping students engage and interact with the course material.

Molecular pathology of bone tumours: diagnostic implications.

PubMed

Puls, Florian; Niblett, Angela J; Mangham, D Chas

2014-03-01

Alongside histomorphology and immunohistochemistry, molecular pathology is now established as one of the cornerstones in the tissue diagnosis of bone tumours. We describe the principal molecular pathological techniques employed, and each of the bone tumour entities where their identified characteristic molecular pathological changes can be detected to support and confirm the suspected histological diagnosis. Tumours discussed include fibrous dysplasia, classical and subtype osteosarcomas, central and surface cartilaginous tumours, Ewing's sarcoma, vascular tumours, aneurysmal bone cyst, chordoma, myoepithelioma, and angiomatoid fibrous histiocytoma. This is a rapidly evolving field with discoveries occurring every few months, and some of the newer entities (the Ewing's-like sarcomas), which are principally identified by their molecular pathology characteristics, are discussed. © 2013 John Wiley & Sons Ltd.

White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

PubMed

Craggs, Lucinda J L; Yamamoto, Yumi; Ihara, Masafumi; Fenwick, Richard; Burke, Matthew; Oakley, Arthur E; Roeber, Sigrun; Duering, Marco; Kretzschmar, Hans; Kalaria, Raj N

2014-08-01

Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM. We used post-mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro-caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles. The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (P<0.01) with the WM underlying the primary motor cortex exhibiting the most severe change. SMI32 immunoreactive axons in CADASIL were invariably increased compared with controls (P<0.01), with most prominent axonal abnormalities observed in the frontal WM (P<0.05). The SIs of arterioles in CADASIL were increased by 25-45% throughout the regions assessed, with the highest change in the mid-frontal region (P=0.000). Our results suggest disruption of either cortico-cortical or subcortical-cortical networks in the WM of the frontal lobe that may explain motor deficits and executive dysfunction in CADASIL. Widespread WM axonal changes arise from differential stenosis and sclerosis of arterioles in the WM of CADASIL subjects, possibly affecting some axons of projection neurones connecting to targets in the subcortical structures. © 2013 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Normative development of the Child Behavior Checklist Dysregulation Profile from early childhood to adolescence: Associations with personality pathology.

PubMed

Deutz, Marike H F; Vossen, Helen G M; De Haan, Amaranta D; Deković, Maja; Van Baar, Anneloes L; Prinzie, Peter

2018-05-01

The Dysregulation Profile (DP) is a broad indicator of concurrent affective, behavioral, and cognitive dysregulation, often measured with the anxious/depressed, aggressive behavior, and attention problems syndrome scales of the Child Behavior Checklist. Despite an expanding body of research on the DP, knowledge of the normative developmental course of the DP from early childhood to adolescence is lacking. Furthermore, although we know that the DP longitudinally predicts personality pathology, no research yet has examined whether next to the DP in early childhood, the rate of change of the DP across development predicts personality pathology. Therefore, using cohort-sequential latent growth modeling in a population-based sample (N = 668), we examined the normative developmental course of mother-reported DP from ages 4 to 17 years and its associations with a wide range of adolescent-reported personality pathology dimensions 3 years later. The results showed that the DP follows a nonlinear developmental course with a peak in early adolescence. The initial level of the DP at age 4 and, to a lesser extent, the rate of change in the DP predicted a range of personality pathology dimensions in late adolescence. The findings suggest that the DP is a broad developmental precursor of personality pathology in late adolescence.

Imaging-Assisted Large-Format Breast Pathology: Program Rationale and Development in a Nonprofit Health System in the United States

PubMed Central

Tucker, F. Lee

2012-01-01

Modern breast imaging, including magnetic resonance imaging, provides an increasingly clear depiction of breast cancer extent, often with suboptimal pathologic confirmation. Pathologic findings guide management decisions, and small increments in reported tumor characteristics may rationalize significant changes in therapy and staging. Pathologic techniques to grossly examine resected breast tissue have changed little during this era of improved breast imaging and still rely primarily on the techniques of gross inspection and specimen palpation. Only limited imaging information is typically conveyed to pathologists, typically in the form of wire-localization images from breast-conserving procedures. Conventional techniques of specimen dissection and section submission destroy the three-dimensional integrity of the breast anatomy and tumor distribution. These traditional methods of breast specimen examination impose unnecessary limitations on correlation with imaging studies, measurement of cancer extent, multifocality, and margin distance. Improvements in pathologic diagnosis, reporting, and correlation of breast cancer characteristics can be achieved by integrating breast imagers into the specimen examination process and the use of large-format sections which preserve local anatomy. This paper describes the successful creation of a large-format pathology program to routinely serve all patients in a busy interdisciplinary breast center associated with a community-based nonprofit health system in the United States. PMID:23316372

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2011-10-01

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

Radiological-Pathological Correlation in Alzheimer's Disease: Systematic Review of Antemortem Magnetic Resonance Imaging Findings.

PubMed

Dallaire-Théroux, Caroline; Callahan, Brandy L; Potvin, Olivier; Saikali, Stéphan; Duchesne, Simon

2017-01-01

The standard method of ascertaining Alzheimer's disease (AD) remains postmortem assessment of amyloid plaques and neurofibrillary degeneration. Vascular pathology, Lewy bodies, TDP-43, and hippocampal sclerosis are frequent comorbidities. There is therefore a need for biomarkers that can assess these etiologies and provide a diagnosis in vivo. We conducted a systematic review of published radiological-pathological correlation studies to determine the relationship between antemortem magnetic resonance imaging (MRI) and neuropathological findings in AD. We explored PubMed in June-July 2015 using "Alzheimer's disease" and combinations of radiological and pathological terms. After exclusion following screening and full-text assessment of the 552 extracted manuscripts, three others were added from their reference list. In the end, we report results based on 27 articles. Independently of normal age-related brain atrophy, AD pathology is associated with whole-brain and hippocampal atrophy and ventricular expansion as observed on T1-weighted images. Moreover, cerebral amyloid angiopathy and cortical microinfarcts are also related to brain volume loss in AD. Hippocampal sclerosis and TDP-43 are associated with hippocampal and medial temporal lobe atrophy, respectively. Brain volume loss correlates more strongly with tangles than with any other pathological finding. White matter hyperintensities observed on proton density, T2-weighted and FLAIR images are strongly related to vascular pathologies, but are also associated with other histological changes such as gliosis or demyelination. Cerebral atrophy and white matter changes in the living brain reflect underlying neuropathology and may be detectable using antemortem MRI. In vivo MRI may therefore be an avenue for AD pathological staging.

Effects of Asymptomatic Rotator Cuff Pathology On In-Vivo Shoulder Motion and Clinical Outcomes

PubMed Central

Baumer, Timothy G.; Dischler, Jack; Mende, Veronica; Zauel, Roger; van Holsbeeck, Marnix; Siegal, Daniel S.; Divine, George; Moutzouros, Vasilios; Bey, Michael J.

2017-01-01

Background The incidence of asymptomatic rotator cuff tears has been reported to range from 15–39%, but the influence of asymptomatic rotator cuff pathology on shoulder function is not well understood. The objective of this study was to assess the effects of asymptomatic rotator cuff pathology on shoulder kinematics, strength, and patient-reported outcomes. Methods 46 asymptomatic volunteers (age: 60.3±7.5) with normal shoulder function underwent a clinical ultrasound exam to document the condition of their rotator cuff. The ultrasound imaging identified subjects as healthy (n=14) or pathologic (n=32). Shoulder motion was measured with a biplane x-ray imaging system, strength was assessed with a Biodex, and patient-reported outcomes were assessed using the Western Ontario Rotator Cuff Index and VAS pain scores. Results Compared to healthy subjects, the subjects with rotator cuff pathology had significantly less abduction (p=0.050) and elevation (p=0.041) strength, their humerus was positioned more inferiorly on the glenoid (p=0.018), and the glenohumeral contact path length was longer (p=0.007). No significant differences were detected in terms of WORC, VAS, ROM, or acromiohumeral distance. Discussion The differences observed between the healthy subjects and subjects with asymptomatic rotator cuff pathology lend insight into the changes in joint mechanics, shoulder strength, and conventional clinical outcomes associated with the early stages of rotator cuff pathology. Furthermore, these findings suggest a plausible mechanical progression of kinematic and strength changes associated with the development of rotator cuff pathology. Level of evidence Basic Science Study, Kinesiology PMID:28131679

[Study on ultra-structural pathological changes of rats poisoned by tetramine].

PubMed

Zhi, Chuan-hong; Liu, Liang; Liu, Yan

2005-05-01

To observe ultra-structural pathological changes of materiality viscera of rats poisoned by different dose of tetramine and to study the toxic mechanism. Acute and subacute tetramine toxicity models were made by oral administration with different dose of tetramine. Brain, heart, liver, spleen and kidney were extracted and observed by electromicroscopic examination. The injuries of brain cells, cardiocytes and liver cells were induced by different dose of tetramine. These were not obviously different of the injuries of the kindy cells and spleen cells of rats poisoned by different dose of tetramine. Ultra-structural pathological changes were abserved including mitochondria slight swelling and neurolemma's array turbulence in the brain cells, mitochondria swelling or abolish and rupture of muscle fiber in the heart cells, mitochondria swelling and the glycogen decreased in the liver cells. The toxic target organs of tetramine are the heart, brain and liver.

The Changes of Energy Interactions between Nucleus Function and Mitochondria Functions Causing Transmutation of Chronic Inflammation into Cancer Metabolism.

PubMed

Ponizovskiy, Michail R

2016-01-01

Interactions between nucleus and mitochondria functions induce the mechanism of maintenance stability of cellular internal energy according to the first law of thermodynamics in able-bodied cells and changes the mechanisms of maintenance stability of cellular internal energy creating a transition stationary state of ablebodied cells into quasi-stationary pathologic states of acute inflammation transiting then into chronic inflammation and then transmuting into cancer metabolism. The mechanisms' influences of intruding etiologic pathologic agents (microbe, virus, etc.) lead to these changes of energy interactions between nucleus and mitochondria functions causing general acute inflammation, then passing into local chronic inflammation, and reversing into cancer metabolism transmutation. Interactions between biochemical processes and biophysical processes of cellular capacitors' operations create a supplementary mechanism of maintenance stability of cellular internal energy in the norm and in pathology. Discussion of some scientific works eliminates doubts of the authors of these works.

Multiple pathologies are common and related to dementia in the oldest-old

PubMed Central

Kim, Ronald C.; Sonnen, Joshua A.; Bullain, Szofia S.; Trieu, Thomas; Corrada, María M.

2015-01-01

Objective: The purpose of this study was to examine the role of multiple pathologies in the expression of dementia in the oldest-old. Methods: A total of 183 participants of The 90+ Study with longitudinal follow-up and autopsy were included in this clinical-pathologic investigation. Eight pathologic diagnoses (Alzheimer disease [AD], microinfarcts, hippocampal sclerosis, macroinfarcts, Lewy body disease, cerebral amyloid angiopathy, white matter disease, and others) were dichotomized. We estimated the odds of dementia in relation to each individual pathologic diagnosis and to the total number of diagnoses. We also examined dementia severity in relation to number of pathologic diagnoses. Results: The presence of multiple pathologic diagnoses was common and occurred more frequently in those with dementia compared with those without dementia (45% vs 14%). Higher numbers of pathologic diagnoses were also associated with greater dementia severity. Participants with intermediate/high AD pathology alone were 3 times more likely to have dementia (odds ratio = 3.5), but those with single non-AD pathologies were 12 times more likely to have dementia (odds ratio = 12.4). When a second pathology was present, the likelihood of dementia increased 4-fold in those with intermediate/high AD pathology but did not change in those with non-AD pathologies, suggesting that pathologies may interrelate in different ways. Conclusions: In the oldest-old, the presence of multiple pathologies is associated with increased likelihood and severity of dementia. The effect of the individual pathologies may be additive or perhaps synergistic and requires further research. Multiple pathologies will need to be targeted to reduce the burden of dementia in the population. PMID:26180144

MRI for transformation of preserved organs and their pathologies into digital formats for medical education and creation of a virtual pathology museum. A pilot study.

PubMed

Venkatesh, S K; Wang, G; Seet, J E; Teo, L L S; Chong, V F H

2013-03-01

To evaluate the feasibility of magnetic resonance imaging (MRI) for the transformation of preserved organs and their disease entities into digital formats for medical education and creation of a virtual museum. MRI of selected 114 pathology specimen jars representing different organs and their diseases was performed using a 3 T MRI machine with two or more MRI sequences including three-dimensional (3D) T1-weighted (T1W), 3D-T2W, 3D-FLAIR (fluid attenuated inversion recovery), fat-water separation (DIXON), and gradient-recalled echo (GRE) sequences. Qualitative assessment of MRI for depiction of disease and internal anatomy was performed. Volume rendering was performed on commercially available workstations. The digital images, 3D models, and photographs of specimens were archived into a workstation serving as a virtual pathology museum. MRI was successfully performed on all specimens. The 3D-T1W and 3D-T2W sequences demonstrated the best contrast between normal and pathological tissues. The digital material is a useful aid for understanding disease by giving insights into internal structural changes not apparent on visual inspection alone. Volume rendering produced vivid 3D models with better contrast between normal tissue and diseased tissue compared to real specimens or their photographs in some cases. The digital library provides good illustration material for radiological-pathological correlation by enhancing pathological anatomy and information on nature and signal characteristics of tissues. In some specimens, the MRI appearance may be different from corresponding organ and disease in vivo due to dead tissue and changes induced by prolonged contact with preservative fluid. MRI of pathology specimens is feasible and provides excellent images for education and creating a virtual pathology museum that can serve as permanent record of digital material for self-directed learning, improving teaching aids, and radiological-pathological correlation. Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The impact of early symptom change and therapeutic alliance on treatment outcome in cognitive-behavioural therapy for eating disorders.

PubMed

Turner, Hannah; Bryant-Waugh, Rachel; Marshall, Emily

2015-10-01

The present study explored the impact of early symptom change (cognitive and behavioural) and the early therapeutic alliance on treatment outcome in cognitive-behavioural therapy (CBT) for the eating disorders. Participants were 94 adults with diagnosed eating disorders who completed 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, following the 6th session and at the end of treatment. They also completed a measure of therapeutic alliance following the 6th session. Greater early reduction in dietary restraint and eating concerns, and smaller levels of change in shape concern, significantly predicted later reduction in global eating pathology. The early therapeutic alliance was strong across the three domains of tasks, goals and bond. Early symptom reduction was a stronger predictor of later reduction in eating pathology than early therapeutic alliance. The early therapeutic alliance did not mediate the relationship between early symptom reduction and later reduction in global eating pathology. Instead, greater early symptom reduction predicted a strong early therapeutic alliance. Early clinical change was the strongest predictor of treatment outcome and this also facilitated the development of a strong early alliance. Clinicians should be encouraged to deliver all aspects of evidence-based CBT, including behavioural change. The findings suggest that this will have a positive impact on both the early therapeutic alliance and later change in eating pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Critical leadership and management skills for pathology practice.

PubMed

Brimhall, Bradley B; Wright, Louis D; McGregor, Kelli L; Hernandez, James S

2007-10-01

Managed care has changed the nature of medical practice. The practice of pathology has also changed and is likely to undergo further modification. Additional skills in leadership and management are needed to perform optimally in the current medical marketplace. To determine whether pathologists view business and informatics skills as being important and valuable in their practices. A survey was sent electronically (via e-mail) to 2566 pathologists and pathology administrators. Two hundred sixteen survey recipients (8.4%) responded to the survey. The response rate to individual questions ranged from 86% to 99% (186 to 214 of 216 total respondents). Most who took the survey ranked communication (203/209; 97%), leadership skills (165/209; 79%), and systems thinking skills (155/209; 74%) as either "very important" or "essential." Fewer respondents were willing to offer salary premiums for marketing (108/196; 55%), business or finance (92/196; 47%), or staff leadership (95/196; 48%) skills unless the candidate had a track record of measurable achievement using these skills. Those practicing in academia as well as those making hiring decisions by themselves were more likely to value leadership and management skills. Fewer than 1% of respondents in any category considered current pathology residency training in leadership and management to be adequate. Prospective employers value leadership and management skills. Pathology residency programs must include meaningful training in pathology practice management and informatics to satisfy the demand for these skills in the modern pathology marketplace.

Atlas of neuroanatomy with radiologic correlation and pathologic illustration

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

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

1982-01-01

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

A Disease or Not a Disease? Aging As a Pathology.

PubMed

Gladyshev, Timothy V; Gladyshev, Vadim N

2016-12-01

The debate on the relationship between aging and disease is centered on whether aging is a normal/natural/physiological process or it represents a pathology. Considering this relationship from medical, molecular, social, and historical perspectives, we argue that aging is neither a disease, nor a non-disease. Instead, it combines all age-related diseases and their preclinical forms, in addition to other pathological changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pathogenesis of Idiopathic Pulmonary Fibrosis

PubMed Central

Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.

2014-01-01

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627

Selective pathology fellowships: diverse, innovative, and valuable subspecialty training.

PubMed

Iezzoni, Julia C; Ewton, April; Chévez-Barrios, Patricia; Moore, Stephen; Thorsen, Linda M; Naritoku, Wesley Y

2014-04-01

Although selective pathology fellowships have a long-standing history of developing trainees with advanced expertise in specific areas of pathology other than those of the American Board of Pathology-certified subspecialties, the widespread interest in this training continues to grow. To describe the historical background and current status of selective pathology fellowships, and to provide examples of 3 programs. In addition, Accreditation Council for Graduate Medical Education (ACGME)-accredited programs and nonaccredited programs in Selective Pathology are compared. ACGME data banks and publicly available online materials were used. Program directors of the fellowships examples in this paper provided program-specific information. Additionally, an online survey of the program directors and program coordinators of ACGME-accredited programs and nonaccredited programs in selective pathology was performed. There are currently 76 ACGME-accredited selective pathology programs. The programs are distributed between 3 major categories: surgical pathology, focused anatomic pathology, and focused clinical pathology. Although the vast majority of programs are concerned that their funding source may be cut in the next 3 years, most programs will not change the number of fellowship positions in their programs. Program requirements devoted specifically and solely to selective pathology have been developed and are in effect. The value of this training is recognized not only by pathologists, but by clinicians as well, in both academia and private practice. Importantly, the diversity and innovation inherent in selective pathology allow these programs to adeptly address new subspecialty areas and technologic advances in the current and evolving practice of pathology.

Analysis of tau post-translational modifications in rTg4510 mice, a model of tau pathology.

PubMed

Song, Lixin; Lu, Sherry X; Ouyang, Xuesong; Melchor, Jerry; Lee, Julie; Terracina, Giuseppe; Wang, Xiaohai; Hyde, Lynn; Hess, J Fred; Parker, Eric M; Zhang, Lili

2015-03-26

Microtubule associated protein tau is the major component of the neurofibrillary tangles (NFTs) found in the brains of patients with Alzheimer's disease and several other neurodegenerative diseases. Tau mutations are associated with frontotemperal dementia with parkinsonism on chromosome 17 (FTDP-17). rTg4510 mice overexpress human tau carrying the P301L FTDP-17 mutation and develop robust NFT-like pathology at 4-5 months of age. The current study is aimed at characterizing the rTg4510 mice to better understand the genesis of tau pathology and to better enable the use of this model in drug discovery efforts targeting tau pathology. Using a panel of immunoassays, we analyzed the age-dependent formation of pathological tau in rTg4510 mice and our data revealed a steady age-dependent accumulation of pathological tau in the insoluble fraction of brain homogenates. The pathological tau was associated with multiple post-translational modifications including aggregation, phosphorylation at a wide variety of sites, acetylation, ubiquitination and nitration. The change of most tau species reached statistical significance at the age of 16 weeks. There was a strong correlation between the different post-translationally modified tau species in this heterogeneous pool of pathological tau. Total tau in the cerebrospinal fluid (CSF) displayed a multiphasic temporal profile distinct from the steady accumulation of pathological tau in the brain. Female rTg4510 mice displayed significantly more aggressive accumulation of pathological tau in the brain and elevation of total tau in CSF than their male littermates. The immunoassays described here were used to generate the most comprehensive description of the changes in various tau species across the lifespan of the rTg4510 mouse model. The data indicate that development of tauopathy in rTg4510 mice involves the accumulation of a pool of pathological tau that carries multiple post-translational modifications, a process that can be detected well before the histological detection of NFTs. Therapeutic treatment targeting tau should therefore aim to reduce all tau species associated with the pathological tau pool rather than reduce specific post-translational modifications. There is still much to learn about CSF tau in physiological and pathological processes in order to use it as a translational biomarker in drug discovery.

[EEG changes in symptomatic headache caused by bruxism].

PubMed

Wieselmann, G; Grabmair, W; Logar, C; Permann, R; Moser, F

1987-02-20

EEG recordings were carried out on 36 patients with the verified diagnosis of bruxism and unilateral headache. Occlusal splints were applied in the long-term management of these patients. Initial EEG recordings showed pathological changes in 56% of the patients. The EEG recordings were repeated two and six weeks later in these patients and following improvement in the clinical symptomatology pathological EEG patterns were detected in only 22% of all cases. This decrease is of statistical significance.

Cerebellar pathology in childhood-onset vs. adult-onset essential tremor.

PubMed

Louis, Elan D; Kuo, Sheng-Han; Tate, William J; Kelly, Geoffrey C; Faust, Phyllis L

2017-10-17

Although the incidence of ET increases with advancing age, the disease may begin at any age, including childhood. The question arises as to whether childhood-onset ET cases manifest the same sets of pathological changes in the cerebellum as those whose onset is during adult life. We quantified a broad range of postmortem features (Purkinje cell [PC] counts, PC axonal torpedoes, a host of associated axonal changes [PC axonal recurrent collateral count, PC thickened axonal profile count, PC axonal branching count], heterotopic PCs, and basket cell rating) in 60 ET cases (11 childhood-onset and 49 adult-onset) and 30 controls. Compared to controls, childhood-onset ET cases had lower PC counts, higher torpedo counts, higher heterotopic PC counts, higher basket cell plexus rating, and marginally higher PC axonal recurrent collateral counts. The median PC thickened axonal profile count and median PC axonal branching count were two to five times higher in childhood-onset ET than controls, but the differences did not reach statistical significance. Childhood-onset and adult-onset ET had similar PC counts, torpedo counts, heterotopic PC counts, basket cell plexus rating, PC axonal recurrent collateral counts, PC thickened axonal profile count and PC axonal branching count. In conclusion, we found that childhood-onset and adult-onset ET shared similar pathological changes in the cerebellum. The data suggest that pathological changes we have observed in the cerebellum in ET are a part of the pathophysiological cascade of events in both forms of the disease and that both groups seem to reach the same pathological endpoints at a similar age of death. Copyright © 2017 Elsevier B.V. All rights reserved.

Vocal Fold Vibration Following Surgical Intervention in Three Vocal Pathologies: A Preliminary Study.

PubMed

Chen, Wenli; Woo, Peak; Murry, Thomas

2017-09-01

High-speed videoendoscopy captures the cycle-to-cycle vibratory motion of each individual vocal fold in normal and severely disordered phonation. Therefore, it provides a direct method to examine the specific vibratory changes following vocal fold surgery. The purpose of this study was to examine the vocal fold vibratory pattern changes in the surgically treated pathologic vocal fold and the contralateral vocal fold in three vocal pathologies: vocal polyp (n = 3), paresis or paralysis (n = 3), and scar (n = 3). Digital kymography was used to extract high-speed kymographic vocal fold images at the mid-membranous region of the vocal fold. Spectral analysis was subsequently applied to the digital kymography to quantify the cycle-to-cycle movements of each vocal fold, expressed as a spectrum. Surgical modification resulted in significantly improved spectral power of the treated pathologic vocal fold. Furthermore, the contralateral vocal fold also presented with improved spectral power irrespective of vocal pathology. In comparison with normal vocal fold spectrum, postsurgical vocal fold vibrations continued to demonstrate decreased vibratory amplitude in both vocal folds. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Mobile Technology for the Practice of Pathology.

PubMed

Hartman, Douglas J

2016-03-01

Recently, several technological advances have been introduced to mobile phones leading some people to refer to them as "smartphones." These changes have led to widespread consumer adoption. A similar adoption has occurred within the medical field and this revolution is changing the practice of medicine, including pathology. Several mobile applications have been published for dermatology, orthopedics, ophthalmology, neurosurgery, and clinical pathology. The applications are wide ranging, including mobile technology to increase patient engagement, self-monitoring by patients, clinical algorithm calculation, facilitation between experts to resource-poor environments. These advances have been received with mixed reviews. For anatomic pathology, mobile technology applications can be broken into 4 broad categories: (a) educational uses, (b) microscope with mobile phone, (c) mobile phone as microscope/acquisition device, and (d) miscellaneous. Using a mobile phone as an acquisition device paired with a microscope seems to be the most interesting current application because of the need for expert consultation with resource-poor environments. However, several emerging uses for mobile technology may become more prominent as the technology matures including image analysis, alternative light sources, and increased opportunities for clinician and patient engagement. The flexibility represented by mobile technology represents a burgeoning field in pathology informatics.

Use of Severity Grades to Characterize Histopathologic Changes.

PubMed

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

2018-04-01

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

Prostate cancer: from Gleason scoring to prognostic grade grouping.

PubMed

Montironi, Rodolfo; Santoni, Matteo; Mazzucchelli, Roberta; Burattini, Luciano; Berardi, Rossana; Galosi, Andrea B; Cheng, Liang; Lopez-Beltran, Antonio; Briganti, Alberto; Montorsi, Francesco; Scarpelli, Marina

2016-01-01

The Gleason grading system was developed in the late 1960s by Dr. Donald F. Gleason. Due to changes in prostatic adenocarcinoma (PAC) detection and treatment, newer technologies to better characterize prostatic pathology, subsequently described variants of PAC and further data relating various morphologic patterns to prognosis, the application of the Gleason grading system changed substantially in surgical pathology. First in 2005 and more recently in 2014, consensus conferences were held to update PAC grading. Here, we review of the successive changes in the grading of PAC from the original system, with emphasis on the newest prognostic grade grouping.

Effects of asymptomatic rotator cuff pathology on in vivo shoulder motion and clinical outcomes.

PubMed

Baumer, Timothy G; Dischler, Jack; Mende, Veronica; Zauel, Roger; van Holsbeeck, Marnix; Siegal, Daniel S; Divine, George; Moutzouros, Vasilios; Bey, Michael J

2017-06-01

The incidence of asymptomatic rotator cuff tears has been reported to range from 15% to 39%, but the influence of asymptomatic rotator cuff pathology on shoulder function is not well understood. This study assessed the effects of asymptomatic rotator cuff pathology on shoulder kinematics, strength, and patient-reported outcomes. A clinical ultrasound examination was performed in 46 asymptomatic volunteers (age: 60.3 ± 7.5 years) with normal shoulder function to document the condition of their rotator cuff. The ultrasound imaging identified the participants as healthy (n = 14) or pathologic (n = 32). Shoulder motion was measured with a biplane x-ray imaging system, strength was assessed with a Biodex (Biodex Medical Systems, Inc., Shirley, NY, USA), and patient-reported outcomes were assessed using the Western Ontario Rotator Cuff Index and visual analog scale pain scores. Compared with healthy volunteers, those with rotator cuff pathology had significantly less abduction (P = .050) and elevation (P = .041) strength, their humerus was positioned more inferiorly on the glenoid (P = .018), and the glenohumeral contact path length was longer (P = .007). No significant differences were detected in the Western Ontario Rotator Cuff Index, visual analog scale, range of motion, or acromiohumeral distance. The differences observed between the healthy volunteers and those with asymptomatic rotator cuff pathology lend insight into the changes in joint mechanics, shoulder strength, and conventional clinical outcomes associated with the early stages of rotator cuff pathology. Furthermore, these findings suggest a plausible mechanical progression of kinematic and strength changes associated with the development of rotator cuff pathology. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

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

PubMed

Zhang, Xun; Zhang, Miaomiao; Du, Panpan

2012-02-01

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

APPswe/PS1dE9 mice with cortical amyloid pathology show a reduced NAA/Cr ratio without apparent brain atrophy: A MRS and MRI study.

PubMed

Kuhla, Angela; Rühlmann, Claire; Lindner, Tobias; Polei, Stefan; Hadlich, Stefan; Krause, Bernd J; Vollmar, Brigitte; Teipel, Stefan J

2017-01-01

Transgenic animal models of Aβ pathology provide mechanistic insight into some aspects of Alzheimer disease (AD) pathology related to Aβ accumulation. Quantitative neuroimaging is a possible aid to improve translation of mechanistic findings in transgenic models to human end phenotypes of brain morphology or function. Therefore, we combined MRI-based morphometry, MRS-based NAA-assessment and quantitative histology of neurons and amyloid plaque load in the APPswe/PS1dE9 mouse model to determine the interrelationship between morphological changes, changes in neuron numbers and amyloid plaque load with reductions of NAA levels as marker of neuronal functional viability. The APPswe/PS1dE9 mouse showed an increase of Aβ plaques, loss of neurons and an impairment of NAA/Cr ratio, which however was not accompanied with brain atrophy. As brain atrophy is one main characteristic in human AD, conclusions from murine to human AD pathology should be drawn with caution.

[Pulmonary pathology in fatal human influenza A (H1N1) infection].

PubMed

Duan, Xue-jing; Li, Yong; Gong, En-cong; Wang, Jue; Lü, Fu-dong; Zhang, He-qiu; Sun, Lin; Yue, Zhu-jun; Song, Chen-chao; Zhang, Shi-Jie; Li, Ning; Dai, Jie

2011-12-01

To study the pulmonary pathology in patients died of fatal human influenza A(H1N1) infection. Eight cases of fatal human influenza A (H1N1) infection, including 2 autopsy cases and 6 paramortem needle puncture biopsies, were enrolled into the study. Histologic examination, immunohistochemitry, flow cytometry and Western blotting were carried out. The major pathologic changes included necrotizing bronchiolitis with surrounding inflammation, diffuse alveolar damage and pulmonary hemorrhage. Influenza viral antigen expression was detected in the lung tissue by Western blotting. Immunohistochemical study demonstrated the presence of nuclear protein and hemagglutinin virus antigens in parts of trachea, bronchial epithelium and glands, alveolar epithelium, macrophages and endothelium. Flow cytometry showed that the apoptotic rate of type II pneumocytes (32.15%, 78.15%) was significantly higher than that of the controls (1.93%, 3.77%). Necrotizing bronchiolitis, diffuse alveolar damage and pulmonary hemorrhage followed by pulmonary fibrosis in late stage are the major pathologic changes in fatal human influenza A (H1N1) infection.

Dysregulation of prefrontal cortex-mediated slow evolving limbic dynamics drives stress-induced emotional pathology

PubMed Central

Hultman, Rainbo; Mague, Stephen D.; Li, Qiang; Katz, Brittany M.; Michel, Nadine; Lin, Lizhen; Wang, Joyce; David, Lisa K.; Blount, Cameron; Chandy, Rithi; Carlson, David; Ulrich, Kyle; Carin, Lawrence; Dunson, David; Kumar, Sunil; Deisseroth, Karl; Moore, Scott D.; Dzirasa, Kafui

2016-01-01

Summary Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social-defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. PMID:27346529

Value of repeat CT scans in low back pain and radiculopathy.

PubMed

Schroeder, Josh E; Barzilay, Yair; Kaplan, Leon; Itshayek, Eyal; Hiller, Nurith

2016-02-01

We assessed the clinical value of repeat spine CT scan in 108 patients aged 18-60 years who underwent repeat lumbar spine CT scan for low back pain or radiculopathy from January 2008 to December 2010. Patients with a neoplasm or symptoms suggesting underlying disease were excluded from the study. Clinical data was retrospectively reviewed. Index examinations and repeat CT scan performed at a mean of 24.3 ± 11.3 months later were compared by a senior musculoskeletal radiologist. Disc abnormalities (herniation, sequestration, bulge), spinal stenosis, disc space narrowing, and bony changes (osteophytes, fractures, other changes) were documented. Indications for CT scan were low back pain (60 patients, 55%), radiculopathy (46 patients, 43%), or nonspecific back pain (two patients, 2%). A total of 292 spine pathologies were identified in 98 patients (90.7%); in 10 patients (9.3%) no spine pathology was seen on index or repeat CT scan. At repeat CT scan, 269/292 pathologies were unchanged (92.1%); 10/292 improved (3.4%), 8/292 worsened (2.8%, disc herniation or spinal stenosis), and five new pathologies were identified. No substantial therapeutic change was required in patients with worsened or new pathology. Added diagnostic value from repeat CT scan performed within 2-3 years was rare in patients suffering chronic or recurrent low back pain or radiculopathy, suggesting that repeat CT scan should be considered only in patients with progressive neurologic deficits, new neurologic complaints, or signs implying serious underlying conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pathology Informatics Essentials for Residents: A Flexible Informatics Curriculum Linked to Accreditation Council for Graduate Medical Education Milestones.

PubMed

Henricks, Walter H; Karcher, Donald S; Harrison, James H; Sinard, John H; Riben, Michael W; Boyer, Philip J; Plath, Sue; Thompson, Arlene; Pantanowitz, Liron

2017-01-01

-Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics has been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. -To develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills, and meets Accreditation Council for Graduate Medical Education Informatics Milestones. -The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. -Pathology Informatics Essentials for Residents (PIER) is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http://www.apcprods.org/PIER (accessed April 6, 2016). -PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time.

Capillary Thrombosis in the Skin: A Pathologic Hallmark of Severe/Chronic Rejection of Human Vascularized Composite Tissue Allografts?

PubMed

Kanitakis, Jean; Petruzzo, Palmina; Gazarian, Aram; Karayannopoulou, Georgia; Buron, Fannie; Dubois, Valérie; Thaunat, Olivier; Badet, Lionel; Morelon, Emmanuel

2016-04-01

Vascularized composite tissue allografts (VCA) can undergo rejection, manifesting pathologically with skin changes that form the basis of the Banff 2007 classification of VCA rejection. We have followed 10 human VCA recipients (7 with hand allografts, 3 with face allografts) for pathological signs of rejection. All of them developed episodes of acute rejection. Two patients with hand allografts presented in some of their skin biopsies an as yet unreported pathological finding in human VCA, consisting of capillary thromboses (CT) in the upper dermis. Capillary thrombosis was associated with other typical changes of grade II to III VCA rejection, namely, perivascular T cell infiltrates, but not with vascular C4d deposits (in formalin-fixed tissue). Clinically, the lesions presented as red or violaceous (lichenoid) cutaneous maculopapules. The first patient had several episodes of acute rejection during the 7-year follow-up. The second patient developed donor-specific antibodies; some months after CT were first observed, he developed chronic rejection leading to partial amputation of the allograft. Pathological examination of the skin showed graft vasculopathy and occasional C4d deposits in cutaneous capillaries. Capillary thrombosis seems to be a novel pathologic finding associated with human VCA rejection. Although its mechanism (immunologic vs nonimmunologic) remains unclear, this finding could carry an unfavorable prognostic significance, prompting close monitoring of the patients for severe/chronic rejection.

Clinico-pathological features of kidney disease in diabetic cases.

PubMed

Furuichi, Kengo; Shimizu, Miho; Okada, Hirokazu; Narita, Ichiei; Wada, Takashi

2018-03-21

Diabetic kidney disease is the major cause of end-stage kidney disease in developed countries. However, the onset of kidney disorder and the progression pattern of kidney dysfunction and proteinuria greatly vary cases by cases. Therefore, risk classification with clinical data and pathological findings is important. Recent clinico-pathological study with kidney biopsy samples from diabetic patients revealed that pathological changes of diabetic nephropathy are characteristic and have special impacts on prognosis in each clinical stage. Moreover, comparison of the clinico-pathological findings of diabetic nephropathy with hypertensive nephrosclerosis revealed that there are few differences in their pathological findings in cases with low albuminuria and preserved estimated glomerular filtration rate (eGFR). Because it is so difficult to clearly distinguish pure kidney lesions caused by diabetes and kidney lesions due to effects other than diabetes, it is vital that these overlapped pathological findings be confirmed on kidney biopsy in cases of early stage diabetes. Further research is warranted regarding the pathogenesis of diabetic nephropathy and indication of kidney biopsy in diabetic cases.

Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology.

PubMed

Bhargava, Rohit; Madabhushi, Anant

2016-07-11

Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area.

Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology

PubMed Central

Bhargava, Rohit; Madabhushi, Anant

2017-01-01

Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area. PMID:27420575

Consequences of "going digital" for pathology professionals - entering the cloud.

PubMed

Laurinavicius, Arvydas; Raslavicus, Paul

2012-01-01

New opportunities and the adoption of digital technologies will transform the way pathology professionals and services work. Many areas of our daily life as well as medical professions have experienced this change already which has resulted in a paradigm shift in many activities. Pathology is an image-based discipline, therefore, arrival of digital imaging into this domain promises major shift in our work and required mentality. Recognizing the physical and digital duality of the pathology workflow, we can prepare for the imminent increase of the digital component, synergize and enjoy its benefits. Development of a new generation of laboratory information systems along with seamless integration of digital imaging, decision-support, and knowledge databases will enable pathologists to work in a distributed environment. The paradigm of "cloud pathology" is proposed as an ultimate vision of digital pathology workstations plugged into the integrated multidisciplinary patient care systems.

Motivation to change in the eating disorders: a systematic review.

PubMed

Clausen, Loa; Lübeck, Marlene; Jones, Allan

2013-12-01

The aim of the study was to review the eating disorder literature in order to examine the effect of pretreatment autonomous/level of motivation to change on treatment outcome as measured by change in eating disorder pathology. Relevant databases were systematically searched for studies in which motivation to change prior to treatment was examined in relation to treatment outcome. Pretreatment autonomous/level of motivation were associated with change in restrictive eating behaviors, bingeing behaviors, and cognitive/affective measures of eating disorder pathology. There was mixed support for the effect of motivation to change on global measures of eating disorder symptoms and virtually no support for the effect of motivation to change on purging behavior. The level of pretreatment motivation the person exhibits prior to commencement of treatment appears to be helpful in predicting treatment outcome. Copyright © 2013 Wiley Periodicals, Inc.

Neuroglia in ageing and disease.

PubMed

Verkhratsky, Alexei; Rodríguez, José J; Parpura, Vladimir

2014-08-01

The proper operation of the mammalian brain requires dynamic interactions between neurones and glial cells. Various types of glial cells are susceptible to morpho-functional changes in a variety of brain pathological states, including toxicity, neurodevelopmental, neurodegenerative and psychiatric disorders. Morphological modifications include a change in the glial cell size and shape; the latter is evident by changes of the appearance and number of peripheral processes. The most blatant morphological change is associated with the alteration of the sheer number of neuroglia cells in the brain. Functionally, glial cells can undergo various metabolic and biochemical changes, the majority of which reflect upon homeostasis of neurotransmitters, in particular that of glutamate, as well as on defence mechanisms provided by neuroglia. Not only glial cells exhibit changes associated with the pathology of the brain but they also change with brain aging.

Review of approaches to the recording of background lesions in toxicologic pathology studies in rats.

PubMed

McInnes, E F; Scudamore, C L

2014-08-17

Pathological evaluation of lesions caused directly by xenobiotic treatment must always take into account the recognition of background (incidental) findings. Background lesions can be congenital or hereditary, histological variations, changes related to trauma or normal aging and physiologic or hormonal changes. This review focuses on the importance and correct approach to recording of background changes and includes discussion on sources of variability in background changes, the correct use of terminology, the concept of thresholds, historical control data, diagnostic drift, blind reading of slides, scoring and artifacts. The review is illustrated with background lesions in Sprague Dawley and Wistar rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Forensic Pathology Education in Pathology Residency

PubMed Central

Ross, Wayne K.; Domen, Ronald E.

2017-01-01

Forensic pathology is a fundamental part of anatomic pathology training during pathology residency. However, the lack of information on forensic teaching suggests the highly variable nature of forensic education. A survey of pathology residency program directors was performed to determine key aspects of their respective forensic rotations and curriculum. A total of 38.3% of programs from across the country responded, and the survey results show 5.6% don’t require a forensic pathology rotation. In those that do, most forensic pathology rotations are 4 weeks long, are done at a medical examiner’s office, and require set prerequisites. A total of 21.1% of responding programs have residents who are not receiving documented evaluations for this rotation. While 39.6% of programs have a defined forensics curriculum, as many as 15% do not. Furthermore, nearly 43% of programs place no limit on counting forensic autopsies when applying for pathology board examinations. Our survey confirmed the inconsistent nature of forensic pathology training in resident education. Additionally, our curriculum was reorganized to create a more robust educational experience. A pre- and post-forensic lecture quiz and Resident In-Service Examination scores were analyzed to determine our curriculum’s impact and effectiveness. Analysis of our pre- and post-lecture quiz showed an improved overall average as well as an increase in Resident In-Service Examination scores, indicating improved general forensic pathology knowledge. Using this knowledge, along with changes in our curriculum, we generated a number of recommendations for improving forensic pathology education in pathology residency. PMID:28913415

Childhood chronic gastritis and duodenitis: Role of altered sensory neuromediators.

PubMed

Islek, Ali; Yilmaz, Aygen; Elpek, Gulsum Ozlem; Erin, Nuray

2016-10-07

To investigate the roles of the neuropeptides vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) in chronic gastritis and duodenitis in children. Biopsy samples from the gastric and duodenal mucosa of 52 patients and 30 control subjects were obtained. Samples were taken for pathological examination, immunohistochemical staining, enzyme activity measurements and quantitative measurements of tissue peptide levels. We observed differential effects of the disease on peptide levels, which were somewhat different from previously reported changes in chronic gastritis in adults. Specifically, SP was increased and CGRP and VIP were decreased in patients with gastritis. The changes were more prominent at sites where gastritis was severe, but significant changes were also observed in neighboring areas where gastritis was less severe. Furthermore, the degree of changes was correlated with the pathological grade of the disease. The expression of CD10, the enzyme primarily involved in SP hydrolysis, was also decreased in patients with duodenitis. Based on these findings, we propose that decreased levels of VIP and CGRP and increased levels of SP contribute to pathological changes in gastric mucosa. Hence, new treatments targeting these molecules may have therapeutic and preventive effects.

Childhood chronic gastritis and duodenitis: Role of altered sensory neuromediators

PubMed Central

Islek, Ali; Yilmaz, Aygen; Elpek, Gulsum Ozlem; Erin, Nuray

2016-01-01

AIM To investigate the roles of the neuropeptides vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) in chronic gastritis and duodenitis in children. METHODS Biopsy samples from the gastric and duodenal mucosa of 52 patients and 30 control subjects were obtained. Samples were taken for pathological examination, immunohistochemical staining, enzyme activity measurements and quantitative measurements of tissue peptide levels. RESULTS We observed differential effects of the disease on peptide levels, which were somewhat different from previously reported changes in chronic gastritis in adults. Specifically, SP was increased and CGRP and VIP were decreased in patients with gastritis. The changes were more prominent at sites where gastritis was severe, but significant changes were also observed in neighboring areas where gastritis was less severe. Furthermore, the degree of changes was correlated with the pathological grade of the disease. The expression of CD10, the enzyme primarily involved in SP hydrolysis, was also decreased in patients with duodenitis. CONCLUSION Based on these findings, we propose that decreased levels of VIP and CGRP and increased levels of SP contribute to pathological changes in gastric mucosa. Hence, new treatments targeting these molecules may have therapeutic and preventive effects. PMID:27729741

Evaluation of blood and bone marrow in selected canine vector-borne diseases.

PubMed

De Tommasi, Anna S; Otranto, Domenico; Furlanello, Tommaso; Tasca, Silvia; Cantacessi, Cinzia; Breitschwerdt, Edward B; Stanneck, Dorothee; Dantas-Torres, Filipe; Baneth, Gad; Capelli, Gioia; de Caprariis, Donato

2014-12-02

Bone marrow (BM) is a major hematopoietic organ that can harbour a variety of vector-borne pathogens; however, knowledge of BM pathological changes in dogs infected with vector-borne pathogens is limited. Thus, the aim of the present study was to assess the pathological changes in canine BM associated with natural infections by four vector-borne pathogens, as well as to determine the relationships between such changes and abnormalities of the peripheral blood. Cytological disorders and pathological changes of the BM of 83 dogs naturally-infected with one or more of four vector-borne pathogens (i.e., Anaplasma platys, Leishmania infantum, Babesia vogeli and Hepatozoon canis) were evaluated and compared with the corresponding hematological findings. Dysgranulopoiesis and dysmegakaryocytopoiesis were the most frequently observed BM abnormalities in infected dogs. Erythroid suppression, and lymphocytic, monocytic and macrophage hyperplasia were also observed. Interestingly, associations between suppression and hyperplasia of specific cell lines in the marrow and corresponding changes in numbers of circulating peripheral blood cells were not observed. Infections with one or more of the vector-borne pathogens examined in this study should be considered as differential diagnoses for secondary dysmyelopoiesis.

[Study on the tectology change of rectum wall above the hemorrhoids].

PubMed

Zhang, Li; Yang, Bin; Zhang, Yu-Chao; Fu, Yu-Ru; Chen, Shuang

2009-06-15

To investigate the histomorphological characteristics and its significance of rectum wall above hemorrhoids. Tissues of rectum wall above hemorrhoids were obtained after stapled hemorrhoidopexy from 21 patients with grade III-IV internal hemorrhoids. Seven macroscopically normal rectal tissues collected from upper rectal cancer patients without a history of hemorrhoids served as control. Masson trichrome staining was performed for detecting smooth muscles and collagen in the tissues. The expression of type III collagen was detected by using immunohistochemical staining in the two groups. Morphological abnormalities, such as fragment, rupture, disorganization were found in smooth muscle of proximal rectal tissues above the piles, and it was statistically different from the distal rectal tissues above the piles and control tissues (all P < 0.05). Moreover, hyperplasia of type III collagen in both muscularis mucosa and rectum wall in tissues above hemorrhoids were observed, no such changes was found in the control tissues. The range of pathological changes in hemorrhoids is beyond the anal cushions. The pathological changes of the smooth muscle and the type III collagen in the tissues above the piles are the pathological basis of hemorrhoids.

[Histological effects of short term endocrine therapy on prostatic cancer].

PubMed

Irisawa, C; Yoshimura, Y; Yokota, T; Yamaguchi, O; Kondou, Y; Hamasaki, T; Yamad, Y; Kurosu, S; Chiba, R

1996-07-01

The objective of this study is to investigate the pathological changes which occurred in prostatic cancer shortly after the commencement of endocrine therapy. Fourty-three patients underwent radical prostatectomy immediately after the short term endocrine therapy (treatment period was within one month) and the histological pictures of operative specimens were compared to those obtained from the pretreatment biopsy specimens. Degenerative changes of cancer cells, such as nuclear and cytoplasmic vacuole, collapse of the cytoplasm and the appearance of naked hyperchromatic nucleus were noticed after the short term endocrine therapy. Especially in the cases which were histologically evaluated to be poorly differentiated in the biopsy specimens, not only degenerative changes but also destruction of cancer nests caused by cell death were observed. The histological effects affected by short term endocrine treatment had no relation to the prognosis, but in the cases of stage D2, the pathological grade judged by post-therapeutic specimens were found to be useful for the prediction of prognosis. Endocrine therapy induces remarkable pathological changes in prostatic cancer within a very short time after beginning treatment.

Pathology of lethal and sublethal doses of aerosolized ricin in rhesus macaques.

PubMed

Bhaskaran, Manoj; Didier, Peter J; Sivasubramani, Satheesh K; Doyle, Lara A; Holley, Jane; Roy, Chad J

2014-01-01

Ricin toxin, a type 2 ribosome-inactivating protein and a category B bioterrorism agent, is produced from the seeds of castor oil plant (Ricinus communis). Chronic pathological changes in survivors of aerosolized ricin exposure have not been reported in primates. Here we compare and contrast the pathological changes manifested between rhesus macaques (RM) that succumbed to lethal dose of ricin (group I) and survivor RM exposed to low dose of ricin (group II). All animals in group I exhibited severe diffuse, necrotizing bronchiolitis and alveolitis with fibrinopurulent bronchointerstitial pneumonia, massive alveolar, perivascular and peribronchial/bronchiolar edema with hemorrhage, and necropurulent and hemorrhagic tracheobronchial lymphadenitis. All animals from group II had multifocal, fibrosing interstitial pneumonia with prominent alveolar histiocytosis and type II pneumocyte hyperplasia. Subacute changes like infiltration by lymphocytes and plasma cells and persistence of edematous fluid were occasionally present in lung and tracheobronchial lymph nodes. The changes appear to be a continuum wherein the inflammatory response shifts from an acute to subacute/chronic reparative process if the animals can survive the initial insult.

Value of Specialist Pathology Review in a Single Statewide Gynecologic Cancer Service.

PubMed

Melon, Jerome; Leung, Yee; Salfinger, Stuart G; Tan, Jason; Mohan, Ganendra; Cohen, Paul A

2017-01-01

A case review by specialist diagnostic pathologists as part of a Gynecologic Oncology Multi-disciplinary Tumor group has the potential to influence the management of patients with cancer. The primary aim of this study was to determine the frequency of diagnostic discrepancies between the initial (nonspecialist) and final pathological diagnoses in cases referred to the Gynecologic Oncology Tumor Conference (TC) in Western Australia and the impact of such revised diagnosis on clinical management. A secondary aim was to assess the evolving workload encountered by the TC during a 5-year interval. The records of the weekly TC for the 2 calendar years 2008 and 2013 were examined, and histological and cytological specimens that had been initially assessed by "outside" (nonspecialist) pathology departments, and subsequently reviewed by specialist pathologists, were assessed. The initial and final diagnoses were compared, and where the pathological findings were amended upon review, it was determined whether the change affected clinical management. Diagnostic discrepancies that resulted in a change in patient management were classified as major, whereas discrepancies that did not affect patient management were classified as minor. A total of 481 outside cases were included among 2387 cases presented for histological review at the TC during the 2 years. For outside cases alone, the incidence of major diagnostic discrepancies was 3.4% in 2008, 5.5% in 2013 (no significant difference, P = 0.3787), and 4.6% for the 2 years combined. A recommendation for surgery was the most common change in clinical management as a result of major discrepancy. The minor discrepancy rate was 4.4% of outside cases for both years combined. Pathological discrepancies (major and minor) of the uterine corpus and cervix were most frequent, followed by those of the vulva and ovary. There was a 48.4% increase in total case discussions at the TC during the interval period with a significant rise in nonmalignant cases, 29.8% of the total cases in 2008 compared with 36.8% in 2013 (P = 0.0004). Nonspecialist pathology departments maintained a high level of reporting accuracy during the interval period, with the major discrepancy rate not changing significantly between 2008 and 2013. Specimens from the uterine corpus and cervix in particular may prove diagnostically challenging on occasion. A pathology review of outside cases by a tertiary-based laboratory in conjunction with a TC can identify a small but clinically significant number of cases that lead to a change in clinical management. It is uncertain whether this affects patient outcomes.

Pathology resident and fellow education in a time of disruptive technologies.

PubMed

Ziai, James M; Smith, Brian R

2012-12-01

The development of disruptive technologies is changing the practice of pathology. Their implementation challenges traditional educational paradigms. Training programs must adapt to these heuristic needs. The dual explosion of new medical knowledge and innovative methodologies adds new practice aspects to the pathologist's areas of expertise. This transformation potentially challenges the traditional core model of training. It raises questions as to how pathology should incorporate future expanding subspecialty needs into educational and practice models. This article examines the impact of these disruptive technologies on resident and fellow education and explores alternative educational and practice models that may better accommodate pathology's future. Copyright © 2012 Elsevier Inc. All rights reserved.

Different Achilles Tendon Pathologies Show Distinct Histological and Molecular Characteristics

PubMed Central

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

2018-01-01

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

What is normal in normal aging? Effects of Aging, Amyloid and Alzheimer’s Disease on the Cerebral Cortex and the Hippocampus

PubMed Central

Fjell, Anders M.; McEvoy, Linda; Holland, Dominic; Dale, Anders M.; Walhovd, Kristine B

2015-01-01

What can be expected in normal aging, and where does normal aging stop and pathological neurodegeneration begin? With the slow progression of age-related dementias such as Alzheimer’s Disease (AD), it is difficult to distinguish age-related changes from effects of undetected disease. We review recent research on changes of the cerebral cortex and the hippocampus in aging and the borders between normal aging and AD. We argue that prominent cortical reductions are evident in fronto-temporal regions in elderly even with low probability of AD, including regions overlapping the default mode network. Importantly, these regions show high levels of amyloid deposition in AD, and are both structurally and functionally vulnerable early in the disease. This normalcy-pathology homology is critical to understand, since aging itself is the major risk factor for sporadic AD. Thus, rather than necessarily reflecting early signs of disease, these changes may be part of normal aging, and may inform on why the aging brain is so much more susceptible to AD than is the younger brain. We suggest that regions characterized by a high degree of life-long plasticity are vulnerable to detrimental effects of normal aging, and that this age-vulnerability renders them more susceptible to additional, pathological AD-related changes. We conclude that it will be difficult to understand AD without understanding why it preferably affects older brains, and that we need a model that accounts for age-related changes in AD-vulnerable regions independently of AD-pathology. PMID:24548606

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

PubMed

Landa, Carrie E; Bybee, Jane A

2007-01-01

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

Induction process of trainees in pathology residency

PubMed Central

Siddiqui, Imran; Ali, Natasha

2016-01-01

This article describes the evolution of the induction process of pathology residency at The Aga Khan University hospital. The Department of Postgraduate Medical Education was established in 1985. The induction process is an exhaustive exercise that includes an admission test held simultaneously in Karachi, Hyderabad, Lahore, and Rawalpindi, followed by an interview of the shortlisted candidates. The pathology residency program was started 25 years ago and since then the induction process has undergone major changes with the course of time. PMID:27313487

Pathological and immunohistochemical study of lethal primary brain stem injuries

PubMed Central

2012-01-01

Background Many of the deaths that occur shortly after injury or in hospitals are caused by mild trauma. Slight morphological changes are often found in the brain stems of these patients during autopsy. The purpose of this study is to investigate the histopathological changes involved in primary brain stem injuries (PBSI) and their diagnostic significance. Methods A total of 65 patients who had died of PBSI and other conditions were randomly selected. They were divided into 2 groups, an injury group (25 cases) and a control group (20 cases). Slides of each patient’s midbrain, pons, and medulla oblongata were prepared and stained with HE, argentaffin, and immunohistochemical agents (GFAP, NF, amyloid-ß, MBP). Under low power (×100) and NF staining, the diameter of the thickest longitudinal axon was measured at its widest point. Ten such diameters were collected for each part of the brain (midbrain, pons, and medulla oblongata). Data were recorded and analyzed statistically. Results Brain stem contusions, astrocyte activity, edema, and pathological changes in the neurons were visibly different in the injury and control groups (P < 0.05). Characteristic changes occurred in the neural axons, axon diameter varied from axon to axon and even over different segments of one axon, and several pathological phenomena were observed. These included segmental thickening and curving, wave-like processing, disarrangement, and irregular swelling. A few axons ruptured and intumesced into retraction balls. Immunohistochemical MBP staining showed enlargement and curving of spaces between the myelin sheaths and axons in certain areas. The myelin sheaths lining the surfaces of the axons were in some cases incomplete and even exfoliated, and segmentation disappeared. These pathological changes increased in severity over time (P < 0.05). Conclusions These histopathological changes may prove beneficial to the pathological diagnosis of PBSI during autopsy. The measurement of axon diameters provides a referent quantitative index for the diagnosis of the specific causes of death involved in PBSI. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1345298818712204 PMID:22613041

Age related increase in mTOR activity contributes to the pathological changes in ovarian surface epithelium

PubMed Central

Bajwa, Preety; Nagendra, Prathima B.; Nielsen, Sarah; Sahoo, Subhransu S.; Bielanowicz, Amanda; Lombard, Janine M.; Wilkinson, Erby J.; Miller, Richard A.; Tanwar, Pradeep S.

2016-01-01

Ovarian cancer is a disease of older women. However, the molecular mechanisms of ovarian aging and their contribution to the pathogenesis of ovarian cancer are currently unclear. mTOR signalling is a major regulator of aging as suppression of this pathway extends lifespan in model organisms. Overactive mTOR signalling is present in up to 80% of ovarian cancer samples and is associated with poor prognosis. This study examined the role of mTOR signalling in age-associated changes in ovarian surface epithelium (OSE). Histological examination of ovaries from both aged mice and women revealed OSE cell hyperplasia, papillary growth and inclusion cysts. These pathological lesions expressed bonafide markers of ovarian cancer precursor lesions, Pax8 and Stathmin 1, and were presented with elevated mTOR signalling. To understand whether overactive mTOR signalling is responsible for the development of these pathological changes, we analysed ovaries of the Pten trangenic mice and found significant reduction in OSE lesions compared to controls. Furthermore, pharmacological suppression of mTOR signalling significantly decreased OSE hyperplasia in aged mice. Treatment with mTOR inhibitors reduced human ovarian cancer cell viability, proliferation and colony forming ability. Collectively, we have established the role of mTOR signalling in age-related OSE pathologies and initiation of ovarian cancer. PMID:27036037

Reliable landmarks for precise topographical analyses of pathological structural changes of the ovine tibial plateau in 2-D and 3-D subspaces.

PubMed

Oláh, Tamás; Reinhard, Jan; Gao, Liang; Goebel, Lars K H; Madry, Henning

2018-01-08

Selecting identical topographical locations to analyse pathological structural changes of the osteochondral unit in translational models remains difficult. The specific aim of the study was to provide objectively defined reference points on the ovine tibial plateau based on 2-D sections of micro-CT images useful for reproducible sample harvesting and as standardized landmarks for landmark-based 3-D image registration. We propose 5 reference points, 11 reference lines and 12 subregions that are detectable macroscopically and on 2-D micro-CT sections. Their value was confirmed applying landmark-based rigid and affine 3-D registration methods. Intra- and interobserver comparison showed high reliabilities, and constant positions (standard errors < 1%). Spatial patterns of the thicknesses of the articular cartilage and subchondral bone plate were revealed by measurements in 96 individual points of the tibial plateau. As a case study, pathological phenomena 6 months following OA induction in vivo such as osteophytes and areas of OA development were mapped to the individual subregions. These new reference points and subregions are directly identifiable on tibial plateau specimens or macroscopic images, enabling a precise topographical location of pathological structural changes of the osteochondral unit in both 2-D and 3-D subspaces in a region-appropriate fashion relevant for translational investigations.

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

PubMed

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

2018-02-06

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

Pathology Informatics Essentials for Residents: A flexible informatics curriculum linked to Accreditation Council for Graduate Medical Education milestones

PubMed Central

Henricks, Walter H; Karcher, Donald S; Harrison, James H; Sinard, John H; Riben, Michael W; Boyer, Philip J; Plath, Sue; Thompson, Arlene; Pantanowitz, Liron

2016-01-01

Context: Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics have been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. Objective: The objective of the study is to develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills and meets Accreditation Council for Graduate Medical Education Informatics Milestones. Design: The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. Results: Pathology Informatics Essentials for Residents (PIER) is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http://www.apcprods.org/PIER (accessed April 6, 2016). Conclusions: PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time. PMID:27563486

White matter changes in Alzheimer's disease: a focus on myelin and oligodendrocytes.

PubMed

Nasrabady, Sara E; Rizvi, Batool; Goldman, James E; Brickman, Adam M

2018-03-02

Alzheimer's disease (AD) is conceptualized as a progressive consequence of two hallmark pathological changes in grey matter: extracellular amyloid plaques and neurofibrillary tangles. However, over the past several years, neuroimaging studies have implicated micro- and macrostructural abnormalities in white matter in the risk and progression of AD, suggesting that in addition to the neuronal pathology characteristic of the disease, white matter degeneration and demyelination may be also important pathophysiological features. Here we review the evidence for white matter abnormalities in AD with a focus on myelin and oligodendrocytes, the only source of myelination in the central nervous system, and discuss the relationship between white matter changes and the hallmarks of Alzheimer's disease. We review several mechanisms such as ischemia, oxidative stress, excitotoxicity, iron overload, Aβ toxicity and tauopathy, which could affect oligodendrocytes. We conclude that white matter abnormalities, and in particular myelin and oligodendrocytes, could be mechanistically important in AD pathology and could be potential treatment targets.

Overview: the role of Propionibacterium acnes in nonpyogenic intervertebral discs.

PubMed

Chen, Zhe; Cao, Peng; Zhou, Zezhu; Yuan, Ye; Jiao, Yucheng; Zheng, Yuehuan

2016-06-01

Propionibacterium acnes (P. acnes), an important opportunistic anaerobic Gram-positive bacterium, causes bone and joint infections, discitis and spondylodiscitis. Accumulated evidence suggested that this microbe can colonise inside intervertebral discs without causing symptoms of discitis. Epidemiological investigation shows that the prevalence ranges from 13 % to 44 %. Furthermore, colonisation by P. acnes inside nonpyogenic intervertebral discs is thought to be one pathogen causing sciatica, Modic changes and nonspecific low back pain. Specially, patients can attain significant relief of low back pain, amelioration of Modic changes and alleviation of sciatica after antibiotic therapy, indicating the role of P. acnes in these pathological changes. However, until now, there were hypotheses only to explain problems such as how P. acnes access intervertebral discs and what the exact pathological mechanism it employs during its latent infection period. In addition, research regarding diagnostic procedures and treatment strategies were also rare. Overall, the prevalence and possible pathological role that P. acnes plays inside nonpyogenic intervertebral discs is summarised in this paper.

Low-Intensity Shock Wave Therapy and Its Application to Erectile Dysfunction

PubMed Central

Lei, Hongen; Liu, Jing; Li, Huixi; Wang, Lin; Xu, Yongde; Tian, Wenjie; Lin, Guiting

2013-01-01

Although phosphodiesterase type 5 inhibitors (PDE5Is) are a revolution in the treatment of erectile dysfunction (ED) and have been marketed since 1998, they cannot restore pathological changes in the penis. Low-energy shock wave therapy (LESWT) has been developed for treating ED, and clinical studies have shown that LESWT has the potential to affect PDE5I non-responders with ED with few adverse effects. Animal studies have shown that LESWT significantly improves penile hemodynamics and restores pathological changes in the penis of diabetic ED animal models. Although the mechanisms remain to be investigated, recent studies have reported that LESWT could partially restore corpus cavernosum fibromuscular pathological changes, endothelial dysfunction, and peripheral neuropathy. LESWT could be a novel modality for treating ED, and particularly PDE5I non-responders with organic ED, in the near future. However, further extensive evidence-based basic and clinical studies are needed. This review intends to summarize the scientific background underlying the effect of LESWT on ED. PMID:24459653

Low-intensity shock wave therapy and its application to erectile dysfunction.

PubMed

Lei, Hongen; Liu, Jing; Li, Huixi; Wang, Lin; Xu, Yongde; Tian, Wenjie; Lin, Guiting; Xin, Zhongcheng

2013-12-01

Although phosphodiesterase type 5 inhibitors (PDE5Is) are a revolution in the treatment of erectile dysfunction (ED) and have been marketed since 1998, they cannot restore pathological changes in the penis. Low-energy shock wave therapy (LESWT) has been developed for treating ED, and clinical studies have shown that LESWT has the potential to affect PDE5I non-responders with ED with few adverse effects. Animal studies have shown that LESWT significantly improves penile hemodynamics and restores pathological changes in the penis of diabetic ED animal models. Although the mechanisms remain to be investigated, recent studies have reported that LESWT could partially restore corpus cavernosum fibromuscular pathological changes, endothelial dysfunction, and peripheral neuropathy. LESWT could be a novel modality for treating ED, and particularly PDE5I non-responders with organic ED, in the near future. However, further extensive evidence-based basic and clinical studies are needed. This review intends to summarize the scientific background underlying the effect of LESWT on ED.

Change in the immunophenotype of a somatotroph adenoma resulting in gigantism.

PubMed

Thawani, Jayesh P; Bailey, Robert L; Burns, Carrie M; Lee, John Y K

2014-01-01

Examining the pathologic progression of a pituitary adenoma from the point of a prepubescent child to an adult with gigantism affords us an opportunity to consider why patients may develop secretory or functioning tumors and raises questions about whether therapeutic interventions and surveillance strategies could be made to avoid irreversible phenotypic changes. A patient underwent a sublabial transsphenoidal resection for a clinically non-functioning macroadenoma in 1999. He underwent radiation treatment and was transiently given growth hormone (GH) supplementation as an adolescent. His growth rapidly traversed several percentiles and he was found to have elevated GH levels. The patient became symptomatic and was taken for a second neurosurgical procedure. Pathology and immunohistochemical staining demonstrated a significantly higher proportion of somatotroph cells and dense granularity; he was diagnosed with a functional somatotroph adenoma. While it is likely that the described observations reflect the manifestations of a functional somatotroph adenoma in development, it is possible that pubertal growth, GH supplementation, its removal, or radiation therapy contributed to the described endocrine and pathologic changes.

[Topographological-anatomic changes in the structure of temporo-mandibular joint in case of fracture of the mandible condylar process at cervical level].

PubMed

Volkov, S I; Bazhenov, D V; Semkin, V A

2011-01-01

Pathological changes in soft tissues surrounding the fracture site as well as in the structural elements of temporo-mandibular joint always occured in condylar process fracture with shift at cervical mandibular jaw level. Other changes were also seen in the joint on the opposite normal side. Modelling of condylar process fracture at mandibular cervical level by means of three-dimensional computer model of temporo-mandibular joint contributed to proper understanding of this pathology emergence as well as to prediction and elimination of disorders arising in adjacent to the fracture site tissues.

Maternal separation exacerbates Alzheimer's disease-like behavioral and pathological changes in adult APPswe/PS1dE9 mice.

PubMed

Hui, Jianjun; Feng, Gaifeng; Zheng, Caifeng; Jin, Hui; Jia, Ning

2017-02-01

Alzheimer's disease (AD), the most common neurodegenerative disorder that gradually destroys memory and cognitive abilities in the elderly, makes a huge emotional and economic burden on the patients and their families. The presence of senile plaques and the loss of cholinergic neurons in the brain are two neuropathological hallmarks of AD. Maternal separation (MS) is an animal paradigm designed to make early life stress. Studies on wild type rodents showed that MS could induce AD-like cognitive deficit and pathological changes. However, the effects of MS on AD susceptible population or AD animal models are still unclear. In the present study, male APPswe/PS1dE9 transgenic mice were separated from dam and pups 3h per day from postnatal day 2 to day 21. After weaning, all animals were housed under normal conditions (4 mice per cage). At 9-month age, MWM tests were performed to evaluate the learning and memory abilities. Then the pathological changes in the brain were measured by histology staining. The results showed MS mice had more severe deficit of learning and memory. Compared to the control, there were more senile plaques in cortex and hippocampus, fewer cholinergic neurons in nucleus basalis of Meynert in MS mice. These results indicate that MS exacerbates Alzheimer's disease-like behavioral and pathological changes in APPswe/PS1dE9 mice. Copyright © 2016 Elsevier B.V. All rights reserved.

Histomorphology and innate immunity during the progression of osteoarthritis: Does synovitis affect cartilage degradation?

PubMed

Wang, Huan; Wang, Qingguo; Yang, Meijuan; Yang, Lili; Wang, Weili; Ding, Haobin; Zhang, Dong; Xu, Jing; Tang, Xuezhang; Ding, Haitao; Wang, Qingfu

2018-02-01

Osteoarthritis (OA) is a common chronic degenerative disease that affects all joints. At present, the pathological processes and mechanisms of OA are still unclear. Innate immunity, a key player in damage to the structure of the joint and the mechanism by which the host attempts to repair OA, affects all pathological stages of the disease. In the present study, our aim was to assess changes in innate immunity during the pathological processes of OA in articular cartilage (AC) and the synovial membrane (SM), which are the major structures in joints, and to systematically examine the histological changes in AC and SM in mild, moderate and severe cases of OA, in order to further speculate about the manner in which the interactions of AC and SM are facilitated by innate immunity. Histological methods (including HE and Safranin O-fast green staining), immunofluorescent double staining, TUNEL stain, and Western blots were used to assess the morphological changes within AC and SM tissues in healthy and mild, moderate, or severe OA rats. Our results showed that the damage to AC and SM within the joints progressively worsened in different degrees during the course of the disease, and that the innate immune system was closely involved in the AC and SM during each stage of OA. These findings also confirmed that SM may affect the pathological changes in AC through the innate immune system, and therefore affect the progress of OA. © 2017 Wiley Periodicals, Inc.

Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

PubMed

Ishii, Makoto; Iadecola, Costantino

2016-05-01

Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

Forensic Pathology Education in Pathology Residency: A Survey of Current Practices, a Novel Curriculum, and Recommendations for the Future.

PubMed

Spencer, Amanda; Ross, Wayne K; Domen, Ronald E

2017-01-01

Forensic pathology is a fundamental part of anatomic pathology training during pathology residency. However, the lack of information on forensic teaching suggests the highly variable nature of forensic education. A survey of pathology residency program directors was performed to determine key aspects of their respective forensic rotations and curriculum. A total of 38.3% of programs from across the country responded, and the survey results show 5.6% don't require a forensic pathology rotation. In those that do, most forensic pathology rotations are 4 weeks long, are done at a medical examiner's office, and require set prerequisites. A total of 21.1% of responding programs have residents who are not receiving documented evaluations for this rotation. While 39.6% of programs have a defined forensics curriculum, as many as 15% do not. Furthermore, nearly 43% of programs place no limit on counting forensic autopsies when applying for pathology board examinations. Our survey confirmed the inconsistent nature of forensic pathology training in resident education. Additionally, our curriculum was reorganized to create a more robust educational experience. A pre- and post-forensic lecture quiz and Resident In-Service Examination scores were analyzed to determine our curriculum's impact and effectiveness. Analysis of our pre- and post-lecture quiz showed an improved overall average as well as an increase in Resident In-Service Examination scores, indicating improved general forensic pathology knowledge. Using this knowledge, along with changes in our curriculum, we generated a number of recommendations for improving forensic pathology education in pathology residency.

Developing Disease-Modifying Treatments in Alzheimer's Disease - A Perspective from Roche and Genentech.

PubMed

Doody, R

2017-01-01

Alzheimer's disease (AD) is a chronic neurodegenerative disease for which no preventative or disease-modifying treatments currently exist. Pathological hallmarks include amyloid plaques and neurofibrillary tangles composed of hyper-phosphorylated tau protein. Evidence suggests that both pathologies are self-propagating once established. However, the lag time between neuropathological changes in the brain and the onset of even subtle clinical symptomatology means that patients are often diagnosed late when pathology, and neurodegeneration secondary to these changes, may have been established for several years. Complex pathological pathways associated with susceptibility to AD and changes that occur downstream of the neuropathologic process further contribute to the challenging endeavour of developing novel disease-modifying therapy. Recognising this complexity, effective management of AD must include reliable screening and early diagnosis in combination with effective therapeutic management of the pathological processes. Roche and Genentech are committed to addressing these unmet needs through developing a comprehensive portfolio of diagnostics and novel therapies. Beginning with the most scientifically supported targets, this approach includes two targeted amyloid-β monoclonal antibody therapies, crenezumab and gantenerumab, and an anti-tau monoclonal antibody, RO7105705, as well as a robust biomarker platform to aid in the early identification of people at risk or in the early stages of AD. Identification and implementation of diagnostic tools will support the enrolment of patients into clinical trials; furthermore, these tools should also support evaluation of the clinical efficacy and safety profile of the novel therapeutic agents tested in these trials. This review discusses the therapeutic agents currently under clinical development.

Primary age-related tauopathy (PART): a common pathology associated with human aging

PubMed Central

Crary, John F.; Trojanowski, John Q.; Schneider, Julie A.; Abisambra, Jose F.; Abner, Erin L.; Alafuzoff, Irina; Arnold, Steven E.; Attems, Johannes; Beach, Thomas G.; Bigio, Eileen H.; Cairns, Nigel J.; Dickson, Dennis W.; Gearing, Marla; Grinberg, Lea T.; Hof, Patrick R.; Hyman, Bradley T.; Jellinger, Kurt; Jicha, Gregory A.; Kovacs, Gabor G.; Knopman, David S.; Kofler, Julia; Kukull, Walter A.; Mackenzie, Ian R.; Masliah, Eliezer; McKee, Ann; Montine, Thomas J.; Murray, Melissa E.; Neltner, Janna H.; Santa-Maria, Ismael; Seeley, William W.; Serrano-Pozo, Alberto; Shelanski, Michael L.; Stein, Thor; Takao, Masaki; Thal, Dietmar R.; Toledo, Jonathan B.; Troncoso, Juan C.; Vonsattel, Jean Paul; White, Charles L.; Wisniewski, Thomas; Woltjer, Randall L.; Yamada, Masahito; Nelson, Peter T.

2014-01-01

We recommend a new term, “primary age-related tauopathy” (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFT) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (Aβ) plaques. For these “NFT+/Aβ−” brains, for which formal criteria for AD neuropathologic changes are not met, the NFT are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as “tangle-only dementia” and “tangle-predominant senile dementia”, are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of Aβ accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed. PMID:25348064

Oral pathology diagnosis by means of micro-Raman spectroscopy on biopsies and blood serum

NASA Astrophysics Data System (ADS)

Zenone, F.; Lepore, M.; Perna, G.; Carmone, P.; Delfino, I.; Gaeta, G. M.; Capozzi, V.

2007-02-01

Pemphigus vulgaris is a chronic, autoimmune, blistering disease of the skin and mucous membranes with a potentially fatal outcome. In this case micro-Raman spectroscopy (μ-RS) can provide a powerful tool for a not invasive analysis of biological tissue for biopsy and in vivo investigation. Based on the evaluation of molecular vibration frequencies, the μ-RS is able to detect the main molecular bonds of protein constituents, as the C-H and C-C ones. Changes in frequency or in the relative intensity of the vibration modes revealed by μ-RS can be related to changes of chemical bond and of protein structure induced by pathology. Quantitative information on the intensity variation of specific Raman lines can be extracted by Partial Least Square (PLS) analysis. μ-RS was performed on some samples of oral tissue and blood serum from informed patients affected by pemphigus vulgaris (an oral pathology) at different pathology stages. The spectra were measured by means of a Raman confocal microspectrometer apparatus using the 633 nm line of a He- Ne laser source. The main protein bonds are clearly detectable in the considered samples giving important information on the integrity and on the state of tissue and blood serum components (lipids and proteins), and consequently on the occurrence of pathology.

[Intra-articular injections of hyaluronic acid for anterior disc displacement of temporomandibular joint].

PubMed

Long, X

2017-03-09

Anterior disc displacement (ADD) of temporomandibular joint (TMJ) is regarded as one of the major findings in temporomandibular disorders (TMD). It is related to joint noise, pain, mandibular dysfunction, degenerative change and osteoarthritis. In the mean time, the pathological changes were found in synovial membrane and synovial fluid. Hyaluronic acid is a principal component of the synovial fluid which plays an important role in nutrition, lubrication, anti-inflammation and cartilage repair. The synthesis, molecule weight, and concentration of hyaluronic acid are decreased during TMD and cause TMJ degenerative changes. The clinical conditions, pathological changes, the mechanism of action for hyaluronic acid and the treatment of anterior disc displacement of TMJ are discussed in this article.

Panning artifacts in digital pathology images

NASA Astrophysics Data System (ADS)

Avanaki, Ali R. N.; Lanciault, Christian; Espig, Kathryn S.; Xthona, Albert; Kimpe, Tom R. L.

2017-03-01

In making a pathologic diagnosis, a pathologist uses cognitive processes: perception, attention, memory, and search (Pena and Andrade-Filho, 2009). Typically, this involves focus while panning from one region of a slide to another, using either a microscope in a traditional workflow or software program and display in a digital pathology workflow (DICOM Standard Committee, 2010). We theorize that during panning operation, the pathologist receives information important to diagnosis efficiency and/or correctness. As compared to an optical microscope, panning in a digital pathology image involves some visual artifacts due to the following: (i) the frame rate is finite; (ii) time varying visual signals are reconstructed using imperfect zero-order hold. Specifically, after pixel's digital drive is changed, it takes time for a pixel to emit the expected amount of light. Previous work suggests that 49% of navigation is conducted in low-power/overview with digital pathology (Molin et al., 2015), but the influence of display factors has not been measured. We conducted a reader study to establish a relationship between display frame rate, panel response time, and threshold panning speed (above which the artifacts become noticeable). Our results suggest visual tasks that involve tissue structure are more impacted by the simulated panning artifacts than those that only involve color (e.g., staining intensity estimation), and that the panning artifacts versus normalized panning speed has a peak behavior which is surprising and may change for a diagnostic task. This is work in progress and our final findings should be considered in designing future digital pathology systems.

Constant-Murley Score: systematic review and standardized evaluation in different shoulder pathologies.

PubMed

Vrotsou, Kalliopi; Ávila, Mónica; Machón, Mónica; Mateo-Abad, Maider; Pardo, Yolanda; Garin, Olatz; Zaror, Carlos; González, Nerea; Escobar, Antonio; Cuéllar, Ricardo

2018-05-10

The objective of this study was to evaluate the psychometric properties of the Constant-Murley Score (CMS) in various shoulder pathologies, based on a systematic review and expert standardized evaluations. A systematic review was performed in MEDLINE and EMBASE databases. Titles and abstracts were reviewed and finally the included articles were grouped according to patients' pathologies. Two expert evaluators independently assessed the CMS properties of reliability, validity, responsiveness to change, interpretability and burden score in each group, using the EMPRO (Evaluating Measures of Patient Reported Outcomes) tool. The CMS properties were assessed per attribute and overall for each considered group. Only the concept and measurement model was assessed globally. Five individual pathologies (i.e. subacromial, fractures, arthritis, instability and frozen shoulder) and two additional groups (i.e. various pathologies and healthy subjects) were considered. Overall EMPRO scores ranged from 58.6 for subacromial to 30.6 points for instability. Responsiveness to change was the only quality to obtain at least 50 points across all groups, but for frozen shoulder. Insufficient information was obtained in relation to the concept and measurement model and great variability was seen in the other evaluated attributes. The current evidence does not support the CMS as a gold standard in shoulder evaluation. Its use is advisable for subacromial pathology; but data are inconclusive for other shoulder conditions. Prospective studies exploring the psychometric properties of the scale, particularly for fractures, arthritis, instability and frozen shoulder are needed. Systematic review.

17β-Estradiol and/or estrogen receptor alpha signaling blocks protein phosphatase 1 mediated ISO induced cardiac hypertrophy.

PubMed

Fang, Hsin-Yuan; Hung, Meng-Yu; Lin, Yueh-Min; Pandey, Sudhir; Chang, Chia-Chien; Lin, Kuan-Ho; Shen, Chia-Yao; Viswanadha, Vijaya Padma; Kuo, Wei-Wen; Huang, Chih-Yang

2018-01-01

Earlier studies have shown that estrogen possess protective function against the development of pathological cardiac hypertrophy. However, the molecular mechanisms of estrogens (E2) protective effect are poorly understood. Additionally, abnormal activation of β-adrenergic signaling have been implicated in the development of pathological cardiac remodeling. However, the role of serine/threonine protein phosphatase 1 (PP1) in pathological cardiac remodeling under the influence of β-adrenergic signaling have been sparsely investigated. In this study, we assessed the downstream effects of abnormal activation of PP1 upon isoproterenol (ISO) induced pathological cardiac changes. We found that pre-treatment of 17β-estradiol (E2), tet-on estrogen receptor-α, or both significantly inhibited ISO-induced increase in cell size, hypertrophy marker gene expression and cytosolic calcium accumulation in H9c2 cells. Additionally, treatment with estrogen receptor inhibitor (ICI) reversed those effects, implicating role of E2 in inhibiting pathological cardiac remodeling. However, specific inhibition of ERα using melatonin, reduced ISO-induced PP1c expression and enhanced the level of ser-16 phosphorylated phospholamban (PLB), responsible for regulation of sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity. Furthermore, hypertrophic effect caused by overexpression of PP1cα was reduced by treatment with specific inhibitor of ERα. Collectively, we found that estrogen and estrogen receptor-α have protective effect against pathological cardiac changes by suppressing PP1 expression and its downstream signaling pathway, which further needs to be elucidated.

Trends in Pathology Graduate Medical Education Programs and Positions, 2001 to 2017.

PubMed

Petriceks, Aldis H; Salmi, Darren

2018-01-01

The US medical workforce is facing an impending physician shortage. This shortage holds special concern for pathologists, as many senior practitioners are set to retire in the coming years. Indeed, studies indicate a "pathologist gap" may grow through 2030. As such, it is important to understand current and future trends in US pathology. One key factor is graduate medical education. In this study, we analyzed data from the Accreditation Council of Graduate Medical Education, to determine the change in pathology graduate medical education programs and positions, from 2001 to 2017. We found that pathology programs and positions have increased since the 2001 to 2002 academic year, even after adjusting for population growth. However, this increase is much lower than that of total graduate medical education. Furthermore, many pathology subspecialties have declined in population-adjusted levels. Other subspecialties, such as selective pathology, have grown disproportionately. Our findings may be valuable for understanding the state of US pathology, now and in the future. They imply that more resources-or technological innovations-may be needed for specific pathology programs, in hopes of closing the pathologist gap for both this specialty and its subspecialties.

Pathological gambling in Estonia: relationships with personality, self-esteem, emotional States and cognitive ability.

PubMed

Kaare, Pille-Riin; Mõttus, René; Konstabel, Kenn

2009-09-01

Due to changes in gambling accessibility during the last decade gambling has become more widespread in Estonia and the prevalence of pathological gambling has sharply increased. The present study attempts to identify psychological characteristics of Estonian pathological gamblers. It has been shown that a wide range of social, economic, and individual factors (e.g. personality traits and emotional states) predict the likelihood of becoming a pathological gambler. In the present study, pathological gamblers' (N = 33) personality traits, self-esteem, self-reported emotional states and cognitive ability were compared to the respective characteristics in a non-gambling control group (N = 42) matched for age, gender and educational level. It was found that compared to controls, pathological gamblers had higher scores on Neuroticism (especially on its immoderation facet) and lower scores on Conscientiousness (especially on its dutifulness and cautiousness facets) and on self-esteem scale. They reported more negative emotional states during the previous month (especially depression and anxiety). Finally, pathological gamblers had lower general cognitive ability. In a logistic regression model, the likelihood of being a pathological gambler was best predicted by high immoderation score and low cognitive ability.

Building blocks of the GIPU, Italian Group of Ultrastructural Pathology.

PubMed

Papa, V; Costa, R; Cenacchi, G

2016-06-01

The Italian Group of Ultrastructural Pathology, GIPU, is a scientific organization committed to promote the art and science of Electron Microscopy (EM) in the pathology field in Italy, sharing its professional work with a public audience. The history of the GIPU goes back to 1990s when a founder group set up the Italian Group of Ultrastructural Diagnostic (GIDU) in Milan. The central focus of annual meetings was on EM, transmission and scanning one, about interesting cases in which it was instrumental in diagnosis. In the 1990s, ultrastructure was still the gold standard for cell/tissue morphology, biology, biochemistry, diagnostic pathology, and played an important role in tailored medicine. So, especially transmission EM, could play a critical role in the diagnosis of various diseases as in human as in animals. Best topics of the annual scientific meetings of the group were kidney, muscle, heart, and liver pathology, infertility, neuropathology, respiratory diseases, skin diseases, storage diseases, tumor pathology, infectious diseases, parasitology, veterinary pathology and more. Nowadays, EM is a method whose importance for diagnosis and pathology is well established: it is still essential in several pathologies, helpful in others, and welcome implemented in eclectic research pathology. Omission of EM likely makes the studies suboptimal and wasteful. So, from 2007 the name of the group has been changed to the Italian Group of Ultrastructural Pathology (GIPU) to favor broader applications of EM also to pathology research field. During last decades, GIDU/GIPU has interconnected with international (Society for Ultrastructural Pathology) and european (European Society of Pathology and Joint Meeting with the European Electron Microscopy Working Group) scientific society, according its statute. By 1991, GIPU has had 40 members: membership in this Group is still open and welcome to all pathologists, PhD, electron microscopy technologists, pathology trainees, and researchers interested in pathology and electron microscopy. © Copyright Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.

A survey study on student preferences regarding pathology teaching in Germany: a call for curricular modernization.

PubMed

Herrmann, Florian E M; Lenski, Markus; Steffen, Julius; Kailuweit, Magdalena; Nikolaus, Marc; Koteeswaran, Rajasekaran; Sailer, Andreas; Hanszke, Anna; Wintergerst, Maximilian; Dittmer, Sissi; Mayr, Doris; Genzel-Boroviczény, Orsolya; Eley, Diann S; Fischer, Martin R

2015-06-02

Pathology is a discipline that provides the basis of the understanding of disease in medicine. The past decades have seen a decline in the emphasis laid on pathology teaching in medical schools and outdated pathology curricula have worsened the situation. Student opinions and thoughts are central to the questions of whether and how such curricula should be modernized. A survey was conducted among 1018 German medical students regarding their preferences in pathology teaching modalities and their satisfaction with lecture-based courses. A qualitative analysis was performed comparing a recently modernized pathology curriculum with a traditional lecture-based curriculum. The differences in modalities of teaching used were investigated. Student satisfaction with the lecture-based curriculum positively correlated with student grades (spearman's correlation coefficient 0.24). Additionally, students with lower grades supported changing the curriculum (spearman's correlation coefficient 0.47). The majority supported virtual microscopy, autopsies, seminars and podcasts as preferred didactic methods. The data supports the implementation of a pathology curriculum where tutorials, autopsies and supplementary computer-based learning tools play important roles.

Introducing Gross Pathology to Undergraduate Medical Students in the Dissecting Room

ERIC Educational Resources Information Center

Wood, Andrew; Struthers, Kate; Whiten, Susan; Jackson, David; Herrington, C. Simon

2010-01-01

Pathology and anatomy are both sciences that contribute to the foundations of a successful medical career. In the past decade, medical education has undergone profound changes with the development of a core curriculum combined with student selected components. There has been a shift from discipline-based teaching towards problem-based learning.…

Knowledge of Normal versus Pathological Memory Aging among Police Officers

ERIC Educational Resources Information Center

Hawley, Karri S.; Garrity, April W.; Cherry, Katie E.

2005-01-01

The authors examined police officers' knowledge of memory changes in adulthood utilizing the Knowledge of Memory Aging Questionnaire (KMAQ). The KMAQ is a 28-item true/false questionnaire that covers a broad range of topics related to normal memory aging due to maturational processes and pathological memory aging, such as adult dementia. Results…

The microbiome in urogenital schistosomiasis and induced bladder pathologies

PubMed Central

Adebayo, Adewale S.; Survayanshi, Mangesh; Bhute, Shrikanth; Agunloye, Atinuke M.; Isokpehi, Raphael D.; Shouche, Yogesh S.

2017-01-01

Background Human schistosomiasis is a highly prevalent neglected tropical disease (NTD) caused by Schistosoma species. Research on the molecular mechanisms influencing the outcomes of bladder infection by Schistosoma haematobium is urgently needed to develop new diagnostics, therapeutics and infection prevention strategies. The objective of the research study was to determine the microbiome features and changes in urine during urogenital schistosomiasis and induced bladder pathologies. Methodology Seventy participants from Eggua, southwestern Nigeria provided morning urine samples and were screened for urogenital schistosomiasis infection and bladder pathologies in a cross-sectional study. Highthroughput NGS sequencing was carried out, targeting the 16S V3 region. Filtered reads were processed and analyzed in a bioinformatics pipeline. Principal findings The study participants (36 males and 34 females, between ages 15 and 65) were categorized into four groups according to status of schistosomiasis infection and bladder pathology. Data analytics of the next-generation sequencing reads revealed that Proteobacteria and Firmicutes dominated and had influence on microbiome structure of both non-infected persons and persons with urogenital schistosomiasis. Furthermore, gender and age influenced taxa abundance independent of infection or bladder pathology. Several taxa distinguished urogenital schistosomiasis induced bladder pathologies from urogenital schistosomiasis infection alone and from healthy persons, including known immune-stimulatory taxa such as Fusobacterium, Sphingobacterium and Enterococcus. Some of these significant taxa, especially Sphingobacterium were projected as markers of infection, while several genera including potentially beneficial taxa such as Trabulsiella and Weissella, were markers of the non-infected. Finally, expected changes in protein functional categories were observed to relate to cellular maintenance and lipid metabolism. Conclusion The urinary microbiome is a factor to be considered in developing biomarkers, diagnostic tools, and new treatment for urogenital schistosomiasis and induced bladder pathologies. PMID:28793309

DTI and pathological changes in a rabbit model of radiation injury to the spinal cord after 125I radioactive seed implantation

PubMed Central

Cao, Xia; Fang, Le; Cui, Chuan-yu; Gao, Shi; Wang, Tian-wei

2018-01-01

Excessive radiation exposure may lead to edema of the spinal cord and deterioration of the nervous system. Magnetic resonance imaging can be used to judge and assess the extent of edema and to evaluate pathological changes and thus may be used for the evaluation of spinal cord injuries caused by radiation therapy. Radioactive 125I seeds to irradiate 90% of the spinal cord tissue at doses of 40–100 Gy (D90) were implanted in rabbits at T10 to induce radiation injury, and we evaluated their safety for use in the spinal cord. Diffusion tensor imaging showed that with increased D90, the apparent diffusion coefficient and fractional anisotropy values were increased. Moreover, pathological damage of neurons and microvessels in the gray matter and white matter was aggravated. At 2 months after implantation, obvious pathological injury was visible in the spinal cords of each group. Magnetic resonance diffusion tensor imaging revealed the radiation injury to the spinal cord, and we quantified the degree of spinal cord injury through apparent diffusion coefficient and fractional anisotropy. PMID:29623940

Dysregulation of Prefrontal Cortex-Mediated Slow-Evolving Limbic Dynamics Drives Stress-Induced Emotional Pathology.

PubMed

Hultman, Rainbo; Mague, Stephen D; Li, Qiang; Katz, Brittany M; Michel, Nadine; Lin, Lizhen; Wang, Joyce; David, Lisa K; Blount, Cameron; Chandy, Rithi; Carlson, David; Ulrich, Kyle; Carin, Lawrence; Dunson, David; Kumar, Sunil; Deisseroth, Karl; Moore, Scott D; Dzirasa, Kafui

2016-07-20

Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1 Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

Hemifacial Pain and Hemisensory Disturbance Referred from Occipital Neuralgia Caused by Pathological Vascular Contact of the Greater Occipital Nerve

PubMed Central

Choi, Jin-gyu

2017-01-01

Here we report a unique case of chronic occipital neuralgia caused by pathological vascular contact of the left greater occipital nerve. After 12 months of left-sided, unremitting occipital neuralgia, a hypesthesia and facial pain developed in the left hemiface. The decompression of the left greater occipital nerve from pathological contacts with the occipital artery resulted in immediate relief for hemifacial sensory change and facial pain, as well as chronic occipital neuralgia. Although referral of pain from the stimulation of occipital and cervical structures innervated by upper cervical nerves to the frontal head of V1 trigeminal distribution has been reported, the development of hemifacial sensory change associated with referred trigeminal pain from chronic occipital neuralgia is extremely rare. Chronic continuous and strong afferent input of occipital neuralgia caused by pathological vascular contact with the greater occipital nerve seemed to be associated with sensitization and hypersensitivity of the second-order neurons in the trigeminocervical complex, a population of neurons in the C2 dorsal horn characterized by receiving convergent input from dural and cervical structures. PMID:28331643

Hemifacial Pain and Hemisensory Disturbance Referred from Occipital Neuralgia Caused by Pathological Vascular Contact of the Greater Occipital Nerve.

PubMed

Son, Byung-Chul; Choi, Jin-Gyu

2017-01-01

Here we report a unique case of chronic occipital neuralgia caused by pathological vascular contact of the left greater occipital nerve. After 12 months of left-sided, unremitting occipital neuralgia, a hypesthesia and facial pain developed in the left hemiface. The decompression of the left greater occipital nerve from pathological contacts with the occipital artery resulted in immediate relief for hemifacial sensory change and facial pain, as well as chronic occipital neuralgia. Although referral of pain from the stimulation of occipital and cervical structures innervated by upper cervical nerves to the frontal head of V1 trigeminal distribution has been reported, the development of hemifacial sensory change associated with referred trigeminal pain from chronic occipital neuralgia is extremely rare. Chronic continuous and strong afferent input of occipital neuralgia caused by pathological vascular contact with the greater occipital nerve seemed to be associated with sensitization and hypersensitivity of the second-order neurons in the trigeminocervical complex, a population of neurons in the C2 dorsal horn characterized by receiving convergent input from dural and cervical structures.

Correlation between MRI evidence of degenerative condylar surface changes, induction of articular disc displacement and pathological joint sounds in the temporomandibular joint.

PubMed

Honda, Kosuke; Natsumi, Yoshiko; Urade, Masahiro

2008-12-01

The relationship of bony changes in the condylar surfaces in articular disc displacement without reduction in temporomandibular joint (TMJ) was investigated using diagnostic imaging. The study also evaluated whether the bony changes in the condylar surfaces limit disc and condyle motion, and produce pathological joint sounds. Thirty-seven joints in 28 patients diagnosed with degenerative bony changes in the condylar surfaces radiographically and anterior disc displacement without reduction using magnetic resonance imaging (MRI) were studied. The bony changes were assessed by radiographic examination and classified into two types: pathological bone changes (PBCs) including erosion, osteophyte formation and deformity, and adaptive bone changes (ABCs) including flattening and concavity. MRI was performed on the TMJ to examine the configuration and position of the discs. Joint sounds in the TMJ were determined using electrovibratograghy with a joint vibration analysis. The articular disc motion to the condyle in the PBC group was smaller than in the ABC group irrespective of the configuration of the disc, even though there were no significant differences between the two types of bony changes in the disc position during jaw closing. The joint vibration analysis of the TMJ showed that joint sounds with a higher frequency were observed in the PBC group than in the ABC group. High energy levels needed to produce the higher frequencies (over 300 Hz) were observed only in the PBC group.

The pathology of methylmercury poisoning (Minamata disease): The 50th Anniversary of Japanese Society of Neuropathology.

PubMed

Eto, Komyo; Marumoto, Masumi; Takeya, Motohiro

2010-10-01

Methylmercury (Me-Hg) poisoning (Minamata disease: MD) is one of the most severe types of disease caused by humans to humans in Japan. The disease is a special class of food-borne methylmercury intoxication in humans as typified by the outbreak that began in 1953 in Minamata and its vicinity in Kumamoto Prefecture, Japan. There are 450 autopsy cases in Kumamoto and 30 autopsy cases in Niigata Prefecture related to MD in Japan. Two hundred and one cases in Kumamoto and 22 cases in Niigata showed pathological changes of MD. This report provides a brief research history and overview of the pathological changes of MD, and also presents representative cases of adult, infantile and fetal forms of MD among the 450 MD-related autopsy cases in Kumamoto Prefecture. © 2010 Japanese Society of Neuropathology.

[Nystagmus].

PubMed

Jutila, Topi; Hirvonen, Timo P

2013-01-01

Physiological nystagmus stabilizes gaze during head movements and pathological nystagmus reflects a disorder of the vestibulo-ocular reflex (VOR). Pathological nystagmus appears or strengthens usually during change in head position. Therefore, dizziness or nystagmus associated with head movements is not specific to benign paroxysmal positional vertigo unless it is verified in specific positional test. Peripheral nystagmus decelerates during visual fixation, accelerates when gaze is turned towards the fast phase, does not change direction, and is usually composed of several directional components unlike central nystagmus. The velocity and frequency of the slow phase of nystagmus can be measured with electronystagmography or video-oculography.

Impact of therapist change after initial contact and traumatic burden on dropout in a naturalistic sample of inpatients with borderline pathology receiving dialectical behavior therapy.

PubMed

Steuwe, Carolin; Berg, Michaela; Driessen, Martin; Beblo, Thomas

2017-01-01

This study focused on the predictors of therapy dropout in a naturalistic sample of patients with borderline pathology receiving dialectical behavior therapy (DBT) in an inpatient setting. We assumed that the change of the therapist between DBT-briefing and start of DBT-treatment as well as comorbid posttraumatic stress disorder (PTSD) and childhood trauma history were associated with elevated dropout. Eighty-nine participants with borderline pathology (≥ 3 borderline personality disorder criteria) receiving an inpatient DBT program completed a quality assurance questionnaire set assessing demographic information and pretreatment psychopathology during the days of their inpatient stay. Beyond that, changes of therapists were documented. The predictor analyses were investigated with generalized estimating equations. The dropout rate was 24.7%. A change of therapist between DBT-briefing and treatment as well as high childhood emotional abuse was associated with premature termination of treatment. Higher values of physical neglect during childhood were associated with a protective effect on treatment dropout. Surprisingly, this was also true for comorbid PTSD. This study supports the importance of therapy process variables as predictors of therapy dropout in borderline pathology. A change of therapist between DBT-briefing and treatment was associated with an increased vulnerability for dropping out of treatment and should therefore be avoided if possible. Against our hypotheses, a comorbid PTSD was even protective with regard to DBT dropout. Therefore, this severely suffering patient group should not be rejected from treatment assuming them to be too unstable for psychotherapy. However, results need to be replicated. ClinicalTrials.gov Identifier: NCT03018639, retrospectively registered on January 9, 2017.

Within-persons predictors of change during eating disorders treatment: An examination of self-compassion, self-criticism, shame, and eating disorder symptoms.

PubMed

Kelly, Allison C; Tasca, Giorgio A

2016-07-01

Attempts to identify the predictors of change during eating disorders treatment have focused almost exclusively on identifying between-persons factors (i.e., differences between patients). Research on within-person predictors of change (i.e., variations within patients over time) may provide novel and clinically useful information. To illustrate, we test the theory that within patients, self-compassion, self-criticism, shame, and eating disorder symptoms reciprocally influence one another over time. Seventy-eight patients with an eating disorder completed the Self-Compassion Scale, Experience of Shame Scale, and Eating Disorder Examination Questionnaire every three weeks across 12 weeks of treatment. Multilevel modeling revealed that following periods of increased shame, a patient's eating pathology was more severe than usual. Following periods of increased self-compassion or decreased eating pathology, a patient's level of shame was lower than usual. Between-person differences in the relationships among study variables also emerged. Results support the theory that shame and eating pathology influence one another cyclically within patients over time, and suggest that time-dependent increases in self-compassion may interrupt this cycle. If replicated, these results might suggest that assessing and intervening with increases in a patient's level of shame may help to reduce her eating pathology, and improving a patient's level of self-compassion or eating disorder symptomology may lower her subsequent experiences of shame. Findings highlight the value of administering and examining repeatedly measured within-person predictors of change during eating disorders treatment, and suggest that it may be clinically important to attend to the changes that occur within a given patient over time. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:716-722). © 2016 Wiley Periodicals, Inc.

Mitochondria are targets for the antituberculosis drug rifampicin in cultured epithelial cells.

PubMed

Erokhina, M V; Kurynina, A V; Onishchenko, G E

2013-10-01

Rifampicin is a widely used drug for antituberculosis therapy. Its target is the bacterial RNA polymerase. After entry into the human or mammalian organism, rifampicin is accumulated in cells of epithelial origin (kidneys, liver, lungs) where it induces apoptosis, necrosis, and fibrosis. The purpose of this study was to determine the intracellular mechanisms leading to rifampicin-induced pathological changes and cell death. We analyzed the survival and state of the chondriome of cultured epithelial cells of the SPEV line under the influence of rifampicin. Our data show that the drug induces pronounced pathological changes in the network and ultrastructure of mitochondria, and their dysfunction results in excessive production of reactive oxygen species and release of cytochrome c. These data suggest the initiation of the mitochondrial pathway of apoptosis. Simultaneously, we observed inhibition of cell proliferation and changes in morphology of the epithelial cells toward fibroblast-like appearance, which could indicate induction of epithelial-mesenchymal transition. Thus, mitochondria are the main potential target for rifampicin in cells of epithelial origin. We suggest that similar mechanisms of pathological changes can be induced in vivo in organs and tissues accumulating rifampicin during chemotherapy of bacterial infectious diseases.

Ultrasound Dopplerography of abdomen pathology using statistical computer programs

NASA Astrophysics Data System (ADS)

Dmitrieva, Irina V.; Arakelian, Sergei M.; Wapota, Alberto R. W.

1998-04-01

The modern ultrasound dopplerography give us the big possibilities in investigation of gemodynamical changes in all stages of abdomen pathology. Many of researches devoted to using of noninvasive methods in practical medicine. Now ultrasound Dopplerography is one of the basic one. We investigated 250 patients from 30 to 77 ages, including 149 men and 101 women. The basic diagnosis of all patients was the Ischaemic Pancreatitis. The Second diagnoses of pathology were the Ischaemic Disease of Heart, Gypertension, Atherosclerosis, Diabet, Vascular Disease of Extremities. We researched the abdominal aorta and her branches: Arteria Mesenterica Superior (AMS), truncus coeliacus (TC), arteria hepatica communis (AHC), arteria lienalis (AL). For investigation we use the following equipment: ACUSON 128 XP/10c, BIOMEDIC, GENERAL ELECTRIC (USA, Japan). We analyzed the following componetns of gemodynamical changes of abdominal vessels: index of pulsation, index of resistance, ratio of systol-dystol, speed of blood circulation. Statistical program included the following one: 'basic statistic's,' 'analytic program.' In conclusion we determined that the all gemodynamical components of abdominal vessels had considerable changes in abdominal ischaemia than in normal situation. Using the computer's program for definition degree of gemodynamical changes, we can recommend the individual plan of diagnostical and treatment program.

Risk Factors and Pathological Substrates Associated with Agitation/Aggression in Alzheimer's Disease: A Preliminary Study using NACC Data.

PubMed

Sennik, Simrin; Schweizer, Tom A; Fischer, Corinne E; Munoz, David G

2017-01-01

Neuropsychiatric symptoms are common manifestations of Alzheimer's disease (AD). A number of studies have targeted psychosis, i.e., hallucinations and delusions in AD, but few have assessed agitation/aggression in AD. To investigate the risk factors and pathological substrates associated with presence [A(+)] and absence [A(-)] of agitation/aggression (A) in autopsy-confirmed AD. Data was collected from the UDS data as of 2015 on the NACC database. Patients were stratified as intermediate (IAD) or high (HAD) pathological load of AD. Clinical diagnoses were not considered; additional pathological diagnoses were treated as variables. Analysis of data did not include a control group or corrections for multiple comparisons. 1,716 patients met the eligibility criteria; 31.2% of the IAD and 47.8% of the HAD patients were A(+), indicating an association with severity of pathology (p = 0.001). Risk factors for A(+) included: age at initial visit, age at death, years of education, smoking (in females), recent cardiac events (in males), and clinical history of traumatic brain injury (TBI) (in males). A history of hypertension was not related to A(+). In terms of comorbidity, clinical diagnosis of Lewy body dementia syndrome was associated with A(+) but the association was not confirmed when pathological diagnosis based on demonstration of Lewy bodies was used as the criterion. The additional presence of phosphorylated TDP-43, but not tau pathologies, was associated with A(+)HAD. Vascular lesions, including lacunes, large arterial infarcts, and severity of atherosclerosis were negatively associated with A(+). Associated symptoms included delusions, hallucinations, and depression, but not irritability, aberrant motor behavior, sleep and night time behavioral changes, or changes in appetite and eating habits. Smoking, TBI, and phosphorylated TDP-43 are associated with A(+)AD in specific groups, respectively. A(+) is directly associated with AD pathology load and inversely with vascular lesions.

Current issues in diagnostic breast pathology.

PubMed

Walker, Rosemary A; Hanby, Andy; Pinder, Sarah E; Thomas, Jeremy; Ellis, Ian O

2012-09-01

On behalf of the NHS Breast Screening Programme Pathology Coordinating Group we present recommendations for terminology and diagnostic criteria for a number of key areas of practice in breast pathology where terminology can be confusing and where accurate communication will ensure appropriate clinical management. These recommendations cover columnar cell lesions and the spectrum of changes that can be seen in these epithelial proliferations, lobular neoplasia, micrometastases and isolated tumour cells in axillary lymph nodes, the use of basal/myoepithelial markers in diagnostic practice and oestrogen receptor testing in ductal carcinoma in situ.

Toxicity of dietary Heliotropium dolosum seed to broiler chickens.

PubMed

Eröksüz, Y; Eröksüz, H; Ozer, H; Canatan, H; Yaman, I; Cevik, A

2001-12-01

Five groups of 20 female broiler chicks were fed different levels of dehulled Heliotropium dolosum seed (w/w%; 0.0, 1.0, 3.0, 5.0 or 10.0%) from 10 to 52 d of age. In all doses the seed caused decreases in daily feed intake, weight gain, and feed efficiency, and biochemical findings, severity of pathologic changes, and mortality rate increased in a dose-dependent manner. Acute toxicity was observed in livers of chicks fed 10% seed. Other test groups had chronic changes. Livers had massive to submassive necrosis, hepatic megalocytosis, bile duct proliferation, fatty change, and periportal fibrosis. Biochemical evaluations revealed hypoalbuminemia, hypoprotienemia and increased ALP activity and billuribin. The seed of Heliotropium dolosum produced biochemical and specific pathologic changes in broiler chicks, as well as decreased food intake and feed efficiency. Higher seed levels induced more pronounced changes.

[Effect of Cordyceps sinensis on the expression of HIF-1α and NGAL in rats with renal ischemia-reperfusion injury].

PubMed

Yu, Honglei; Zhou, Qiaoling; Huang, Renfa; Yuan, Mingxia; Ao, Xiang; Yang, Jinghua

2012-01-01

To observe the level of urinary neutrophil gelatinase-associated lipocalin (NGAL), the expression of hypoxia inducible factor-1α (HIF-1α) and NGAL in rat kidney after renal ischemia and reperfusion (I/R), before and after the treatment with Cordyceps Sinensis (C. sinensis), and to explore the mechanism of C. sinensis against I/R injury. A total of 45 healthy male Sprague-Dawley rats were randomly divided into a sham group, a renal I/R model group, and a C. sinensis group (15 in each group).The rats in the sham group and the renal I/R model group were intragastrically administered saline (2 mL/d), and rats in the treatment group were intragastricabby administered of C. sinensis [5.0 g/(kg.d)]. The rats were sacrificed at 24, 48, and 72 h, respectively after the reperfusion and urinary N-acetyl-β-D-glucosaminidase (NAG) level was measured, renal function in rats was detected, and the pathological changes were observed with HE staining. We determined the urinary NGAL levels in the rats by ELISA, the expression of HIF-1α mRNA by RT-PCR, and the expressions of HIF-1α and NGAL proteins by confocal immunofluorescence. Compared with the sham group, the levels of BUN, SCr, levels of NAG and NGAL in urine were increased in the I/R group and the C. sinensis group, reached a peak at 24 h after the reperfusion and slowly declined at 48 and 72 h. Glomerular and tubulointerstitial areas in the sham group did not show any pathological change. Induced pathological changes included tubular cell necrosis, focal areas of proximal tubular dilation, distal tubular casts, effacement and loss of proximal tubule brush border, etc. Compared with the sham group, the expression of HIF-1α and NGAL in the kidney tissues of the I/R group and the C. sinensis group increased. C. sinensis can lower the level of NAG and NGAL in the urine and the expression of NGAL protein in the kidney tissues. It up-regulated the expression of HIF-1α mRNA and protein in the kidney tissues whilst attenuated the pathological changes. Renal I/R injury in rats can lead to pathological changes in renal tubular epithelial cells and renal interstitial damage, which are consistent with the pathological features of acute kidney injury (AKI).The level of urinary NAGL increases after the I/R, and positively correlates with the level of urinary NAG and pathological changes, suggesting that urinary NGAL may serve as a urinary biomarker for specific detection of tubular injury in AKI. C. sinensis can attenuate the renal I/ R-induced AKI. Its mechanism may be associated with up-regulating the expression of HIF-1α and down-regulating the expression of NGAL in the kidney tissues.

Characteristics of renal papillae in kidney stone formers.

PubMed

Marien, Tracy P; Miller, Nicole L

2016-12-01

The mechanism of kidney stone formation is not well understood. In order to better understand the pathophysiology for specific kidney stone compositions and systemic diseases associated with kidney stones, endoscopic papillary mapping studies with concurrent biopsies have been conducted. This review will summarize the findings of these studies and proposed mechanisms for thirteen disease processes associated with kidney stones. A review of the literature was performed identifying thirteen studies that endoscopically mapped and biopsied renal papillae of different stone formers. These studies characterized renal papillae based on amount of Randall's plaque, Bellini's duct pathology, papillary contour changes, presence of attached stones, pitting, and frequently papillary and cortical biopsies. The groups studied and reviewed here are kidney stone formers who have a history of idiopathic calcium oxalate stone formation, cystinuria, brushite stones, gastric bypass, ileostomy, small bowel resection, primary hyperparathyroidism, distal renal tubular acidosis (dRTA), primary hyperoxaluria, idiopathic calcium phosphate stone formation, medullary sponge kidney (MSK), uric acid stones, and struvite stones. A proposed standardized scoring system for papillary pathology was also reviewed. The series showed various degrees and types of changes to the renal papillae and corresponding histopathologic changes for each type of stone former reviewed. Those with predominantly alone Randall's plaque pathology had less tissue damage versus those with extensive Bellini's duct lesions who had more interstitial fibrosis and cortical pathology. Randall's plaques are associated with stone formers who have low urinary volume, high urinary calcium, and acidic urine and thus are frequently seen in those with brushite stones, primary hyperparathyroidism, small bowel resection, and idiopathic calcium phosphate stone formers. Bellini's duct plugging and pathology is theorized to occur via free solution crystallization, ductal obstruction, inflammation, cellular injury, fibrosis, and acidification defects. Ureteroscopic manifestations of stone disease can vary from normal appearing papillae to significantly diseased appearing papillae. Some diseases have very characteristic papillary changes. Further studies are necessary to fully elucidate the mechanisms of stone formation in patients with nephrolithiasis.

FLUID-STRUCTURE INTERACTION MODELS OF THE MITRAL VALVE: FUNCTION IN NORMAL AND PATHOLOGIC STATES

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

Kunzelman, K. S.; Einstein, Daniel R.; Cochran, R. P.

2007-08-29

Successful mitral valve repair is dependent upon a full understanding of normal and abnormal mitral valve anatomy and function. Computational analysis is one such method that can be applied to simulate mitral valve function in order to analyze the roles of individual components, and evaluate proposed surgical repair. We developed the first three-dimensional, finite element (FE) computer model of the mitral valve including leaflets and chordae tendineae, however, one critical aspect that has been missing until the last few years was the evaluation of fluid flow, as coupled to the function of the mitral valve structure. We present here ourmore » latest results for normal function and specific pathologic changes using a fluid-structure interaction (FSI) model. Normal valve function was first assessed, followed by pathologic material changes in collagen fiber volume fraction, fiber stiffness, fiber splay, and isotropic stiffness. Leaflet and chordal stress and strain, and papillary muscle force was determined. In addition, transmitral flow, time to leaflet closure, and heart valve sound were assessed. Model predictions in the normal state agreed well with a wide range of available in-vivo and in-vitro data. Further, pathologic material changes that preserved the anisotropy of the valve leaflets were found to preserve valve function. By contrast, material changes that altered the anisotropy of the valve were found to profoundly alter valve function. The addition of blood flow and an experimentally driven microstructural description of mitral tissue represent significant advances in computational studies of the mitral valve, which allow further insight to be gained. This work is another building block in the foundation of a computational framework to aid in the refinement and development of a truly noninvasive diagnostic evaluation of the mitral valve. Ultimately, it represents the basis for simulation of surgical repair of pathologic valves in a clinical and educational setting.« less

The effect of progressive hearing loss on the morphology of endbulbs of Held and bushy cells.

PubMed

Connelly, Catherine J; Ryugo, David K; Muniak, Michael A

2017-01-01

Studies of congenital and early-onset deafness have demonstrated that an absence of peripheral sound-evoked activity in the auditory nerve causes pathological changes in central auditory structures. The aim of this study was to establish whether progressive acquired hearing loss could lead to similar brain changes that would degrade the precision of signal transmission. We used complementary physiologic hearing tests and microscopic techniques to study the combined effect of both magnitude and duration of hearing loss on one of the first auditory synapses in the brain, the endbulb of Held (EB), along with its bushy cell (BC) target in the anteroventral cochlear nucleus. We compared two hearing mouse strains (CBA/Ca and heterozygous shaker-2 +/- ) against a model of early-onset progressive hearing loss (DBA/2) and a model of congenital deafness (homozygous shaker-2 -/- ), examining each strain at 1, 3, and 6 months of age. Furthermore, we employed a frequency model of the mouse cochlear nucleus to constrain our analyses to regions most likely to exhibit graded changes in hearing function with time. No significant differences in the gross morphology of EB or BC structure were observed in 1-month-old animals, indicating uninterrupted development. However, in animals with hearing loss, both EBs and BCs exhibited a graded reduction in size that paralleled the hearing loss, with the most severe pathology seen in deaf 6-month-old shaker-2 -/- mice. Ultrastructural pathologies associated with hearing loss were less dramatic: minor changes were observed in terminal size but mitochondrial fraction and postsynaptic densities remained relatively stable. These results indicate that acquired progressive hearing loss can have consequences on auditory brain structure, with prolonged loss leading to greater pathologies. Our findings suggest a role for early intervention with assistive devices in order to mitigate long-term pathology and loss of function. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2018-01-01

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

Are there healthy obese?

PubMed

Griera Borrás, José Luis; Contreras Gilbert, José

2014-01-01

It is currently postulated that not all obese individuals have to be considered as pathological subjects. From 10% to 20% of obese people studied do not show the metabolic changes common in obese patients. The term "healthy obese" has been coined to refer to these patients and differentiate them from the larger and more common group of pathological obese subjects. However, the definition of "healthy obese" is not clear. Use of "healthy obese" as a synonym for obese without metabolic complications is risky. Clinical markers such as insulin resistance are used to identify this pathology. It is not clear that healthy obese subjects have lower morbidity and mortality than pathologically obese patients. According to some authors, healthy obese would represent an early stage in evolution towards pathological obesity. There is no agreement as to the need to treat healthy obese subjects. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Neuropathological and transcriptomic characteristics of the aged brain

PubMed Central

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

2017-01-01

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

Ultra-Early Phase pathologies of Alzheimer's disease and other neurodegenerative diseases.

PubMed

Okazawa, Hitoshi

2017-01-01

The concept of neurodegenerative diseases and the therapeutics targeting these intractable diseases are changing rapidly. Protein aggregation as the top of pathological cascade is now challenged, and many alternative ideas are proposed. Early molecular pathologies before microscopic detection of diseases protein aggregates, which I propose to call "Ultra-Early Phase pathologies or phase 0 pathologies", are the focus of research that might explain the failures of clinical trials with anti-Aβ antibodies against Alzheimer's disease. In this review article, I summarize the critical issues that should be successfully and consistently answered by a new concept of neurodegeneration. For reevaluating old concepts and reconstructing a new concept of neurodegeneration that will replace the old ones, non-biased comprehensive approaches including proteome combined with systems biology analyses will be a powerful tool. I introduce our recent efforts in this orientation that have reached to the stage of non-clinical proof of concept applicable to clinical trials.

A brief review of some pathology research supported by the Georgia Commodity Commission for Pecans at the USDA-ARS, Byron

USDA-ARS?s Scientific Manuscript database

With the changes currently taking place nationally in the pecan industry, and the production issues faced specifically by growers in Georgia and elsewhere in the southeastern region, the pathology research projects funded by the Georgia Commodity Commission for Pecans (CC) are reviewed. The results ...

[Pathological changes in hepatocytes of mice with obesity-induced type 2 diabetes by monosodium glutamate].

PubMed

Nakadate, Kazuhiko; Motojima, Kento; Kamata, Sumito; Yoshida, Testuro; Hikita, Masaaki; Wakamatsu, Hisanori

2014-01-01

Type 2 diabetes caused by chronic obesity is a major lifestyle-related disease. The present study aimed to determine the pathological changes in hepatocytes in chronic obesity. To develop our type 2 diabetes mouse model, we induced chronic obesity to mice by monosodium glutamate. By overeating, the mice significantly increased their body weight compared with age-matched healthy animals. To analyze the pathological changes in hepatocytes of chronic obesity before preclinical stage of type 2 diabetes, the mice were analyzed by hematoxylin-eosin staining of tissue sections at 15 w of age. In these mice, we observed eosin-negative accumulations of hepatocytes around central veins in the hepatic lobule. By Oil-Red O staining, the eosin-negative granules were identified in the lipid droplets. We then ascertained whether these lipid droplets of hepatocytes in the obese mice could be modified by diet. After 24 h of diet restriction, the lipid droplets of hepatocytes in the obese mice were swollen. Furthermore, after 48 h of the diet restriction, the lipid droplets continued swelling and the autophagy-like structures that were found in the healthy mice under the same condition in the obese mice were not observed. These results suggest that the obese mice might have delayed energy metabolism, which might have influenced the mechanisms of hepatocytes. These findings provide new insight into the functional changes in chronic obesity-induced type 2 diabetes and it is possible that the pathological feature make a contribution to promise the target of pharmacological therapy.

Internet-based motivation program for women with eating disorders: eating disorder pathology and depressive mood predict dropout.

PubMed

von Brachel, Ruth; Hötzel, Katrin; Hirschfeld, Gerrit; Rieger, Elizabeth; Schmidt, Ulrike; Kosfelder, Joachim; Hechler, Tanja; Schulte, Dietmar; Vocks, Silja

2014-03-31

One of the main problems of Internet-delivered interventions for a range of disorders is the high dropout rate, yet little is known about the factors associated with this. We recently developed and tested a Web-based 6-session program to enhance motivation to change for women with anorexia nervosa, bulimia nervosa, or related subthreshold eating pathology. The aim of the present study was to identify predictors of dropout from this Web program. A total of 179 women took part in the study. We used survival analyses (Cox regression) to investigate the predictive effect of eating disorder pathology (assessed by the Eating Disorders Examination-Questionnaire; EDE-Q), depressive mood (Hopkins Symptom Checklist), motivation to change (University of Rhode Island Change Assessment Scale; URICA), and participants' age at dropout. To identify predictors, we used the least absolute shrinkage and selection operator (LASSO) method. The dropout rate was 50.8% (91/179) and was equally distributed across the 6 treatment sessions. The LASSO analysis revealed that higher scores on the Shape Concerns subscale of the EDE-Q, a higher frequency of binge eating episodes and vomiting, as well as higher depression scores significantly increased the probability of dropout. However, we did not find any effect of the URICA or age on dropout. Women with more severe eating disorder pathology and depressive mood had a higher likelihood of dropping out from a Web-based motivational enhancement program. Interventions such as ours need to address the specific needs of women with more severe eating disorder pathology and depressive mood and offer them additional support to prevent them from prematurely discontinuing treatment.

Internet-Based Motivation Program for Women With Eating Disorders: Eating Disorder Pathology and Depressive Mood Predict Dropout

PubMed Central

Hirschfeld, Gerrit; Rieger, Elizabeth; Schmidt, Ulrike; Kosfelder, Joachim; Hechler, Tanja; Schulte, Dietmar; Vocks, Silja

2014-01-01

Background One of the main problems of Internet-delivered interventions for a range of disorders is the high dropout rate, yet little is known about the factors associated with this. We recently developed and tested a Web-based 6-session program to enhance motivation to change for women with anorexia nervosa, bulimia nervosa, or related subthreshold eating pathology. Objective The aim of the present study was to identify predictors of dropout from this Web program. Methods A total of 179 women took part in the study. We used survival analyses (Cox regression) to investigate the predictive effect of eating disorder pathology (assessed by the Eating Disorders Examination-Questionnaire; EDE-Q), depressive mood (Hopkins Symptom Checklist), motivation to change (University of Rhode Island Change Assessment Scale; URICA), and participants’ age at dropout. To identify predictors, we used the least absolute shrinkage and selection operator (LASSO) method. Results The dropout rate was 50.8% (91/179) and was equally distributed across the 6 treatment sessions. The LASSO analysis revealed that higher scores on the Shape Concerns subscale of the EDE-Q, a higher frequency of binge eating episodes and vomiting, as well as higher depression scores significantly increased the probability of dropout. However, we did not find any effect of the URICA or age on dropout. Conclusions Women with more severe eating disorder pathology and depressive mood had a higher likelihood of dropping out from a Web-based motivational enhancement program. Interventions such as ours need to address the specific needs of women with more severe eating disorder pathology and depressive mood and offer them additional support to prevent them from prematurely discontinuing treatment. PMID:24686856

[Pathological neocortical findings in patients with medication-resistant medial temporal lobe epilepsy submitted to surgery].

PubMed

Estupiñán-Díaz, B; Morales-Chacón, L M; Lorigados-Pedre, L; García-Maeso, I; Bender-del Busto, J E; Trápaga-Quincoses, O; Hidalgo-Portal, L; García-Navarro, M E; Sánchez-Coroneaux, A; Orozco-Suárez, S

The dual pathology consisting of hippocampal sclerosis plus focal cortical dysplasia (FCD) is often reported in patients with medication-resistant medial temporal lobe epilepsy (MTLE). To determine the histopathological changes that take place in the neocortex of patients with medication-resistant MTLE submitted to surgery and to evaluate the relation between the histopathological changes, pathological background and the clinical course of patients who had received surgical treatment. Tissue obtained by en bloc resection from the neocortex of 18 patients with MTLE refractory to medical treatment was processed histologically and a tailored temporal lobectomy was performed with electrocorticography. Dual pathology was diagnosed in 13 patients (72.2%). Imaging studies confirmed the existence of mesial sclerosis of the temporal in 100% of cases and there was no evidence of neocortical lesions. Histologically, 46.15% and 38.46% of the patients were diagnosed as belonging to FCD type 1a and FCD type 1b, respectively. Only one patient presented FCD type 2a. A statistically significant relation was found between the presence of dual pathology and the existence of an early precipitating injury (p = 0.04). One year after surgery, 72.7% (8/11) patients with dual pathology were classified as belonging to Engel class I. In patients with MTLE there are microscopic FCD-type alterations in the neocortex. There is an association between these alterations and the existence of an initial precipitating injury. Complete resection of the epileptogenic area, which is guaranteed by the lobectomy tailored by electrocorticography, allows patients to enjoy a favourable post-surgical progression one year after surgery.

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

PubMed

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

2018-04-21

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

Clinical rotation in pathology: description of a case based approach.

PubMed

Bezuidenhout, J; Wasserman, E; Mansvelt, E; Meyer, C; van Zyl, G; Orth, H; Els, A

2006-04-01

The implementation of a system based, integrated curriculum at the Faculty of Health Sciences of Stellenbosch University, Western Cape, South Africa, resulted in less contact time for the pathology disciplines during theoretical modules, while a weekly rotation in pathology was introduced during clinical training in the fourth and fifth years. To describe a problem based approach for this rotation. Students are presented with a clinical "paper" case daily, integrating as many of the pathology disciplines as possible to demonstrate the interdependence of the various disciplines. They receive chemical pathology tutorials, visit the various laboratories, and receive practical training in fine needle aspiration biopsy. On the final day, the case studies are assessed and discussed. Most students appreciated all activities. This rotation enhanced student interactivity and autonomy and guaranteed immediate feedback. On evaluation of the rotation it was found that the students enjoyed the rotation, learnt something new, and realised the value of group work. This innovation integrates pathology with clinical practice and illustrates the use of laboratory medicine in the management of common diseases seen in this country. Students appreciate learning practical skills and having to request special investigations under a pathologist's supervision changes their approach to pathology requests. Familiarity with the pathology environment empowers the student to use pathology with greater ease. A bank of case studies that can be expanded to include all medical disciplines will facilitate the application of a problem based approach and enhance communication between the basic science disciplines and the clinical and pathology disciplines.

Lacunar infarction and small vessel disease: pathology and pathophysiology.

PubMed

Caplan, Louis R

2015-01-01

Two major vascular pathologies underlie brain damage in patients with disease of small size penetrating brain arteries and arterioles; 1) thickening of the arterial media and 2) obstruction of the origins of penetrating arteries by parent artery intimal plaques. The media of these small vessels may be thickened by fibrinoid deposition and hypertrophy of smooth muscle and other connective tissue elements that accompanies degenerative changes in patients with hypertension and or diabetes or can contain foreign deposits as in amyloid angiopathy and genetically mediated conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These pathological changes lead to 2 different pathophysiologies: 1) brain ischemia in regions supplied by the affected arteries. The resultant lesions are deep small infarcts, most often involving the basal ganglia, pons, thalami and cerebral white matter. And 2) leakage of fluid causing edema and later gliosis in white matter tracts. The changes in the media and adventitia effect metalloproteinases and other substances within the matrix of the vessels and lead to abnormal blood/brain barriers in these small vessels. and chronic gliosis and atrophy of cerebral white matter.

The Gastrointestinal Microbiome: Alcohol Effects on the Composition of Intestinal Microbiota.

PubMed

Engen, Phillip A; Green, Stefan J; Voigt, Robin M; Forsyth, Christopher B; Keshavarzian, Ali

2015-01-01

The excessive use of alcohol is a global problem causing many adverse pathological health effects and a significant financial health care burden. This review addresses the effect of alcohol consumption on the microbiota in the gastrointestinal tract (GIT). Although data are limited in humans, studies highlight the importance of changes in the intestinal microbiota in alcohol-related disorders. Alcohol-induced changes in the GIT microbiota composition and metabolic function may contribute to the well-established link between alcohol-induced oxidative stress, intestinal hyperpermeability to luminal bacterial products, and the subsequent development of alcoholic liver disease (ALD), as well as other diseases. In addition, clinical and preclinical data suggest that alcohol-related disorders are associated with quantitative and qualitative dysbiotic changes in the intestinal microbiota and may be associated with increased GIT inflammation, intestinal hyperpermeability resulting in endotoxemia, systemic inflammation, and tissue damage/organ pathologies including ALD. Thus, gut-directed interventions, such as probiotic and synbiotic modulation of the intestinal microbiota, should be considered and evaluated for prevention and treatment of alcohol-associated pathologies.

Giant fibroadenomatoid hyperplasia of the breast: a case report.

PubMed

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

2014-01-01

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

Change in the immunophenotype of a somatotroph adenoma resulting in gigantism

PubMed Central

Thawani, Jayesh P.; Bailey, Robert L.; Burns, Carrie M.; Lee, John Y. K.

2014-01-01

Background: Examining the pathologic progression of a pituitary adenoma from the point of a prepubescent child to an adult with gigantism affords us an opportunity to consider why patients may develop secretory or functioning tumors and raises questions about whether therapeutic interventions and surveillance strategies could be made to avoid irreversible phenotypic changes. Case Description: A patient underwent a sublabial transsphenoidal resection for a clinically non-functioning macroadenoma in 1999. He underwent radiation treatment and was transiently given growth hormone (GH) supplementation as an adolescent. His growth rapidly traversed several percentiles and he was found to have elevated GH levels. The patient became symptomatic and was taken for a second neurosurgical procedure. Pathology and immunohistochemical staining demonstrated a significantly higher proportion of somatotroph cells and dense granularity; he was diagnosed with a functional somatotroph adenoma. Conclusions: While it is likely that the described observations reflect the manifestations of a functional somatotroph adenoma in development, it is possible that pubertal growth, GH supplementation, its removal, or radiation therapy contributed to the described endocrine and pathologic changes. PMID:25396071

Between DSM and ICD: Paraphilias and the Transformation of Sexual Norms.

PubMed

Giami, Alain

2015-07-01

The simultaneous revision of the two major international classifications of disease, the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases, serves as an opportunity to observe the dynamic processes through which social norms of sexuality are constructed and are subject to change in relation to social, political, and historical context. This article argues that the classifications of sexual disorders, which define pathological aspects of "sexually arousing fantasies, sexual urges or behaviors" are representations of contemporary sexual norms, gender identifications, and gender relations. It aims to demonstrate how changes in the medical treatment of sexual perversions/paraphilias passed, over the course of the 20th century, from a model of pathologization (and sometimes criminalization) of non-reproductive sexual behaviors to a model that reflects and privileges sexual well-being and responsibility, and pathologizes the absence or the limitation of consent in sexual relations.

Postmortem diagnostic investigation of disease in free-ranging marine turtle populations: A review of common pathologic findings and protocols

USGS Publications Warehouse

Flint, Mark; Patterson-Kane, Janet C.; Limpus, C.J.; Work, Thierry M.; Blair, David; Mills, Paul C.

2009-01-01

Over the past few decades, there have been increasing numbers of reports of diseases in marine turtles. Furthermore, in recent years, there have been documented instances of apparently new diseases emerging in these species of which the etiology and/or pathogenesis remain unknown. These instances i) raise concern for the survival of marine turtles, and ii) question the health and stability of the benthic marine environments in which turtles live. Knowledge of common disease processes and pathologic changes in lesions, along with a standardized approach to postmortem and sample collection are required to document and understand the host-agent-environment interactions in marine turtle health. This review combines, for the first time, a standardized approach to the postmortem of marine turtles for veterinary clinicians, with a concurrent descriptive review of the gross and microscopic pathologic changes in lesions commonly seen.

Melatonin: a chemical photoperiodic signal with clinical significance in humans.

PubMed

Pang, S F; Pang, C S; Poon, A M; Lee, P P; Liu, Z M; Shiu, S Y

1998-03-01

Secretion of pineal melatonin exhibits a diumal rhythm and a seasonal rhythm in humans. Night-time melatonin is high at 3-5 year-old and decreases with age. Many drugs and pathological conditions also change melatonin levels in the circulation. Melatonin has a mild sedative effect and has been used effectively in synchronizing the sleep-wake cycle of patients with sleep disorders. Immunoenhancing, anti-cancer, anti-aging and anti-oxidant effects of melatonin have been proposed. Recent studies suggest that melatonin receptors are present in central and peripheral tissues. The importance of melatonin receptors on the nervous, reproductive, immune and renal functions is implicated. Studies on the molecular biology, physiology and pathology of melatonin receptors in different tissues are progressing rapidly. The physiological and pathological changes in melatonin secretion, multifarious melatonin actions, and diverse melatonin receptors reported suggest that melatonin is a photoperiodic signal with clinical significance in humans.

[Ultrastructural changes of myelinated fibers in the brain in continuous and attack-like paranoid schizophrenia].

PubMed

Uranova, N A; Kolomeets, N S; Vikhreva, O V; Zimina, I S; Rakhmanova, V I; Orlovskaya, D D

Previously the authors have reported the ultrastructural pathology of myelinated fibers (MF) in the brain in schizophrenia. The aim of the present study was to compare the effect of disease course on ultrastructural changes of MF. Postmortem electron microscopic morphometric study of MF was performed in the prefrontal cortex, caudate nucleus and hippocampus in 19 cases of paranoid schizophrenia. Fourteen cases of continuous schizophrenia, 5 cases of attack-like schizophrenia and 25 normal matched control cases were studied. The proportion (percentage) of pathological MF was estimated in the prefrontal cortex, layer 5, CA3 area of hippocampus, pyramidal layer, and in the head of the caudate nucleus. The percentage of MF having axonal atrophy and swelling of periaxonal oligodendrocyte process was significantly higher in both continuous and attack-like schizophrenia in all brain structures studied as compared to the control group. In the hippocampus and caudate nucleus, this parameter was increased significantly in attack-like schizophrenia as compared to continuous schizophrenia. In the prefrontal cortex. The percentage of the pathological MF having signs of deformation and destruction of myelin sheaths increased significantly only in continuous schizophrenia as compared to the control group. MF pathology is similar in attack-like and continuous paranoid schizophrenia but differ by the degree of severity of pathological MF. Abnormalities in MF contribute to the disconnectivity between the prefrontal cortex, caudate nucleus and hippocampus.

Error-free pathology: applying lean production methods to anatomic pathology.

PubMed

Condel, Jennifer L; Sharbaugh, David T; Raab, Stephen S

2004-12-01

The current state of our health care system calls for dramatic changes. In their pathology department, the authors believe these changes may be accomplished by accepting the long-term commitment of applying a lean production system. The ideal state of zero pathology errors is one that should be pursued by consistently asking, "Why can't we?" The philosophy of lean production systems began in the manufacturing industry: "All we are doing is looking at the time from the moment the customer gives us an order to the point when we collect the cash. And we are reducing that time line by removing non-value added wastes". The ultimate goals in pathology and overall health care are not so different. The authors' intention is to provide the patient (customer) with the most accurate diagnostic information in a timely and efficient manner. Their lead histotechnologist recently summarized this philosophy: she indicated that she felt she could sleep better at night knowing she truly did the best job she could. Her chances of making an error (in cutting or labeling) were dramatically decreased in the one-by-one continuous flow work process compared with previous practices. By designing a system that enables employees to be successful in meeting customer demand, and by empowering the frontline staff in the development and problem solving processes, one can meet the challenges of eliminating waste and build an improved, efficient system.

Mechanical and hypoxia stress can cause chondrocytes apoptosis through over-activation of endoplasmic reticulum stress.

PubMed

Huang, Ziwei; Zhou, Min; Wang, Qian; Zhu, Mengjiao; Chen, Sheng; Li, Huang

2017-12-01

To examine the role of mechanical force and hypoxia on chondrocytes apoptosis and osteoarthritis (OA)-liked pathological change on mandibular cartilage through over-activation of endoplasmic reticulum stress (ERS). We used two in vitro models to examine the effect of mechanical force and hypoxia on chondrocytes apoptosis separately. The mandibular condylar chondrocytes were obtained from three-week-old male Sprague-Dawley rats. Flexcell 5000T apparatus was used to produce mechanical forces (12%, 0.5Hz, 24h vs 20%, 0.5Hz, 24h) on chondrocytes. For hypoxia experiment, the concentration of O 2 was down regulated to 5% or 1%. Cell apoptosis rates were quantified by annexin V and propidium iodide (PI) double staining and FACS analysis. Quantitative real-time PCR and western blot were performed to evaluate the activation of ERS and cellular hypoxia. Then we used a mechanical stress loading rat model to verify the involvement of ERS in OA-liked mandibular cartilage pathological change. Histological changes in mandibular condylar cartilage were assessed via hematoxylin & eosin (HE) staining. Immunohistochemistry of GRP78, GRP94, HIF-1α, and HIF-2α were performed to evaluate activation of the ERS and existence of hypoxia. Apoptotic cells were detected by the TUNEL method. Tunicamycin, 20% mechanical forces and hypoxia (1% O 2 ) all significantly increased chondrocytes apoptosis rates and expression of ERS markers (GRP78, GRP94 and Caspase 12). However, 12% mechanical forces can only increase the apoptotic sensitivity of chondrocytes. Mechanical stress resulted in OA-liked pathological change on rat mandibular condylar cartilage which included thinning cartilage and bone erosion. The number of apoptotic cells increased. ERS and hypoxia markers expressions were also enhanced. Salubrinal, an ERS inhibitor, can reverse these effects in vitro and in vivo through the down-regulation of ERS markers and hypoxia markers. We confirmed that mechanical stress and local hypoxia both contributed to the chondrocytes apoptosis. Mechanical stress can cause OA-like pathological change in rat mandibular condylar cartilage via ERS activation and hypoxia existed in the meantime. Both mechanical forces and hypoxia can induce ERS and cause chondrocytes apoptosis only if the stimulate was in higher level. Salubrinal can protect chondrocytes from apoptosis, and relieve OA-liked pathological change on mandibular condylar cartilage under mechanical stress stimulation. Copyright © 2017. Published by Elsevier Ltd.

State of the art and trends for digital pathology.

PubMed

García Rojo, Marcial

2012-01-01

Anatomic pathology is a medical specialty where both information management systems and digital images systems paly a most important role. Digital pathology is a new concept that considers all uses of this information, including diagnosis, biomedical research and education. Virtual microscopy or whole slide imaging, resulting in digital slides, is an outreaching technology in anatomic pathology. Limiting factors in the expansion of virtual microscopy are formidable storage dimension, scanning speed, quality of image and cultural change. Anatomic pathology data and images should be an important part of the patient electronic health records as well as of clinical data warehouse, epidemiological or biomedical research databases, and platforms dedicated to translational medicine. Integrating anatomic pathology to the "healthcare enterprise" can only be achieved using existing and emerging medical informatics standards like Digital Imaging and Communications in Medicine (DICOM®¹), Health Level Seven (HL7®), and Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT®), following the recommendations of Integrating the Healthcare Enterprise (IHE®). The consequences of the full digitalization of pathology departments are hard to foresee, but short term issues have arisen that imply interesting challenges for health care standards bodies.

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

Altered resting-state functional activity in isolated pontine infarction patients with pathological laughing and crying.

PubMed

Liu, Tao; Li, Jianjun; Huang, Shixiong; Li, Changqinq; Zhao, Zhongyan; Wen, Guoqiang; Chen, Feng

2017-10-13

We used resting-state functional magnetic resonance imaging to investigate the global spontaneous neural activity involved in pathological laughing and crying after stroke. Twelve pathological laughing and crying patients with isolated pontine infarction were included, along with 12 age- and gender-matched acute isolated pontine infarction patients without pathological laughing and crying, and 12 age- and gender-matched healthy controls. We examined both the amplitude of low-frequency fluctuation and the regional homogeneity in order to comprehensively evaluate the intrinsic activity in patients with post-stroke pathological laughing and crying. In the post-stroke pathological laughing and crying group, changes in these measures were observed mainly in components of the default mode network (medial prefrontal cortex/anterior cingulate cortex, middle temporal gyrus, inferior temporal gyrus, superior frontal gyrus, middle frontal gyrus and inferior parietal lobule), sensorimotor network (supplementary motor area, precentral gyrus and paracentral lobule), affective network (medial prefrontal cortex/anterior cingulate cortex, parahippocampal gyrus, middle temporal gyrus and inferior temporal gyrus) and cerebellar lobes (cerebellum posterior lobe). We therefore speculate that when disinhibition of the volitional system is lost, increased activation of the emotional system causes pathological laughing and crying.

Precursor or Sequela: Pathological Disorders in People with Internet Addiction Disorder

PubMed Central

Dong, Guangheng; Lu, Qilin; Zhou, Hui; Zhao, Xuan

2011-01-01

Background This study aimed to evaluate the roles of pathological disorders in Internet addiction disorder and identify the pathological problems in IAD, as well as explore the mental status of Internet addicts prior to addiction, including the pathological traits that may trigger Internet addiction disorder. Methods and Findings 59 students were measured by Symptom CheckList-90 before and after they became addicted to the Internet. A comparison of collected data from Symptom Checklist-90 before Internet addiction and the data collected after Internet addiction illustrated the roles of pathological disorders among people with Internet addiction disorder. The obsessive-compulsive dimension was found abnormal before they became addicted to the Internet. After their addiction, significantly higher scores were observed for dimensions on depression, anxiety, hostility, interpersonal sensitivity, and psychoticism, suggesting that these were outcomes of Internet addiction disorder. Dimensions on somatisation, paranoid ideation, and phobic anxiety did not change during the study period, signifying that these dimensions are not related to Internet addiction disorder. Conclusions We can not find a solid pathological predictor for Internet addiction disorder. Internet addiction disorder may bring some pathological problems to the addicts in some ways. PMID:21358822

[Structural changes in the tibial bones from an excessive load].

PubMed

Moshiashvili, B I

1977-10-01

80 cases of pathological reconstruction of the tibia in young men at the age of 18--20 are described. The pathology developed as a result of intense regular physical exercise. In 53 patients the process was localized in the upper third of the tibia, in 20--in the middle third and in 7--in the lower third of the bone. In 6 cases the fracture of the tibial proximal metaphysis happened against the background of pathological reconstruction of the tibia; 3 of them sustained simultaneously a fracture of the fibular head. Some recommendations of practical importance are suggested.

Variation in dielectric properties due to pathological changes in human liver.

PubMed

Peyman, Azadeh; Kos, Bor; Djokić, Mihajlo; Trotovšek, Blaž; Limbaeck-Stokin, Clara; Serša, Gregor; Miklavčič, Damijan

2015-12-01

Dielectric properties of freshly excised human liver tissues (in vitro) with several pathological conditions including cancer were obtained in frequency range 100 MHz-5 GHz. Differences in dielectric behavior of normal and pathological tissues at microwave frequencies are discussed based on histological information for each tissue. Data presented are useful for many medical applications, in particular nanosecond pulsed electroporation techniques. Knowledge of dielectric properties is vital for mathematical calculations of local electric field distribution inside electroporated tissues and can be used to optimize the process of electroporation for treatment planning procedures. © 2015 Wiley Periodicals, Inc.

Dermatology and pathology arrangements: navigating the compliance risks.

PubMed

Wood, Jane Pine; Cougevan, Bridget; McGovern, Jenny

2013-12-01

Purchased service arrangements, establishing in-house professional pathology services, conducting technical component histology within a dermatology practice, and electronic medical records technology donations are ways that dermatology practices are responding to the current health care delivery and payment changes. This article will provide a general framework for navigating the compliance risks and structure considerations associated with these relationships between dermatologists and pathologists.

George Henry Hepting: Pioneer Leader in Forest Pathology

Treesearch

Ellis B. Cowling; Arthur Kelman; Harry R. Powers

1999-01-01

George Henry Hepting grew up in the city environment of Brooklyn, but early in his life developed a deep love and scientific interest in forestry. He became America's most skilled scientist in the theory and practice of forest pathology. He studied how long-lived forest trees, unlike most plants, cope with the long-term changes in their biological, physical, and...

Optical biopsy of pre-malignant or degenerative lesions: the role of the inflammatory process

NASA Astrophysics Data System (ADS)

da Silva Martinho, Herculano

2011-03-01

Recent technological advances in fiber optics, light sources, detectors, and molecular biology have stimulated unprecedented development of optical methods to detect pathological changes in tissues. These methods, collectively termed "optical biopsy," are nondestructive in situ and real-time assays. Optical biopsy techniques as fluorescence spectroscopy, polarized light scattering spectroscopy, optical coherence tomography, confocal reflectance microscopy, and Raman spectroscopy had been extensively used to characterize several pathological tissues. In special, Raman spectroscopy technique had been able to probe several biochemical alterations due to pathology development as change in the DNA, glycogen, phospholipid, non-collagenous proteins. All studies claimed that the optical biopsy methods were able to discriminate normal and malignant tissues. However, few studies had been devoted to the discrimination of very common subtle or early pathological states as inflammatory process, which are always present on, e.g., cancer lesion border. In this work we present a systematic comparison of optical biopsy data on several kinds of lesions were inflammatory infiltrates play the role (breast, cervical, and oral lesion). It will be discussed the essential conditions for the optimization of discrimination among normal and alterated states based on statistical analysis.

Task-evoked fMRI changes in attention networks are associated with preclinical Alzheimer's disease biomarkers.

PubMed

Gordon, Brian A; Zacks, Jeffrey M; Blazey, Tyler; Benzinger, Tammie L S; Morris, John C; Fagan, Anne M; Holtzman, David M; Balota, David A

2015-05-01

There is a growing emphasis on examining preclinical levels of Alzheimer's disease (AD)-related pathology in the absence of cognitive impairment. Previous work examining biomarkers has focused almost exclusively on memory, although there is mounting evidence that attention also declines early in disease progression. In the current experiment, 2 attentional control tasks were used to examine alterations in task-evoked functional magnetic resonance imaging data related to biomarkers of AD pathology. Seventy-one cognitively normal individuals (females = 44, mean age = 63.5 years) performed 2 attention-demanding cognitive tasks in a design that modeled both trial- and task-level functional magnetic resonance imaging changes. Biomarkers included amyloid β42, tau, and phosphorylated tau measured from cerebrospinal fluid and positron emission tomography measures of amyloid deposition. Both tasks elicited widespread patterns of activation and deactivation associated with large task-level manipulations of attention. Importantly, results from both tasks indicated that higher levels of tau and phosphorylated tau pathologies were associated with block-level overactivations of attentional control areas. This suggests early alteration in attentional control with rising levels of AD pathology. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2012-01-01

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

Blast-Induced Color Change in Photonic Crystals Corresponds with Brain Pathology

PubMed Central

Cullen, D. Kacy; Browne, Kevin D.; Xu, Yongan; Adeeb, Saleena; Wolf, John A.; McCarron, Richard M.; Yang, Shu; Chavko, Mikulas

2011-01-01

Abstract A high incidence of blast exposure is a 21st century reality in counter-insurgency warfare. However, thresholds for closed-head blast-induced traumatic brain injury (bTBI) remain unknown. Moreover, without objective information about relative blast exposure, warfighters with bTBI may not receive appropriate medical care and may remain in harm's way. Accordingly, we have engineered a blast injury dosimeter (BID) using a photonic crystalline material that changes color following blast exposure. The photonic crystals are fabricated using SU-8 via multi-beam interference laser lithography. The final BID is similar in appearance to an array of small colored stickers that may be affixed to uniforms or helmets in multiple locations. Although durable under normal conditions, the photonic crystalline micro- and nano-structure are precisely altered by blast to create a color change. These BIDs were evaluated using a rat model of bTBI, for which blast shockwave exposure was generated via a compressed air-driven shock tube. With prototype BID arrays affixed to the animals, we found that BID color changes corresponded with subtle brain pathologies, including neuronal degeneration and reactive astrocytosis. These subtle changes were most notable in the dentate gyrus of the hippocampus, cerebral cortex, and cerebellum. These data demonstrate the feasibility of using a materials-based, power-free colorimetric BID as the first self-contained blast sensor calibrated to correspond with brain pathology. PMID:22082449

Autoantibody response and pregnancy-related pathology induced by combined LPS and tetanus toxoid hyperimmunization in BALB/c and C57BL/6 mice.

PubMed

Petrušić, Vladimir; Todorović, Nevena; Živković, Irena; Dimitrijević, Rajna; Muhandes, Lina; Rajnpreht, Irena; Dimitrijević, Ljiljana

2015-03-01

Recent data concerning antiphospholipid syndrome (APS) induction have shown that β2-glycoprotein I (β2GPI) binds lipopolysaccharide (LPS), which results in conformational changes, exposition of a cryptic epitope and possible pathological anti-β2GPI antibody production. In order to investigate the effects of LPS on the induction of APS-related pathology, we performed hyperimmunization of BALB/c and C57BL/6 mice with LPS, alone or in combination with tetanus toxoid (TTd), a protein structurally similar to β2GPI. We report that, although high affinity pathological anti-β2GPI antibodies were produced in all groups of animals, the reproductive pathology was recorded only in mice that received both LPS and TTd, implying on the important roles of both infections and molecular mimicry in APS pathogenesis. Moreover, APS-related reproductive pathology was more pronounced in BALB/c (lowered fertility and fecundity) than C57BL/6 mice (lowered fecundity), which correlated well with the disruption in natural antibody network observed in BALB/c mouse strain.

Inclusion bodies in cerebral cortical astrocytes: a new change of astrocytes.

PubMed

Minagawa, M; Shioda, K; Shimizu, Y; Isshiki, T

1992-01-01

A unique pathological finding of astrocytes was observed in the brain of a 20-year-old man who had severe physical and mental retardation. The brain was malformed showing micropolygyria in several cortical areas. A large number of hypertrophic astrocytes with eosinophilic granular substances in their cytoplasm were found throughout the cerebral cortex. Several staining procedures and electron microscopical examinations were carried out on these intracytoplasmic inclusion. It was found that the appearance and staining character of these inclusions were different from other astrocytic changes, especially the Rosenthal fiber, described so far. The authors consider that these inclusion bodies in cerebral cortical astrocytes represent new pathological changes of astrocytes that appear to be associated with malformation of the brain.

Environmental Disruption of Circadian Rhythm Predisposes Mice to Osteoarthritis-Like Changes in Knee Joint

PubMed Central

Voigt, Robin M; Ellman, Michael B; Summa, Keith C; Vitaterna, Martha Hotz; Keshavarizian, Ali; Turek, Fred W; Meng, Qing-Jun; Stein, Gary S.; van Wijnen, Andre J.; Chen, Di; Forsyth, Christopher B; Im, Hee-Jeong

2015-01-01

Circadian rhythm dysfunction is linked to many diseases, yet pathophysiological roles in articular cartilage homeostasis and degenerative joint disease including osteoarthritis (OA) remains to be investigated in vivo. Here, we tested whether environmental or genetic disruption of circadian homeostasis predisposes to OA-like pathological changes. Male mice were examined for circadian locomotor activity upon changes in the light:dark (LD) cycle or genetic disruption of circadian rhythms. Wild-type (WT) mice were maintained on a constant 12 hour:12 hour LD cycle (12:12 LD) or exposed to weekly 12 hour phase shifts. Alternatively, male circadian mutant mice (ClockΔ19 or Csnk1etau mutants) were compared with age-matched WT littermates that were maintained on a constant 12:12 LD cycle. Disruption of circadian rhythms promoted osteoarthritic changes by suppressing proteoglycan accumulation, upregulating matrix-degrading enzymes and downregulating anabolic mediators in the mouse knee joint. Mechanistically, these effects involved activation of the PKCδ-ERK-RUNX2/NFκB and β-catenin signaling pathways, stimulation of MMP-13 and ADAMTS-5, as well as suppression of the anabolic mediators SOX9 and TIMP-3 in articular chondrocytes of phase-shifted mice. Genetic disruption of circadian homeostasis does not predispose to OA-like pathological changes in joints. Our results, for the first time, provide compelling in vivo evidence that environmental disruption of circadian rhythms is a risk factor for the development of OA-like pathological changes in the mouse knee joint. PMID:25655021

Biochemical metabolic changes assessed by 31P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

PubMed Central

Yu, Ri-Sheng; Hao, Liang; Dong, Fei; Mao, Jian-Shan; Sun, Jian-Zhong; Chen, Ying; Lin, Min; Wang, Zhi-Kang; Ding, Wen-Hong

2009-01-01

AIM: To compare the features of biochemical metabolic changes detected by hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) with the liver damage score (LDS) and pathologic changes in rabbits and to investigate the diagnostic value of 31P MRS in acute hepatic radiation injury. METHODS: A total of 30 rabbits received different radiation doses (ranging 5-20 Gy) to establish acute hepatic injury models. Blood biochemical tests, 31P MRS and pathological examinations were carried out 24 h after irradiation. The degree of injury was evaluated according to LDS and pathology. Ten healthy rabbits served as controls. The MR examination was performed on a 1.5 T imager using a 1H/31P surface coil by the 2D chemical shift imaging technique. The relative quantities of phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured. The data were statistically analyzed. RESULTS: (1) Relative quantification of phosphorus metabolites: (a) ATP: there were significant differences (P < 0.05) (LDS-groups: control group vs mild group vs moderate group vs severe group, 1.83 ± 0.33 vs 1.55 ± 0.24 vs 1.27 ± 0.09 vs 0.98 ± 0.18; pathological groups: control group vs mild group vs moderate group vs severe group, 1.83 ± 0.33 vs 1.58 ± 0.25 vs 1.32 ± 0.07 vs 1.02 ± 0.18) of ATP relative quantification among control group, mild injured group, moderate injured group, and severe injured group according to both LDS grading and pathological grading, respectively, and it decreased progressively with the increased degree of injury (r = -0.723, P = 0.000). (b) PME and Pi; the relative quantification of PME and Pi decreased significantly in the severe injured group, and the difference between the control group and severe injured group was significant (P < 0.05) (PME: LDS-control group vs LDS-severe group, 0.86 ± 0.23 vs 0.58 ± 0.22, P = 0.031; pathological control group vs pathological severe group, 0.86 ± 0.23 vs 0.60 ± 0.21, P = 0.037; Pi: LDS-control group vs LDS-severe group, 0.74 ± 0.18 vs 0.43 ± 0.14, P = 0.013; pathological control group vs pathological severe group, 0.74 ± 0.18 vs 0.43 ± 0.14, P = 0.005) according to LDS grading and pathological grading, respectively. (c) PDE; there were no significant differences among groups according to LDS grading, and no significant differences between the control group and experimental groups according to pathological grading. (2) The ratio of relative quantification of phosphorus metabolites: significant differences (P < 0.05) (LDS-moderate group and LDS-severe group vs LDS-control group and LDS-mild group, 1.94 ± 0.50 and 1.96 ± 0.72 vs 1.43 ± 0.31 and 1.40 ± 0.38) were only found in PDE/ATP between the moderate injured group, the severe injured group and the control group, the mild injured group. No significant difference was found in other ratios of relative quantification of phosphorus metabolites. CONCLUSION: 31P MRS is a useful method to evaluate early acute hepatic radiation injury. The relative quantification of hepatic ATP levels, which can reflect the pathological severity of acute hepatic radiation injury, is correlated with LDS. PMID:19522022

Family History of Alzheimer's Disease is Associated with Impaired Perceptual Discrimination of Novel Objects.

PubMed

Mason, Emily J; Hussey, Erin P; Molitor, Robert J; Ko, Philip C; Donahue, Manus J; Ally, Brandon A

2017-01-01

Early detection may be the key to developing therapies that will combat Alzheimer's disease (AD). It has been consistently demonstrated that one of the main pathologies of AD, tau, is present in the brain decades before a clinical diagnosis. Tau pathology follows a stereotypical route through the medial temporal lobe beginning in the entorhinal and perirhinal cortices. If early pathology leads to very subtle changes in behavior, it may be possible to detect these changes in subjects years before a clinical diagnosis can currently be made. We aimed to discover if cognitively normal middle-aged adults (40-60 years old) at increased risk for AD due to family history would have impaired performance on a cognitive task known to challenge the perirhinal cortex. Using an oddity detection task, we found that subjects with a family history of AD had lowered accuracy without demonstrating differences in rate of acquisition. There were no differences between subjects' medial temporal lobe volume or cortical thickness, indicating that the changes in behavior were not due to significant atrophy. These results demonstrate that subtle changes in perceptual processing are detectable years before a typical diagnosis even when there are no differences detectable in structural imaging data. Anatomically-targeted cognitive testing may be useful in identifying subjects in the earliest stages of AD.

Pathological patterns of primary nephrotic syndrome in Central China: a retrospective study of 627 cases.

PubMed

Chu, Fenfen; Chen, Guochun; Liu, Yinghong

2014-05-01

The pathological patterns underlying PNS in adult are poorly studied in Central China. This is a retrospective analysis of the clinical and pathologic data involving 627 adult patients with PNS who have been finished the renal biopsies from January 2009 to September 2012 in XiangYa 2nd Hospital of Central South University. Patients enrolled in our study were all from Central China. There were 379 males and 248 females, formed the ratio of 1.53:1. There existed three main sorts of pathological patterns underlying PNS: membranous nephropathy (MN) 26.63%, minimal change disease (MCD) 23.60%, IgA nephropathy (IgAN) 23.39%. Among all biopsies, the proportion of FSGS underlying PNS increased from 5.8% during the period from 2009 to 2010 to 14.7% during the period from 2011 to 2012. The most common complication of PNS was infectious diseases, and MCD underlying PNS ran a higher risk of encountering acute renal injury. IgAN had the highest incidence of hematuresis. The common pathological patterns of PNS differed in age-brackets: IgAN and MCD were the main pathological lesions in patients aged from 16 to 30 years; MN mostly occurs in patients over 30. MCD was the dominating pathological lesions underlying IgAN which expressed as PNS. (1) MN was the most frequent pathological pattern underlying PNS, the proportion of FSGS underlying PNS increased during the last 2 years. (2) The common pathological patterns of PNS differed in age-brackets and pathological patterns correlated to the complications or comorbidities of PNS to some extent.

Neuropathologic features of the hippocampus and amygdala in cats with familial spontaneous epilepsy.

PubMed

Yu, Yoshihiko; Hasegawa, Daisuke; Hamamoto, Yuji; Mizoguchi, Shunta; Kuwabara, Takayuki; Fujiwara-Igarashi, Aki; Tsuboi, Masaya; Chambers, James Ken; Fujita, Michio; Uchida, Kazuyuki

2018-03-01

OBJECTIVE To investigate epilepsy-related neuropathologic changes in cats of a familial spontaneous epileptic strain (ie, familial spontaneous epileptic cats [FSECs]). ANIMALS 6 FSECs, 9 age-matched unrelated healthy control cats, and 2 nonaffected (without clinical seizures)dams and 1 nonaffected sire of FSECs. PROCEDURES Immunohistochemical analyses were used to evaluate hippocampal sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell pathological changes. Values were compared between FSECs and control cats. RESULTS Significantly fewer neurons without gliosis were detected in the third subregion of the cornu ammonis (CA) of the dorsal and ventral aspects of the hippocampus as well as the central nucleus of the amygdala in FSECs versus control cats. Gliosis without neuronal loss was also observed in the CA4 subregion of the ventral aspect of the hippocampus. No changes in mossy fiber sprouting and granule cell pathological changes were detected. Moreover, similar changes were observed in the dams and sire without clinical seizures, although to a lesser extent. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that the lower numbers of neurons in the CA3 subregion of the hippocampus and the central nucleus of the amygdala were endophenotypes of familial spontaneous epilepsy in cats. In contrast to results of other veterinary medicine reports, severe epilepsy-related neuropathologic changes (eg, hippocampal sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell pathological changes) were not detected in FSECs. Despite the use of a small number of cats with infrequent seizures, these findings contributed new insights on the pathophysiologic mechanisms of genetic-related epilepsy in cats.

Pathological Correlates of Cognitive Impairment in The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age.

PubMed

Robinson, Andrew C; Davidson, Yvonne S; Horan, Michael A; Pendleton, Neil; Mann, David M A

2018-01-01

The neuropathological changes responsible for cognitive impairment and dementia remain incompletely understood. Longitudinal studies with a brain donation end point allow the opportunity to examine relationships between cognitive status and neuropathology. We report on the first 97 participants coming to autopsy with sufficient clinical information from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age. This study began in 1983 and recruited 6,542 healthy individuals between 1983 and 1994, 312 of whom consented to brain donation. Alzheimer-type pathology was common throughout the cohort and generally correlated well with cognitive status. However, there was some overlap between cognitive status and measures of Alzheimer pathology with 26% of cognitively intact participants reaching either CERAD B or C, 11% reaching Thal phase 4 or 5, and 29% reaching Braak stage III- VI. Cerebral amyloid angiopathy(CAA), α-synuclein, and TDP-43 pathology was less common, but when present correlated well with cognitive status. Possession of APOEɛ4 allele(s) was associated with more severe Alzheimer-type and CAA pathology and earlier death, whereas possession of APOEɛ2 allele(s) had no effect on pathology but was more common in cognitively intact individuals. The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age cohort is pathologically representative when compared with similar studies. Cognitive impairment in life correlates strongly with all pathologies examined and the APOE status of an individual can affect pathology severity and longevity.

Bacterial DNA detected on pathologically changed heart valves using 16S rRNA gene amplification.

PubMed

Chalupova, Miroslava; Skalova, Anna; Hajek, Tomas; Geigerova, Lenka; Kralova, Dana; Liska, Pavel; Hecova, Hana; Molacek, Jiri; Hrabak, Jaroslav

2018-05-22

Nowadays, dental diseases are one of the most common illnesses in the world. Some of them can lead to translocation of oral bacteria to the bloodstream causing intermittent bacteraemia. Therefore, a potential association between oral infection and cardiovascular diseases has been discussed in recent years as a result of adhesion of oral microbes to the heart valves. The aim of this study was to detect oral bacteria on pathologically changed heart valves not caused by infective endocarditis. In the study, patients with pathologically changed heart valves were involved. Samples of heart valves removed during heart valve replacement surgery were cut into two parts. One aliquot was cultivated aerobically and anaerobically. Bacterial DNA was extracted using Ultra-Deep Microbiome Prep (Molzym GmbH, Bremen, Germany) followed by a 16S rRNA gene PCR amplification using Mastermix 16S Complete kit (Molzym GmbH, Bremen, Germany). Positive PCR products were sequenced and the sequences were analyzed using BLAST database ( http://www.ncbi.nlm.nih/BLAST ). During the study period, 41 samples were processed. Bacterial DNA of the following bacteria was detected in 21 samples: Cutibacterium acnes (formerly Propionibacterium acnes) (n = 11; 52.38% of patients with positive bacterial DNA detection), Staphylococcus sp. (n = 9; 42.86%), Streptococcus sp. (n = 1; 4.76%), Streptococcus sanguinis (n = 4; 19.05%), Streptococcus oralis (n = 1; 4.76%), Carnobacterium sp. (n = 1; 4.76%), Bacillus sp. (n = 2; 9.52%), and Bergeyella sp. (n = 1; 4.76%). In nine samples, multiple bacteria were found. Our results showed significant appearance of bacteria on pathologically changed heart valves in patients with no symptoms of infective endocarditis.

Pulmonary and cardiac pathology in sudden unexpected death in epilepsy (SUDEP).

PubMed

Nascimento, Fábio A; Tseng, Zian H; Palmiere, Cristian; Maleszewski, Joseph J; Shiomi, Takayuki; McCrillis, Aileen; Devinsky, Orrin

2017-08-01

To review studies on structural pulmonary and cardiac changes in SUDEP cases as well as studies showing pulmonary or cardiac structural changes in living epilepsy patients. We conducted electronic literature searches using the PubMed database for articles published in English, regardless of publication year, that included data on cardiac and/or pulmonary structural abnormalities in SUDEP cases or in living epilepsy patients during the postictal period. Fourteen postmortem studies reported pulmonary findings in SUDEP cases. Two focused mainly on assessing lung weights in SUDEP cases versus controls; no group difference was found. The other 12 reported descriptive autopsy findings. Among all SUDEP cases with available descriptive postmortem pulmonary examination, 72% had pulmonary changes, most often pulmonary edema/congestion, and, less frequently, intraalveolar hemorrhage. Eleven studies reported on cardiac pathology in SUDEP. Cardiac abnormalities were found in approximately one-fourth of cases. The most common findings were myocyte hypertrophy and myocardial fibrosis of various degrees. Among living epilepsy patients, postictal pulmonary pathology was the most commonly reported pulmonary abnormality and the most common postictal cardiac abnormality was transient left ventricular dysfunction - Takotsubo or neurogenic stunned myocardium. Cardiac and pulmonary pathological abnormalities are frequent among SUDEP cases, most commonly pulmonary edema/congestion and focal interstitial myocardial fibrosis. Most findings are not quantified, with subjective elements and undefined interobserver reliability, and lack of controls such as matched epilepsy patients who died from other causes. Further, studies have not systematically evaluated potential confounding factors, including postmortem interval to autopsy, paramedic resuscitation and IV fluids administration, underlying heart/lung disease, and risk factors for cardiac or pulmonary disease. Prospective studies with controls are needed to define the heart and lung changes in SUDEP and understand their potential relationship to mechanisms of death in SUDEP. Copyright © 2017 Elsevier Inc. All rights reserved.

Incidence of Appendicitis over Time: A Comparative Analysis of an Administrative Healthcare Database and a Pathology-Proven Appendicitis Registry

PubMed Central

Clement, Fiona; Zimmer, Scott; Dixon, Elijah; Ball, Chad G.; Heitman, Steven J.; Swain, Mark; Ghosh, Subrata

2016-01-01

Importance At the turn of the 21st century, studies evaluating the change in incidence of appendicitis over time have reported inconsistent findings. Objectives We compared the differences in the incidence of appendicitis derived from a pathology registry versus an administrative database in order to validate coding in administrative databases and establish temporal trends in the incidence of appendicitis. Design We conducted a population-based comparative cohort study to identify all individuals with appendicitis from 2000 to2008. Setting & Participants Two population-based data sources were used to identify cases of appendicitis: 1) a pathology registry (n = 8,822); and 2) a hospital discharge abstract database (n = 10,453). Intervention & Main Outcome The administrative database was compared to the pathology registry for the following a priori analyses: 1) to calculate the positive predictive value (PPV) of administrative codes; 2) to compare the annual incidence of appendicitis; and 3) to assess differences in temporal trends. Temporal trends were assessed using a generalized linear model that assumed a Poisson distribution and reported as an annual percent change (APC) with 95% confidence intervals (CI). Analyses were stratified by perforated and non-perforated appendicitis. Results The administrative database (PPV = 83.0%) overestimated the incidence of appendicitis (100.3 per 100,000) when compared to the pathology registry (84.2 per 100,000). Codes for perforated appendicitis were not reliable (PPV = 52.4%) leading to overestimation in the incidence of perforated appendicitis in the administrative database (34.8 per 100,000) as compared to the pathology registry (19.4 per 100,000). The incidence of appendicitis significantly increased over time in both the administrative database (APC = 2.1%; 95% CI: 1.3, 2.8) and pathology registry (APC = 4.1; 95% CI: 3.1, 5.0). Conclusion & Relevance The administrative database overestimated the incidence of appendicitis, particularly among perforated appendicitis. Therefore, studies utilizing administrative data to analyze perforated appendicitis should be interpreted cautiously. PMID:27820826

Colony Collapse Disorder (CCD) and bee age impact honey bee pathophysiology

PubMed Central

Traynor, Kirsten S.; Andree, Michael; Lichtenberg, Elinor M.; Chen, Yanping; Saegerman, Claude; Cox-Foster, Diana L.

2017-01-01

Honey bee (Apis mellifera) colonies continue to experience high annual losses that remain poorly explained. Numerous interacting factors have been linked to colony declines. Understanding the pathways linking pathophysiology with symptoms is an important step in understanding the mechanisms of disease. In this study we examined the specific pathologies associated with honey bees collected from colonies suffering from Colony Collapse Disorder (CCD) and compared these with bees collected from apparently healthy colonies. We identified a set of pathological physical characteristics that occurred at different rates in CCD diagnosed colonies prior to their collapse: rectum distension, Malpighian tubule iridescence, fecal matter consistency, rectal enteroliths (hard concretions), and venom sac color. The multiple differences in rectum symptomology in bees from CCD apiaries and colonies suggest effected bees had trouble regulating water. To ensure that pathologies we found associated with CCD were indeed pathologies and not due to normal changes in physical appearances that occur as an adult bee ages (CCD colonies are assumed to be composed mostly of young bees), we documented the changes in bees of different ages taken from healthy colonies. We found that young bees had much greater incidences of white nodules than older cohorts. Prevalent in newly-emerged bees, these white nodules or cellular encapsulations indicate an active immune response. Comparing the two sets of characteristics, we determined a subset of pathologies that reliably predict CCD status rather than bee age (fecal matter consistency, rectal distension size, rectal enteroliths and Malpighian tubule iridescence) and that may serve as biomarkers for colony health. In addition, these pathologies suggest that CCD bees are experiencing disrupted excretory physiology. Our identification of these symptoms is an important first step in understanding the physiological pathways that underlie CCD and factors impacting bee health. PMID:28715431

Colony Collapse Disorder (CCD) and bee age impact honey bee pathophysiology.

PubMed

vanEngelsdorp, Dennis; Traynor, Kirsten S; Andree, Michael; Lichtenberg, Elinor M; Chen, Yanping; Saegerman, Claude; Cox-Foster, Diana L

2017-01-01

Honey bee (Apis mellifera) colonies continue to experience high annual losses that remain poorly explained. Numerous interacting factors have been linked to colony declines. Understanding the pathways linking pathophysiology with symptoms is an important step in understanding the mechanisms of disease. In this study we examined the specific pathologies associated with honey bees collected from colonies suffering from Colony Collapse Disorder (CCD) and compared these with bees collected from apparently healthy colonies. We identified a set of pathological physical characteristics that occurred at different rates in CCD diagnosed colonies prior to their collapse: rectum distension, Malpighian tubule iridescence, fecal matter consistency, rectal enteroliths (hard concretions), and venom sac color. The multiple differences in rectum symptomology in bees from CCD apiaries and colonies suggest effected bees had trouble regulating water. To ensure that pathologies we found associated with CCD were indeed pathologies and not due to normal changes in physical appearances that occur as an adult bee ages (CCD colonies are assumed to be composed mostly of young bees), we documented the changes in bees of different ages taken from healthy colonies. We found that young bees had much greater incidences of white nodules than older cohorts. Prevalent in newly-emerged bees, these white nodules or cellular encapsulations indicate an active immune response. Comparing the two sets of characteristics, we determined a subset of pathologies that reliably predict CCD status rather than bee age (fecal matter consistency, rectal distension size, rectal enteroliths and Malpighian tubule iridescence) and that may serve as biomarkers for colony health. In addition, these pathologies suggest that CCD bees are experiencing disrupted excretory physiology. Our identification of these symptoms is an important first step in understanding the physiological pathways that underlie CCD and factors impacting bee health.

Early Alzheimer's Disease Neuropathology Detected by Proton MR Spectroscopy

PubMed Central

Murray, Melissa E.; Przybelski, Scott A.; Lesnick, Timothy G.; Liesinger, Amanda M.; Spychalla, Anthony; Zhang, Bing; Gunter, Jeffrey L.; Parisi, Joseph E.; Boeve, Bradley F.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.; Dickson, Dennis W.

2014-01-01

Proton magnetic resonance spectroscopy (1H-MRS) is sensitive to early neurodegenerative processes associated with Alzheimer's disease (AD). Although 1H-MRS metabolite ratios of N-acetyl aspartate (NAA)/creatine (Cr), NAA/myoinositol (mI), and mI/Cr measured in the posterior cingulate gyrus reveal evidence of disease progression in AD, pathologic underpinnings of the 1H-MRS metabolite changes in AD are unknown. Pathologically diagnosed human cases ranging from no likelihood to high likelihood AD (n = 41, 16 females and 25 males) who underwent antemortem 1H-MRS of the posterior cingulate gyrus at 3 tesla were included in this study. Immunohistochemical evaluation was performed on the posterior cingulate gyrus using antibodies to synaptic vesicles, hyperphosphorylated tau (pTau), neurofibrillary tangle conformational-epitope (cNFT), amyloid-β, astrocytes, and microglia. The slides were digitally analyzed using Aperio software, which allows neuropathologic quantification in the posterior cingulate gray matter. MRS and pathology associations were adjusted for time from scan to death. Significant associations across AD and control subjects were found between reduced synaptic immunoreactivity and both NAA/Cr and NAA/mI in the posterior cingulate gyrus. Higher pTau burden was associated with lower NAA/Cr and NAA/mI. Higher amyloid-β burden was associated with elevated mI/Cr and lower NAA/mI ratios, but not with NAA/Cr. 1H-MRS metabolite levels reveal early neurodegenerative changes associated with AD pathology. Our findings support the hypothesis that a decrease in NAA/Cr is associated with loss of synapses and early pTau pathology, but not with amyloid-β or later accumulation of cNFT pathology in the posterior cingulate gyrus. In addition, elevation of mI/Cr is associated with the occurrence of amyloid-β plaques in AD. PMID:25471565

Spectrum and Prevalence of Pathological Intracranial Magnetic Resonance Imaging Findings in Acute Bacterial Meningitis.

PubMed

Lummel, N; Koch, M; Klein, M; Pfister, H W; Brückmann, H; Linn, J

2016-06-01

Aim of this study was to determine the spectrum and prevalence of pathological intracranial magnetic resonance imaging (MRI) findings in patients with acute bacterial meningitis. We retrospectively identified all consecutive patients with cerebral spinal fluid proven bacterial meningitis who presented at our neurology department between 2007 and 2012. Pathogenic agents and clinical symptoms were noted. MR-examinations were evaluated regarding presence and localization of pathological signal alterations in the different sequences by two neuroradiologists in consensus. A total of 136 patients with purulent bacterial meningitis were identified. In 114 cases the bacterial pathogen agent was proven and in 75 patients an MRI was available. In 62 of the 75 (82.7 %) patients meningitis-associated pathologic imaging findings were evident on MRI. Overall, intraventricular signal alterations, i.e., signs of pyogenic ventriculitis, were present in 41 cases (54.7 %), while sulcal signal changes were found in 22 cases (29.3 %). Intraparenchymatous signal alterations affected the cortex in 15 cases (20 %), and the white matter in 20 patients (26.7 %). The diffusion-weighted imaging and fluid attenuated inversion recovery sequences were most sensitive in the detection of these changes and showed any pathologic findings in 67.6 and 79.6 %, respectively. Patients with streptococcal meningitis showed significantly more often (n = 29 of 34, 85.3 %) intraventricular and/or sulcal diffusion restrictions than patients with meningitis caused by other agents (n = 12 of 37, 32.4 %) (p< 0.0001). Pathological MR findings are frequently found in patients with acute bacterial meningitis. Intraventricular diffusion restrictions, i.e., signs of pyogenic ventriculitis, are more often found in patients with streptococcal, especially pneumococcal, infection.

Intake of melatonin is associated with amelioration of physiological changes, both metabolic and morphological pathologies associated with obesity: an animal model.

PubMed

Hussein, Mahmoud R; Ahmed, Omyma G; Hassan, Asmaa F; Ahmed, Marwa A

2007-02-01

Obesity and its associated metabolic pathologies are the most common and detrimental diseases, affecting over 50% of the adult population. Our knowledge about the protective effects of melatonin against high-fat diet (HFD)-induced obesity is still marginal. In this investigation, we hypothesized that melatonin can minimize the metabolic pathologies and morphological changes associated with obesity in animals receiving an HFD. To examine these effects, and to test our hypothesis, an animal model formed of male Boscat white rabbits was established. The animals were divided into three groups: (i) a control group fed regular diet; (ii) an obesity group fed an HFD for 12 weeks; and (iii) a treated group fed HFD for 12 weeks and then treated with melatonin for 4 weeks. The animals were killed and their serum and tissues were evaluated for: (i) lipid profile (cholesterol, triglycerides and low-density lipoprotein) and glucose; (ii) antioxidant enzyme (serum glutathione peroxidase, GSH-PX); and (iii) fatty changes (liver, kidney and blood vessels). Compared with the control group, intake of HFD (obesity group) was associated with: (i) a statistically significant increase in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) decreased level of GSH-PX and high-density lipoprotein (HDL); and (iii) fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. Compared with the obesity group, intake of melatonin (treated group) was associated with: (i) a statistically significant decrease in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) increased level of GSH-PX and HDL; and (iii) disappearance of fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. The administration of melatonin reduced the metabolic pathologies associated with the intake of HFD, suggesting a protective role. Although the underlying mechanisms are unclear, they may include its antioxidant and receptor-mediated effects. The clinical ramifications of these effects await further investigations.

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

PubMed

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

2010-08-01

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

Pathology and distribution of velogenic viscerotropic newcastle disease virus in the reproductive system of vaccinated and unvaccinated laying hens (gallus gallus domesticus) by immunohistochemical labelling

USDA-ARS?s Scientific Manuscript database

This study investigated the pathological changes in the reproductive system of laying hens that lead to the poor egg production and quality in Newcastle disease (ND) and the distribution of the virus in the system. Two hundred and forty Isa-Brown pullets were divided randomly into vaccinated and unv...

Diffusion Geometry Based Nonlinear Methods for Hyperspectral Change Detection

DTIC Science & Technology

2010-05-12

for matching biological spectra across a data base of hyperspectral pathology slides acquires with different instruments in different conditions, as...generalizing wavelets and similar scaling mechanisms. Plain Sight Systems, Inc. -7- Proprietary and Confidential To be specific, let the bi-Markov...remarkably well. Conventional nearest neighbor search , compared with a diffusion search. The data is a pathology slide ,each pixel is a digital

Informatics and the Clinical Laboratory

PubMed Central

Jones, Richard G; Johnson, Owen A; Batstone, Gifford

2014-01-01

The nature of pathology services is changing under the combined pressures of increasing workloads, cost constraints and technological advancement. In the face of this, laboratory systems need to meet new demands for data exchange with clinical electronic record systems for test requesting and results reporting. As these needs develop, new challenges are emerging especially with respect to the format and content of the datasets which are being exchanged. If the potential for the inclusion of intelligent systems in both these areas is to be realised, the continued dialogue between clinicians and laboratory information specialists is of paramount importance. Requirements of information technology (IT) in pathology, now extend well beyond the provision of purely analytical data. With the aim of achieving seamless integration of laboratory data into the total clinical pathway, ‘Informatics’ – the art and science of turning data into useful information – is becoming increasingly important in laboratory medicine. Informatics is a powerful tool in pathology – whether in implementing processes for pathology modernisation, introducing new diagnostic modalities (e.g. proteomics, genomics), providing timely and evidence-based disease management, or enabling best use of limited and often costly resources. Providing appropriate information to empowered and interested patients – which requires critical assessment of the ever-increasing volume of information available – can also benefit greatly from appropriate use of informatics in enhancing self-management of long term conditions. The increasing demands placed on pathology information systems in the context of wider developmental change in healthcare delivery are explored in this review. General trends in medical informatics are reflected in current priorities for laboratory medicine, including the need for unified electronic records, computerised order entry, data security and recovery, and audit. We conclude that there is a need to rethink the architecture of pathology systems and in particular to address the changed environment in which electronic patient record systems are maturing rapidly. The opportunity for laboratory-based informaticians to work collaboratively with clinical systems developers to embed clinically intelligent decision support systems should not be missed. PMID:25336763

Brain imaging and behavioral outcome in traumatic brain injury.

PubMed

Bigler, E D

1996-09-01

Brain imaging studies have become an essential diagnostic assessment procedure in evaluating the effects of traumatic brain injury (TBI). Such imaging studies provide a wealth of information about structural and functional deficits following TBI. But how pathologic changes identified by brain imaging methods relate to neurobehavioral outcome is not as well known. Thus, the focus of this article is on brain imaging findings and outcome following TBI. The article starts with an overview of current research dealing with the cellular pathology associated with TBI. Understanding the cellular elements of pathology permits extrapolation to what is observed with brain imaging. Next, this article reviews the relationship of brain imaging findings to underlying pathology and how that pathology relates to neurobehavioral outcome. The brain imaging techniques of magnetic resonance imaging, computerized tomography, and single photon emission computed tomography are reviewed. Various image analysis procedures, and how such findings relate to neuropsychological testing, are discussed. The importance of brain imaging in evaluating neurobehavioral deficits following brain injury is stressed.

Information management and informatics: need for a modern pathology service.

PubMed

Jones, Rick; O'Connor, John

2004-05-01

Requirements for information technology in pathology now extend well beyond the provision of purely analytical data. With the aim of achieving seamless integration of laboratory data into the total clinical pathway, "informatics"--the art and science of turning data into useful information--is becoming increasingly important in laboratory medicine. Informatics is a powerful tool in pathology--whether in implementing processes for pathology modernization, introducing new diagnostic modalities (e.g. proteomics, genomics), providing timely and evidence-based disease management, or enabling best use of limited and often costly resources. Providing appropriate information to empowered and interested patients--which requires critical assessment of the ever-increasing volume of information available--can also benefit greatly from appropriate use of informatics. General trends in medical informatics are reflected in current priorities for laboratory medicine, including the need for unified electronic records, computerized order entry, data security and recovery, and audit. The increasing demands placed on pathology information systems in the context of wider developmental change in healthcare delivery are explored in this paper.

Interpreting and Integrating Clinical and Anatomic Pathology Results.

PubMed

Ramaiah, Lila; Hinrichs, Mary Jane; Skuba, Elizabeth V; Iverson, William O; Ennulat, Daniela

2017-01-01

The continuing education course on integrating clinical and anatomical pathology data was designed to communicate the importance of using a weight of evidence approach to interpret safety findings in toxicology studies. This approach is necessary, as neither clinical nor anatomic pathology data can be relied upon in isolation to fully understand the relationship between study findings and the test article. Basic principles for correlating anatomic pathology and clinical pathology findings and for integrating these with other study end points were reviewed. To highlight these relationships, a series of case examples, presented jointly by a clinical pathologist and an anatomic pathologist, were used to illustrate the collaborative effort required between clinical and anatomical pathologists. In addition, the diagnostic utility of traditional liver biomarkers was discussed using results from a meta-analysis of rat hepatobiliary marker and histopathology data. This discussion also included examples of traditional and novel liver and renal biomarker data implementation in nonclinical toxicology studies to illustrate the relationship between discrete changes in biochemistry and tissue morphology.

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

PubMed

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

2013-10-01

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

Comparative Study of the Pathological Effects of Western Equine Encephalomyelitis Virus in Four Strains of Culex tarsalis Coquillett (Diptera: Culicidae)

PubMed Central

Neira, Marco V.; Mahmood, Farida; Reisen, William K.; James, Calvin B. L.; Romoser, William S.

2014-01-01

Early reports suggested that mosquito cells infected with arboviruses remain viable and undamaged. However, more recent experimental evidence suggests that arboviral infection of mosquito tissues might indeed result in pathological changes, with potential implications for vector survival and virus transmission. Here, we compare the pathological effects of western equine encephalomyelitis virus (WEEV) infection in four strains of Culex tarsalis previously reported to differ in their competence as WEEV vectors. Pathological effects were observed in cells of the midgut epithelium, salivary glands, and eggs. Cell rounding and sloughing of midgut epithelial cells was associated with those strains reported to be the least susceptible to WEEV infection, whereas midgut necrosis and vacuolation upon infection were associated with strains showing higher susceptibility. Although pathological effects were sporadically observed in infected salivary glands, further studies are required to evaluate their impact on vector competence. Additionally, the potential implications of observed C. tarsalis egg infection with WEEV are discussed. PMID:25346928

Sequential pathological changes during malignant transformation of a craniopharyngioma: A case report and review of the literature

PubMed Central

Negoto, Tetsuya; Sakata, Kiyohiko; Aoki, Takachika; Orito, Kimihiko; Nakashima, Shinji; Hirohata, Masaru; Sugita, Yasuo; Morioka, Motohiro

2015-01-01

Background: Malignant transformation of craniopharyngiomas is quite rare, and the etiology of transformation remains unclear. The prognosis of malignantly transformed craniopharyngiomas is very poor. Case Description: A 36-year-old male had five craniotomies, five transsphenoidal surgeries, and two radiation treatments until 31 years of age after diagnosis of craniopharyngioma at 12 years of age. All serial pathological findings indicated adamantinomatous craniopharyngioma including those of a surgery performed for tumor regrowth at 31 years of age. However, when the tumor recurred approximately 5 years later, the pathological findings showed squamous metaplasia. The patient received CyberKnife surgery, but the tumor rapidly regrew within 4 months. The tumor was resected with the cavernous sinus via a dual approach: Transcranial and transsphenoidal surgery with an extracranial-intracranial bypass using the radial artery. Pathologic examination of a surgical specimen showed that it consisted primarily of squamous cells; the lamina propria was collapsed, and the tumor cells had enlarged nuclei and clarification of the nucleolus. The tumor was ultimately diagnosed as malignant transformation of craniopharyngioma. After surgery, he received combination chemotherapy (docetaxel, cisplatin, and fluorouracil). The tumor has been well controlled for more than 12 months. Conclusion: Serial pathological changes of the craniopharyngioma and a review of the 20 cases reported in the literature suggest that radiation of the squamous epithelial cell component of the craniopharyngioma led to malignant transformation via squamous metaplasia. We recommend aggressive surgical removal of craniopharyngiomas and avoidance of radiotherapy if possible. PMID:25883842

Breakfast skipping as a risk correlate of overweight and obesity in school-going ethnic Fijian adolescent girls

PubMed Central

Thompson-McCormick, Jonas J; Thomas, Jennifer J; Bainivualiku, Asenaca; Khan, A Nisha; Becker, Anne E

2013-01-01

The prevalence of overweight and obesity has increased globally, and population data suggest that it is also increasing among ethnic Fijian youth. Among numerous behavioural changes contributing to overweight in youth residing in nations undergoing rapid economic and social change, meal skipping has not been examined as a potential risk factor. The study objectives were to assess the prevalence of overweight, obesity, and breakfast skipping and examine their cross-sectional association in a community sample of school-going ethnic Fijian adolescent girls (n=523). We measured height and weight, and assessed dietary patterns, eating pathology, dimensions of acculturation, and other socio-demographic and cultural data by self-report. We observed a high prevalence of both overweight (41%, including 15% who were obese) and breakfast skipping (68%). In addition, in multivariable analyses unadjusted for eating pathology, we found that more frequent breakfast skipping was associated with greater odds of overweight (odds ratio (OR)=1.15, confidence interval (CI)=1.06, 1.26, p<0.01) and obesity (OR=1.18, CI=1.05, 1.33, p<0.01). Regression models adjusting for eating pathology attenuated this relation so that it was non-significant, but demonstrated that greater eating pathology was associated with greater odds of both overweight and obesity. Future research is necessary to clarify the relation among breakfast skipping, eating pathology, and overweight in ethnic Fijian girls, and to identify whether breakfast skipping may be a modifiable risk factor for overweight in this population. PMID:20805082

Cortical Iron Reflects Severity of Alzheimer’s Disease

PubMed Central

van Duijn, Sara; Bulk, Marjolein; van Duinen, Sjoerd G.; Nabuurs, Rob J.A.; van Buchem, Mark A.; van der Weerd, Louise; Natté, Remco

2017-01-01

Abnormal iron distribution in the isocortex is increasingly recognized as an in vivo marker for Alzheimer’s disease (AD). However, the contribution of iron accumulation to the AD pathology is still poorly understood. In this study, we investigated: 1) frontal cortical iron distribution in AD and normal aging and 2) the relation between iron distribution and degree of AD pathology. We used formalin fixed paraffin embedded frontal cortex from 10 AD patients, 10 elder, 10 middle aged, and 10 young controls and visualized iron with a modified Perl’s histochemical procedure. AD and elderly subjects were not different with respect to age and sex distribution. Iron distribution in the frontal cortex was not affected by normal aging but was clearly different between AD and controls. AD showed accumulation of iron in plaques, activated microglia, and, in the most severe cases, in the mid-cortical layers along myelinated fibers. The degree of altered iron accumulations was correlated to the amount of amyloid-β plaques and tau pathology in the same block, as well as to Braak stage (p < 0.001). AD and normal aging show different iron and myelin distribution in frontal cortex. These changes appear to occur after the development of the AD pathological hallmarks. These findings may help the interpretation of high resolution in vivo MRI and suggest the potential of using changes in iron-based MRI contrast to indirectly determine the degree of AD pathology in the frontal cortex. PMID:29081415

Low-field and high-field magnetic resonance contrast imaging of magnetoferritin as a pathological model system of iron accumulation

NASA Astrophysics Data System (ADS)

Strbak, Oliver; Balejcikova, Lucia; Baciak, Ladislav; Kovac, Jozef; Masarova-Kozelova, Marta; Krafcik, Andrej; Dobrota, Dusan; Kopcansky, Peter

2017-09-01

Various pathological processes including neurodegenerative disorders are associated with the accumulation of iron, while it is believed that a precursor of iron accumulation is ferritin. Physiological ferritin is due to low relaxivity, which results in only weak detection by magnetic resonance imaging (MRI) techniques. On the other hand, pathological ferritin is associated with disrupted iron homeostasis and structural changes in the mineral core, and should increase the hypointensive artefacts in MRI. On the basis of recent findings in respect to the pathological ferritin structure, we prepared the magnetoferritin particles as a possible pathological ferritin model system. The particles were characterised with dynamic light scattering, as well as with superconducting quantum interference device measurements. With the help of low-field (0.2 T) and high-field (4.7 T) MRI standard T 2-weighted protocols we found that it is possible to clearly distinguish between native ferritin as a physiological model system, and magnetoferritin as a pathological model system. Surprisingly, the T 2-weighted short TI inversion recovery protocol at low-field system showed the optimum contrast differentiation. Such findings are highly promising for exploiting the use of iron accumulation as a noninvasive diagnostics tool of pathological processes, where the magnetoferritin particles could be utilised as MRI iron quantification calibration samples.

Exercise training improves obesity‐related lymphatic dysfunction

PubMed Central

Hespe, Geoffrey E.; Kataru, Raghu P.; Savetsky, Ira L.; García Nores, Gabriela D.; Torrisi, Jeremy S.; Nitti, Matthew D.; Gardenier, Jason C.; Zhou, Jie; Yu, Jessie Z.; Jones, Lee W.

2016-01-01

Key points Obesity results in perilymphatic inflammation and lymphatic dysfunction.Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells.Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Abstract Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P < 0.01). Aerobic exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti‐inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic specific genes, including VEGFR‐3 and Prox1. Taken together, our findings suggest that obesity impairs lymphatic function via multiple mechanisms and that these pathological changes can be reversed, in part, with aerobic exercise, independent of weight loss. In addition, our study shows that obesity‐induced lymphatic endothelial cell gene expression changes are reversible with behavioural modifications. PMID:26931178

Molecular Imaging Markers to Track Huntington's Disease Pathology.

PubMed

Wilson, Heather; De Micco, Rosa; Niccolini, Flavia; Politis, Marios

2017-01-01

Huntington's disease (HD) is a progressive, monogenic dominant neurodegenerative disorder caused by repeat expansion mutation in the huntingtin gene. The accumulation of mutant huntingtin protein, forming intranuclear inclusions, subsequently leads to degeneration of medium spiny neurons in the striatum and cortical areas. Genetic testing can identify HD gene carriers before individuals develop overt cognitive, psychiatric, and chorea symptoms. Thus, HD gene carriers can be studied in premanifest stages to understand and track the evolution of HD pathology. While advances have been made, the precise pathophysiological mechanisms underlying HD are unclear. Magnetic resonance imaging (MRI) and positron emission tomography (PET) have been employed to understand HD pathology in presymptomatic and symptomatic disease stages. PET imaging uses radioactive tracers to detect specific changes, at a molecular level, which could be used as markers of HD progression and to monitor response to therapeutic treatments for HD gene expansion carriers (HDGECs). This review focuses on available PET techniques, employed in cross-sectional and longitudinal human studies, as biomarkers for HD, and highlights future potential PET targets. PET studies have assessed changes in postsynaptic dopaminergic receptors, brain metabolism, microglial activation, and recently phosphodiesterase 10A (PDE10A) as markers to track HD progression. Alterations in PDE10A expression are the earliest biochemical change identified in HD gene carriers up to 43 years before predicted symptomatic onset. Thus, PDE10A expression could be a promising marker to track HD progression from early premanifest disease stages. Other PET targets which have been less well investigated as biomarkers include cannabinoid, adenosine, and GABA receptors. Future longitudinal studies are required to fully validate these PET biomarkers for use to track disease progression from far-onset premanifest to manifest HD stages. PET imaging is a crucial neuroimaging tool, with the potential to detect early changes and validate sensitivity of biomarkers for tracking HD pathology. Moreover, continued development of novel PET tracers provides exciting opportunities to investigate new molecular targets, such as histamine and serotonin receptors, to further understand the mechanisms underlying HD pathology.

Pathology of mitochondria in MELAS syndrome: an ultrastructural study.

PubMed

Felczak, Paulina; Lewandowska, Eliza; Stępniak, Iwona; Ołdak, Monika; Pollak, Agnieszka; Lechowicz, Urszula; Pasennik, Elżbieta; Stępień, Tomasz; Wierzba-Bobrowicz, Teresa

Ultrastructural changes in skeletal muscle biopsy in a 24-year-old female patient with clinically suspected mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) syndrome are presented. We observed proliferation and/or pleomorphism of mitochondria in skeletal muscle and smooth muscle cells of arterioles, as well as in pericytes of capillaries. Paracrystalline inclusions were found only in damaged mitochondria of skeletal muscle. Genetic testing revealed a point mutation in A3243G tRNALeu(UUR) typical for MELAS syndrome. We conclude that differentiated pathological changes of mitochondria in the studied types of cells may be associated with the different energy requirements of these cells.

Retinopathy of prematurity - from recognition of risk factors to treatment recommendations.

PubMed

Fagerholm, Reija; Vesti, Eija

Retinopathy of prematurity is a proliferative retinal disorder diagnosed exclusively in prematurely born infants. In retinopathy of prematurity, growth of the retinal vasculature is disturbed, leading to hypoxia-induced pathological changes typical of retinopathy of prematurity, in the worst case resulting in retinal detachment. The most typical risk factors predisposing to the disease include hyperoxemia, low levels of insulin-like growth factor 1 (IGF-I), and low birth weight in relation to weeks of pregnancy. Laser therapy of peripheral retina is the currently established form of treatment. Screening is applied in order to recognize the pathological changes in retinopathy of prematurity early enough.

Expression and clinical significance of rhubarb on serum amylase and TNF-alpha of rat model of acute pancreatitis.

PubMed

Zhang, W F; Li, Z T; Fang, J J; Wang, G B; Yu, Y; Liu, Z Q; Wu, Y N; Zheng, S S; Cai, L

2017-01-01

The aim of this study was to evaluate the therapeutic effect of rhubarb extract on acute pancreatitis. Ninety-six healthy Sprague Dawley rats, weighing 301±5.12 g were randomly divided into 4 groups: sham surgery (group A), acute pancreatitis model (group B), acute pancreatitis with normal saline (group C), and acute pancreatitis model with rhubarb (group D). The levels of serum amylase (AMY) and TNF-α were measured at 1st, 6th, 12th and 24th hour after modeling, and the pancreatic tissue were used to observe the pathologic changes. Compared to the sham group, the serum AMY and serum tumor necrosis factor (TNF-α) levels were significantly increased in the other groups (p <0.05). Compared to the model group and the saline group, the serum AMY, serum TNF-α level and pathological changes of rats in the rhubarb group were significantly lower (p <0.05). The serum AMY and TNF-α levels increased in acute pancreatitis. The rhubarb reduced the serum AMY and TNF-α level in rats with acute pancreatitis and reduced the pathological changes of pancreas and other tissues.

Fingolimod (FTY-720) is Capable of Reversing Tumor Necrosis Factor Induced Decreases in Cochlear Blood Flow.

PubMed

Bertlich, Mattis; Ihler, Friedrich; Weiss, Bernhard G; Freytag, Saskia; Jakob, Mark; Strupp, Michael; Pellkofer, Hannah; Canis, Martin

2017-09-01

The potential of Fingolimod (FTY-720), a sphingosine-1-phosphate analogue, to revoke the changes in cochlear blood flow induced by tumor necrosis factor (TNF) was investigated. Impairment of cochlear blood flow has often been considered as the common final pathway of various inner ear pathologies. TNF, an ubiquitous cytokine, plays a major role in these pathologies, reducing cochlear blood flow via sphingosine-1-phosphate-signaling. Fifteen Dunkin-Hartley guinea pigs were randomly assigned to one of three groups (placebo/placebo, TNF/placebo, TNF/FTY-720). Cochlear microcirculation was quantified over 60 minutes by in vivo fluorescence microscopy before and after topical application of placebo or TNF (5 ng/ml) and after subsequent application of placebo or FTY-720 (200 μg/ml). Treatment with TNF led to a significant decrease of cochlear blood flow.Following this, application of placebo caused no significant changes while application of FTY-720 caused a significant rise in cochlear blood flow. FTY-720 is capable of reversing changes in cochlear blood flow induced by application of TNF. This makes FTY-720 a valid candidate for potential treatment of numerous inner ear pathologies.

[IDENTIFICATION OF CAUSES OF EARLY PREGNANCY LOSSES ACCORDING TO HYSTOMORPHOLOGIC FEATURES].

PubMed

Gotsiridze, K; Kintraia, N; Pailodze, M; Gogia, T; Tsaava, F

2017-01-01

Retrospective analysis of the early spontaneous abortions has been conducted (486 cases). Histomorphologic analysis of the curettage material contents erveledinvolutive-regressive developmental chsnges in 108 (22,28%) cases, in 370 cases (77.78%) pathologic changes, like inflammatory changes of deciduas and chorionic villis in 302 cases (80.2%), pathologic prematurity of chorionic vili in 48 cases (12.6%), hydatidiform mole in 28 cases (7.4%). As most cases of pregnancy loss has been reported at 7-9 weeks /172 cases/, we compared histomorphologic data revealed at 7-8 (71 cases) weeks to 5-6 (135 cases) and 10-12 weeks of gestation. Morphologic research data confimed, that at 7-8 weeks compared to 5-6 weeks leading reason ofpregnancy loss was inflammatory changes (OR-1,584), what can be cause of 110 pregnancy losses at 1000 pregnant women (AR-0.11). Data comparing7-9 weeks to 10-12 weeks pregnancy losses, confirm the priority of pathologic immaturity (OR-1,279) and hydatidiform mole (OR-1,557) and could be the risk of 100 cases of pregnancy termination at 1000 pregnant women (AR-0.10).Existing results are of great importance for the preconceptional preparation of women.

The Existence of Primary Age-Related Tauopathy Suggests that not all the Cases with Early Braak Stages of Neurofibrillary Pathology are Alzheimer's Disease.

PubMed

Giaccone, Giorgio

2015-01-01

The distinction between Alzheimer's disease (AD) and Primary Age-Related Tauopathy (PART) is a hotly debated issue. As most lines of evidence support the tenet that tau pathology occurs downstream of amyloid-β deposition, it seems reasonable to consider PART as a separate disease process not necessarily related to Aβ and hence AD. Following this view, the early stages of neurofibrillary pathology may not always be the forerunner of diffuse neurofibrillary changes and AD. The ongoing debate further enhances the need for greater caution against any future predictions using tau cerebrospinal fluid and imaging biomarkers.

Fibroadenomatosis (fibroadenomatoid mastopathy): a benign breast lesion with composite pathologic features.

PubMed

Hanson, C A; Snover, D C; Dehner, L P

1987-10-01

A benign breast lesion with the composite histologic features of a fibroadenoma and fibrocystic changes has been referred to previously as fibroadenomatosis or fibroadenomatoid mastopathy; this lesion is distinct from the typical well circumscribed fibroadenoma that may have fibrocystic changes. The purpose of our study was to ascertain the frequency of this change among 200 consecutive breast biopsies and excisions with a coded pathologic diagnosis of fibroadenoma and/or "fibrocystic disease"; we identified these changes in 23 (11.5%) specimens. The lesion was characterized by microscopic fibroadenomatoid foci intermingled with dilated ducts, epitheliosis, and adenosis. It is suggested that fibroadenomatosis is yet another pattern in the complex morphologic spectrum known as benign proliferative breast disease. From our experience, this particular lesion was often appreciated as a unique finding, but the appropriate diagnostic designation was in question. The natural history of fibroadenomatosis is essentially unknown. It may represent a morphologic stage in the development of fibroadenoma(s).

[Epigenetics, interface between environment and genes: role in complex diseases].

PubMed

Scheen, A J; Junien, C

2012-01-01

Epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. Epigenetics is one of the major mechanisms explaining the "Developmental Origin of Health and Diseases" (DOHaD). Besides genetic background inherited from parents, which confers susceptibility to certain pathologies, epigenetic changes constitute the memory of previous events, either positive or negative, along the life cycle, including at the in utero stage. The later exposition to hostile environment may reveal such susceptibility, with the development of various pathologies, among them numerous chronic complex diseases. The demonstration of such a sequence of events has been shown for metabolic diseases as obesity, metabolic syndrome and type 2 diabetes, cardiovascular disease and cancer. In contrast to genetic predisposition, which is irreversible, epigenetic changes are potentially reversible, thus giving targets not only for prevention, but possibly also for the treatment of certain complex diseases.

Clinical image and pathology of hypertrophic cranial pachymeningitis.

PubMed

Shi, C H; Niu, S T; Zhang, Z Q

2014-12-12

The objective of this study was to examine the clinical findings, magnetic resonance imaging (MRI), pathological features, and treatment experiments of patients with hypertrophic cranial pachymeningitis (HCP). The clinical findings, MRI, and pathological appearances of 9 patients with HCP were analyzed retrospectively. The thickened dura mater was markedly enhanced after contrast media injection. The lesion near the brain hemisphere presented long regions of T1- and T2-weighted abnormal signal intensities. The abnormal signal intensities of the brain tissue were decreased significantly. Pathological examination demonstrated chronic inflammation changes, with cerebral dura mater fibrous tissue showing obvious hyperplasia, and the periphery of the blood vessel showing a great quantity of infiltrating phlegmonosis cells. HCP mainly presents headache and paralysis of multiple cranial nerves. The distinctive signs on brain MRIs involve strengthening the signal in the cerebral dura.

A template for a clinico-pathological audit of medical liver biopsies.

PubMed

Colling, Richard; Fryer, Eve; Cobbold, Jeremy; Collier, Jane; Collantes, Elena; Wang, Lai Mun; Hubscher, Stefan; Wyatt, Judith; Fleming, Kenneth

2015-11-01

With changing indications for performing medical liver biopsies, we aimed to develop a tool to allow pathologists to evaluate the current usefulness, value and impact of their medical liver biopsy service. We designed and piloted a questionnaire-based clinico-pathological audit for medical liver biopsies. The audit tool was simple to implement and provided useful information about our service. Hepatologists felt that 96% of reports were clinically useful. 56% of biopsies confirmed clinical diagnoses, 46% helped differentiate between diagnoses and 42% were able to exclude possible diagnoses. 74% resulted in a change of management and 27% of liver biopsies resulted in a diagnosis which was not clinically suspected. We demonstrate the usefulness of an audit tool in providing evidence of the value of the liver pathology service in a large UK regional centre. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Peculiarities of mitosis and nucleolar characteristics of the birch plantlets under antropogenous pollution].

PubMed

Butorina, A K; Kalaev, V N; Karpova, S S

2002-01-01

A study was made of some cytogenetic characteristics (mitotic activity, the level and spectrum of pathological mitosis, nucleolar features in root tip cells) in birch plantlets. The seeds were collected in four districts of Voronezh and in the ecologically clean territory. The index of mitotic activity has a considerable resistance to anthropogenous pollution. In the experimental areas, the level and spectrum of pathological mitosis increase. In contaminated areas we observed changes of nucleolar characteristics (the increased surface area of nucleoli and their higher number in cells, the increased number of cells with highly active types of nucleoli, the appearance of residual nucleoli). These changes can be considered as possible mechanisms of adaptation to stress due to antropogenous pollution. It is suggested that the use of such indices as single nucleolar surface area or the level of pathological mitosis may be perspective for cytogenetic monitoring of the environment, and for prognostification of environmental conditions suitable or unsuitable for the human health.

A study on effects of glutathione s-transferase from silkworm on CCL4-induced mouse liver injury.

PubMed

Yan, Hui; Gui, Zhongzheng; Wang, Bochu

2011-01-01

To assess the hepatoprotective activity of Glutathione S-transferase(GSTsw), extracted and purified from silkworm, in experimental acute mice liver injury and explore mechanisms. Mice were divided into five groups: control group, carbon tetrachloride (CCl4) group, and three treatment groups that received CCl4 and GSTsw at doses of 0.083 mg•g(-1), 0.0415 mg•g(-1) and 0.0207 mg•g(-1) for 3 days. ALT in serum, GST, SOD and T-AOC in liver tissue homogenate, and changes in liver pathology in the five groups were studied. CCl4 administration led to pathological and biochemical evidence of liver injury as compared to untreated controls. GSTsw administration led to significant protection against CCl4-induced changes in liver pathology. It was also associatedwith significantly lower serum ALT levels, higher GST-SOD and T-AOC level in live tissue homogenate. Thus, GSTsw showed protective activity against CCl4-induced hepatotoxicity in mice.

Alzheimer's disease: a correlative study.

PubMed Central

Neary, D; Snowden, J S; Mann, D M; Bowen, D M; Sims, N R; Northen, B; Yates, P O; Davison, A N

1986-01-01

In a study of 17 patients with histologically proven Alzheimer's disease the relationship between psychological, pathological and chemical measures of disorder was examined. Severity of dementia, determined by mental test performance, correlated highly with pathological change in large cortical neurons (cell loss and reduction in nuclear and nucleolar volume and cytoplasmic RNA content), to a lesser extent with cortical senile plaque and neurofibrillary tangle frequency and reduction in acetylcholine (ACh) synthesis, and not with reduction in choline acetyltransferase (CAT) activity. A strongly significant relationship was demonstrated between cell loss and reductions in nuclear and nucleolar volume and cytoplasmic RNA content. Reduction in CAT activity and senile plaque frequency were significantly correlated, thereby linking changes in the sub-cortical projection system of the nucleus basalis with the cortical pathology. The pattern of correlations suggests that the dementia of Alzheimer's disease is largely a reflection of the state of large cortical neurons, and it is argued that abnormalities in the latter may not be directly related to primary loss of cholinergic neurons in the subcortex. PMID:2420941

[Fetal bone and joint disorders].

PubMed

Jakobovits, Akos

2008-12-21

The article discusses the physiology and pathology of fetal bone and joint development and functions. The bones provide static support for the body. The skull and the bones of spinal column encase the central and part of the peripheral nervous system. The ribs and the sternum shield the heart and the lungs, while the bones of the pelvis protect the intraabdominal organs. Pathological changes of these bony structures may impair the functions of the respective systems or internal organs. Movements of the bones are brought about by muscles. The deriving motions are facilitated by joints. Bony anomalies of the extremities limit their effective functions. Apart from skeletal and joint abnormalities, akinesia may also be caused by neurological, muscular and skin diseases that secondarily affect the functions of bones and joints. Such pathological changes may lead to various degrees of physical disability and even to death. Some of the mentioned anomalies are recognizable in utero by ultrasound. The diagnosis may serve as medical indication for abortion in those instances when the identified abnormality is incompatible with independent life.

The coming paradigm shift: A transition from manual to automated microscopy.

PubMed

Farahani, Navid; Monteith, Corey E

2016-01-01

The field of pathology has used light microscopy (LM) extensively since the mid-19(th) century for examination of histological tissue preparations. This technology has remained the foremost tool in use by pathologists even as other fields have undergone a great change in recent years through new technologies. However, as new microscopy techniques are perfected and made available, this reliance on the standard LM will likely begin to change. Advanced imaging involving both diffraction-limited and subdiffraction techniques are bringing nondestructive, high-resolution, molecular-level imaging to pathology. Some of these technologies can produce three-dimensional (3D) datasets from sampled tissues. In addition, block-face/tissue-sectioning techniques are already providing automated, large-scale 3D datasets of whole specimens. These datasets allow pathologists to see an entire sample with all of its spatial information intact, and furthermore allow image analysis such as detection, segmentation, and classification, which are impossible in standard LM. It is likely that these technologies herald a major paradigm shift in the field of pathology.

Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states

PubMed Central

Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki

2017-01-01

Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases. PMID:29267380

Towards Comprehensive Cardiac Repair and Regeneration after Myocardial Infarction: Aspects to Consider and Proteins to Deliver

PubMed Central

Awada, Hassan K.; Hwang, Mintai P.; Wang, Yadong

2016-01-01

Ischemic heart disease is a leading cause of death worldwide. After the onset of myocardial infarction, many pathological changes take place and progress the disease towards heart failure. Pathologies such as ischemia, inflammation, cardiomyocyte death, ventricular remodeling and dilation, and interstitial fibrosis, develop and involve the signaling of many proteins. Proteins can play important roles in limiting or countering pathological changes after infarction. However, they typically have short half-lives in vivo in their free form and can benefit from the advantages offered by controlled release systems to overcome their challenges. The controlled delivery of an optimal combination of proteins per their physiologic spatiotemporal cues to the infarcted myocardium holds great potential to repair and regenerate the heart. The effectiveness of therapeutic interventions depends on the elucidation of the molecular mechanisms of the cargo proteins and the spatiotemporal control of their release. It is likely that multiple proteins will provide a more comprehensive and functional recovery of the heart in a controlled release strategy. PMID:26757257

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Application of SEC-ICP-MS for comparative analyses of metal-containing species in cancerous and healthy human thyroid samples.

PubMed

Boulyga, Sergei F; Loreti, Valeria; Bettmer, Jörg; Heumann, Klaus G

2004-09-01

Size exclusion chromatography (SEC) was coupled on-line to inductively coupled plasma mass spectrometry (ICP-MS) for speciation study of trace metals in cancerous thyroid tissues in comparison to healthy thyroids aimed to estimation of changes in metalloprotein speciation in pathological tissue. The study showed a presence of species binding Cu, Zn, Cd and Pb in healthy thyroid tissue with a good reproducibility of chromatographic results, whereas the same species could not be detected in cancerous tissues. Thus, remarkable differences with respect to metal-binding species were revealed between healthy and pathological thyroid samples, pointing out a completely different distribution of trace metals in cancerous tissues. The metal-binding species could not be identified in the frame of this work because of a lack of appropriate standards. Nevertheless, the results obtained confirm the suitability of SEC-ICP-MS for monitoring of changes in trace metal distribution in cancerous tissue and will help to better understand the role of metal-containing species in thyroid pathology.

The personality of past, present and future speech-language pathology students.

PubMed

Byrne, Nicole

2018-03-01

As allied health professions change over time to keep up with and reflect a rapidly changing society, it is quite possible that the people attracted to the profession may also change. If this is the case, then knowing this could be critical for future workforce marketing, training and planning. The aim was to investigate whether the personality of students entering a speech-language pathology (SLP) program had changed over time and whether there were generational differences in personality. The study used the Big Five personality inventory to consider whether there were differences in the personality in speech-language pathology (SLP) students enrolled in the same regional university in Australia in 2005 and 2016. The results showed there were significant differences between the two groups on the Agreeableness and Extroversion scales. The students who were more Conscientious were also more Confident in their ability to perform as an SLP. Generational differences across the two cohorts were also considered. SLP is a dynamic profession that is reflected through an evolving scope of practice, increasing utilization of technology and specialization. As careers evolve it is logical that the people attracted to those careers may also shift; as demonstrated here via changes in the personality of SLP students. Understanding the personality of current SLP students and future Generation Z students may assist universities to identify specific skills and experiences students need to be successful in the workforce. © 2017 Royal College of Speech and Language Therapists.

Environmental disruption of circadian rhythm predisposes mice to osteoarthritis-like changes in knee joint.

PubMed

Kc, Ranjan; Li, Xin; Voigt, Robin M; Ellman, Michael B; Summa, Keith C; Vitaterna, Martha Hotz; Keshavarizian, Ali; Turek, Fred W; Meng, Qing-Jun; Stein, Gary S; van Wijnen, Andre J; Chen, Di; Forsyth, Christopher B; Im, Hee-Jeong

2015-09-01

Circadian rhythm dysfunction is linked to many diseases, yet pathophysiological roles in articular cartilage homeostasis and degenerative joint disease including osteoarthritis (OA) remains to be investigated in vivo. Here, we tested whether environmental or genetic disruption of circadian homeostasis predisposes to OA-like pathological changes. Male mice were examined for circadian locomotor activity upon changes in the light:dark (LD) cycle or genetic disruption of circadian rhythms. Wild-type (WT) mice were maintained on a constant 12 h:12 h LD cycle (12:12 LD) or exposed to weekly 12 h phase shifts. Alternatively, male circadian mutant mice (Clock(Δ19) or Csnk1e(tau) mutants) were compared with age-matched WT littermates that were maintained on a constant 12:12 LD cycle. Disruption of circadian rhythms promoted osteoarthritic changes by suppressing proteoglycan accumulation, upregulating matrix-degrading enzymes and downregulating anabolic mediators in the mouse knee joint. Mechanistically, these effects involved activation of the PKCδ-ERK-RUNX2/NFκB and β-catenin signaling pathways, stimulation of MMP-13 and ADAMTS-5, as well as suppression of the anabolic mediators SOX9 and TIMP-3 in articular chondrocytes of phase-shifted mice. Genetic disruption of circadian homeostasis does not predispose to OA-like pathological changes in joints. Our results, for the first time, provide compelling in vivo evidence that environmental disruption of circadian rhythms is a risk factor for the development of OA-like pathological changes in the mouse knee joint. © 2015 Wiley Periodicals, Inc.

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

PubMed

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

2014-03-06

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

Shimizu, Jun; Mimori, Tsuneyo

2014-01-01

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

The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features.

PubMed

Fan, Shengtao; Cai, Hongzhi; Xu, Xingli; Feng, Min; Wang, Lichun; Liao, Yun; Zhang, Ying; He, Zhanlong; Yang, Fengmei; Yu, Wenhai; Wang, Jingjing; Zhou, Jumin; Li, Qihan

2017-01-30

As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1.Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection,and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG)on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues.

Impact of immediate access to the electronic medical record on anatomic pathology performance.

PubMed

Renshaw, Andrew A; Gould, Edwin W

2013-07-01

To assess the overall impact of access to the electronic medical record (EMR) on anatomic pathology performance. We reviewed the results of all use of the EMR by 1 pathologist over an 18-month period. Of the 10,107 cases (913 cytology and 9,194 surgical pathology) reviewed, the EMR (excluding anatomic pathology records) was accessed in 222 (2.2% of all cases, 6.5% of all cytology cases, and 1.8% of all surgical pathology cases). The EMR was used to evaluate a critical value in 20 (9.0%) cases and make a more specific diagnosis in 77 (34.7%) cases, a less specific diagnosis in 4 (1.8%) cases, and a systemic rather than localized diagnosis in 4 (1.8%) cases. The percentage of cases in which the physician was contacted decreased from 7.3% for the prior 18 months to 6.7%, but this change was not significant (P = .13). Twelve cases were subsequently sent for interinstitutional consultation, and no disagreements were identified. The EMR was accessed in 2.2% of all surgical pathology and cytology cases and affected the diagnosis in 48% of these cases.

[Adolescent pathological gambling].

PubMed

Petit, A; Karila, L; Lejoyeux, M

2015-05-01

Although experts have long thought that the problems of gambling involved only adults, recent studies tend to show that teenagers are also affected. The objective of this paper is to show the characteristics of pathological gambling in adolescents. This review focuses on the clinical features, prevalence, psychopathology, prevention and treatment of this disorder. A review of the medical literature was conducted, using PubMed, using the following keywords alone or combined: pathological gambling, dependence, addiction and adolescents. We selected 12 English articles from 1997 to 2014. Recent work estimate that between 4 and 8% of adolescents suffer from problem gambling, and the prevalence of pathological gambling is 2-4 times higher in adolescents than in adults. The term adolescent pathological gambler starts early around the age of 10-12 years, with a quick change of status from casual to that of problem gambler and player. Complications appear quickly and comorbidities are common. There is no curative pharmacological treatment approved by health authorities. Pathological gambling among adolescents has grown significantly in recent years and should be promptly taken care of. Further studies must be performed to improve our understanding of this problem among adolescents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A New Classification for Pathologies of Spinal Meninges, Part 1: Dural Cysts, Dissections, and Ectasias.

PubMed

Klekamp, Jörg

2017-07-01

The clinical significance of pathologies of the spinal dura is often unclear and their management controversial. To classify spinal dural pathologies analogous to vascular aneurysms, present their symptoms and surgical results. Among 1519 patients with spinal space-occupying lesions, 66 patients demonstrated dural pathologies. Neuroradiological and surgical features were reviewed and clinical data analyzed. Saccular dural diverticula (type I, n = 28) caused by defects of both dural layers, dissections between dural layers (type II, n = 29) due to defects of the inner layer, and dural ectasias (type III, n = 9) related to structural changes of the dura were distinguished. For all types, symptoms consisted of local pain followed by signs of radiculopathy or myelopathy, while one patient with dural ectasia presented a low-pressure syndrome and 10 patients with dural dissections additional spinal cord herniation. Type I and type II pathologies required occlusion of their dural defects via extradural (type I) or intradural (type II) approaches. For type III pathologies of the dural sac no surgery was recommended. Favorable results were obtained in all 14 patients with type I and 13 of 15 patients with type II pathologies undergoing surgery. The majority of dural pathologies involving root sleeves remain asymptomatic, while those of the dural sac commonly lead to pain and neurological symptoms. Type I and type II pathologies were treated with good long-term results occluding their dural defects, while ectasias of the dural sac (type III) were managed conservatively. Copyright © 2017 by the Congress of Neurological Surgeons

Early Detection of Ovarian Cancer by Molecular Targeted Ultrasound Imaging Together with Serum Markers of Tumor-Associated Nuclear Change and Angiogenesis

DTIC Science & Technology

2014-03-01

Pincas; Rush University Medical Center, Pathology, Obstetrics and Gynecology Basu, Sanjib; Rush University Medical Center, Preventive Medicine ...and Jacques S Abramowicz 2, 5 Departments of 1 Pharmacology, 2 Obstetrics and Gynecology, 3 Pathology, 5 Preventive Medicine (Biostatistics...Animal Sciences, University of Illinois at Urbana-Champaign, Urbana (Dr Bahr Obstetrics and Gynecology, Wayne State University School of Medicine

The Evoked Potential. An Experimental Method for Biomechanical Analysis of Brain and Spinal Injury

DTIC Science & Technology

1980-01-01

Newtons produced marked changes in blood pressure, heart rate and distraction of the cervical spinal column with minimal ligamentous disruption...pathologic distraction and pathologic flexion of the thoracic ver- tebral column (8). Cerebral responses were lost within two minutes aftex complete...However, the immediate flexion and distraction responses were not altered. These findings suggest that mechanical trauma alters the spinal cord evoked

[Comparative pathology of the microcirculatory bed].

PubMed

Strukov, A I; Vorob'eva, A A

1976-11-01

This paper presents an analysis of publications, mostly by Soviet authores, on clinical studies and morphological examinations of the microcirculatory bed in different pathology. It is concluded that the microcirculatory bed should be regarded as an integral system responding to the pathological effects by a local and general reaction of its structural components and by changing the rheological properties of blood. Two types of changes develop in the microcirculatory system -- sterotyped ones, typical for extreme states (various kinds of shock, hypertensive crisis, stress situations), and those specific for certain diseases (diabetes melitus, essential hypertension, athersclerosis, collagenoses, etc.). In all the above diseases the pathological process affects the functional structures of microcirculation that undergo a rearrangement in accordance with the requirements of the body. In the initial period of the disease this re-arrangement is of a compensatory nature and passes ahead of the clinical manifestations. A comparison of the pictutrs obtained by biomicroscopy of the bulbconjunctiva of the eye and of other mucosae with film preparations of the serosae demonstrates their complete similarity. Therefore, the method of biomicroscopy of the eyeball and of the mucosae as a method reflecting the state of microcirculation in the body as a whole should become an integral part of the clinical examination of patients.

Detection of tuberculosis patterns in digital photographs of chest X-ray images using Deep Learning: feasibility study.

PubMed

Becker, A S; Blüthgen, C; Phi van, V D; Sekaggya-Wiltshire, C; Castelnuovo, B; Kambugu, A; Fehr, J; Frauenfelder, T

2018-03-01

To evaluate the feasibility of Deep Learning-based detection and classification of pathological patterns in a set of digital photographs of chest X-ray (CXR) images of tuberculosis (TB) patients. In this prospective, observational study, patients with previously diagnosed TB were enrolled. Photographs of their CXRs were taken using a consumer-grade digital still camera. The images were stratified by pathological patterns into classes: cavity, consolidation, effusion, interstitial changes, miliary pattern or normal examination. Image analysis was performed with commercially available Deep Learning software in two steps. Pathological areas were first localised; detected areas were then classified. Detection was assessed using receiver operating characteristics (ROC) analysis, and classification using a confusion matrix. The study cohort was 138 patients with human immunodeficiency virus (HIV) and TB co-infection (median age 34 years, IQR 28-40); 54 patients were female. Localisation of pathological areas was excellent (area under the ROC curve 0.82). The software could perfectly distinguish pleural effusions from intraparenchymal changes. The most frequent misclassifications were consolidations as cavitations, and miliary patterns as interstitial patterns (and vice versa). Deep Learning analysis of CXR photographs is a promising tool. Further efforts are needed to build larger, high-quality data sets to achieve better diagnostic performance.

Dynamic changes of the intraocular pressure and the pressure of cerebrospinal fluid in nonglaucomatous neurological patients.

PubMed

González-Camarena, Pedro Iván; San-Juan, Daniel; González-Olhovich, Irene; Rodríguez-Arévalo, David; Lozano-Elizondo, David; Trenado, Carlos; Anschel, David J

2017-03-01

To describe the dynamic changes of the intraocular pressure (IOP) and intracranial pressure (ICP) with normal or pathological values (intracranial hypertension) in nonglaucomatous neurological patients during lumbar punction (LP). Case-control study, prospective measurement of tonometry in both groups referred for LP. Intraocular pressure, ICP and translaminar pressure difference (TPD) were compared pre- and post-LP. Thirty-six patients (72 eyes) with mean age of 38.5 (16-64) years and BMI of 26.81 kg/m 2 were analysed. The initial mean ICP was 12.81 (± 6.6) mmHg. The mean TPD before and after the LP was 1.48 mmHg and 0.65 mmHg, respectively. The mean IOP of both eyes decreased to 0.8 mmHg post-LP in patients with pathological ICP (p = 0.0193) and normal ICP (p = 0.006). We found a statistically significant decrease of the IOP post-LP compared to the pre-LP in both groups, being higher in patients with pathological ICP. There were no significant differences of the IOP in patients with normal versus pathological ICP pre-LP/post-LP; neither was found a correlation between ICP and IOP. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[Eye and the pregnacy].

PubMed

Dima, Anne Marie

2012-01-01

Pregnancy is associated with changes in many organs and systems including the eyes. Sometimes in pregnancy may appear physiological and pathological ocular changes that may be associated with pre-existing problems. In such cases it is very important interdisciplinary collaboration gynecologist, ophthalmologist.

Sex steroid levels and AD-like pathology in 3xTgAD mice

PubMed Central

Ma, Chunqi; Taves, Matthew D.; Soma, Kiran K.; Mufson, Elliott J.

2014-01-01

Decreases in testosterone (T) and 17β-oestradiol (E2) are associated with an increased risk for Alzheimer's disease (AD), which has been attributed to an increase in beta amyloid (Aβ) and tau pathologic lesions. While recent studies have used transgenic animal models to test the effects of sex steroid manipulations on AD-like pathology, virtually none have systematically characterised the associations between AD lesions and sex steroid levels in the blood or brain in any mutant model. The present study evaluated age-related changes in T and E2 concentrations, as well as androgen receptor (AR) and oestrogen receptor (ER) α and β expression, in brain regions displaying AD pathology in intact male and female 3xTgAD and non-transgenic (ntg) mice. We report for the first time that circulating and brain T levels significantly increase in male 3xTgAD mice with age, but without changes in AR-immunoreactive (ir) cell number in either the hippocampal CA1 or medial amygdala. The age-related increase in hippocampal T levels correlated positively with increases in the conformational tau isoform, Alz50. These data suggest that the over-expression of human tau may up regulate the hypothalamic-pituitary-gonadal axis in these mice. Although circulating and brain E2 levels remained stable with age in both male and female 3xTgAD and ntg mice, ER-ir cell number in the hippocampus and medial amygdala decreased with age in female transgenic mice. Further, E2 levels were significantly higher in the hippocampus than in serum, suggesting local production of E2. Although triple transgenic mice mimic AD-like pathology, they do not fully replicate changes in human sex steroid levels, and may not be the best model for studying the effects of sex steroids on AD lesions. PMID:22889357

Change in the Pathologic Supraspinatus: A Three-Dimensional Model of Fiber Bundle Architecture within Anterior and Posterior Regions

PubMed Central

Kim, Soo Y.; Sachdeva, Rohit; Li, Zi; Rosser, Benjamin W. C.

2015-01-01

Supraspinatus tendon tears are common and lead to changes in the muscle architecture. To date, these changes have not been investigated for the distinct regions and parts of the pathologic supraspinatus. The purpose of this study was to create a novel three-dimensional (3D) model of the muscle architecture throughout the supraspinatus and to compare the architecture between muscle regions and parts in relation to tear severity. Twelve cadaveric specimens with varying degrees of tendon tears were used. Three-dimensional coordinates of fiber bundles were collected in situ using serial dissection and digitization. Data were reconstructed and modeled in 3D using Maya. Fiber bundle length (FBL) and pennation angle (PA) were computed and analyzed. FBL was significantly shorter in specimens with large retracted tears compared to smaller tears, with the deeper fibers being significantly shorter than other parts in the anterior region. PA was significantly greater in specimens with large retracted tears, with the superficial fibers often demonstrating the largest PA. The posterior region was absent in two specimens with extensive tears. Architectural changes associated with tendon tears affect the regions and varying depths of supraspinatus differently. The results provide important insights on residual function of the pathologic muscle, and the 3D model includes detailed data that can be used in future modeling studies. PMID:26413533

Supersonic Shear Wave Elastography of Response to Anti-cancer Therapy in a Xenograft Tumor Model.

PubMed

Chamming's, Foucauld; Le-Frère-Belda, Marie-Aude; Latorre-Ossa, Heldmuth; Fitoussi, Victor; Redheuil, Alban; Assayag, Franck; Pidial, Laetitia; Gennisson, Jean-Luc; Tanter, Mickael; Cuénod, Charles-André; Fournier, Laure S

2016-04-01

Our objective was to determine if supersonic shear wave elastography (SSWE) can detect changes in stiffness of a breast cancer model under therapy. A human invasive carcinoma was implanted in 22 mice. Eleven were treated with an anti-angiogenic therapy and 11 with glucose for 24 d. Tumor volume and stiffness were assessed during 2 wk before treatment and 0, 7, 12, 20 and 24 d after the start of therapy using SSWE. Pathology was assessed after 12 and 24 d of treatment. We found that response to therapy was associated with early softening of treated tumors only, resulting in a significant difference from non-treated tumors after 12 d of treatment (p = 0.03). On pathology, large areas of necrosis were observed at 12 d in treated tumors. Although treatment was still effective, treated tumors subsequently stiffened during a second phase of the treatment (days 12-24), with a small amount of necrosis observed on pathology on day 24. In conclusion, SSWE was able to measure changes in the stiffness of tumors in response to anti-cancer treatment. However, stiffness changes associated with good response to treatment may change over time, and increased stiffness may also reflect therapy efficacy. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Sulforaphane attenuation of type 2 diabetes-induced aortic damage was associated with the upregulation of Nrf2 expression and function.

PubMed

Wang, Yonggang; Zhang, Zhiguo; Sun, Wanqing; Tan, Yi; Liu, Yucheng; Zheng, Yang; Liu, Quan; Cai, Lu; Sun, Jian

2014-01-01

Type 2 diabetes mellitus (T2DM) significantly increases risk for vascular complications. Diabetes-induced aorta pathological changes are predominantly attributed to oxidative stress. Nuclear factor E2-related factor-2 (Nrf2) is a transcription factor orchestrating antioxidant and cytoprotective responses to oxidative stress. Sulforaphane protects against oxidative damage by increasing Nrf2 expression and its downstream target genes. Here we explored the protective effect of sulforaphane on T2DM-induced aortic pathogenic changes in C57BL/6J mice which were fed with high-fat diet for 3 months, followed by a treatment with streptozotocin at 100 mg/kg body weight. Diabetic and nondiabetic mice were randomly divided into groups with and without 4-month sulforaphane treatment. Aorta of T2DM mice exhibited significant increases in the wall thickness and structural derangement, along with significant increases in fibrosis (connective tissue growth factor and transforming growth factor), inflammation (tumor necrosis factor-α and vascular cell adhesion molecule 1), oxidative/nitrative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal), apoptosis, and cell proliferation. However, these pathological changes were significantly attenuated by sulforaphane treatment that was associated with a significant upregulation of Nrf2 expression and function. These results suggest that sulforaphane is able to upregulate aortic Nrf2 expression and function and to protect the aorta from T2DM-induced pathological changes.

Near-infrared Raman spectroscopy for estimating biochemical changes associated with different pathological conditions of cervix

NASA Astrophysics Data System (ADS)

Daniel, Amuthachelvi; Prakasarao, Aruna; Ganesan, Singaravelu

2018-02-01

The molecular level changes associated with oncogenesis precede the morphological changes in cells and tissues. Hence molecular level diagnosis would promote early diagnosis of the disease. Raman spectroscopy is capable of providing specific spectral signature of various biomolecules present in the cells and tissues under various pathological conditions. The aim of this work is to develop a non-linear multi-class statistical methodology for discrimination of normal, neoplastic and malignant cells/tissues. The tissues were classified as normal, pre-malignant and malignant by employing Principal Component Analysis followed by Artificial Neural Network (PC-ANN). The overall accuracy achieved was 99%. Further, to get an insight into the quantitative biochemical composition of the normal, neoplastic and malignant tissues, a linear combination of the major biochemicals by non-negative least squares technique was fit to the measured Raman spectra of the tissues. This technique confirms the changes in the major biomolecules such as lipids, nucleic acids, actin, glycogen and collagen associated with the different pathological conditions. To study the efficacy of this technique in comparison with histopathology, we have utilized Principal Component followed by Linear Discriminant Analysis (PC-LDA) to discriminate the well differentiated, moderately differentiated and poorly differentiated squamous cell carcinoma with an accuracy of 94.0%. And the results demonstrated that Raman spectroscopy has the potential to complement the good old technique of histopathology.

Tinnitus: A Large VBM-EEG Correlational Study

PubMed Central

Vanneste, Sven; Van De Heyning, Paul; De Ridder, Dirk

2015-01-01

A surprising fact in voxel-based morphometry (VBM) studies performed in tinnitus is that not one single region is replicated in studies of different centers. The question then rises whether this is related to the low sample size of these studies, the selection of non-representative patient subgroups, or the absence of stratification according to clinical characteristics. Another possibility is that VBM is not a good tool to study functional pathologies such as tinnitus, in contrast to pathologies like Alzheimer’s disease where it is known the pathology is related to cell loss. In a large sample of 154 tinnitus patients VBM and QEEG (Quantitative Electroencephalography) was performed and evaluated by a regression analysis. Correlation analyses are performed between VBM and QEEG data. Uncorrected data demonstrated structural differences in grey matter in hippocampal and cerebellar areas related to tinnitus related distress and tinnitus duration. After control for multiple comparisons, only cerebellar VBM changes remain significantly altered. Electrophysiological differences are related to distress, tinnitus intensity, and tinnitus duration in the subgenual anterior cingulate cortex, dorsal anterior cingulate cortex, hippocampus, and parahippocampus, which confirms previous results. The absence of QEEG-VBM correlations suggest functional changes are not reflected by co-occurring structural changes in tinnitus, and the absence of VBM changes (except for the cerebellum) that survive correct statistical analysis in a large study population suggests that VBM might not be very sensitive for studying tinnitus. PMID:25781934

Tinnitus: a large VBM-EEG correlational study.

PubMed

Vanneste, Sven; Van De Heyning, Paul; De Ridder, Dirk

2015-01-01

A surprising fact in voxel-based morphometry (VBM) studies performed in tinnitus is that not one single region is replicated in studies of different centers. The question then rises whether this is related to the low sample size of these studies, the selection of non-representative patient subgroups, or the absence of stratification according to clinical characteristics. Another possibility is that VBM is not a good tool to study functional pathologies such as tinnitus, in contrast to pathologies like Alzheimer's disease where it is known the pathology is related to cell loss. In a large sample of 154 tinnitus patients VBM and QEEG (Quantitative Electroencephalography) was performed and evaluated by a regression analysis. Correlation analyses are performed between VBM and QEEG data. Uncorrected data demonstrated structural differences in grey matter in hippocampal and cerebellar areas related to tinnitus related distress and tinnitus duration. After control for multiple comparisons, only cerebellar VBM changes remain significantly altered. Electrophysiological differences are related to distress, tinnitus intensity, and tinnitus duration in the subgenual anterior cingulate cortex, dorsal anterior cingulate cortex, hippocampus, and parahippocampus, which confirms previous results. The absence of QEEG-VBM correlations suggest functional changes are not reflected by co-occurring structural changes in tinnitus, and the absence of VBM changes (except for the cerebellum) that survive correct statistical analysis in a large study population suggests that VBM might not be very sensitive for studying tinnitus.

MR morphology of triangular fibrocartilage complex: correlation with quantitative MR and biomechanical properties.

PubMed

Bae, Won C; Ruangchaijatuporn, Thumanoon; Chang, Eric Y; Biswas, Reni; Du, Jiang; Statum, Sheronda; Chung, Christine B

2016-04-01

To evaluate pathology of the triangular fibrocartilage complex (TFCC) using high-resolution morphologic magnetic resonance (MR) imaging, and compare with quantitative MR and biomechanical properties. Five cadaveric wrists (22-70 years) were imaged at 3 T using morphologic (proton density weighted spin echo, PD FS, and 3D spoiled gradient echo, 3D SPGR) and quantitative MR sequences to determine T2 and T1rho properties. In eight geographic regions, morphology of TFC disc and laminae were evaluated for pathology and quantitative MR values. Samples were disarticulated and biomechanical indentation testing was performed on the distal surface of the TFC disc. On morphologic PD SE images, TFC disc pathology included degeneration and tears, while that of the laminae included degeneration, degeneration with superimposed tear, mucinous transformation, and globular calcification. Punctate calcifications were highly visible on 3D SPGR images and found only in pathologic regions. Disc pathology occurred more frequently in proximal regions of the disc than distal regions. Quantitative MR values were lowest in normal samples, and generally higher in pathologic regions. Biomechanical testing demonstrated an inverse relationship, with indentation modulus being high in normal regions with low MR values. The laminae studied were mostly pathologic, and additional normal samples are needed to discern quantitative changes. These results show technical feasibility of morphologic MR, quantitative MR, and biomechanical techniques to characterize pathology of the TFCC. Quantitative MRI may be a suitable surrogate marker of soft tissue mechanical properties, and a useful adjunct to conventional morphologic MR techniques.

Customizing Laboratory Information Systems: Closing the Functionality Gap.

PubMed

Gershkovich, Peter; Sinard, John H

2015-09-01

Highly customizable laboratory information systems help to address great variations in laboratory workflows, typical in Pathology. Often, however, built-in customization tools are not sufficient to add all of the desired functionality and improve systems interoperability. Emerging technologies and advances in medicine often create a void in functionality that we call a functionality gap. These gaps have distinct characteristics—a persuasive need to change the way a pathology group operates, the general availability of technology to address the missing functionality, the absence of this technology from your laboratory information system, and inability of built-in customization tools to address it. We emphasize the pervasive nature of these gaps, the role of pathology informatics in closing them, and suggest methods on how to achieve that. We found that a large number of the papers in the Journal of Pathology Informatics are concerned with these functionality gaps, and an even larger proportion of electronic posters and abstracts presented at the Pathology Informatics Summit conference each year deal directly with these unmet needs in pathology practice. A rapid, continuous, and sustainable approach to closing these gaps is critical for Pathology to provide the highest quality of care, adopt new technologies, and meet regulatory and financial challenges. The key element of successfully addressing functionality gaps is gap ownership—the ability to control the entire pathology information infrastructure with access to complementary systems and components. In addition, software developers with detailed domain expertise, equipped with right tools and methodology can effectively address these needs as they emerge.

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

PubMed

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

2016-10-01

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

Disrupted Intrinsic Networks Link Amyloid-β Pathology and Impaired Cognition in Prodromal Alzheimer's Disease.

PubMed

Koch, Kathrin; Myers, Nicholas E; Göttler, Jens; Pasquini, Lorenzo; Grimmer, Timo; Förster, Stefan; Manoliu, Andrei; Neitzel, Julia; Kurz, Alexander; Förstl, Hans; Riedl, Valentin; Wohlschläger, Afra M; Drzezga, Alexander; Sorg, Christian

2015-12-01

Amyloid-β pathology (Aβ) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link Aβ-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: Aβ-pathology affects specific networks in early AD, these networks show disrupted connectivity, and they process specific cognitive functions impaired in AD, like memory or attention. We hypothesized that, in AD, regional changes of ICNs, which persist across rest- and cognitive task-states, might link Aβ-pathology with impaired cognition via impaired intrinsic connectivity. Pittsburgh compound B (PiB)-positron emission tomography reflecting in vivo Aβ-pathology, resting-state fMRI, task-fMRI, and cognitive testing were used in patients with prodromal AD and healthy controls. In patients, default mode network's (DMN) functional connectivity (FC) was reduced in the medial parietal cortex during rest relative to healthy controls, relatively increased in the same region during an attention-demanding task, and associated with patients' cognitive impairment. Local PiB-uptake correlated negatively with DMN connectivity. Importantly, corresponding results were found for the right lateral parietal region of an attentional network. Finally, structural equation modeling confirmed a direct influence of DMN resting-state FC on the association between Aβ-pathology and cognitive impairment. Data provide evidence that disrupted intrinsic network connectivity links Aβ-pathology with cognitive impairment in early AD. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cost-benefit value of microscopic examination of intervertebral discs.

PubMed

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

1998-09-01

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

The DSM-5 and the Politics of Diagnosing Transpeople.

PubMed

Davy, Zowie

2015-07-01

In the DSM-5, there has been a change in the diagnosis for transpeople of all ages from Gender Identity Disorder (GID) to Gender Dysphoria (GD), in part to better indicate the distress that transpeople may experience when their gender identity feels incongruent. The Workgroup for Sexual and Gender Identity Disorders, chaired by Kenneth J. Zucker, was employed by the American Psychiatric Association (APA) to update the DSM-5's GID diagnosis reflecting contemporary scientific knowledge. Additionally, in a pre-publication report to the APA, members of the Workgroup suggested that they would also be concerned with the destigmatization of transpeople while preserving a diagnosis that medical insurance companies would accept for issuing payments for transitioning treatments (Drescher, 2013). The aims of this article are, firstly, to question whether changing the diagnosis lessens the stigmatization of transpeople. I will suggest that the semantic change from GID to GD marks "inverted" gendered expressions as pathological and, thus, continues to stigmatize transpeople. Secondly, the article explores the development of the GD diagnosis, and illustrates how the scientific data this were founded on are contentious. The article then demonstrates how the trans anti-pathologization movement has challenged the perceived pathologizing effects of the DSM-5 classification of GD. The article examines a selection of Western transgender community advocates' websites, forums, and blogs. From these sources, the article then explores the different narratives of transpeople and political groups who offer details of their praxis, and evidences how the trans anti-pathologization advocates use the available science and human rights discourses to contest the role of psychiatry in the treatment of transpeople.

Spinal Cord Injury Causes Chronic Liver Pathology in Rats

PubMed Central

Sauerbeck, Andrew D.; Laws, J. Lukas; Bandaru, Veera V.R.; Popovich, Phillip G.; Haughey, Norman J.

2015-01-01

Abstract Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1α, IL-1β, chemokine ligand-2, and tumor necrosis factor-α mRNA. These were coincident with increased CD68+ macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI. PMID:25036371

The pathology and pathophysiology of vascular dementia.

PubMed

Kalaria, Raj N

2017-12-19

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

Evidence that iron accelerates Alzheimer's pathology: a CSF biomarker study.

PubMed

Ayton, Scott; Diouf, Ibrahima; Bush, Ashley Ian

2018-05-01

To investigate whether cerebrospinal fluid (CSF) ferritin (reporting brain iron) is associated with longitudinal changes in CSF β-amyloid (Aβ) and tau. Mixed-effects models of CSF Aβ 1-42 and tau were constructed using data from 296 participants who had baseline measurement of CSF ferritin and annual measurement of CSF tau and Aβ 1-42 for up to 5 years. In subjects with biomarker-confirmed Alzheimer's pathology, high CSF ferritin (>6.2 ng/mL) was associated with accelerated depreciation of CSF Aβ 1-42 (reporting increased plaque formation; p=0.0001). CSF ferritin was neither associated with changes in CSF tau in the same subjects, nor longitudinal changes in CSF tau or Aβ 1-42 in subjects with low baseline pathology. In simulation modelling of the natural history of Aβ deposition, which we estimated to occur over 31.4 years, we predicted that it would take 12.6 years to reach the pathology threshold value of CSF Aβ from healthy normal levels, and this interval is not affected by CSF ferritin. CSF ferritin influences the fall in CSF Aβ over the next phase, where high CSF ferritin accelerated the transition from threshold preclinical Aβ levels to the average level of Alzheimer's subjects from 18.8 to 10.8 years. Iron might facilitate Aβ deposition in Alzheimer's and accelerate the disease process. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Subtle pathological changes in neocortical temporal lobe epilepsy.

PubMed

Ochoa, Juan G; Hentgarden, Diana; Paulzak, Audrey; Ogden, Melissa; Pryson, Richard; Lamle, Markus; Rusyniak, Walter G

2017-06-01

This was a prospective observational study to correlate the clinical symptoms, electrophysiology, imaging, and surgical pathology of patients with temporal lobe epilepsy (TLE) without hippocampal sclerosis. We selected consecutive patients with TLE and normal MRI undergoing temporal lobe resection between April and September 2015. Clinical features, imaging, and functional data were reviewed. Intracranial monitoring and language mapping were performed when it was required according to our team recommendation. Prior to hippocampal resection, intraoperative electrocorticography was performed using depth electrodes in the amygdala and the hippocampus. The resected hippocampus was sent for pathological analysis. Five patients with diagnosis with non-lesional TLE were included. We did not find distinctive clinical features that could be a characteristic of non-lesional TLE. The mean follow-up was 13.2months (11-15months); 80% of patients achieved Engel Class I outcome. There was no distinctive electrographic findings in these patients. Histopathologic analysis was negative for mesial temporal sclerosis. A second blinded independent neuropathologist with expertise in epilepsy found ILAE type I focal cortical dysplasia in the parahippocampal gyrus in all patients. A third independent neuropathologist reported changes in layer 2 with larger pyramidal neurons in 4 cases but concluded that none of these cases met the diagnostic criteria of FCD. Subtle pathological changes could be associated with a parahippocampal epileptic zone and should be investigated in patients with MRI-negative TLE. This study also highlights the lack of interobserver reliability for the diagnosis of mild cortical dysplasia. Finally, selective amygdalo-hippocampectomy or laser ablation of the hippocampus may not control intractable epilepsy in this specific population. Copyright © 2017 Elsevier Inc. All rights reserved.

From normal fear to pathological anxiety.

PubMed

Rosen, J B; Schulkin, J

1998-04-01

In this article the authors address how pathological anxiety may develop from adaptive fear states. Fear responses (e.g., freezing, startle, heart rate and blood pressure changes, and increased vigilance) are functionally adaptive behavioral and perceptual responses elicited during danger to facilitate appropriate defensive responses that can reduce danger or injury (e.g., escape and avoidance). Fear is a central motive state of action tendencies subserved by fear circuits, with the amygdala playing a central role. Pathological anxiety is conceptualized as an exaggerated fear state in which hyperexcitability of fear circuits that include the amygdala and extended amygdala (i.e., bed nucleus of the stria terminalis) is expressed as hypervigilance and increased behavioral responsivity to fearful stimuli. Reduced thresholds for activation and hyperexcitability in fear circuits develop through sensitization- or kindling-like processes that involve neuropeptides, hormones, and other proteins. Hyperexcitability in fear circuits is expressed as pathological anxiety that is manifested in the various anxiety disorders.

Understanding the Importance of the Teres Minor for Shoulder Function: Functional Anatomy and Pathology.

PubMed

Williams, Matthew D; Edwards, Thomas Bradley; Walch, Gilles

2018-03-01

Although the teres minor is often overlooked in a normal shoulder, it becomes a key component in maintaining shoulder function when other rotator cuff tendons fail. The teres minor maintains a balanced glenohumeral joint and changes from an insignificant to the most significant external rotator in the presence of major rotator cuff pathology. The presence or absence of the teres minor provides prognostic information on the outcomes of reverse total shoulder arthroplasty and tendon transfers. Clinical tests include the Patte test, the Neer dropping sign, the external rotation lag sign, and the Hertel drop sign. Advanced imaging of the teres minor can be used for classification using the Walch system. Understanding the function and pathology surrounding the teres minor is paramount in comprehensive management of the patient with shoulder pathology. Appropriate clinical examination and imaging of the teres minor are important for preoperative stratification and postoperative expectations.

Historical development of the renal histopathology services in Malaysia.

PubMed

Looi, Lai-Meng; Cheah, Phaik-Leng

2009-06-01

Western-style medicine was introduced to Malaya by the Portuguese, Dutch and British between the 1500s and 1800s. Although the earliest pathology laboratories were developed within hospitals towards the end of the 19th Century, histopathology emerged much later than the biochemistry and bacteriology services. The University Departments of Pathology were the pioneers of the renal histopathology diagnostic services. The Department of Pathology, University of Malaya (UM) received its first renal biopsy on 19 May 1968. Hospital Universiti Kebangsaan Malaysia (HUKM) and Hospital Universiti Sains Malaysia (HUSM) started their services in 1979 and 1987 respectively. It is notable that the early services in these University centres caterred for both the university hospitals and the Ministry of Health (MOH) until the mid-1990s when MOH began to develop its own services, pivoted on renal pathologists trained through Fellowship programmes. Currently, key centres in the MOH are Kuala Lumpur Hospital, Sultanah Aminah Hospital Johor Bahru and Malacca Hospital. With the inclusion of renal biopsy interpretation in the Master of Pathology programmes, basic renal histopathology services became widely available throughout the country from 2000. This subsequently filtered out to the private sector as more histopathologists embraced private practice. There is now active continuing professional development in renal histopathology through clinicopathological dicussions, seminars and workshops. Renal research on amyloid nephropathy, minimal change disease, IgA nephropathy, fibrillary glomerulonephritis, lupus nephritis and microwave technology have provided an insight into the patterns of renal pathology and changing criteria for biopsy. More recently, there has been increasing involvement of renal teams in clinical trials, particularly for lupus nephritis and renal transplant modulation.

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan.

PubMed

Ashpole, Nicole M; Logan, Sreemathi; Yabluchanskiy, Andriy; Mitschelen, Matthew C; Yan, Han; Farley, Julie A; Hodges, Erik L; Ungvari, Zoltan; Csiszar, Anna; Chen, Sixia; Georgescu, Constantin; Hubbard, Gene B; Ikeno, Yuji; Sonntag, William E

2017-04-01

Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igf f/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

Neuropathology of supercentenarians - four autopsy case studies.

PubMed

Takao, Masaki; Hirose, Nobuyoshi; Arai, Yasumichi; Mihara, Ban; Mimura, Masaru

2016-09-02

Supercentenarians (aged 110 years old or more) are extremely rare in the world population (the number of living supercentenarians is estimated as 47 in the world), and details about their neuropathological information are limited. Based on previous studies, centenarians (aged 100-109 years old) exhibit several types of neuropathological changes, such as Alzheimer's disease and Lewy body disease pathology, primary age-related tauopathy, TDP-43 pathology, and hippocampal sclerosis. In the present study, we provide results from neuropathological analyses of four supercentenarian autopsy cases using conventional and immunohistochemical analysis for neurodegenerative disorders. In particular, we focused on the pathology of Alzheimer's disease and Lewy body disease, as well as the status of hippocampal sclerosis, TDP-43 pathology, aging-related tau astrogliopathy, and cerebrovascular diseases. Three cases were characterized as an "intermediate" level of Alzheimer's disease changes (NIA-AA guideline) and one was characterized as primary age-related tauopathy. TDP-43 deposits were present in the hippocampus in two cases. Neither Lewy body pathology nor hippocampal sclerosis was observed. Aging-related tau astrogliopathy was consistently observed, particularly in the basal forebrain. Small vessel diseases were also present, but they were relatively mild for cerebral amyloid-beta angiopathy and arteriolosclerosis. Although our study involved a small number of cases, the results provide a better understanding about human longevity. Neuropathological alterations associated with aging were mild to moderate in the supercentenarian brain, suggesting that these individuals might have some neuroprotective factors against aging. Future prospective studies and extensive molecular analyses are needed to determine the mechanisms of human longevity.

Towards machine learned quality control: A benchmark for sharpness quantification in digital pathology.

PubMed

Campanella, Gabriele; Rajanna, Arjun R; Corsale, Lorraine; Schüffler, Peter J; Yagi, Yukako; Fuchs, Thomas J

2018-04-01

Pathology is on the verge of a profound change from an analog and qualitative to a digital and quantitative discipline. This change is mostly driven by the high-throughput scanning of microscope slides in modern pathology departments, reaching tens of thousands of digital slides per month. The resulting vast digital archives form the basis of clinical use in digital pathology and allow large scale machine learning in computational pathology. One of the most crucial bottlenecks of high-throughput scanning is quality control (QC). Currently, digital slides are screened manually to detected out-of-focus regions, to compensate for the limitations of scanner software. We present a solution to this problem by introducing a benchmark dataset for blur detection, an in-depth comparison of state-of-the art sharpness descriptors and their prediction performance within a random forest framework. Furthermore, we show that convolution neural networks, like residual networks, can be used to train blur detectors from scratch. We thoroughly evaluate the accuracy of feature based and deep learning based approaches for sharpness classification (99.74% accuracy) and regression (MSE 0.004) and additionally compare them to domain experts in a comprehensive human perception study. Our pipeline outputs spacial heatmaps enabling to quantify and localize blurred areas on a slide. Finally, we tested the proposed framework in the clinical setting and demonstrate superior performance over the state-of-the-art QC pipeline comprising commercial software and human expert inspection by reducing the error rate from 17% to 4.7%. Copyright © 2017. Published by Elsevier Ltd.

Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer.

PubMed

Kalsbeek, Anton M F; Chan, Eva K F; Grogan, Judith; Petersen, Desiree C; Jaratlerdsiri, Weerachai; Gupta, Ruta; Lyons, Ruth J; Haynes, Anne-Maree; Horvath, Lisa G; Kench, James G; Stricker, Phillip D; Hayes, Vanessa M

2018-01-01

Mitochondrial genome (mtDNA) content is depleted in many cancers. In prostate cancer, there is intra-glandular as well as inter-patient mtDNA copy number variation. In this study, we determine if mtDNA content can be used as a predictor for prostate cancer staging and outcomes. Fresh prostate cancer biopsies from 115 patients were obtained at time of surgery. All cores underwent pathological review, followed by isolation of cancer and normal tissue. DNA was extracted and qPCR performed to quantify the total amount of mtDNA as a ratio to genomic DNA. Differences in mtDNA content were compared for prostate cancer pathology features and disease outcomes. We showed a significantly reduced mtDNA content in prostate cancer compared with normal adjacent prostate tissue (mean difference 1.73-fold, P-value <0.001). Prostate cancer with increased mtDNA content showed unfavorable pathologic characteristics including, higher disease stage (PT2 vs PT3 P-value = 0.018), extracapsular extension (P-value = 0.02) and a trend toward an increased Gleason score (P-value = 0.064). No significant association was observed between changes in mtDNA content and biochemical recurrence (median follow up of 107 months). Contrary to other cancer types, prostate cancer tissue shows no universally depleted mtDNA content. Rather, the change in mtDNA content is highly variable, mirroring known prostate cancer genome heterogeneity. Patients with high mtDNA content have an unfavorable pathology, while a high mtDNA content in normal adjacent prostate tissue is associated with worse prognosis. © 2017 Wiley Periodicals, Inc.

Microvascular Pathology and Morphometrics of Sporadic and Hereditary Small Vessel Diseases of the Brain

PubMed Central

Craggs, Lucinda JL; Yamamoto, Yumi; Deramecourt, Vincent; Kalaria, Raj N

2014-01-01

Small vessel diseases (SVDs) of the brain are likely to become increasingly common in tandem with the rise in the aging population. In recent years, neuroimaging and pathological studies have informed on the pathogenesis of sporadic SVD and several single gene (monogenic) disorders predisposing to subcortical strokes and diffuse white matter disease. However, one of the limitations toward studying SVD lies in the lack of consistent assessment criteria and lesion burden for both clinical and pathological measures. Arteriolosclerosis and diffuse white matter changes are the hallmark features of both sporadic and hereditary SVDs. The pathogenesis of the arteriopathy is the key to understanding the differential progression of disease in various SVDs. Remarkably, quantification of microvascular abnormalities in sporadic and hereditary SVDs has shown that qualitatively the processes involved in arteriolar degeneration are largely similar in sporadic SVD compared with hereditary disorders such as cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Important significant regional differences in lesion location within the brain may enable one to distinguish SVDs, where frontal lobe involvement appears consistently with almost every SVD, but others bear specific pathologies in other lobes, such as the temporal pole in CADASIL and the pons in pontine autosomal dominant microangiopathy and leukoencephalopathy or PADMAL. Additionally, degenerative changes in the vascular smooth muscle cells, the cerebral endothelium and the basal lamina are often rapid and more aggressive in genetic disorders. Further quantification of other microvascular elements and even neuronal cells is needed to fully characterize SVD pathogenesis and to differentiate the usefulness of vascular interventions and treatments on the resulting pathology. PMID:25323665

Microstructural white matter alterations in preclinical Alzheimer’s disease detected using free water elimination diffusion tensor imaging

PubMed Central

Ly, Martina; Carlsson, Cynthia M.; Okonkwo, Ozioma C.; Zetterberg, Henrik; Blennow, Kaj; Sager, Mark A.; Asthana, Sanjay; Johnson, Sterling C.; Alexander, Andrew L.; Bendlin, Barbara B.

2017-01-01

Brain changes associated with Alzheimer’s disease (AD) begin decades before disease diagnosis. While β-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction. Brain imaging methods that are tuned to assess degeneration of myelinated nerve fibers in the brain (collectively called white matter) include diffusion tensor imaging (DTI) and related techniques, and are expected to shed light on disease-related loss of structural connectivity. Participants (N = 70, ages 47–76 years) from the Wisconsin Registry for Alzheimer’s Prevention study underwent DTI and hybrid diffusion imaging to determine a free-water elimination (FWE-DTI) model. The study assessed the extent to which preclinical AD pathology affects brain white matter. Preclinical AD pathology was determined using cerebrospinal fluid (CSF) biomarkers. The sample was enriched for AD risk (APOE ε4 and parental history of AD). AD pathology assessed by CSF analyses was significantly associated with altered microstructure on both DTI and FWE-DTI. Affected regions included frontal, parietal, and especially temporal white matter. The f-value derived from the FWE-DTI model appeared to be the most sensitive to the relationship between the CSF AD biomarkers and microstructural alterations in white matter. These findings suggest that white matter degeneration is an early pathological feature of AD that may have utility both for early disease detection and as outcome measures for clinical trials. More complex models of microstructural diffusion properties including FWE-DTI may provide increased sensitivity to early brain changes associated with AD over standard DTI. PMID:28291839

Pathological examination of cerebral amyloid angiopathy in patients who underwent removal of lobar hemorrhages.

PubMed

Lin, Chien-Min; Arishima, Hidetaka; Kikuta, Ken-Ichiro; Naiki, Hironobu; Kitai, Ryuhei; Kodera, Toshiaki; Matsuda, Ken; Hashimoto, Norichika; Isozaki, Makoto; Tsunetoshi, Kenzo; Neishi, Hiroyuki; Higashino, Yoshifumi; Akazawa, Ayumi; Arai, Hiroshi; Yamada, Shinsuke

2018-03-01

Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-β (Aβ) deposition in the brain microvessels. CAA is also known to contribute not only to cortical microbleeds but also lobar hemorrhages. This retrospective study examined CAA pathologically in patients who underwent direct surgeries for lobar hemorrhage. Thirty-three patients with lobar hemorrhage underwent open surgery with biopsy from 2007 to 2016 in our hospital. Cortical tissues over hematomas obtained surgically were pathologically examined using hematoxylin, eosin stain, and anti-Aβ antibody to diagnose CAA. We also investigated the advanced degree of CAA and clinical features of each patient with lobar hemorrhage. In the 33 patients, 4 yielded specimens that were insufficient to evaluate CAA pathologically. Twenty-four of the remaining 29 patients (82.8%) were pathologically diagnosed with CAA. The majority of CAA-positive patients had moderate or severe CAA based on a grading scale to estimate the advanced degree of CAA. About half of the CAA-positive patients had hypertension, and four took anticoagulant or antiplatelet agents. In five patients who were not pathologically diagnosed with CAA, one had severe liver function disorder, three had uncontrollable hypertension, and one had no obvious risk factor. Our pathological findings suggest that severe CAA with vasculopathic change markedly contributes to lobar hemorrhage. The coexistence of severe CAA and risk factors such as hypertension, anticoagulants or antiplatelets may readily induce lobar hemorrhage.

Scores Obtained from a Simple Cognitive Test of Visuospatial Episodic Memory Performed Decades before Death Are Associated with the Ultimate Presence of Alzheimer Disease Pathology.

PubMed

Robinson, Andrew C; McNamee, Roseanne; Davidson, Yvonne S; Horan, Michael A; Snowden, Julie S; McInnes, Lynn; Pendleton, Neil; Mann, David M A

2018-04-25

Community- or population-based longitudinal studies of cognitive ability with a brain donation end point offer an opportunity to examine relationships between pathology and cognitive state prior to death. Discriminating the earliest signs of dementing disorders, such as Alzheimer disease (AD), is necessary to undertake early interventions and treatments. The neuropathological profile of brains donated from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, including CERAD (Consortium to Establish a Registry for Alzheimer's Disease) and Braak stage, was assessed by immunohistochemistry. Cognitive test scores collected 20 years prior to death were correlated with the extent of AD pathology present at death. Baseline scores from the Memory Circle test had the ability to distinguish between individuals who developed substantial AD pathology and those with no, or low, AD pathology. Predicted test scores at the age of 65 years also discriminated between these pathology groups. The addition of APOE genotype further improved the discriminatory ability of the model. The results raise the possibility of identifying individuals at future risk of the neuropathological changes associated with AD over 20 years before death using a simple cognitive test. This work may facilitate early interventions, therapeutics and treatments for AD by identifying at-risk and minimally affected (in pathological terms) individuals. © 2018 S. Karger AG, Basel.

Association of Glucocerebrosidase Mutations With Dementia With Lewy Bodies

PubMed Central

Clark, Lorraine N.; Kartsaklis, Lykourgos A.; Wolf Gilbert, Rebecca; Dorado, Beatriz; Ross, Barbara M.; Kisselev, Sergey; Verbitsky, Miguel; Mejia-Santana, Helen; Cote, Lucien J.; Andrews, Howard; Vonsattel, Jean-Paul; Fahn, Stanley; Mayeux, Richard; Honig, Lawrence S.; Marder, Karen

2009-01-01

Background Mutations in the glucocerebrosidase (GBA) gene are associated with Lewy body (LB) disorders. Objective To determine the relationship of GBA mutations and APOE4 genotype to LB and Alzheimer disease (AD) pathological findings. Design Case-control study. Setting Academic research. Participants The 187 subjects included patients with primary neuropathological diagnoses of LB disorders with or without AD changes (95 cases), randomly selected patients with AD (without significant LB pathological findings; 60 cases), and controls with neither LB nor AD pathological findings (32 cases). Main Outcome Measures GBA mutation status, APOE4 genotype, LB pathological findings (assessed according to the third report of the Dementia With Lewy Body Consortium), and Alzheimer plaque and tangle pathological findings (rated by criteria of Braak and Braak, the Consortium to Establish a Registry for Alzheimer Disease, and the National Institute on Aging–Reagan Institute). Results GBA mutations were found in 18% (34 of 187) of all subjects, including 28% (27 of 95) of those with primary LB pathological findings compared with 10% (6 of 60) of those with AD pathological findings and 3% (1 of 32) of those without AD or LB pathological findings (P=.001). GBA mutation status was significantly associated with the presence of cortical LBs (odds ratio, 6.48; 95% confidence interval, 2.45–17.16; P<.001), after adjusting for sex, age at death, and presence of APOE4. GBA mutation carriers were significantly less likely to meet AD pathological diagnostic (National Institute on Aging–Reagan Institute intermediate or high likelihood) criteria (odds ratio, 0.35; 95% confidence interval, 0.15–0.79; P=.01) after adjustment for sex, age at death, and APOE4. Conclusion GBA mutations may be associated with pathologically “purer” LB disorders, characterized by more extensive (cortical) LB, and less severe AD pathological findings and may be a useful marker for LB disorders. PMID:19433657

Non-Alzheimer's contributions to dementia and cognitive resilience in The 90+ Study.

PubMed

Robinson, John L; Corrada, Maria M; Kovacs, Gabor G; Dominique, Myrna; Caswell, Carrie; Xie, Sharon X; Lee, Virginia M-Y; Kawas, Claudia H; Trojanowski, John Q

2018-06-18

The diagnosis of Alzheimer's disease (AD) in the oldest-old is complicated by the increasing prevalence of age-related neurofibrillary tangles, plaques and non-AD pathologies such as cerebrovascular disease (CVD), hippocampal sclerosis (HS), aging-related tau astrogliopathy (ARTAG), as well as TDP-43 and Lewy pathology. The contribution of these non-AD pathologies to dementia and cognitive resilience is unclear. We assessed the level of AD neuropathologic change (ADNPC) and non-AD pathology in 185 participants enrolled in The 90+ Study with available cognitive assessments and brain tissue. Logistic regression models-adjusting for age, sex and education-determined the association between each pathology and dementia or between subgroups. 53% had dementia, primarily AD or mixed AD; 23% had cognitive impairment without dementia (CIND); 23% were not impaired. Both AD and non-AD pathology was prevalent. 100% had tangles, 81% had plaques, and both tangles and plaques associated with dementia. ARTAG distributed across limbic (70%), brainstem (39%) and cortical regions (24%). 49% had possible CVD and 26% had definite CVD, while HS was noted in 15%. Cortical ARTAG, CVD and HS were each associated with dementia, but limbic and brainstem ARTAGs were not. TDP-43 and Lewy pathologies were found in 36 and 17% and both associated with dementia. No pathology distinguished CIND and the not impaired. By NIA-AA criteria and dementia status, the cohort was subdivided into four groups: those with minimal ADNPC included the not dementia (ND) and Not AD dementia groups; and those with significant ADNPC included the Resilient without dementia and AD dementia groups. Compared to the ND group, the Not AD dementia group had more HS, cortical ARTAG, TDP-43, and Lewy pathology. Compared to the AD dementia group, the Resilient group had less CVD, no HS and less cortical ARTAG, TDP-43 and Lewy pathology. Our findings imply that reductions in non-AD pathologies including CVD contribute to cognitive resilience in the oldest-old.

Causes, effects and connectivity changes in MS-related cognitive decline.

PubMed

Rimkus, Carolina de Medeiros; Steenwijk, Martijn D; Barkhof, Frederik

2016-01-01

Cognitive decline is a frequent but undervalued aspect of multiple sclerosis (MS). Currently, it remains unclear what the strongest determinants of cognitive dysfunction are, with grey matter damage most directly related to cognitive impairment. Multi-parametric studies seem to indicate that individual factors of MS-pathology are highly interdependent causes of grey matter atrophy and permanent brain damage. They are associated with intermediate functional effects (e.g. in functional MRI) representing a balance between disconnection and (mal) adaptive connectivity changes. Therefore, a more comprehensive MRI approach is warranted, aiming to link structural changes with functional brain organization. To better understand the disconnection syndromes and cognitive decline in MS, this paper reviews the associations between MRI metrics and cognitive performance, by discussing the interactions between multiple facets of MS pathology as determinants of brain damage and how they affect network efficiency.

Correlative Light and Scanning X-Ray Scattering Microscopy of Healthy and Pathologic Human Bone Sections

PubMed Central

Giannini, C.; Siliqi, D.; Bunk, O.; Beraudi, A.; Ladisa, M.; Altamura, D.; Stea, S.; Baruffaldi, F.

2012-01-01

Scanning small and wide angle X-ray scattering (scanning SWAXS) experiments were performed on healthy and pathologic human bone sections. Via crystallographic tools the data were transformed into quantitative images and as such compared with circularly polarized light (CPL) microscopy images. SWAXS and CPL images allowed extracting information of the mineral nanocrystalline phase embedded, with and without preferred orientation, in the collagen fibrils, mapping local changes at sub-osteon resolution. This favorable combination has been applied for the first time to biopsies of dwarfism syndrome and Paget's disease to shed light onto the cortical structure of natural bone in healthy and pathologic sections. PMID:22666538

The role of animal models in tendon research

PubMed Central

Hast, M. W.; Zuskov, A.; Soslowsky, L. J.

2014-01-01

Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the structural, mechanical, and biological changes that occur throughout tendon pathology in animal models, as well as strategies for the improvement of tendon healing. Cite this article: Bone Joint Res 2014;3:193–202. PMID:24958818

Frontal lobe dementia and motor neuron disease.

PubMed Central

Neary, D; Snowden, J S; Mann, D M; Northen, B; Goulding, P J; Macdermott, N

1990-01-01

Four patients are described, in whom a profound and rapidly progressive dementia occurred in association with clinical features of motor neuron disease. The pattern of dementia indicated impaired frontal lobe function, confirmed by reduced tracer uptake in the frontal lobes on single photon emission computed tomography (SPECT). Pathological examination of the brains of two patients revealed frontal-lobe atrophy, with mild gliosis and spongiform change. The spinal cord changes were consistent with motor neuron disease. The clinical picture and pathological findings resembled those of dementia of frontal-lobe type and were distinct from those of Alzheimer's disease. The findings have implications for the understanding of the spectrum of non-Alzheimer forms of primary degenerative dementia. Images PMID:2303828

Osteosarcoma of the mandible mimicking an odontogenic abscess: a case report and review of the literature.

PubMed

Bhadage, Chetan J; Vaishampayan, Sagar; Kolhe, Swapnil; Umarji, Hemant

2013-04-01

Inflammatory lesions, like periapical/odontogenic abscesses, are by far the most common pathologic condition of the jaws. Radiographically, these lesions commonly manifest as widening of periodontal ligament space, discontinuity of lamina dura and ill-defined periapical radiolucency. There are some rare disorders which could cause similar radiographic changes in the jaw bone. With careful scrutiny of periapical radiolucency, regular periodic follow-up radiographs and histo-pathologic examination, the periapical abscess or infection can be differentiated from rare fatal disorders. This paper highlights the need for vigilant examination of even the commonest, innocuous-appearing periapical changes which sometimes are produced by some rare fatal disorders.

Diagnostic Imaging of Reproductive Tract Disorders in Reptiles.

PubMed

Gumpenberger, Michaela

2017-05-01

Diagnostic imaging of the reproductive tract in reptiles is used for gender determination, evaluation of breeding status, detection of pathologic changes, and supervising treatment. Whole-body radiographs provide an overview and support detection of mineralized egg shells. Sonography is used to evaluate follicles, nonmineralized eggs, and the salpinx in all reptiles. Computed tomography is able to overcome imaging limitations in chelonian species. This article provides detailed information about the performance of different imaging techniques. Multiple images demonstrate the physiologic appearance of the male and female reproductive tract in various reptile species and pathologic changes. Advantages and disadvantages of radiography, sonography, and computed tomography are described. Copyright © 2016 Elsevier Inc. All rights reserved.

Morphological effects of tributyltin (TBT) in vitro on the genital system of the mesogastropoda Littorina littorea (Prosobranchia)

NASA Astrophysics Data System (ADS)

Deutsch, U.; Brick, M.

1993-02-01

This ultrastructural study investigates the pathological changes in the penial, the sperm groove and the glandular cushion epithelium in male Littorina littorea (Mesogastropoda) related to TBT (tributyltin) contamination. The results are compared with those on Ocinebrina aciculata (Neogastropoda), which shows a wide range of cell changes in the penis epithelia of male and imposex affected females. The investigation of the different penis epithelia of L. littorea revealed that the cells analysed show a low sensibility towards TBT. The cells display normal metabolism. Certain atypical structures like swelling microvilli and cristae which tend to lie parallel to the long axis in the mitochondria, were detected as pathological effects.

[The experimental research of inner ear metabolism and electrical physiology of autoimmune sensorineural hearing loss].

PubMed

Tan, C; Cao, Y; Hu, P

1998-09-01

Inquire into the mechanism of inner ear pathological physiology in autoimmune sensorineural hearing loss (ASHL). With the auditory electric-physiological techniques and enzyme-histochemical method, the change of inner ear hearing function and enzyme activity were observed. These animals, which threshold of auditory nerve compound active potential (CAP) and cochlear microphonic potential(CM) heightening evidently, showed that the amplitude of endolymphatic potential(EP) (include-EP) bring down in various degrees, which was related to the change of the active of Na(+)-K(+)-ATPase and SDH in vascularis stria and endolymphatic sac. The abnormality of enzymes metabolism in inner ear tissues, which following autoimmune inflammation damage, is the pathological foundation of hearing dysfunction.

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

PubMed

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

2013-01-01

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

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

PubMed Central

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

2018-01-01

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

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

PubMed Central

Ramirez, Jan-Marino

2015-01-01

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

Comparison study of five different display modalities for whole slide images in surgical pathology and cytopathology in Europe

NASA Astrophysics Data System (ADS)

D'Haene, Nicky; Maris, Calliope; Rorive, Sandrine; Moles Lopez, Xavier; Rostang, Johan; Marchessoux, Cédric; Pantanowitz, Liron; Parwani, Anil V.; Salmon, Isabelle

2013-03-01

User experience with viewing images in pathology is crucial for accurate interpretation and diagnosis. With digital pathology, images are being read on a display system, and this poses new types of questions: such as what is the difference in terms of pixelation, refresh lag or obscured features compared to an optical microscope. Is there a resultant change in user performance in terms of speed of slide review, perception of adequacy and quality or in diagnostic confidence? A prior psychophysical study was carried out comparing various display modalities on whole slide imaging (WSI) in pathology at the University of Pittsburgh Medical Center (UPMC) in the USA. This prior study compared professional and non-professional grade display modalities and highlighted the importance of using a medical grade display to view pathological digital images. This study was duplicated in Europe at the Department of Pathology in Erasme Hospital (Université Libre de Bruxelles (ULB)) in an attempt to corroborate these findings. Digital WSI with corresponding glass slides of 58 cases including surgical pathology and cytopathology slides of varying difficulty were employed. Similar non-professional and professional grade display modalities were compared to an optical microscope (Olympus BX51). Displays ranged from a laptop (DELL Latitude D620), to a consumer grade display (DELL E248WFPb), to two professional grade monitors (Eizo CG245W and Barco MDCC-6130). Three pathologists were selected from the Department of Pathology in Erasme Hospital (ULB) in Belgium to view and interpret the pathological images on these different displays. The results show that non-professional grade displays (laptop and consumer) have inferior user experience compared to professional grade monitors and the optical microscope.

Arthroscopic findings of a diagnostic dilemma- hip pathology with normal imaging.

PubMed

Buikstra, Joel Glenn; Fary, Camdon; Tran, Phong

2017-03-21

Patients with groin, hip and pelvic pain but normal findings on MRI and minimal changes on x-ray can be a diagnostic problem. This paper looks at the arthroscopic findings of patients who have had hip pain and a positive response to an intra-articular anaesthetic but have non-contributory imaging. We hypothesized that standard MRI's were missing significant pathology and if there was a response to intra-articular local anaesthesia, pathology found during arthroscopy was likely. A retrospective review of all hip arthroscopies performed from March 2011 to January 2015 by two orthopaedic surgeons specializing in hip arthroscopy was conducted to identify patients with clinically suspected intra-articular hip pathology despite a normal MRI report and X-ray. Clinical suspicion of intra-articular hip pathology was confirmed with a positive response to a fluoroscopically guided intra-articular injection of local anaesthetic and corticosteroid. Pathologic findings were collated from the standardised operative notes. Fifty-three hip arthroscopies performed in 51 patients met the inclusion criteria from a total of 1348 hip arthroscopies performed over a 46-month period. All but one of the 53 (98%) hips had arthroscopically confirmed pathology. Mean patient age was 32.5 years [15 to 67 years] with 40 (78%) females and 11 (22%) males. 92.5% of the hips (49/53) were FADIR (flexion, adduction and internal rotation) positive on clinical examination, giving this test a positive predictive value of 98% (95% CI: 89.31 to 99.67%) for intra-articular pathology. In patients with a normal MRI without contrast and a positive response (relief of pain) to an intra-articular injection that failed conservative management, there is a 98% chance of intra-articular hip pathology being discovered on hip arthroscopy.

Using histopathological changes as a biomarker to trace contamination loading of Musa Creeks (Persian Gulf).

PubMed

Salamat, Negin; Soleimani, Zahra; Safahieh, Alireza; Savari, Ahmad; Ronagh, Mohammad Taghi

2013-08-01

Gill histological changes were used as a biomarker to evaluate the health of yellowfin seabream, Acanthopagrus latus (A. latus), collected from different sites in Musa Creeks including: (A) Petrochemical, (B) Jaafari, (C) Ghazaleh, (D) Majidieh, and (E) Zangi creeks. Also Genaveh with relatively clean water was selected as reference. The gills of 60 A. latus were fixed in Bouin's solution for 12 hr, dehydrated in a graded series of ethanol, and embedded in paraffin. Five micrometer thick sections were stained in H&E and Periodic Acid Schiff for microscopic examination. Also, the presence of gill histological alterations was assessed by the histopathologic alteration index (HAI). The gill morphological abnormalities include mucus secretion increase, debris, blood plaque, and shortening of filaments. The gill pathological changes included lamellar cells hyperplasia, aneurysm, lamellar fusion, and epithelial lifting. The HAI means were varied from moderate to severe in sites A and B, thus these sites are considered as being of low quality. Some severe pathological alterations were observed in site D, but their distribution was lower than sites A and B. The least HAI means of sites C and E demonstrated their good environmental quality. The results suggest that there is close relation between amounts of pathological alterations and environmental contamination.

[Use of magnetic therapy for treatment of early symptoms of vascular-type vibration syndrome in forestry workers].

PubMed

Karczewska, M

1996-01-01

The objective of the study was to evaluate the efficacy of the use of magnetic fields (ELF-MF) of therapeutic parameters in the treatment of early symptoms of vascular-type vibration syndrome in forestry workers. The study covered 96 forestry workers, and the control group was composed of 29 sawyers who underwent a simulated treatment. Each worker was granted sick leave and applied 20 procedures by employing an Aplhatron 4100 device under the ambulatory conditions. The outcome of the treatment was evaluated directly after the last procedure and 3 months later. A diversified positive influence on individual subjective and objective pathological changes in regard to both direct and late effects was observed. The abatement of subjective disorders right after termination of the treatment was observed in 67.7% and objective disorders in 57.3%. A long-term improvement (after 3 months) was found in a smaller proportion of persons as the abatement of subjective disorders was reported by 59.3% while objective disorders persisted in 43.7%. The results obtained prove that the application of variable magnetic fields (ELF-MF) of therapeutic parameters is useful in the prophylaxis and treatment of pathological changes during the period of prodromal symptoms and early pathological changes in vascular-type vibration syndrome induced by local magnetic vibrations.

Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma

NASA Astrophysics Data System (ADS)

Rohrbach, Daniel J.; Rigual, Nestor; Arshad, Hassan; Tracy, Erin C.; Cooper, Michelle T.; Shafirstein, Gal; Wilding, Gregory; Merzianu, Mihai; Baumann, Heinz; Henderson, Barbara W.; Sunar, Ulas

2016-01-01

This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR). In addition, biopsies were acquired after PDT to assess the STAT3 crosslinking. Parameters measured with DOS, including blood volume fraction, blood oxygen saturation (StO2), HPPH concentration (cHPPH), HPPH fluorescence, and blood flow index (BFI), were compared to the pathologic response and the STAT3 crosslinking. The best individual predictor of pathological response was a change in cHPPH (sensitivity=60%, specificity=100%), while discrimination analysis using a two-parameter classifier (change in cHPPH and change in StO2) classified pathological response with 100% sensitivity and 100% specificity. BFI showed the best correlation with the crosslinking of STAT3. These results indicate that DOS-derived parameters can assess the clinical response in the OR, allowing for earlier reintervention if needed.

Speech and Communication Changes Reported by People with Parkinson's Disease.

PubMed

Schalling, Ellika; Johansson, Kerstin; Hartelius, Lena

2017-01-01

Changes in communicative functions are common in Parkinson's disease (PD), but there are only limited data provided by individuals with PD on how these changes are perceived, what their consequences are, and what type of intervention is provided. To present self-reported information about speech and communication, the impact on communicative participation, and the amount and type of speech-language pathology services received by people with PD. Respondents with PD recruited via the Swedish Parkinson's Disease Society filled out a questionnaire accessed via a Web link or provided in a paper version. Of 188 respondents, 92.5% reported at least one symptom related to communication; the most common symptoms were weak voice, word-finding difficulties, imprecise articulation, and getting off topic in conversation. The speech and communication problems resulted in restricted communicative participation for between a quarter and a third of the respondents, and their speech caused embarrassment sometimes or more often to more than half. Forty-five percent of the respondents had received speech-language pathology services. Most respondents reported both speech and language symptoms, and many experienced restricted communicative participation. Access to speech-language pathology services is still inadequate. Services should also address cognitive/linguistic aspects to meet the needs of people with PD. © 2018 S. Karger AG, Basel.

Mouse models for the study of postnatal cardiac hypertrophy.

PubMed

Del Olmo-Turrubiarte, A; Calzada-Torres, A; Díaz-Rosas, G; Palma-Lara, I; Sánchez-Urbina, R; Balderrábano-Saucedo, N A; González-Márquez, H; Garcia-Alonso, P; Contreras-Ramos, A

2015-06-01

The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH), in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP) isoproterenol (ISO) was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB), neonates (7-15 days) and young adults (6 weeks of age). Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR), alpha and beta myosins (α-MHC, β-MHC) and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS). Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

Data-Driven Sequence of Changes to Anatomical Brain Connectivity in Sporadic Alzheimer's Disease.

PubMed

Oxtoby, Neil P; Garbarino, Sara; Firth, Nicholas C; Warren, Jason D; Schott, Jonathan M; Alexander, Daniel C

2017-01-01

Model-based investigations of transneuronal spreading mechanisms in neurodegenerative diseases relate the pattern of pathology severity to the brain's connectivity matrix, which reveals information about how pathology propagates through the connectivity network. Such network models typically use networks based on functional or structural connectivity in young and healthy individuals, and only end-stage patterns of pathology, thereby ignoring/excluding the effects of normal aging and disease progression. Here, we examine the sequence of changes in the elderly brain's anatomical connectivity over the course of a neurodegenerative disease. We do this in a data-driven manner that is not dependent upon clinical disease stage, by using event-based disease progression modeling. Using data from the Alzheimer's Disease Neuroimaging Initiative dataset, we sequence the progressive decline of anatomical connectivity, as quantified by graph-theory metrics, in the Alzheimer's disease brain. Ours is the first single model to contribute to understanding all three of the nature, the location, and the sequence of changes to anatomical connectivity in the human brain due to Alzheimer's disease. Our experimental results reveal new insights into Alzheimer's disease: that degeneration of anatomical connectivity in the brain may be a viable, even early, biomarker and should be considered when studying such neurodegenerative diseases.

The Anti-Inflammatory Effects of a Yin Zhi Huang Soup in an Experimental Autoimmune Prostatitis Rat Model

PubMed Central

Zhang, Xikui; Zhu, Weikun; Lu, Taikun; Chen, Jinchun; Zou, Qiang; Zheng, Qizhong; Chen, Junying; Jiang, Changming; Jin, Guanyu

2017-01-01

The present study aimed to investigate the therapeutic effects of the Chinese herbal medicine Yin Zhi Huang soup (YZS) in an experimental autoimmune prostatitis (EAP) rat model. In total, 48 rats were randomly divided into the following four groups (n = 12/group): saline group, pathological model group, Qianlietai group, and YZS group. We determined the average wet weight of the prostate tissue, the ratio of the wet weight of the prostate tissue to body weight, tumor necrosis factor-alpha (TNF-α) levels in the blood serum, the expression of inducible nitric oxide synthase (iNOS) in the rats' prostate tissues, and the pathological changes in the prostate tissue using light microscopy. YZS reduced the rats' prostate wet weight, the ratio of the prostate wet weight to body weight, and TNF-α levels in the blood serum and inhibited the expression of iNOS in the rats' prostate tissues (P < 0.05). Following YZS treatment, the pathological changes in the rats' prostates were improved compared with those in the model group (P < 0.05). Furthermore, YZS treatment reduced inflammatory changes in the prostate tissue. It also significantly suppressed proinflammatory cytokines, such as TNF-α, and chemokines, such as iNOS, in the rat model of EAP. PMID:29430255

The Anti-Inflammatory Effects of a Yin Zhi Huang Soup in an Experimental Autoimmune Prostatitis Rat Model.

PubMed

Deng, Longsheng; Zhang, Xikui; Zhu, Weikun; Lu, Taikun; Chen, Jinchun; Zou, Qiang; Zheng, Qizhong; Chen, Junying; Jiang, Changming; Jin, Guanyu

2017-01-01

The present study aimed to investigate the therapeutic effects of the Chinese herbal medicine Yin Zhi Huang soup (YZS) in an experimental autoimmune prostatitis (EAP) rat model. In total, 48 rats were randomly divided into the following four groups ( n = 12/group): saline group, pathological model group, Qianlietai group, and YZS group. We determined the average wet weight of the prostate tissue, the ratio of the wet weight of the prostate tissue to body weight, tumor necrosis factor-alpha (TNF- α ) levels in the blood serum, the expression of inducible nitric oxide synthase (iNOS) in the rats' prostate tissues, and the pathological changes in the prostate tissue using light microscopy. YZS reduced the rats' prostate wet weight, the ratio of the prostate wet weight to body weight, and TNF- α levels in the blood serum and inhibited the expression of iNOS in the rats' prostate tissues ( P < 0.05). Following YZS treatment, the pathological changes in the rats' prostates were improved compared with those in the model group ( P < 0.05). Furthermore, YZS treatment reduced inflammatory changes in the prostate tissue. It also significantly suppressed proinflammatory cytokines, such as TNF- α , and chemokines, such as iNOS, in the rat model of EAP.

Gambling experiences, problems, research and policy: gambling in Germany.

PubMed

Ludwig, Monika; Kräplin, Anja; Braun, Barbara; Kraus, Ludwig

2013-09-01

The objective of this paper is to present an overview of gambling in Germany, including historical development, legislative and economic changes as well as treatment options and their effectiveness. The available scientific literature and research reports on gambling in Germany were reviewed to obtain relevant information on history, commercialization, legislation, treatment and research agenda. Gambling in Germany is characterized by compromises between protective and economic efforts. At present, gambling is illegal in Germany, and provision is subject to the state monopoly. Mere gaming machines (specific slot machines) are not classified as gambling activity, permitting commercial providers. In recent years, implementing regulations for state gambling and gaming machines have been changed. Concerning the treatment of pathological gambling, various options exist; treatment costs have been covered by health and pension insurance since 2001. Information on the effectiveness of treatment in Germany is limited. Similarly, the number of peer-reviewed publications on gambling is small. German gambling legislation was subject to major changes in the past years. Based on the available body of research (longitudinal), studies on risk and protective factors and the aetiology of pathological gambling are needed. The effectiveness of pathological gambling treatment in Germany and the impact of gambling regulations on gambling behaviour also need to be investigated. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

The clinico-pathology and mechanisms of trypanosomosis in captive and free-living wild animals: a review.

PubMed

Mbaya, A W; Aliyu, M M; Ibrahim, U I

2009-10-01

Reports on the clinico-pathology and mechanisms of trypanosomosis in free-living and captive wild animals showed that clinical disease and outbreaks occur more commonly among captive than free-living wild animals. This is because the free-living wild animals co-exist with the disease until subjected to captivity. In exceptional cases however, draught, starvation and intercurrent diseases often compromised trypanotolerance leading to overt trypanosomosis in free-living wild animals. Meanwhile, in captivity, space restriction, reduced social interactions, change in social herd structure, reduced specie-to-specie specific behaviors, altered habitat and translocation were the major stressors that precipitated the disease. The cumulative effect of these factors produced severe physiological and somatic stress leading to diminished immune response due to increased blood cortisol output from adrenal cortex. The major symptoms manifested were pyrexia, innapetence, increased respiration, anaemia, cachexia and death. At necropsy, pulmonary oedema, splenomegally, hepatomegally, lympadenopathy and atrophy of body fats were the gross changes encountered. At the ultra-structural level, the tissues manifested degenerative changes, haemorghages, necrosis and mononuclear cellular infiltrations. The mechanisms of cellular and tissue injuries were primarily associated with physical and metabolic activities of the organisms. From the foregoing, it is evident that stress is the underlying mechanism that compromises trypanotolerance in wild animals leading to severe clinico-pathological effects.

The impact of change in albumin assay on reference intervals, prevalence of 'hypoalbuminaemia' and albumin prescriptions.

PubMed

Coley-Grant, Deon; Herbert, Mike; Cornes, Michael P; Barlow, Ian M; Ford, Clare; Gama, Rousseau

2016-01-01

We studied the impact on reference intervals, classification of patients with hypoalbuminaemia and albumin infusion prescriptions on changing from a bromocresol green (BCG) to a bromocresol purple (BCP) serum albumin assay. Passing-Bablok regression analysis and Bland-Altman plot were used to compare Abbott BCP and Roche BCG methods. Linear regression analysis was used to compare in-house and an external laboratory Abbott BCP serum albumin results. Reference intervals for Abbott BCP serum albumin were derived in two different laboratories using pathology data from adult patients in primary care. Prescriptions for 20% albumin infusions were compared one year before and one year after changing the albumin method. Abbott BCP assay had a negative bias of approximately 6 g/L compared with Roche BCG method.There was good agreement (y = 1.04 x - 1.03; R(2 )= 0.9933) between in-house and external laboratory Abbott BCP results. Reference intervals for the serum albumin Abbott BCP assay were 31-45 g/L, different to those recommended by Pathology Harmony and the manufacturers (35-50 g/L). Following the change in method there was a large increase in the number of patients classified as hypoalbuminaemic using Pathology Harmony references intervals (32%) but not when retrospectively compared to locally derived reference intervals (16%) compared with the previous year (12%). The method change was associated with a 44.6% increase in albumin prescriptions. This equated to an annual increase in expenditure of £35,234. We suggest that serum albumin reference intervals be method specific to prevent misclassification of albumin status in patients. Change in albumin methodology may have significant impact on hospital resources. © The Author(s) 2015.

The efficacy and utilisation of preoperative multiparametric magnetic resonance imaging in robot-assisted radical prostatectomy: does it change the surgical dissection plan?

PubMed

Tavukçu, Hasan Hüseyin; Aytaç, Ömer; Balcı, Numan Cem; Kulaksızoğlu, Haluk; Atuğ, Fatih

2017-12-01

We investigated the effect of the use of multiparametric prostate magnetic resonance imaging (mp-MRI) on the dissection plan of the neurovascular bundle and the oncological results of our patients who underwent robot-assisted radical prostatectomy. We prospectively evaluated 60 consecutive patients, including 30 patients who had (Group 1), and 30 patients who had not (Group 2) mp-MRI before robot-assisted radical prostatectomy. Based on the findings of mp-MRI, the dissection plan was changed as intrafascial, interfascial, and extrafascial in the mp-MRI group. Two groups were compared in terms of age, prostate-specific antigen (PSA), Gleason sum scores and surgical margin positivity. There was no statistically significant difference between the two groups in terms of age, PSA, biopsy Gleason score, final pathological Gleason score and surgical margin positivity. mp-MRI changed the initial surgical plan in 18 of 30 patients (60%) in Group 1. In seventeen of these patients (56%) surgical plan was changed from non-nerve sparing to interfascial nerve sparing plan. In one patient dissection plan was changed to non-nerve sparing technique which had extraprostatic extension on final pathology. Surgical margin positivity was similar in Groups 1, and 2 (16% and 13%, respectively) although, Group 1 had higher number of high- risk patients. mp-MRI confirmed the primary tumour localisation in the final pathology in 27 of of 30 patients (90%). Preoperative mp-MRI effected the decision to perform a nerve-sparing technique in 56% of the patients in our study; moreover, changing the dissection plan from non-nerve-sparing technique to a nerve sparing technique did not increase the rate of surgical margin positivity.

Vital signs in older patients: age-related changes.

PubMed

Chester, Jennifer Gonik; Rudolph, James L

2011-06-01

Vital signs are objective measures of physiological function that are used to monitor acute and chronic disease and thus serve as a basic communication tool about patient status. The purpose of this analysis was to review age-related changes of traditional vital signs (blood pressure, pulse, respiratory rate, and temperature) with a focus on age-related molecular changes, organ system changes, systemic changes, and altered compensation to stressors. The review found that numerous physiological and pathological changes may occur with age and alter vital signs. These changes tend to reduce the ability of organ systems to adapt to physiological stressors, particularly in frail older patients. Because of the diversity of age-related physiological changes and comorbidities in an individual, single-point measurements of vital signs have less sensitivity in detecting disease processes. However, serial vital sign assessments may have increased sensitivity, especially when viewed in the context of individualized reference ranges. Vital sign change with age may be subtle because of reduced physiological ranges. However, change from an individual reference range may indicate important warning signs and thus may require additional evaluation to understand potential underlying pathological processes. As a result, individualized reference ranges may provide improved sensitivity in frail, older patients. Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.

Brain Stimulation Studies of Social Norm Compliance: Implications for Personality Disorders?

PubMed

Ruff, Christian C

2018-01-01

Several personality disorders involve pathological behaviors that violate social norms, commonly held expectations about what ought to be done in specific situations. These symptoms usually emerge early in development, are persistent and hard to treat, and are often ego-syntonic. Here I present some recent brain stimulation studies suggesting that pathological changes in different aspects of norm-compliant behavior reflect dysfunctions of brain circuits involving distinct prefrontal brain areas. One set of studies shows that transcranial direct current stimulation of the right lateral prefrontal cortex changes the behavioral sensitivity to social incentives for norm-compliant behavior. Crucially, social norm compliance in response to such incentives could even be increased during excitatory stimulation, demonstrating that the affected neural process is a biological prerequisite for appropriate reaction to social signals that trigger norm compliance. In another set of studies, we show that stimulation of a different (more dorsal) part of the right prefrontal cortex enhances honesty in a realistic setting where participants had the opportunity to cheat for real monetary gains. Interestingly, these stimulation-induced increases in both socially cued or purely voluntary norm compliance were not linked to changes in other aspects of decision- making (such as risk or impatience), and they did not reflect changes in beliefs about what is appropriate behavior. These results suggest that disorders of distinct brain circuits may causally underlie egosyntotic changes in norm-compliant behavior. This raises the tantalizing possibility that pathologies of norm-compliant behavior may be ameliorated by interventions targeting the function of these brain circuits. © 2018 S. Karger AG, Basel.

Early fear memory defects are associated with altered synaptic plasticity and molecular architecture in the TgCRND8 Alzheimer's disease mouse model.

PubMed

Steele, John W; Brautigam, Hannah; Short, Jennifer A; Sowa, Allison; Shi, Mengxi; Yadav, Aniruddha; Weaver, Christina M; Westaway, David; Fraser, Paul E; St George-Hyslop, Peter H; Gandy, Sam; Hof, Patrick R; Dickstein, Dara L

2014-07-01

Alzheimer's disease (AD) is a complex and slowly progressing dementing disorder that results in neuronal and synaptic loss, deposition in brain of aberrantly folded proteins, and impairment of spatial and episodic memory. Most studies of mouse models of AD have employed analyses of cognitive status and assessment of amyloid burden, gliosis, and molecular pathology during disease progression. Here we sought to understand the behavioral, cellular, ultrastructural, and molecular changes that occur at a pathological stage equivalent to the early stages of human AD. We studied the TgCRND8 mouse, a model of aggressive AD amyloidosis, at an early stage of plaque pathology (3 months of age) in comparison to their wildtype littermates and assessed changes in cognition, neuron and spine structure, and expression of synaptic glutamate receptor proteins. We found that, at this age, TgCRND8 mice display substantial plaque deposition in the neocortex and hippocampus and impairment on cued and contextual memory tasks. Of particular interest, we also observed a significant decrease in the number of neurons in the hippocampus. Furthermore, analysis of CA1 neurons revealed significant changes in apical and basal dendritic spine types, as well as altered expression of GluN1 and GluA2 receptors. This change in molecular architecture within the hippocampus may reflect a rising representation of inherently less stable thin spine populations, which can cause cognitive decline. These changes, taken together with toxic insults from amyloid-β protein, may underlie the observed neuronal loss. Copyright © 2014 Wiley Periodicals, Inc.

Biomarkers, ketone bodies, and the prevention of Alzheimer's disease.

PubMed

VanItallie, Theodore B

2015-03-01

Sporadic Alzheimer's disease (spAD) has three successive phases: preclinical, mild cognitive impairment, and dementia. Individuals in the preclinical phase are cognitively normal. Diagnosis of preclinical spAD requires evidence of pathologic brain changes provided by established biomarkers. Histopathologic features of spAD include (i) extra-cellular cerebral amyloid plaques and intracellular neurofibrillary tangles that embody hyperphosphorylated tau; and (ii) neuronal and synaptic loss. Amyloid-PET brain scans conducted during spAD's preclinical phase have disclosed abnormal accumulations of amyloid-beta (Aβ) in cognitively normal, high-risk individuals. However, this measure correlates poorly with changes in cognitive status. In contrast, MRI measures of brain atrophy consistently parallel cognitive deterioration. By the time dementia appears, amyloid deposition has already slowed or ceased. When a new treatment offers promise of arresting or delaying progression of preclinical spAD, its effectiveness must be inferred from intervention-correlated changes in biomarkers. Herein, differing tenets of the amyloid cascade hypothesis (ACH) and the mitochondrial cascade hypothesis (MCH) are compared. Adoption of the ACH suggests therapeutic research continue to focus on aspects of the amyloid pathways. Adoption of the MCH suggests research emphasis be placed on restoration and stabilization of mitochondrial function. Ketone ester (KE)-induced elevation of plasma ketone body (KB) levels improves mitochondrial metabolism and prevents or delays progression of AD-like pathologic changes in several AD animal models. Thus, as a first step, it is imperative to determine whether KE-caused hyperketonemia can bring about favorable changes in biomarkers of AD pathology in individuals who are in an early stage of AD's preclinical phase. Copyright © 2015 Elsevier Inc. All rights reserved.

PC61 (Anti-CD25) Treatment Inhibits Influenza A Virus-Expanded Regulatory T Cells and Severe Lung Pathology during a Subsequent Heterologous Lymphocytic Choriomeningitis Virus Infection

PubMed Central

Kraft, Anke R. M.; Wlodarczyk, Myriam F.; Kenney, Laurie L.

2013-01-01

Prior immunity to influenza A virus (IAV) in mice changes the outcome to a subsequent lymphocytic choriomeningitis virus (LCMV) infection and can result in severe lung pathology, similar to that observed in patients that died of the 1918 H1N1 pandemic. This pathology is induced by IAV-specific memory CD8+ T cells cross-reactive with LCMV. Here, we discovered that IAV-immune mice have enhanced CD4+ Foxp3+ T-regulatory (Treg) cells in their lungs, leading us to question whether a modulation in the normal balance of Treg and effector T-cell responses also contributes to enhancing lung pathology upon LCMV infection of IAV-immune mice. Treg cell and interleukin-10 (IL-10) levels remained elevated in the lungs and mediastinal lymph nodes (mLNs) throughout the acute LCMV response of IAV-immune mice. PC61 treatment, used to decrease Treg cell levels, did not change LCMV titers but resulted in a surprising decrease in lung pathology upon LCMV infection in IAV-immune but not in naive mice. Associated with this decrease in pathology was a retention of Treg in the mLN and an unexpected partial clonal exhaustion of LCMV-specific CD8+ T-cell responses only in IAV-immune mice. PC61 treatment did not affect cross-reactive memory CD8+ T-cell proliferation. These results suggest that in the absence of IAV-expanded Treg cells and in the presence of cross-reactive memory, the LCMV-specific response was overstimulated and became partially exhausted, resulting in a decreased effector response. These studies suggest that Treg cells generated during past infections can influence the characteristics of effector T-cell responses and immunopathology during subsequent heterologous infections. Thus, in humans with complex infection histories, PC61 treatment may lead to unexpected results. PMID:24049180

Correlation of hemorrhage, axonal damage, and blood-tissue barrier disruption in brain and retina of Malawian children with fatal cerebral malaria.

PubMed

Greiner, Jesse; Dorovini-Zis, Katerina; Taylor, Terrie E; Molyneux, Malcolm E; Beare, Nicholas A V; Kamiza, Steve; White, Valerie A

2015-01-01

The retinal and brain histopathological findings in children who died from cerebral malaria (CM) have been recently described. Similar changes occur in both structures, but the findings have not been directly compared in the same patients. In this study, we compared clinical retinal findings and retinal and cerebral histopathological changes in a series of patients in Blantyre, Malawi, who died of CM. The features systematically compared in the same patient were: (1) clinical, gross and microscopic retinal hemorrhages with microscopic cerebral hemorrhages, (2) retinal and cerebral hemorrhage-associated and -unassociated axonal damage, and fibrinogen leakage, and (3) differences in the above features between the pathological categories of CM without microvascular pathology (CM1) and CM with microvascular pathology (CM2) in retina and brain. Forty-seven patients were included: seven CM1, 28 CM2, and 12 controls. In the 35 malaria cases retinal and cerebral pathology correlated in all features except for non-hemorrhage associated fibrinogen leakage. Regarding CM1 and CM2 cases, the only differences were in the proportion of patients with hemorrhage-associated cerebral pathology, and this was expected, based on the definitions of CM1 and CM2. The retina did not show this difference. Non-hemorrhage associated pathology was similar for the two groups. As postulated, histopathological features of hemorrhages, axonal damage and non-hemorrhage associated fibrinogen leakage correlated in the retina and brain of individual patients, although the difference in hemorrhages between the CM1 and CM2 groups was not consistently observed in the retina. These results help to underpin the utility of ophthalmoscopic examination and fundus findings to help in diagnosis and assessment of cerebral malaria patients, but may not help in distinguishing between CM1 and CM2 patients during life.

Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer's disease.

PubMed

Roh, Jee Hoon; Jiang, Hong; Finn, Mary Beth; Stewart, Floy R; Mahan, Thomas E; Cirrito, John R; Heda, Ashish; Snider, B Joy; Li, Mingjie; Yanagisawa, Masashi; de Lecea, Luis; Holtzman, David M

2014-12-15

Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer's disease (AD) pathogenesis, and it disrupts the sleep-wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. Amyloid precursor protein (APP)/Presenilin 1 (PS1) transgenic mice, in which the orexin gene is knocked out, showed a marked decrease in the amount of Aβ pathology in the brain with an increase in sleep time. Focal overexpression of orexin in the hippocampus in APP/PS1 mice did not alter the total amount of sleep/wakefulness and the amount of Aβ pathology. In contrast, sleep deprivation or increasing wakefulness by rescue of orexinergic neurons in APP/PS1 mice lacking orexin increased the amount of Aβ pathology in the brain. Collectively, modulation of orexin and its effects on sleep appear to modulate Aβ pathology in the brain. © 2014 Roh et al.

Second opinion oral pathology referrals in New Zealand.

PubMed

Seo, B; Hussaini, H M; Rich, A M

2017-04-01

Referral for a second opinion is an important aspect of pathology practice, which reduces the rate of diagnostic error and ensures consistency with diagnoses. The Oral Pathology Centre (OPC) is the only specialist oral diagnostic centre in New Zealand. OPC provides diagnostic services to dentists and dental specialists throughout New Zealand and acts as a referral centre for second opinions for oral pathology specimens that have been sent to anatomical pathologists. The aim of this study was to review second opinion referral cases sent to the OPC over a 15-year period and to assess the levels of concordance between the original and final diagnoses. The findings indicated that the majority of referred cases were odontogenic lesions, followed by connective tissue, epithelial and salivary lesions. The most prevalent diagnoses were ameloblastoma and keratocystic odontogenic tumour, followed by oral squamous cell carcinoma. Discordant diagnoses were recorded in 24% of cases. Diagnostic discrepancies were higher in odontogenic and salivary gland lesions, resulting in the change of diagnoses. Second opinion of oral pathology cases should be encouraged in view of the relative rarity of these lesions in general pathology laboratories and the rates of diagnostic discrepancy, particularly for odontogenic and salivary gland lesions. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Neo-epitope Peptides as Biomarkers of Disease Progression for Muscular Dystrophies and Other Myopathies

PubMed Central

Arvanitidis, A.; Henriksen, K.; Karsdal, M.A.; Nedergaard, A.

2016-01-01

For several decades, serological biomarkers of neuromuscular diseases as dystrophies, myopathies and myositis have been limited to routine clinical biochemistry panels. Gauging the pathological progression is a prerequisite for proper treatment and therefore identifying accessible, easy to monitor biomarkers that can predict the disease progression would be an important advancement. Most muscle diseases involve accelerated muscle fiber degradation, inflammation, fatty tissue substitution and/or fibrosis. All these pathological traits have been shown to give rise to serological peptide biomarkers in other tissues, underlining the potential application of existing biomarkers of such traits in muscle disorders. A significant quantity of tissue is involved in these pathological mechanisms alongside with qualitative changes in protein turnover in myofibrillar, extra-cellular matrix and immunological cell protein fractions accompanied by alterations in body fluids. We propose that protein and peptides can leak out of the afflicted muscles and can be of use in diagnosis, prediction of pathology trajectory and treatment efficacy. Proteolytic cleavage systems are especially modulated during a range of muscle pathologies, thereby giving rise to peptides that are differentially released during disease manifestation. Therefore, we believe that pathology-specific post-translational modifications like cleavages can give rise to neoepitope peptides that may represent a promising class of peptides for discovery of biomarkers pertaining to neuromuscular diseases. PMID:27854226

MR Morphology of Triangular Fibrocartilage Complex: Correlation with Quantitative MR and Biomechanical Properties

PubMed Central

Bae, Won C.; Ruangchaijatuporn, Thumanoon; Chang, Eric Y; Biswas, Reni; Du, Jiang; Statum, Sheronda

2016-01-01

Objective To evaluate pathology of the triangular fibrocartilage complex (TFCC) using high resolution morphologic magnetic resonance (MR) imaging, and compare with quantitative MR and biomechanical properties. Materials and Methods Five cadaveric wrists (22 to 70 yrs) were imaged at 3T using morphologic (proton density weighted spin echo, PD FS, and 3D spoiled gradient echo, 3D SPGR) and quantitative MR sequences to determine T2 and T1rho properties. In eight geographic regions, morphology of TFC disc and laminae were evaluated for pathology and quantitative MR values. Samples were disarticulated and biomechanical indentation testing was performed on the distal surface of the TFC disc. Results On morphologic PD SE images, TFC disc pathology included degeneration and tears, while that of the laminae included degeneration, degeneration with superimposed tear, mucinous transformation, and globular calcification. Punctate calcifications were highly visible on 3D SPGR images and found only in pathologic regions. Disc pathology occurred more frequently in proximal regions of the disc than distal regions. Quantitative MR values were lowest in normal samples, and generally higher in pathologic regions. Biomechanical testing demonstrated an inverse relationship, with indentation modulus being high in normal regions with low MR values. The laminae studied were mostly pathologic, and additional normal samples are needed to discern quantitative changes. Conclusion These results show technical feasibility of morphologic MR, quantitative MR, and biomechanical techniques to characterize pathology of the TFCC. Quantitative MRI may be a suitable surrogate marker of soft tissue mechanical properties, and a useful adjunct to conventional morphologic MR techniques. PMID:26691643

Forensic molecular pathology of violent deaths.

PubMed

Maeda, Hitoshi; Zhu, Bao-li; Ishikawa, Takaki; Michiue, Tomomi

2010-12-15

In forensic pathology, while classical morphology remains a core procedure to investigate deaths, a spectrum of ancillary procedures has been developed and incorporated to detail the pathology. Among them, postmortem biochemistry is important to investigate the systemic pathophysiological changes involved in the dying process that cannot be detected by morphology. In addition, recent advances in molecular biology have provided a procedure to investigate genetic bases of diseases that might present with sudden death, which is called 'molecular autopsy'. Meanwhile, the practical application of RNA analyses to postmortem investigation has not been accepted due to rapid decay after death; however, recent experimental and practical studies using real-time reverse transcription-PCR have suggested that the relative quantification of mRNA transcripts can be applied in molecular pathology for postmortem investigation of deaths, which may be called 'advanced molecular autopsy'. In a broad sense, forensic molecular pathology implies applied medical sciences to investigate the genetic basis of diseases, and the pathophysiology of diseases and traumas leading to death at a biological molecular level in the context of forensic pathology. The possible applications include analyses of local pathology, including tissue injury, ischemia/hypoxia and inflammation at the site of insult or specific tissue damage from intoxication, systemic responses to violence or environmental hazards, disorders due to intoxication, and systemic pathophysiology of fatal process involving major life-support organs. A review of previous studies suggests that systematic postmortem quantitative analysis of mRNA transcripts can be established from multi-faceted aspects of molecular biology and incorporated into death investigations in forensic pathology, to support and reinforce morphological evidence. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Regulatory T cell activity in immunosuppresive mice model of pseudomonas aeruginosa pneumonia.

PubMed

Li, Jun-Lu; Chen, Ting-Sang; Yuan, Cong-Cong; Zhao, Guo-Qiang; Xu, Min; Li, Xiao-Yan; Cao, Jie; Xing, Li-Hua

2017-08-01

Pseudomonas aeruginosa (PA) pneumonia is a refractory, even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process. We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells, i.e., Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10). Seventy-two BALB/c mice were divided into four groups randomly: control (A), PA pneumonia (B), immunosuppression (C) and immunosuppression with PA pneumonia (D). Mice were sacrificed at 4, 8 and 24 h after establishing experimental models. The pathological changes of lung tissue were graded, and the FOXP3 mRNA and serum IL-10 levels were detected. Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C, but significantly pathological changes were found in groups B and D, especially in group D at 8 h (P<0.05). The expression levels of FOXP3 mRNA in groups A and C showed no significant changes at the three time points, which were significantly lower than those in groups B and D (P<0.05). FOXP3 mRNA levels were lowest at 4 h, and there was significant difference between groups B and D (P<0.05). The serum levels of IL-10 in groups A and C were almost normal at the three time points, but decreased significantly in groups B and D (P<0.05). The serum levels of IL-10 decreased to the lowest at 8 h, especially in group D (P<0.05). The results indicate that PA pneumonia in immunosuppressive individuals worsens rapidly, which may be associated with Treg cells function disturbance. And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.

Identification of microRNAs involved in Alzheimer’s progression using a rabbit model of the disease

PubMed Central

Liu, Qing Yan; Chang, Marilyn N Vera; Lei, Joy X; Koukiekolo, Roger; Smith, Brandon; Zhang, Dongling; Ghribi, Othman

2014-01-01

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by the presence of extracellular plaques of β-amyloid peptides and intracellular tangles of hyperphosphorylated tau proteins in the brain. The vast majority of cases are late onset AD (LOAD), which are genetically heterogeneous and occur sporadically. High blood cholesterol is suggested to be a risk factor for this disease. Several neuropathological changes of LOAD can be reproduced by supplementing a rabbit’s diet with 2% cholesterol for 12 weeks. Accumulating data in the literature suggest that microRNAs (miRNA) participate in the development of AD pathology. The present study focuses on the survey of changes of miRNA expression in rabbit brains during the progression of AD-like pathology using microarray followed by Taq-Man qRT-PCR analyses. Out of 1769 miRNA probes used in the experiments, 99 miRNAs were found to be present in rabbit brain, 57 were newly identified as miRNAs from rabbit brain. Eleven miRNAs showed significant changes over AD-like pathology progression. Among them, the changes of miR-125b, miR-98, miR-107, miR-30, along with 3 members of the let-7 family were similar to those observed in human AD samples, whereas the expression patterns of miR-15a, miR-26b, miR-9 and miR-576-3p were unique to this rabbit LOAD model. The significant up regulation of miR-26b is consistent with the decrease of leptin levels in the brains of cholesterol fed rabbit model for AD, confirming that miR-26b is indeed regulated by leptin and that both leptin and miR-26b may be involved in cholesterol induced AD-like pathology. PMID:24754001

Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study.

PubMed

Coughlin, Jennifer M; Wang, Yuchuan; Munro, Cynthia A; Ma, Shuangchao; Yue, Chen; Chen, Shaojie; Airan, Raag; Kim, Pearl K; Adams, Ashley V; Garcia, Cinthya; Higgs, Cecilia; Sair, Haris I; Sawa, Akira; Smith, Gwenn; Lyketsos, Constantine G; Caffo, Brian; Kassiou, Michael; Guilarte, Tomas R; Pomper, Martin G

2015-02-01

There are growing concerns about potential delayed, neuropsychiatric consequences (e.g, cognitive decline, mood or anxiety disorders) of sports-related traumatic brain injury (TBI). Autopsy studies of brains from a limited number of former athletes have described characteristic, pathologic changes of chronic traumatic encephalopathy (CTE) leading to questions about the relationship between these pathologic and the neuropsychiatric disturbances seen in former athletes. Research in this area will depend on in vivo methods that characterize molecular changes in the brain, linking CTE and other sports-related pathologies with delayed emergence of neuropsychiatric symptoms. In this pilot project we studied former National Football League (NFL) players using new neuroimaging techniques and clinical measures of cognitive functioning. We hypothesized that former NFL players would show molecular and structural changes in medial temporal and parietal lobe structures as well as specific cognitive deficits, namely those of verbal learning and memory. We observed a significant increase in binding of [(11)C]DPA-713 to the translocator protein (TSPO), a marker of brain injury and repair, in several brain regions, such as the supramarginal gyrus and right amygdala, in 9 former NFL players compared to 9 age-matched, healthy controls. We also observed significant atrophy of the right hippocampus. Finally, we report that these same former players had varied performance on a test of verbal learning and memory, suggesting that these molecular and pathologic changes may play a role in cognitive decline. These results suggest that localized brain injury and repair, indicated by increased [(11)C]DPA-713 binding to TSPO, may be linked to history of NFL play. [(11)C]DPA-713 PET is a promising new tool that can be used in future study design to examine further the relationship between TSPO expression in brain injury and repair, selective regional brain atrophy, and the potential link to deficits in verbal learning and memory after NFL play. Copyright © 2014 Elsevier Inc. All rights reserved.

mRNAs and miRNAs in whole blood associated with lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma following multi-walled carbon nanotube inhalation exposure in mice

PubMed Central

Snyder-Talkington, Brandi N.; Dong, Chunlin; Sargent, Linda M.; Porter, Dale W.; Staska, Lauren M.; Hubbs, Ann F.; Raese, Rebecca; McKinney, Walter; Chen, Bean T.; Battelli, Lori; Lowry, David T.; Reynolds, Steven H.; Castranova, Vincent; Qian, Yong; Guo, Nancy L.

2015-01-01

Inhalation exposure to multi-walled carbon nanotubes (MWCNT) in mice results in inflammation, fibrosis, and the promotion of lung adenocarcinoma; however, the molecular basis behind these pathologies is unknown. This study determined global mRNA and miRNA profiles in whole blood from mice exposed by inhalation to MWCNT that correlated with the presence of lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma. Six-week-old, male, B6C3F1 mice received a single intraperitoneal injection of either the DNA-damaging agent methylcholanthrene (MCA, 10 μg/g body weight) or vehicle (corn oil). One week after injections, mice were exposed by inhalation to MWCNT (5 mg/m³, 5 hours/day, 5 days/week) or filtered air (control) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for the development of pathological changes in the lung, and whole blood was collected and analyzed using microarray analysis for global mRNA and miRNA expression. Numerous mRNAs and miRNAs in the blood were significantly up- or down-regulated in animals developing pathological changes in the lung after MCA/corn oil administration followed by MWCNT/air inhalation, including fcrl5 and miR-122-5p in the presence of hyperplasia, mthfd2 and miR-206-3p in the presence of fibrosis, fam178a and miR-130a-3p in the presence of bronchiolo-alveolar adenoma, and il7r and miR-210-3p in the presence of bronchiolo-alveolar adenocarcinoma, among others. The changes in miRNA and mRNA expression, and their respective regulatory networks, identified in this study may potentially serve as blood biomarkers for MWCNT-induced lung pathological changes. PMID:25926378

[Features of neurologic semiotics at chronic obstructive pulmonary disease].

PubMed

Litvinenko, I V; Baranov, V L; Kolcheva, Iu A

2011-01-01

Chronic obstructive pulmonary disease (COPD) is actual pathology, when it forms the mixed hypoxemia. In the conditions of a chronic hypoxemia structures of organism with high level of metabolic processes, namely brain tissues, suffer. Character of defeat of the central nervous system at that pathology is insufficiently studied. In this article we studied and analysed the presence of such changes as depression, anxiety, cognitive impairment and features of neurologic semiotics at COPD in 50 patients.

PATHOLOGY AND MOLECULAR DETECTION OF RABIES VIRUS IN FERRET BADGERS ASSOCIATED WITH A RABIES OUTBREAK IN TAIWAN.

PubMed

Chiou, Hue-Ying; Jeng, Chian-Ren; Wang, Hurng-Yi; Inoue, Satoshi; Chan, Fang-Tse; Liao, Jiunn-Wang; Chiou, Ming-Tang; Pang, Victor Fei

2016-01-01

Until Rabies virus (RABV) infection in Taiwan ferret badgers (TWFB; Melogale moschata subaurantiaca) was diagnosed in mid-June 2013, Taiwan had been considered rabies free for >50 yr. Although rabies has also been reported in ferret badgers in China, the pathologic changes and distribution of viral antigens of ferret badger-associated rabies have not been described. We performed a comprehensive pathologic study and molecular detection of rabies virus in three necropsied rabid TWFBs and evaluated archival paraffin-embedded tissue blocks of six other TWFBs necropsied during 2004 and 2012. As in other RABV-infected species, the characteristic pathologic changes in TWFBs were nonsuppurative meningoencephalomyelitis, ganglionitis, and the formation of typical intracytoplasmic Negri bodies, with the brain stem most affected. There was also variable spongiform degeneration, primarily in the perikaryon of neurons and neuropil, in the cerebral cortex, thalamus, and brain stem. In nonnervous system tissues, representative lesions included adrenal necrosis and lymphocytic interstitial sialadenitis. Immunohistochemical staining and fluorescent antibody test demonstrated viral antigens in the perikaryon of the neurons and axonal or dendritic processes throughout the nervous tissue and in the macrophages in various tissues. Similar to raccoons (Procyon lotor) and skunks (Mephitidae), the nervous tissue of rabid TWFBs displayed widely dispersed lesions, RABV antigens, and large numbers of Negri bodies. We traced the earliest rabid TWFB case back to 2004.

Mental Health and the Economy.

ERIC Educational Resources Information Center

Ferman, Louis A., Ed.; Gordus, Jeanne P., Ed.

This volume offers a collection of papers which explores the relationships between major economic changes and individual and collective mental and physical well-being, including individual distress, deviant behavior, and other symptoms of underlying pathology. The contributors examine the processes leading from macroeconomic change to social and…

The Athletic Heart Syndrome: Ruling Out Cardiac Pathologies.

ERIC Educational Resources Information Center

Puffer, James C.

2002-01-01

People who participate in regular vigorous or strenuous physical activities undergo significant changes in cardiac structure and function. Occasionally, these changes may be confused with those of hypertrophic cardiomyopathy (HCM). Differentiating between athletic heart syndrome and HCM requires careful examination. ECG and echocardiograms may be…

Raman spectroscopy reveals spectroscopic changes in histologically normal retinas in a mouse model of alpha-synucleinopathy

USDA-ARS?s Scientific Manuscript database

The retina is an extension of the nervous system and is accessible for in vivo assessments. We have previously demonstrated changes in retinal function and pathology associated with scrapie, TME and BSE. The purpose of this work was to determine the utility of the retina to identify early CNS change...

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

PubMed

Heinz, A; Friedel, E

2014-05-01

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

Evaluation of chemotherapy response in patients with advanced head and neck cancer using [F-18]fluorodeoxyglucose positron emission tomography.

PubMed

Lowe, V J; Dunphy, F R; Varvares, M; Kim, H; Wittry, M; Dunphy, C H; Dunleavy, T; McDonough, E; Minster, J; Fletcher, J W; Boyd, J H

1997-12-01

[F-18]Fluorodeoxyglucose (FDG)-positron emission tomography (PET) can measure the metabolic activity of tissues; FDG-PET may be able to predict response to chemotherapy by identifying changes in tumor metabolism. Measurement of response to treatment may help improve survival in the management of advanced head and neck cancer. We evaluated this particular use of FDG-PET in patients participating in a neoadjuvant organ-preservation protocol using taxol and carboplatin and compared pathologic response after chemotherapy with changes in tumor metabolism measured by FDG-PET. Serial FDG-PET studies (n = 56) were performed in patients (n = 28) with stage III/IV head and neck cancer participating in a neoadjuvant organ-preservation protocol. The FDG-PET studies were performed before and after chemotherapy. All patients had tissue biopsies before and after chemotherapy. Patients were classified as pathologic complete response (PCR) or residual disease (RD) based on tissue biopsies. Visual analysis of PET scans was performed to identify patients with complete response by PET, and these findings were compared with pathology results. Metabolic changes were also evaluated using standardized uptake ratios (SUR) of FDG. The sensitivity and specificity of PET for residual cancer after therapy was 90% (19/21) and 83% (5/6), respectively. Two patients had initially negative biopsies and positive PET studies for persistent disease. Pathology review and rebiospy led to confirmation of the PET results in these cases, giving a sensitivity of 90% for initial tissue biopsy. In this preliminary analysis, FDG-PET was accurate in classifying response to chemotherapy in most patients. Fluorodeoxyglucose-PET may identify residual viable tumor when it is otherwise undetectable.

Pathology Associated with AAV Mediated Expression of Beta Amyloid or C100 in Adult Mouse Hippocampus and Cerebellum

PubMed Central

Drummond, Eleanor S.; Muhling, Jill; Martins, Ralph N.; Wijaya, Linda K.; Ehlert, Erich M.; Harvey, Alan R.

2013-01-01

Accumulation of beta amyloid (Aβ) in the brain is a primary feature of Alzheimer’s disease (AD) but the exact molecular mechanisms by which Aβ exerts its toxic actions are not yet entirely clear. We documented pathological changes 3 and 6 months after localised injection of recombinant, bi-cistronic adeno-associated viral vectors (rAAV2) expressing human Aβ40-GFP, Aβ42-GFP, C100-GFP or C100V717F-GFP into the hippocampus and cerebellum of 8 week old male mice. Injection of all rAAV2 vectors resulted in wide-spread transduction within the hippocampus and cerebellum, as shown by expression of transgene mRNA and GFP protein. Despite the lack of accumulation of Aβ protein after injection with AAV vectors, injection of rAAV2-Aβ42-GFP and rAAV2- C100V717F-GFP into the hippocampus resulted in significantly increased microgliosis and altered permeability of the blood brain barrier, the latter revealed by high levels of immunoglobulin G (IgG) around the injection site and the presence of IgG positive cells. In comparison, injection of rAAV2-Aβ40-GFP and rAAV2-C100-GFP into the hippocampus resulted in substantially less neuropathology. Injection of rAAV2 vectors into the cerebellum resulted in similar types of pathological changes, but to a lesser degree. The use of viral vectors to express different types of Aβ and C100 is a powerful technique with which to examine the direct in vivo consequences of Aβ expression in different regions of the mature nervous system and will allow experimentation and analysis of pathological AD-like changes in a broader range of species other than mouse. PMID:23516609

Changes in Gene Expression and Metabolism in the Testes of the Rat following Spinal Cord Injury

PubMed Central

Fortune, Ryan D.; Grill, Raymond J.; Beeton, Christine; Tanner, Mark; Huq, Redwan

2017-01-01

Abstract Spinal cord injury (SCI) results in devastating changes to almost all aspects of a patient's life. In addition to a permanent loss of sensory and motor function, males also will frequently exhibit a profound loss of fertility through poorly understood mechanisms. We demonstrate that SCI causes measureable pathology in the testis both acutely (24 h) and chronically up to 1.5 years post-injury, leading to loss in sperm motility and viability. SCI has been shown in humans and rats to induce leukocytospermia, with the presence of inflammatory cytokines, anti-sperm antibodies, and reactive oxygen species found within the ejaculate. Using messenger RNA and metabolomic assessments, we describe molecular and cellular changes that occur within the testis of adult rats over an acute to chronic time period. From 24 h, 72 h, 28 days, and 90 days post-SCI, the testis reveal a distinct time course of pathological events. The testis show an acute drop in normal sexual organ processes, including testosterone production, and establishment of a pro-inflammatory environment. This is followed by a subacute initiation of an innate immune response and loss of cell cycle regulation, possibly due to apoptosis within the seminiferous tubules. At 1.5 years post-SCI, there is a chronic low level immune response as evidenced by an elevation in T cells. These data suggest that SCI elicits a wide range of pathological processes within the testes, the actions of which are not restricted to the acute phase of injury but rather extend chronically, potentially through the lifetime of the subject. The multiplicity of these pathological events suggest a single therapeutic intervention is unlikely to be successful. PMID:27750479

Optical diagnostics based on elastic scattering: Recent clinical demonstrations with the Los Alamos Optical Biopsy System

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

Bigio, I.J.; Loree, T.R.; Mourant, J.

1993-08-01

A non-invasive diagnostic tool that could identify malignancy in situ and in real time would have a major impact on the detection and treatment of cancer. We have developed and are testing early prototypes of an optical biopsy system (OBS) for detection of cancer and other tissue pathologies. The OBS invokes a unique approach to optical diagnosis of tissue pathologies based on the elastic scattering properties, over a wide range of wavelengths, of the microscopic structure of the tissue. The use of elastic scattering as the key to optical tissue diagnostics in the OBS is based on the fact thatmore » many tissue pathologies, including a majority of cancer forms, manifest significant architectural changes at the cellular and sub-cellular level. Since the cellular components that cause elastic scattering have dimensions typically on the order of visible to near-IR wavelengths, the elastic (Mie) scattering properties will be strongly wavelength dependent. Thus, morphology and size changes can be expected to cause significant changes in an optical signature that is derived from the wavelength dependence of elastic scattering. The data acquisition and storage/display time with the OBS instrument is {approximately}1 second. Thus, in addition to the reduced invasiveness of this technique compared with current state-of-the-art methods (surgical biopsy and pathology analysis), the OBS offers the possibility of impressively faster diagnostic assessment. The OBS employs a small fiber-optic probe that is amenable to use with any endoscope, catheter or hypodermic, or to direct surface examination (e.g. as in skin cancer or cervical cancer). It has been tested in vitro on animal and human tissue samples, and clinical testing in vivo is currently in progress.« less

Noninvasive identification of bladder cancer with sub-surface backscattered light

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

Bigio, I.J.; Mourant, J.R.; Boyer, J.

1994-02-01

A non-invasive diagnostic tool that could identify malignancy in situ and in real time would have a major impact on the detection and treatment of cancer. We have developed and are testing early prototypes of an optical biopsy system (OBS) for detection of cancer and other tissue pathologies. The OBS invokes a unique approach to optical diagnosis of tissue pathologies based on the elastic scattering properties, over a wide range of wavelengths, of the microscopic structure of the tissue. Absorption bands in the tissue also add useful complexity to the spectral data collected. The use of elastic scattering as themore » key to optical tissue diagnostics in the OBS is based on the fact that many tissue pathologies, including a majority of cancer forms, manifest significant architectural changes at the cellular and sub-cellular level. Since the cellular components that cause elastic scattering have dimensions typically on the order of visible to near-IR wavelengths, the elastic (Mie) scattering properties will be strongly wavelength dependent. Thus, morphology and size changes can be expected to cause significant changes in an optical signature that is derived from the wavelength-dependence of elastic scattering as well as absorption. The data acquisition and storage/display time with the OBS instrument is {approximately}1 second. Thus, in addition to the reduced invasiveness of this technique compared with current state-of-the-art methods (surgical biopsy and pathology analysis), the OBS offers the possibility of impressively faster diagnostic assessment. The OBS employs a small fiber-optic probe that is amenable to use with any endoscope, catheter or hypodermic, or to direct surface examination (e.g., as in skin cancer or cervical cancer). We report here specifically on its potential application in the detection of bladder cancer.« less

Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease.

PubMed

Dean, Douglas C; Hurley, Samuel A; Kecskemeti, Steven R; O'Grady, J Patrick; Canda, Cristybelle; Davenport-Sis, Nancy J; Carlsson, Cynthia M; Zetterberg, Henrik; Blennow, Kaj; Asthana, Sanjay; Sager, Mark A; Johnson, Sterling C; Alexander, Andrew L; Bendlin, Barbara B

2017-01-01

The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including β-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas preferentially affected in AD. Furthermore, significant age-by-biomarker interactions were observed between myelin water fraction and phosphorylated tau 181/β-amyloid 42, suggesting that phosphorylated tau 181/β-amyloid 42 levels modulate age-related changes in myelin water fraction. These findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process. We expect that clarifying the nature of myelin damage in preclinical AD may be informative on the disease's course and lead to new markers of efficacy for prevention and treatment trials.

Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease

PubMed Central

Dean, Douglas C.; Hurley, Samuel A.; Kecskemeti, Steven R.; O’Grady, J. Patrick; Canda, Cristybelle; Davenport-Sis, Nancy J.; Carlsson, Cynthia M.; Zetterberg, Henrik; Blennow, Kaj; Asthana, Sanjay; Sager, Mark A.; Johnson, Sterling C.; Alexander, Andrew L.; Bendlin, Barbara B.

2016-01-01

IMPORTANCE The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. OBJECTIVE To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. DESIGN, SETTING, AND PARTICIPANTS Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including β-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. MAIN OUTCOMES AND MEASURES Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. RESULTS The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas preferentially affected in AD. Furthermore, significant age-by-biomarker interactions were observed between myelin water fraction and phosphorylated tau 181/β-amyloid 42, suggesting that phosphorylated tau 181/β-amyloid 42 levels modulate age-related changes in myelin water fraction. CONCLUSIONS AND RELEVANCE These findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process. We expect that clarifying the nature of myelin damage in preclinical AD may be informative on the disease’s course and lead to new markers of efficacy for prevention and treatment trials. PMID:27842175

Relationship between the Temporal Changes in Positron-Emission-Tomography-Imaging-Based Textural Features and Pathologic Response and Survival in Esophageal Cancer Patients.

PubMed

Yip, Stephen S F; Coroller, Thibaud P; Sanford, Nina N; Mamon, Harvey; Aerts, Hugo J W L; Berbeco, Ross I

2016-01-01

Although change in standardized uptake value (SUV) measures and PET-based textural features during treatment have shown promise in tumor response prediction, it is unclear which quantitative measure is the most predictive. We compared the relationship between PET-based features and pathologic response and overall survival with the SUV measures in esophageal cancer. Fifty-four esophageal cancer patients received PET/CT scans before and after chemoradiotherapy. Of these, 45 patients underwent surgery and were classified into complete, partial, and non-responders to the preoperative chemoradiation. SUVmax and SUVmean, two cooccurrence matrix (Entropy and Homogeneity), two run-length matrix (RLM) (high-gray-run emphasis and Short-run high-gray-run emphasis), and two size-zone matrix (high-gray-zone emphasis and short-zone high-gray emphasis) textures were computed. The relationship between the relative difference of each measure at different treatment time points and the pathologic response and overall survival was assessed using the area under the receiver-operating-characteristic curve (AUC) and Kaplan-Meier statistics, respectively. All Textures, except Homogeneity, were better related to pathologic response than SUVmax and SUVmean. Entropy was found to significantly distinguish non-responders from the complete (AUC = 0.79, p = 1.7 × 10(-4)) and partial (AUC = 0.71, p = 0.01) responders. Non-responders can also be significantly differentiated from partial and complete responders by the change in the run-length and size-zone matrix textures (AUC = 0.71-0.76, p ≤ 0.02). Homogeneity, SUVmax, and SUVmean failed to differentiate between any of the responders (AUC = 0.50-0.57, p ≥ 0.46). However, none of the measures were found to significantly distinguish between complete and partial responders with AUC <0.60 (p = 0.37). Median Entropy and RLM textures significantly discriminated patients with good and poor survival (log-rank p < 0.02), while all other textures and survival were poorly related (log-rank p > 0.25). For the patients studied, temporal changes in Entropy and all RLM were better correlated with pathological response and survival than the SUV measures. The hypothesis that these metrics can be used as clinical predictors of better patient outcomes will be tested in a larger patient dataset in the future.

[Morphological pathology of vessels in granulomatosis with polyangiitis (Wegener's disease)].

PubMed

Zerbino, D D; Zimba, E A

2015-01-01

to investigate the incidence of injuries in different vascular beds and the morphopathological changes in vessels in granulomatosis with polyangiitis. The morphopathological features of vascular injuries were investigated in 11 dead patients aged 16--74 years with granulomatosis with polyangiitis. Proliferative and destructive angiitis with predominant involvement of microcirculatory vessels and with development of necrosis-prone granulomas in their walls and perivascularly was established to underlie the clinical manifestations of granulomatosis with polyangiitis. The most typical localization of the pathologic process is the vessels of the upper respiratory tract, lungs, and kidneys. Cardiopulmonary and renal failures are causes of death in the majority of cases. It should be noted that the vessels of the heart, liver, and gastrointestinal tract are frequently involved in the pathological process. Vascular changes in these organs determine the clinical features of granulomatosis with polyangiitis and lead to a number of fatal complications. Granulomatosis with polyangiitis is a systemic disease with polymorphism of clinical manifestations, which requires in-depth analysis based on current precision patient examination methods, including a histopathological study.

Histopathologic changes in punctal stenosis.

PubMed

Port, Alexander D; Chen, Yao-Tseng; Lelli, Gary J

2013-01-01

To describe the pathologic changes in punctal stenosis by reporting the histopathologic findings in a series of punctoplasty specimens. Observational retrospective chart review. Electronic health records of all patients having punctoplasty over a 2-year period at an academic oculoplastic practice were examined. All patients whose records included pathology reports were entered into a database. Twenty-four patients, representing 30 eyes, had pathology records in the electronic health records. Patients were 75% women and had an average age of 65 (19-88) years. Associated conditions included blepharitis (71%), dry eye syndrome, or Meibomian gland dysfunction (63%). Histopathologic examination demonstrated chronic inflammation in 11 eyes (36.7%), fibrosis in 7 eyes (23.3%), chronic inflammation and fibrosis in 4 eyes (13.3%), squamous metaplasia in 3 eyes (10%), normal conjunctival mucosa in 3 eyes (10%), and Actinomyces israelii canaliculitis in 2 eyes (6.7%). Nearly all histopathologic specimens revealed findings consistent with inflammation, fibrosis, or both. These findings provide evidence to support the hypothesis that the many etiologic causes of punctal stenosis are linked by a common pathophysiologic mechanism involving inflammation.

Matrix metalloproteinases-2 and -9 in Campylobacter jejuni-induced paralytic neuropathy resembling Guillain-Barré syndrome in chickens.

PubMed

Nyati, Kishan Kumar; Prasad, Kashi Nath; Agrawal, Vinita; Husain, Nuzhat

2017-10-01

Inflammation in Guillain-Barré syndrome (GBS) is manifested by changes in matrix metalloproteinase (MMP) and pro-inflammatory cytokine expression. We investigated the expression of MMP-2, -9 and TNF-α and correlated it with pathological changes in sciatic nerve tissue from Campylobacter jejuni-induced chicken model for GBS. Campylobacter jejuni and placebo were fed to chickens and assessed for disease symptoms. Sciatic nerves were examined by histopathology and immunohistochemistry. Expressions of MMPs and TNF-α, were determined by real-time PCR, and activities of MMPs by zymography. Diarrhea developed in 73.3% chickens after infection and 60.0% of them developed GBS like neuropathy. Pathology in sciatic nerves showed perinodal and/or patchy demyelination, perivascular focal lymphocytic infiltration and myelin swelling on 10th- 20th post infection day (PID). MMP-2, -9 and TNF-α were up-regulated in progressive phase of the disease. Enhanced MMP-2, -9 and TNF-α production in progressive phase correlated with sciatic nerve pathology in C. jejuni-induced GBS chicken model. Copyright © 2017 Elsevier Ltd. All rights reserved.

The transition of renal histopathology after immunosuppressive therapy in a woman with renal limited ANCA-associated vasculitis: a case report and literature review.

PubMed

Li, Xiang-Yang; Liang, Ying-Shan; Pai, Pearl

2016-01-01

The kidneys are frequently involved in antineutrophil cytoplasmic autoantibody (ANCA) associated small-vessel vasculitis (AASVV). The pathological hallmark of ANCA-associated glomerulonephritis (AAGN) is a pauci-immune necrotising crescentic glomerulonephritis. The histopathology of AAGN may change during the course of the disease as a consequence of immunosuppressive therapy. Herein, we report the pathological evolution of a case of AAGN. We report a female presented with renal-limited AASVV, hypocomplementemia and nephrotic syndrome. The first renal biopsy revealed "crescentic" changes at presentation, but after treatment with immunosuppressive treatment, a second renal biopsy four years later showed "mixed" changes of AAGN and immune complex deposition mimicking a mesangial proliferative glomerulonephritis. A literature review was undertaken in order to understand these transformations and factors which determine the pathological transitions. AAGN is commonly described as a pauci-immune necrotising crescentic glomerulonephritis, but immune complex depositions have been frequently identified under electronic microscopy and is associated with greater levels of proteinuria. Acute lesions such as fibrinoid necrosis or glomerular crescent may completely disappear or reduce significantly after immunosuppressive therapy, but chronic changes may increase over time. Based on our review and the illustration of this case, the initial histopathology of an AAGN and its active fibrinoid necrosis and cellular glomerular crescent may disappear or resolve after immunosuppressive therapy with resulting non-distinctive feature. Understanding the transition may facilitate the clinical diagnosis and provide further insight into this disease.

Emergence of pathogenic and multiple-antibiotic-resistant Macrococcus caseolyticus in commercial broiler chickens.

PubMed

Li, Gen; Du, Xusheng; Zhou, Defang; Li, Chengui; Huang, Libo; Zheng, Qiankun; Cheng, Ziqiang

2018-05-25

Macrococcus caseolyticus is generally considered to be a non-pathogenic bacterium that does not cause human or animal diseases. However, recently, a strain of M. caseolyticus (SDLY strain) that causes high mortality rates was isolated from commercial broiler chickens in China. The main pathological changes caused by SDLY included caseous exudation in cranial cavities, inflammatory infiltration, haemorrhages and multifocal necrosis in various organs. The whole genome of the SDLY strain was sequenced and was compared with that of the non-pathogenic JCSC5402 strain of M. caseolyticus. The results showed that the SDLY strain harboured a large quantity of mutations, antibiotic resistance genes and numerous insertions and deletions of virulence genes. In particular, among the inserted genes, there is a cluster of eight connected genes associated with the synthesis of capsular polysaccharide. This cluster encodes a transferase and capsular polysaccharide synthase, promotes the formation of capsules and causes changes in pathogenicity. Electron microscopy revealed a distinct capsule surrounding the SDLY strain. The pathogenicity test showed that the SDLY strain could cause significant clinical symptoms and pathological changes in both SPF chickens and mice. In addition, these clinical symptoms and pathological changes were the same as those observed in field cases. Furthermore, the anti-microbial susceptibility test demonstrated that the SDLY strain exhibits multiple-antibiotic resistance. The emergence of pathogenic M. caseolyticus indicates that more attention should be paid to the effects of this micro-organism on both poultry and public health. © 2018 Blackwell Verlag GmbH.

Sulforaphane Attenuation of Type 2 Diabetes-Induced Aortic Damage Was Associated with the Upregulation of Nrf2 Expression and Function

PubMed Central

Wang, Yonggang; Zhang, Zhiguo; Sun, Wanqing; Tan, Yi; Liu, Yucheng; Zheng, Yang; Liu, Quan; Cai, Lu; Sun, Jian

2014-01-01

Type 2 diabetes mellitus (T2DM) significantly increases risk for vascular complications. Diabetes-induced aorta pathological changes are predominantly attributed to oxidative stress. Nuclear factor E2-related factor-2 (Nrf2) is a transcription factor orchestrating antioxidant and cytoprotective responses to oxidative stress. Sulforaphane protects against oxidative damage by increasing Nrf2 expression and its downstream target genes. Here we explored the protective effect of sulforaphane on T2DM-induced aortic pathogenic changes in C57BL/6J mice which were fed with high-fat diet for 3 months, followed by a treatment with streptozotocin at 100 mg/kg body weight. Diabetic and nondiabetic mice were randomly divided into groups with and without 4-month sulforaphane treatment. Aorta of T2DM mice exhibited significant increases in the wall thickness and structural derangement, along with significant increases in fibrosis (connective tissue growth factor and transforming growth factor), inflammation (tumor necrosis factor-α and vascular cell adhesion molecule 1), oxidative/nitrative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal), apoptosis, and cell proliferation. However, these pathological changes were significantly attenuated by sulforaphane treatment that was associated with a significant upregulation of Nrf2 expression and function. These results suggest that sulforaphane is able to upregulate aortic Nrf2 expression and function and to protect the aorta from T2DM-induced pathological changes. PMID:24707343

Spatiotemporal variations in gene expression, histology and biomechanics in an ovine model of tendinopathy

PubMed Central

Blaker, Carina; Clarke, Elizabeth; Jeffcott, Leo; Little, Christopher

2017-01-01

Flexor tendinopathy is a common problem affecting humans and animals. Tendon healing is poorly understood and the outcomes of conservative and surgical management are often suboptimal. While often considered a localized injury, recent evidence indicates that in the short term, tendinopathic changes are distributed widely throughout the tendon, remote from the lesion itself. Whether these changes persist throughout healing is unknown. The aim of this study was to document gene expression, histopathological and biomechanical changes that occur throughout the superficial digital flexor tendon (SDFT) up to 16 weeks post-injury, using an ovine surgical model of tendinopathy. Partial tendon transection was associated with decreased gene expression for aggrecan, decorin, fibromodulin, tissue inhibitors of metalloproteinases (TIMPS 1, 2 and 3), collagen I and collagen II. Gene expression for collagen III, lumican and matrix metalloproteinase 13 (MMP13) increased locally around the lesion site. Expression of collagen III and MMP13 decreased with time, but compared to controls, collagen III, MMP13 and lumican expression remained regionally high throughout the study. An increase in TIMP3 was observed over time. Histologically, operated tendons had higher pathology scores than controls, especially around the injured region. A chondroid phenotype was observed with increased cellular rounding and marked proteoglycan accumulation which only partially improved with time. Biomechanically, partial tendon transection resulted in a localized decrease in elastic modulus (in compression) but only at 8 weeks postoperatively. This study improves our understanding of tendon healing, demonstrating an early ‘peak’ in pathology characterized by altered gene expression and notable histopathological changes. Many of these pathological changes become more localized to the region of injury during healing. Collagen III and MMP13 expression levels remained high close to the lesion throughout the study and may reflect the production of tendon tissue with suboptimal biomechanical properties. Further studies evaluating the long-term response of tendon to injury (6–12 months) are warranted to provide additional information on tendon healing and provide further understanding of the mechanisms underlying the pathology observed in this study. PMID:29023489

Exercise training improves obesity-related lymphatic dysfunction.

PubMed

Hespe, Geoffrey E; Kataru, Raghu P; Savetsky, Ira L; García Nores, Gabriela D; Torrisi, Jeremy S; Nitti, Matthew D; Gardenier, Jason C; Zhou, Jie; Yu, Jessie Z; Jones, Lee W; Mehrara, Babak J

2016-08-01

Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P < 0.01). Aerobic exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti-inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic specific genes, including VEGFR-3 and Prox1. Taken together, our findings suggest that obesity impairs lymphatic function via multiple mechanisms and that these pathological changes can be reversed, in part, with aerobic exercise, independent of weight loss. In addition, our study shows that obesity-induced lymphatic endothelial cell gene expression changes are reversible with behavioural modifications. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Should centralized histopathological review in penile cancer be the global standard?

PubMed

Tang, Vincent; Clarke, Laurence; Gall, Zara; Shanks, Jonathan H; Nonaka, Daisuke; Parr, Nigel J; Elliott, P Anthony; Clarke, Noel W; Ramani, Vijay; Lau, Maurice W; Sangar, Vijay K

2014-09-01

To assess the role of centralized pathological review in penile cancer management. Newly diagnosed squamous cell carcinomas (SCC) of the penis, including squamous cell carcinoma in situ (CIS), from biopsy specimens were referred from 15 centres to the regional supra-network multidisciplinary team (Sn-MDT) between 1 January 2008 and 30 March 2011. Biopsy histology reports and slides from the respective referring hospitals were reviewed by the Sn-MDT pathologists. The biopsy specimens' histological type, grade and stage reported by the Sn-MDT pathologist were compared with those given in the referring hospital pathology report, as well as with definitive surgery histology. Any changes in histological diagnosis were sub-divided into critical changes (i.e. those that could alter management) and non-critical changes (i.e. those that would not affect management). A total of 155 cases of squamous cell carcinoma or CIS of the penis were referred from 15 different centres in North-West England. After review by the Sn-MDT, the histological diagnosis was changed in 31% of cases and this difference was statistically significant. A total of 60.4% of the changes were deemed to be critical changes that resulted in a significant change in management. When comparing the biopsy histology reported by the Sn-MDT with the final histology from the definitive surgical specimens, a good correlation was generally found. In the present study a significant proportion of penile cancer histology reports were revised after review by the Sn-MDT. Many of these changes altered patient management. The present study shows that accurate pathological diagnosis plays a crucial role in determining the correct treatment and maximizing the potential for good clinical outcomes in penile cancer. In the case of histopathology, centralization has increased exposure to penile cancer and thereby increased diagnostic accuracy, and should therefore be considered the 'gold standard'. © 2013 The Authors. BJU International © 2013 BJU International.

Analysis and Implementation of Methodologies for the Monitoring of Changes in Eye Fundus Images

NASA Astrophysics Data System (ADS)

Gelroth, A.; Rodríguez, D.; Salvatelli, A.; Drozdowicz, B.; Bizai, G.

2011-12-01

We present a support system for changes detection in fundus images of the same patient taken at different time intervals. This process is useful for monitoring pathologies lasting for long periods of time, as are usually the ophthalmologic. We propose a flow of preprocessing, processing and postprocessing applied to a set of images selected from a public database, presenting pathological advances. A test interface was developed designed to select the images to be compared in order to apply the different methods developed and to display the results. We measure the system performance in terms of sensitivity, specificity and computation times. We have obtained good results, higher than 84% for the first two parameters and processing times lower than 3 seconds for 512x512 pixel images. For the specific case of detection of changes associated with bleeding, the system responds with sensitivity and specificity over 98%.

Histopathological changes in Wistar albino rats exposed to aqueous extract of unripe Carica papaya.

PubMed

Oduola, Taofeeq; Bello, Ibrahim; Idowu, Thomas; Avwioro, Godwin; Adeosun, Ganiyu; Olatubosun, Luqman

2010-05-01

Exposure of animals to xenobiotics may or may not trigger adverse response at cellular levels. Aqueous extract of unripe Carica papaya is consumed by sickle cell patients as antisickling agent in Western Nigeria. This study was undertaken to investigate the effects of Carica papaya on certain organs in Wister albino rats exposed to aqueous extract of unripe Carica papaya. Different doses of aqueous extract of unripe Carica papaya were administered orally daily for 42 days to six groups of rats. At the end of exposure, the animals were sacrificed and tissue sections were prepared from livers, kidneys, hearts and small intestines using standard techniques. Histopathological results showed that no pathological changes were observed in tissue sections of experimental animals when compared with tissue sections of the same organs in control animals. No pathological changes were elicited in the organs of rats exposed to aqueous extract of unripe Carica papaya.

Functional Network Disruption in the Degenerative Dementias

PubMed Central

Pievani, Michela; de Haan, Willem; Wu, Tao; Seeley, William W; Frisoni, Giovanni B

2011-01-01

Despite considerable advances toward understanding the molecular pathophysiology of the neurodegenerative dementias, the mechanisms linking molecular changes to neuropathology and the latter to clinical symptoms remain largely obscure. Connectivity is a distinctive feature of the brain and the integrity of functional network dynamics is critical for normal functioning. A better understanding of network disruption in the neurodegenerative dementias may help bridge the gap between molecular changes, pathology and symptoms. Recent findings on functional network disruption as assessed with “resting-state” or intrinsic connectivity fMRI and EEG/MEG have shown distinct patterns of network disruption across the major neurodegenerative diseases. These network abnormalities are relatively specific to the clinical syndromes, and in Alzheimer's disease and frontotemporal dementia network disruption tracks the pattern of pathological changes. These findings may have a practical impact on diagnostic accuracy, allowing earlier detection of neurodegenerative diseases even at the pre-symptomatic stage, and tracking of disease progression. PMID:21778116

Molecular bases of circadian rhythmicity in renal physiology and pathology

PubMed Central

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

2013-01-01

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

Perceptions of Unprofessional Attitudes and Behaviors: Implications for Faculty Role Modeling and Teaching Professionalism During Pathology Residency.

PubMed

Brissette, Mark D; Johnson, Kristen A; Raciti, Patricia M; McCloskey, Cindy B; Gratzinger, Dita A; Conran, Richard Michael; Domen, Ronald E; Hoffman, Robert D; Post, Miriam D; Roberts, Cory Anthony; Rojiani, Amyn M; Powell, Suzanne Zein-Eldin

2017-10-01

- Changes occurring in medicine have raised issues about medical professionalism. Professionalism is included in the Core Competencies and Milestones for all pathology residents. Previous studies have looked at resident professionalism attitudes and behaviors in primary care but none have looked specifically at pathology. - To examine behavior and attitudes toward professionalism within pathology and to determine how professionalism is taught in residency programs. - Surveys were sent to all College of American Pathologists junior members and all pathology residency program directors, and responses were compared. - Although no single behavior received the same professionalism rating among residents and program directors, both groups identified the same behaviors as being the most unprofessional: posting identifiable patient information or case images to social media, making a disparaging comment about a physician colleague or member of the support staff on social media or in a public hospital space, and missing work without reporting the time off. Faculty were observed displaying most of these behaviors as often or more often than residents by both groups. The most common means to teach professionalism in pathology residencies is providing feedback as situations arise and teaching by example. Age differences were found within each group and between groups for observed behaviors and attitudes. - As teaching by example was identified as a common educational method, faculty must be aware of the role their behavior and attitudes have in shaping resident behavior and attitudes. These results suggest a need for additional resources to teach professionalism during pathology residency.

The pathology and medicolegal aspects of sexual activity.

PubMed

Eckert, W G; Katchis, S; Donovan, W

1991-03-01

The pathology of injury and its complications related to sexual activities has changed remarkably when compared with that of the past, which usually involved assaults or murders of female victims of varying ages, with moderate to serve beatings that may have accidentally resulted in the victim's death. Serial murderers, serial rapists, and molesters of both boys and girls have become much more prevalent in the last two decades in the United States. Unorthodox sexual behavior, such as "fisting," has increased in frequency, as has sexual violence related to cults, such as satanism. All of these present many challenges to medicolegal investigators. This report describes general and specific pathological sexual activities and injuries, some characteristics and methods of the perpetrators, and some specific cases as examples.

Diagnostic change and personality stability following functional restoration treatment in chronic low back pain patients.

PubMed

Vittengl, J R; Clark, L A; Owen-Salters, E; Gatchel, R J

1999-03-01

This study examined personality pathology in a group of patients with chronic low back pain (CLBP) using both diagnostic interviews and dimensional self-report instruments. A group of CLBP patients (N = 125) was assessed before functional restoration treatment and compared with a matched normal comparison group (N = 75). The CLBP group evidenced broad personality pathology in all assessment modes pretreatment relative to the normal comparison sample. In addition, two subsamples of CLBP patients (n = 49 and n = 56) were assessed after treatment. Reductions in personality pathology between pre- and posttreatment assessments were more pronounced for diagnostic interview than dimensional self-report assessments. These results are discussed in the context of personality assessment and CLBP.

Innovations in teaching plant pathology.

PubMed

Schumann, G L

2003-01-01

The teaching environment for plant pathology is changing in both positive and negative ways. Teaching expectations are increasing and resources are decreasing, but recent educational research and instructional technology offer new approaches to meet these challenges. Plant pathologists are teaching courses that may attract new students to the discipline or at least improve agricultural awareness. The Internet offers rapid access to information and images for both students and instructors. Instructional technology provides new tools for classroom presentations, communication with students, reaching new audiences, and distance learning, but using these new tools to enhance learning requires skilled and creative instructors. In the past, many plant pathology instructors worked in relative isolation, but new communication technologies and publishing opportunities for teaching scholarship should improve the sharing of instructional resources and methods.

Aetiology and pathology of otitis media with effusion in adult life.

PubMed

Mills, R; Hathorn, I

2016-05-01

To gather and analyse information concerning the aetiology and pathology of otitis media with effusion in adults. A review of the English language literature from 1970 to the present was conducted. The available evidence suggests that otitis media with effusion in adult life is best viewed as a syndrome with a number of causes, including: infiltration of the eustachian tube by nasopharyngeal carcinoma and other local malignancies; changes in the middle ear and eustachian tube induced by radiotherapy; and systemic disease. There is now a body of evidence specifically related to the aetiology and pathology of otitis media with effusion in adult life. However, further research is required to fill in the gaps in our knowledge and understanding of this condition.

[Advance of Forensic Research in Insulin Poisoning].

PubMed

Tong, F; Liang, Y; Shi, Q; Zhang, L; L, W H; Zhou, Y W

2017-02-01

Insulin as a common clinical hypoglycemic agent can effectively control serves to lower the concentration of blood glucose. However, insulin overdose can lead to death. In the whole fatal cases of insulin overdose, medical accident is the most common, followed by suicide. Though insulin homicide is extremely rare, it deserves great attention. Though there are some researches about insulin poisoning on forensic toxicology and pathology, it is still a difficult task in forensic practice. In this paper, the mechanism of death, pathological changes, detection methods and diagnose criteria of insulin overdose will be discussed in the view of forensic toxicology and pathology. We hope that this paper could enhance relative knowledges of insulin poisoning for medical examiners. Copyright© by the Editorial Department of Journal of Forensic Medicine.

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

PubMed

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

2017-05-01

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

Diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) determination in normal and pathological fetal kidneys.

PubMed

Chaumoitre, K; Colavolpe, N; Shojai, R; Sarran, A; D' Ercole, C; Panuel, M

2007-01-01

To assess the use of diffusion-weighted magnetic resonance imaging (DW-MRI) in the evaluation of the fetal kidney and to estimate age-dependent changes in the apparent diffusion coefficient (ADC) of normal and pathological fetal kidneys. DW-MRI was performed on a 1.5-T machine at 23-38 gestational weeks in 51 pregnant women in whom the fetal kidneys were normal and in 10 whose fetuses had renal pathology (three with suspected nephropathy, three with renal tract dilatation, one with unilateral renal venous thrombosis, and three with twin-twin transfusion syndrome (TTTS)). The ADC was measured in an approximately 1-cm2 region of interest within the renal parenchyma. ADC values in normal renal parenchyma ranged from 1.1 to 1.8 10(-3) mm2 s-1. There was no significant age-dependent change in the ADC of normal kidneys. In cases of nephropathy, the ADC value was not always pathological but an ADC map could show abnormal findings. In cases of dilatation, the ADC value was difficult to determine when the dilatation was huge. In cases of TTTS, the ADC of the donor twin was higher than that of the recipient twin and the difference seemed to be related to the severity of the syndrome. Evaluation of the ADC for fetal kidneys is feasible. Fetal measurement of the ADC value and ADC maps may be useful tools with which to explore the fetal kidney when used in conjunction with current methods. DW-MR images, ADC value and ADC map seem to be useful in cases of suspected nephropathy (hyperechoic kidneys), dilated kidney and vascular pathology (renal venous thrombosis, TTTS). Copyright (c) 2006 ISUOG.

Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis.

PubMed

DePianto, Daryle J; Chandriani, Sanjay; Abbas, Alexander R; Jia, Guiquan; N'Diaye, Elsa N; Caplazi, Patrick; Kauder, Steven E; Biswas, Sabyasachi; Karnik, Satyajit K; Ha, Connie; Modrusan, Zora; Matthay, Michael A; Kukreja, Jasleen; Collard, Harold R; Egen, Jackson G; Wolters, Paul J; Arron, Joseph R

2015-01-01

There is microscopic spatial and temporal heterogeneity of pathological changes in idiopathic pulmonary fibrosis (IPF) lung tissue, which may relate to heterogeneity in pathophysiological mediators of disease and clinical progression. We assessed relationships between gene expression patterns, pathological features, and systemic biomarkers to identify biomarkers that reflect the aggregate disease burden in patients with IPF. Gene expression microarrays (N=40 IPF; 8 controls) and immunohistochemical analyses (N=22 IPF; 8 controls) of lung biopsies. Clinical characterisation and blood biomarker levels of MMP3 and CXCL13 in a separate cohort of patients with IPF (N=80). 2940 genes were significantly differentially expressed between IPF and control samples (|fold change| >1.5, p<0.05). Two clusters of co-regulated genes related to bronchiolar epithelium or lymphoid aggregates exhibited substantial heterogeneity within the IPF population. Gene expression in bronchiolar and lymphoid clusters corresponded to the extent of bronchiolisation and lymphoid aggregates determined by immunohistochemistry in adjacent tissue sections. Elevated serum levels of MMP3, encoded in the bronchiolar cluster, and CXCL13, encoded in the lymphoid cluster, corresponded to disease severity and shortened survival time (p<10(-7) for MMP3 and p<10(-5) for CXCL13; Cox proportional hazards model). Microscopic pathological heterogeneity in IPF lung tissue corresponds to specific gene expression patterns related to bronchiolisation and lymphoid aggregates. MMP3 and CXCL13 are systemic biomarkers that reflect the aggregate burden of these pathological features across total lung tissue. These biomarkers may have clinical utility as prognostic and/or surrogate biomarkers of disease activity in interventional studies in IPF. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

PubMed Central

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

2017-01-01

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

A systematic review of definitions and classification systems of adjacent segment pathology.

PubMed

Kraemer, Paul; Fehlings, Michael G; Hashimoto, Robin; Lee, Michael J; Anderson, Paul A; Chapman, Jens R; Raich, Annie; Norvell, Daniel C

2012-10-15

Systematic review. To undertake a systematic review to determine how "adjacent segment degeneration," "adjacent segment disease," or clinical pathological processes that serve as surrogates for adjacent segment pathology are classified and defined in the peer-reviewed literature. Adjacent segment degeneration and adjacent segment disease are terms referring to degenerative changes known to occur after reconstructive spine surgery, most commonly at an immediately adjacent functional spinal unit. These can include disc degeneration, instability, spinal stenosis, facet degeneration, and deformity. The true incidence and clinical impact of degenerative changes at the adjacent segment is unclear because there is lack of a universally accepted classification system that rigorously addresses clinical and radiological issues. A systematic review of the English language literature was undertaken and articles were classified using the Grades of Recommendation Assessment, Development, and Evaluation criteria. RESULTS.: Seven classification systems of spinal degeneration, including degeneration at the adjacent segment, were identified. None have been evaluated for reliability or validity specific to patients with degeneration at the adjacent segment. The ways in which terms related to adjacent segment "degeneration" or "disease" are defined in the peer-reviewed literature are highly variable. On the basis of the systematic review presented in this article, no formal classification system for either cervical or thoracolumbar adjacent segment disorders currently exists. No recommendations regarding the use of current classification of degeneration at any segments can be made based on the available literature. A new comprehensive definition for adjacent segment pathology (ASP, the now preferred terminology) has been proposed in this Focus Issue, which reflects the diverse pathology observed at functional spinal units adjacent to previous spinal reconstruction and balances detailed stratification with clinical utility. A comprehensive classification system is being developed through expert opinion and will require validation as well as peer review. Strength of Statement: Strong.

Antioxidants and the Integrity of Ocular Tissues

PubMed Central

Cabrera, Marcela P.; Chihuailaf, Ricardo H.

2011-01-01

Oxygen-derived free radicals are normally generated in many pathways. These radicals can interact with various cellular components and induce cell injury. When free radicals exceed the antioxidant capacity, cell injury causes diverse pathologic changes in the organs. The imbalance between the generation of free radicals and antioxidant defence is known as oxidative stress. The eye can suffer the effect of oxidative damage due to the etiopathogenesis of some pathological changes related to oxidative stress. This paper reviews the role of oxidative stress in the onset and progression of damage in different eye structures, the involvement of the antioxidant network in protecting and maintaining the homeostasis of this organ, and the potential assessment methodologies used in research and in some cases in clinical practice. PMID:21789267

Adequacy of pathology resident training for employment: a survey report from the Future of Pathology Task Group.

PubMed

Kass, Mary E; Crawford, James M; Bennett, Betsy; Cox, Teresa M; Grimes, Margaret M; LiVolsi, Virginia; Fletcher, Christopher D M; Wilkinson, David S

2007-04-01

The recent change in accreditation requirements for anatomic pathology and clinical pathology residency training from 5 to 4 years and the rapid advances in technologies for pathology services have sparked a renewed debate over the adequacy of pathology residency training. In particular, perceived deficiencies in training have been declared from a variety of sources, both in the form of recent editorial opinions and from surveys of community hospital pathologist employers in 1998, 2003, and 2005 by Dr Richard Horowitz. To obtain more comprehensive data on the perceptions of strengths and weaknesses in pathology residency training. The College of American Pathologists conducted a survey of potential pathology employers (senior College of American Pathologists members, members designated as head of group, and members of the Association of Directors of Anatomic and Surgical Pathology). Also surveyed were recent graduates of pathology residency programs, who were identified as being junior members of the College of American Pathologists, were recent recipients of certification from the American Board of Pathology, or were contacted through their directors of pathology residency programs. There were 559 employer respondents, of whom 384 were responsible for hiring and/or supervising new pathologists. There were 247 recent graduates of pathology residency training programs who responded. From the employers' standpoint, the majority expressed overall satisfaction with recent graduates, but almost one third of employers indicated that new hires had a major deficiency in a critical area. Specific areas of deficiency were clinical laboratory management and judgment in ordering special stains and studies. In addition, one half of employers agreed that more guidance and support for newly trained pathologists is needed now than was required 10 years ago. Academic employers generally were more satisfied than private sector employers. Newly trained pathologists did not appear to be inappropriately overconfident in their abilities. In addition, their perceptions of those specific areas in which they are most and least prepared are very similar to the ratings provided by employers. On average, newly trained pathologists' ratings of their own preparedness are highest for specific aspects of general pathology and anatomic pathology, and lowest for specific aspects of clinical pathology and administration. In selecting new pathologists, employers perceived medical knowledge and interpersonal skills as the most important discriminating applicant characteristics. When new employees were asked why they thought they were offered their position, the discriminating qualifications cited most often were academic background and training, as well as completion of a fellowship and subspecialty training. It is our hope that the results of this survey can be used as input for further discussions and recommendations for training of pathology residents so as to further advance the ability of pathologists to provide quality patient care upon their graduation from training.

[X-ray endoscopic semiotics and diagnostic algorithm of radiation studies of preneoplastic gastric mucosa changes].

PubMed

Akberov, R F; Gorshkov, A N

1997-01-01

The X-ray endoscopic semiotics of precancerous gastric mucosal changes (epithelial dysplasia, intestinal epithelial rearrangement) was examined by the results of 1574 gastric examination. A diagnostic algorithm was developed for radiation studies in the diagnosis of the above pathology.

Greater magnitude tibiofemoral contact forces are associated with reduced prevalence of osteochondral pathologies 2-3 years following anterior cruciate ligament reconstruction.

PubMed

Saxby, David John; Bryant, Adam L; Van Ginckel, Ans; Wang, Yuanyuan; Wang, Xinyang; Modenese, Luca; Gerus, Pauline; Konrath, Jason M; Fortin, Karine; Wrigley, Tim V; Bennell, Kim L; Cicuttini, Flavia M; Vertullo, Christopher; Feller, Julian A; Whitehead, Tim; Gallie, Price; Lloyd, David G

2018-06-07

External loading of osteoarthritic and healthy knees correlates with current and future osteochondral tissue state. These relationships have not been examined following anterior cruciate ligament reconstruction. We hypothesised greater magnitude tibiofemoral contact forces were related to increased prevalence of osteochondral pathologies, and these relationships were exacerbated by concomitant meniscal injury. This was a cross-sectional study of 100 individuals (29.7 ± 6.5 years, 78.1 ± 14.4 kg) examined 2-3 years following hamstring tendon anterior cruciate ligament reconstruction. Thirty-eight participants had concurrent meniscal pathology (30.6 ± 6.6 years, 83.3 ± 14.3 kg), which included treated and untreated meniscal injury, and 62 participants (29.8 ± 6.4 years, 74.9 ± 13.3 kg) were free of meniscal pathology. Magnetic resonance imaging of reconstructed knees was used to assess prevalence of tibiofemoral osteochondral pathologies (i.e., cartilage defects and bone marrow lesions). A calibrated electromyogram-driven neuromusculoskeletal model was used to predict medial and lateral tibiofemoral compartment contact forces from gait analysis data. Relationships between contact forces and osteochondral pathology prevalence were assessed using logistic regression models. In patients with reconstructed knees free from meniscal pathology, greater medial contact forces were related to reduced prevalence of medial cartilage defects (odds ratio (OR) = 0.7, Wald χ 2 (2) = 7.9, 95% confidence interval (CI) = 0.50-95, p = 0.02) and medial bone marrow lesions (OR = 0.8, Wald χ 2 (2) = 4.2, 95% CI = 0.7-0.99, p = 0.04). No significant relationships were found in lateral compartments. In reconstructed knees with concurrent meniscal pathology, no relationships were found between contact forces and osteochondral pathologies. In patients with reconstructed knees free from meniscal pathology, increased contact forces were associated with fewer cartilage defects and bone marrow lesions in medial, but not, lateral tibiofemoral compartments. No significant relationships were found between contact forces and osteochondral pathologies in reconstructed knees with meniscal pathology for any tibiofemoral compartment. Future studies should focus on determining longitudinal effects of contact forces and changes in osteochondral pathologies. IV.

Giovanni Battista Morgagni (1682-1771): his anatomic majesty's contributions to the neurosciences.

PubMed

Tubbs, R Shane; Steck, Dominik T; Mortazavi, Martin M; Shoja, Mohammadali M; Loukas, Marios; Cohen-Gadol, Aaron A

2012-07-01

Giovanni Battista Morgagni is considered the Father of Pathology and contributed much to our early understanding of neuropathology. For example, he introduced the concept that diagnosis, prognosis, and treatment of disease must be based on an exact understanding of the pathologic changes in anatomic structures. Additionally, he contributed to what would become the discipline of neurosurgery and, for example, performed trepanation for head trauma. It is the contributions of such early pioneers as Morgagni that our current understanding of the neurosciences is based.

Risk Factors for Discharge from the Army with a Permanent Disability

DTIC Science & Technology

2008-07-01

U.S. population) and concurrent increased BMI and higher body fat among Army recruits, or it could reflect changes in occupational exposures in the...722.1 Displacement of Thoracic or Lumbar Intervertebral Disc w/o Myelopathy 613 2.45% 733.1 Pathological Fracture 530 2.11% * Percents are given...Percent of total* 414.0 Coronary Atherosclerosis 228 17.97% 733.1 Pathological Fracture 121 9.54% 443.0 Raynaud’s Syndrome 75 5.91% 729.5 Pain in

[Psychophysiological aspects of the problem of narcotic dependency].

PubMed

Tursunkhodzhaev, M Kh; Tursunkhodzhaeva, L A

2002-01-01

An attempt has been made at analyzing mechanisms of formation of addiction to narcotics from the standpoint of a systemic approach to a functional organization of psychic activity. A model is proposed of the pathological functional system as the basis of narcodependence, which combines processes of two adjoining levels--those of psychic activity and of higher nervous activity. It is suggested that pathological hyperactivity of the functional structure maintaining the need for a change in the emotional state might be the basis of addiction to narcotic drugs.

[Free radicals in the origin and clinical manifestation of Down's syndrome].

PubMed

Arbuzova, S B

1996-01-01

The high level of free radicals and antioxidant protection disbalancing cause the chromosome nondisjunction in meiosis, appearance of trisomy 21 and fetuses with Down's syndrome, age-dependent pathology, of parent's mosaic clone, clinical manifestations of the syndrome, diseases in relatives, recurrent cases of trisomy 21. The comparative analysis of clinical traits of Down's syndrome and pathological changes in families with after-effects of radiation exposure was carried out. The factors causing an increase in the level of free radicals were considered.

Apoptosis: a basic pathological reaction of injured neonatal muscle.

PubMed

Fidziańska, A; Kamińska, A

1991-01-01

A light and electron microscopic study of immature muscle cell degeneration induced by bupivacaine (BPVC) was performed. The pattern of muscle cell death is related to muscle maturity; in newborn rats, cell death has the morphology of apoptosis, whereas in the older animals muscle cell death resembles cell necrosis and the ultrastructural feature of these changes are essentially the same as those described in adult muscle. The ability to undergo apoptosis in response to a pathological stimulus is a common effector mechanism of immature muscle.

The Electrophysiological Phenomenon of Alzheimer's Disease: A Psychopathology Theory.

PubMed

Holston, Ezra C

2015-08-01

The current understanding of Alzheimer's disease (AD) is based on the Aβ and tau pathology and the resulting neuropathological changes, which are associated with manifested clinical symptoms. However, electrophysiological brain changes may provide a more expansive understanding of AD. Hence, the objective of this systematic review is to propose a theory about the electrophysiological phenomenon of Alzheimer's disease (EPAD). The review of literature resulted from an extensive search of PubMed and MEDLINE databases. One-hundred articles were purposively selected. They provided an understanding of the concepts establishing the theory of EPAD (neuropathological changes, neurochemical changes, metabolic changes, and electrophysiological brain changes). Changes in the electrophysiology of the brain are foundational to the association or interaction of the concepts. Building on Berger's Psychophysical Model, it is evident that electrophysiological brain changes occur and affect cortical areas to generate or manifest symptoms from onset and across the stages of AD, which may be prior to pathological changes. Therefore, the interaction of the concepts demonstrates how the psychopathology results from affected electrophysiology of the brain. The theory of the EPAD provides a theoretical foundation for appropriate measurements of AD without dependence on neuropathological changes. Future research is warranted to further test this theory. Ultimately, this theory contributes to existing knowledge because it shows how electrophysiological changes are useful in understanding the risk and progression of AD across the stages.

The Personality of Past, Present and Future Speech-Language Pathology Students

ERIC Educational Resources Information Center

Byrne, Nicole

2018-01-01

Background: As allied health professions change over time to keep up with and reflect a rapidly changing society, it is quite possible that the people attracted to the profession may also change. If this is the case, then knowing this could be critical for future workforce marketing, training and planning. Aims: The aim was to investigate whether…

Regulation of immunity and inflammation by hypoxia in immunological niches.

PubMed

Taylor, Cormac T; Colgan, Sean P

2017-12-01

Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

Finfish and aquatic invertebrate pathology resources for now and the future✩

PubMed Central

Spitsbergen, Jan M.; Blazer, Vicki S.; Bowser, Paul R.; Cheng, Keith C.; Cooper, Keith R.; Cooper, Timothy K.; Frasca, Salvatore; Groman, David B.; Harper, Claudia M.; (Mac) Law, Jerry M.; Marty, Gary D.; Smolowitz, Roxanna M.; Leger, Judy St.; Wolf, Douglas C.; Wolf, Jeffrey C.

2009-01-01

Utilization of finfish and aquatic invertebrates in biomedical research and as environmental sentinels has grown dramatically in recent decades. Likewise the aquaculture of finfish and invertebrates has expanded rapidly worldwide as populations of some aquatic food species and threatened or endangered aquatic species have plummeted due to overharvesting or habitat degradation. This increasing intensive culture and use of aquatic species has heightened the importance of maintaining a sophisticated understanding of pathology of various organ systems of these diverse species. Yet, except for selected species long cultivated in aquaculture, pathology databases and the workforce of highly trained pathologists lag behind those available for most laboratory animals and domestic mammalian and avian species. Several factors must change to maximize the use, understanding, and protection of important aquatic species: 1) improvements in databases of abnormalities across species; 2) standardization of diagnostic criteria for proliferative and nonproliferative lesions; and 3) more uniform and rigorous training in aquatic morphologic pathology. PMID:18948226

Investigative pathology: leading the post-genomic revolution.

PubMed

Berman, David M; Bosenberg, Marcus W; Orwant, Robin L; Thurberg, Beth L; Draetta, Gulio F; Fletcher, Christopher D M; Loda, Massimo

2012-01-01

The completion of the Human Genome Project and the development of genome-based technologies over the past decade have set the stage for a new era of personalized medicine. By all rights, molecularly trained investigative pathologists should be leading this revolution. Singularly well suited for this work, molecular pathologists have the rare ability to wed genomic tools with unique diagnostic skills and tissue-based pathology techniques for integrated diagnosis of human disease. However, the number of pathologists with expertise in genome-based research has remained relatively low due to outdated training methods and a reluctance among some traditional pathologists to embrace new technologies. Moreover, because budding pathologists may not appreciate the vast selection of jobs available to them, they often end up choosing jobs that focus almost entirely on routine diagnosis rather than new frontiers in molecular pathology. This review calls for changes aimed at rectifying these troubling trends to ensure that pathology continues to guide patient care in a post-genomic era.

[Role of contemporary pathological diagnostics in the personalized treatment of cancer].

PubMed

Tímár, József

2013-03-01

Due to the developments of pathology in the past decades (immunohistochemistry and molecular pathology) classification of cancers changed fundamentally, laying a ground for personalized management of cancer patients. Our picture of cancer is more complex today, identifying the genetic basis of the morphological variants. On the other hand, this picture has a much higher resolution enabling us to subclassify similar histological cancer types based on molecular markers. This redefined classification of cancers helps us to better predict the possible biological behavior of the disease and/or the therapeutic sensitivity, opening the way toward a more personalized treatment of this disease. The redefined molecular classification of cancer may affect the universal application of treatment protocols. To achieve this goal molecular diagnostics must be an integral and reimbursed part of the routine pathological diagnostics. On the other hand, it is time to extend the multidisciplinary team with molecular pathologist to improve the decision making process of the management of cancer patients.

Absence of Alzheimer Disease Neuropathologic Changes in Eyes of Subjects With Alzheimer Disease.

PubMed

Williams, Erik A; McGuone, Declan; Frosch, Matthew P; Hyman, Bradley T; Laver, Nora; Stemmer-Rachamimov, Anat

2017-05-01

Alzheimer disease (AD) is the most common cause of dementia in the elderly, and is characterized by extracellular deposition of β-amyloid and intracellular accumulation of hyperphosphorylated tau protein in the brain. These pathologic findings are identified postmortem. Various visual deficits in AD have been reported and there have been conflicting reports, through imaging and pathology studies, regarding the presence of changes in the globe that mirror Alzheimer changes in the brain. Moreover, both macular degeneration and glaucoma have been variously characterized as having AD-related features. We examined one or both eyes from 19 autopsy cases, 17 of which had varying degrees of AD-related changes, and 2 of which were age-matched controls. Three cases had glaucoma and 4 had macular degeneration. Immunohistochemistry for tau, β-amyloid, TDP-43, ubiquitin, and α-synuclein showed no evidence of inclusions, deposits or other protein accumulation in any case, in any part of the globe. This finding suggests that regardless of the severity of changes seen in the brain in AD, there are no similar changes in the globe. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Considerations for standardizing predictive molecular pathology for cancer prognosis.

PubMed

Fiorentino, Michelangelo; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

2017-01-01

Molecular tests that were once ancillary to the core business of cyto-histopathology are becoming the most relevant workload in pathology departments after histopathology/cytopathology and before autopsies. This has resulted from innovations in molecular biology techniques, which have developed at an incredibly fast pace. Areas covered: Most of the current widely used techniques in molecular pathology such as FISH, direct sequencing, pyrosequencing, and allele-specific PCR will be replaced by massive parallel sequencing that will not be considered next generation, but rather, will be considered to be current generation sequencing. The pre-analytical steps of molecular techniques such as DNA extraction or sample preparation will be largely automated. Moreover, all the molecular pathology instruments will be part of an integrated workflow that traces the sample from extraction to the analytical steps until the results are reported; these steps will be guided by expert laboratory information systems. In situ hybridization and immunohistochemistry for quantification will be largely digitalized as much as histology will be mostly digitalized rather than viewed using microscopy. Expert commentary: This review summarizes the technical and regulatory issues concerning the standardization of molecular tests in pathology. A vision of the future perspectives of technological changes is also provided.

Factors associated with vocal fold pathologies in teachers.

PubMed

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

2011-10-01

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

Life After Being a Pathology Department Chair II: Lessons Learned.

PubMed

Bailey, David N; Lipscomb, Mary F; Gorstein, Fred; Wilkinson, David; Sanfilippo, Fred

2017-01-01

The 2016 Association of Pathology Chairs annual meeting featured a discussion group of Association of Pathology Chairs senior fellows (former chairs of academic departments of pathology who have remained active in Association of Pathology Chairs) that focused on how they decided to transition from the chair, how they prepared for such transition, and what they did after the transition. At the 2017 annual meeting, the senior fellows (encompassing 481 years of chair service) discussed lessons they learned from service as chair. These lessons included preparation for the chairship, what they would have done differently as chair, critical factors for success as chair, factors associated with failures, stress reduction techniques for themselves and for their faculty and staff, mechanisms for dealing with and avoiding problems, and the satisfaction they derived from their service as chair. It is reasonable to assume that these lessons may be representative of those learned by chairs of other specialties as well as by higher-level academic administrators such as deans, vice presidents, and chief executive officers. Although the environment for serving as a department chair has been changing dramatically, many of the lessons learned by former chairs are still valuable for current chairs of any length of tenure.

Life After Being a Pathology Department Chair II

PubMed Central

Lipscomb, Mary F.; Gorstein, Fred; Wilkinson, David; Sanfilippo, Fred

2017-01-01

The 2016 Association of Pathology Chairs annual meeting featured a discussion group of Association of Pathology Chairs senior fellows (former chairs of academic departments of pathology who have remained active in Association of Pathology Chairs) that focused on how they decided to transition from the chair, how they prepared for such transition, and what they did after the transition. At the 2017 annual meeting, the senior fellows (encompassing 481 years of chair service) discussed lessons they learned from service as chair. These lessons included preparation for the chairship, what they would have done differently as chair, critical factors for success as chair, factors associated with failures, stress reduction techniques for themselves and for their faculty and staff, mechanisms for dealing with and avoiding problems, and the satisfaction they derived from their service as chair. It is reasonable to assume that these lessons may be representative of those learned by chairs of other specialties as well as by higher-level academic administrators such as deans, vice presidents, and chief executive officers. Although the environment for serving as a department chair has been changing dramatically, many of the lessons learned by former chairs are still valuable for current chairs of any length of tenure. PMID:29057316

Pathological speech signal analysis and classification using empirical mode decomposition.

PubMed

Kaleem, Muhammad; Ghoraani, Behnaz; Guergachi, Aziz; Krishnan, Sridhar

2013-07-01

Automated classification of normal and pathological speech signals can provide an objective and accurate mechanism for pathological speech diagnosis, and is an active area of research. A large part of this research is based on analysis of acoustic measures extracted from sustained vowels. However, sustained vowels do not reflect real-world attributes of voice as effectively as continuous speech, which can take into account important attributes of speech such as rapid voice onset and termination, changes in voice frequency and amplitude, and sudden discontinuities in speech. This paper presents a methodology based on empirical mode decomposition (EMD) for classification of continuous normal and pathological speech signals obtained from a well-known database. EMD is used to decompose randomly chosen portions of speech signals into intrinsic mode functions, which are then analyzed to extract meaningful temporal and spectral features, including true instantaneous features which can capture discriminative information in signals hidden at local time-scales. A total of six features are extracted, and a linear classifier is used with the feature vector to classify continuous speech portions obtained from a database consisting of 51 normal and 161 pathological speakers. A classification accuracy of 95.7 % is obtained, thus demonstrating the effectiveness of the methodology.

Cancer of the esophagus and esophagogastric junction-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

PubMed

Rice, Thomas W; Gress, Donna M; Patil, Deepa T; Hofstetter, Wayne L; Kelsen, David P; Blackstone, Eugene H

2017-07-08

Answer questions and earn CME/CNE New to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for epithelial cancers of the esophagus and esophagogastric junction are separate, temporally related cancer classifications: 1) before treatment decision (clinical); 2) after esophagectomy alone (pathologic); and 3) after preresection therapy followed by esophagectomy (postneoadjuvant pathologic). The addition of clinical and postneoadjuvant pathologic stage groupings was driven by a lack of correspondence of survival, and thus prognosis, between both clinical and postneoadjuvant pathologic cancer categories (facts about the cancer) and pathologic categories. This was revealed by a machine-learning analysis of 6-continent data from the Worldwide Esophageal Cancer Collaboration, with consensus of the AJCC Upper GI Expert Panel. Survival is markedly affected by histopathologic cell type (squamous cell carcinoma and adenocarcinoma) in clinically and pathologically staged patients, requiring separate stage grouping for each cell type. However, postneoadjuvant pathologic stage groups are identical. For the future, more refined and granular data are needed. This requires: 1) more accurate clinical staging; 2) innovative solutions to pathologic staging challenges in endoscopically resected cancers; 3) integration of genomics into staging; and 4) precision cancer care with targeted therapy. It is the responsibility of the oncology team to accurately determine and record registry data, which requires eliminating both common errors and those related to incompleteness and inconsistency. Despite the new complexity of eighth edition staging of cancers of the esophagus and esophagogastric junction, these key concepts and new directions will facilitate precision cancer care. CA Cancer J Clin 2017;67:304-317. © 2017 American Cancer Society. © 2017 American Cancer Society.

The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer's disease.

PubMed

Batista, Andre F; Forny-Germano, Leticia; Clarke, Julia R; Lyra E Silva, Natalia M; Brito-Moreira, Jordano; Boehnke, Susan E; Winterborn, Andrew; Coe, Brian C; Lablans, Ann; Vital, Juliana F; Marques, Suelen A; Martinez, Ana Mb; Gralle, Matthias; Holscher, Christian; Klein, William L; Houzel, Jean-Christophe; Ferreira, Sergio T; Munoz, Douglas P; De Felice, Fernanda G

2018-05-01

Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling. Here, we show that liraglutide prevented the loss of brain insulin receptors and synapses, and reversed memory impairment induced by AD-linked amyloid-β oligomers (AβOs) in mice. Using hippocampal neuronal cultures, we determined that the mechanism of neuroprotection by liraglutide involves activation of the PKA signaling pathway. Infusion of AβOs into the lateral cerebral ventricle of non-human primates (NHPs) led to marked loss of insulin receptors and synapses in brain regions related to memory. Systemic treatment of NHPs with liraglutide provided partial protection, decreasing AD-related insulin receptor, synaptic, and tau pathology in specific brain regions. Synapse damage and elimination are amongst the earliest known pathological changes and the best correlates of memory impairment in AD. The results illuminate mechanisms of neuroprotection by liraglutide, and indicate that GLP-1 receptor activation may be harnessed to protect brain insulin receptors and synapses in AD. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Change in fibrinolytic activity under the influence of a constant magnetic field. [blood coagulation normilization in heart patients

NASA Technical Reports Server (NTRS)

Yepishina, S. G.

1974-01-01

The fibrinolytic activity of plasma changes under the influence of a constant magnetic field (CMF) with a strength of 250 or 2500 oersteds. CMF shows a tendency toward normalization of fibrinolytic processes in the presence of pathological disturbances in fibrinolysis activation.

Interim heterogeneity changes measured using entropy texture features on T2-weighted MRI at 3.0 T are associated with pathological response to neoadjuvant chemotherapy in primary breast cancer.

PubMed

Henderson, Shelley; Purdie, Colin; Michie, Caroline; Evans, Andrew; Lerski, Richard; Johnston, Marilyn; Vinnicombe, Sarah; Thompson, Alastair M

2017-11-01

To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. This was a retrospective study of 88 consenting women (age: 30-79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated. Mean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%. Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy. • Texture analysis provides a means of measuring lesion heterogeneity on MRI images. • Heterogeneity changes between baseline/interim MRI can be linked with ultimate pathological response. • Heterogeneity changes give good diagnostic accuracy of pCR response across all immunophenotypes. • Percentage reduction in heterogeneity is associated with pCR with good accuracy and NPV.

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

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

Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh

2016-01-01

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed themore » dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late RILD are also due to different pathologies. As such, new radiation techniques reducing irradiated volume might change the dose-limiting toxicity of the radiation therapy treatment.« less

Gait changes precede overt arthritis and strongly correlate with symptoms and histopathological events in pristane-induced arthritis

PubMed Central

2010-01-01

Introduction Pristane-induced arthritis (PIA) in the rat has been described as an animal model of inflammatory arthritis which exhibits features similar to rheumatoid arthritis in humans, such as a chronic, destructive, and symmetrical involvement of peripheral joints. However, so far little is known about the earliest inflammatory events and their influence on locomotor behaviour during the course of PIA. To investigate this issue a detailed analysis of the pathologic changes occurring during the prodromal and early stages of PIA was performed. Methods Arthritis was induced in DA.rats by injection of 150 μl 2,6,10,4-tetramethyl-pentadecane (pristane) at the base of the tail and changes in locomotor behaviour of the affected paws were monitored using the CatWalk quantitative gait analysis system. The pathologic events occurring in the joints of pristane-injected animals were studied before onset, at onset, and during acute phase of arthritis by histological methods. Results Gait analysis revealed that changes in locomotion such as reduced paw print areas and stance phase time are already apparent before the onset of clinically discernible arthritis symptoms (erythema, paw swelling) and correlate with PIA scores. In agreement with these findings, inflammatory tenosynovitis could be observed by histology already before the onset of erythema and swelling of the respective paws. In the most heavily affected rats also irregularities in step sequence patterns occurred A kinetic analysis of clinical and histological findings demonstrated that gait changes precede the pathological changes occurring during the acute phase of pristane-induced arthritis. Conclusions Gait analysis allows for pinpointing the initial inflammatory changes in experimental arthritis models such as pristane-induced arthritis. Analysis of early clinically relevant symptoms in arthritis models may facilitate the search for novel therapeutics to interfere with pain, inflammation and joint destruction in patients suffering from inflammatory arthritis. PMID:20222952

Gd-EOB-DTPA-enhanced MRI is better than MDCT in decision making of curative treatment for hepatocellular carcinoma.

PubMed

Yoo, Sun Hong; Choi, Jong Young; Jang, Jeong Won; Bae, Si Hyun; Yoon, Seung Kew; Kim, Dong Goo; Yoo, Young Kyoung; Rha, Sung Eun; Lee, Young Joon; Jung, Eun Sun

2013-09-01

We assessed the change in the therapeutic decision among curative treatments after adding Gd-EOB-DTPA-enhanced MRI to triple-phase MDCT for patients with early-stage HCC. This study retrospectively investigated two groups: 33 pathologically confirmed HCC patients after liver transplantation in group 1; 34 HCC patients without pathology in group 2. In group 1, we simulated the therapeutic decision-making process by pretransplant MDCT and Gd-EOB-DTPA-enhanced MRI. In group 2, including the 34 early-stage HCC patients consecutively enrolled, we investigated the change of therapeutic decision after adding Gd-EOB-DTPA-enhanced MRI to MDCT. In the simulation from group 1, after adding Gd-EOB-DTPA-enhanced MRI, 33.3% (11/33 patients) of treatment decisions were changed from the decision based on MDCT alone. Among 22 patients considered eligible for resection and 33 patients for radiofrequency ablation, the therapeutic decision was changed for 10 patients in the surgical group and 4 patients for the RFA group (45.5 and 12.1%). In group 2, the rate of change in the therapeutic decision after adding Gd-EOB-DTPA-enhanced MRI to MDCT was 41.2% (14/34 patients). In group 1 with explants pathology, the median diameter of HCCs not detected by MDCT but detected by Gd-EOB-DTPA-enhanced MRI was 1.15 cm (0.3-3.0 cm). The median diameter of HCCs seen only in the explanted liver was 1.0 cm (0.3-1.7 cm), and 60.7% of them were well-differentiated HCCs. This study suggests that performing Gd-EOB-DTPA-enhanced MRI before deciding on curative treatment for early-stage HCC may improve the accuracy of treatment decision for early-stage HCC.

Quantitative percussion diagnostics as an indicator of the level of the structural pathology of teeth: Retrospective follow-up investigation of high-risk sites that remained pathological after restorative treatment.

PubMed

Sheets, Cherilyn G; Wu, Jean C; Earthman, James C

2017-11-29

Structural damage may remain even after a tooth is restored. Conventional diagnostic aids do not quantify the severity of structural damage or allow the monitoring of structural changes after restoration. The purpose of this retrospective clinical study was to provide an in-depth analysis of 9 high-risk sites after restoration. The analysis followed structural defects found upon disassembly, restorative materials used, therapeutic procedures provided, current longevity, and long-term quantitative percussion diagnostics (QPD) to monitor results. The hypothesis was that QPD can be used to quantify positive and negative changes in structural stability. Sixty sites requiring restoration were part of an institutional review board-approved clinical study. Each participant was examined comprehensively, including QPD testing, at each follow-up. Long-term changes in normal fit error (NFE) values after restoration were evaluated according to a pathology rating system established in an earlier publication. Nine highly compromised sites were chosen for further analysis and monitored for an additional 6 years. Of the 9 high-risk sites (NFE>0.04), 7 sites improved and 2 sites deteriorated. Potential causes for each trend were documented. The data support the hypothesis that QPD can be used to monitor changes in structural stability after restoration. Knowledge of changes in advance of any symptoms allows further preventive or therapeutic intervention before serious structural damage can occur. Follow-up QPD indications of site improvement can also assure the clinician of the desired structural outcome. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

A SYSTEMATIC REVIEW OF PLACENTAL PATHOLOGY IN MATERNAL DIABETES MELLITUS

PubMed Central

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

2014-01-01

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

mNos2 deletion and human NOS2 replacement in Alzheimer disease models.

PubMed

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

2014-08-01

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

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

PubMed

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

2018-04-19

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

The pathology milestones and the next accreditation system.

PubMed

Naritoku, Wesley Y; Alexander, C Bruce; Bennett, Betsy D; Black-Schaffer, W Stephen; Brissette, Mark D; Grimes, Margaret M; Hoffman, Robert D; Hunt, Jennifer L; Iezzoni, Julia C; Johnson, Rebecca; Kozel, Jessica; Mendoza, Ricardo M; Post, Miriam D; Powell, Suzanne Z; Procop, Gary W; Steinberg, Jacob J; Thorsen, Linda M; Nestler, Steven P

2014-03-01

In the late 1990s, the Accreditation Council for Graduate Medical Education developed the Outcomes Project and the 6 general competencies with the intent to improve the outcome of graduate medical education in the United States. The competencies were used as the basis for developing learning goals and objectives and tools to evaluate residents' performance. By the mid-2000s the stakeholders in resident education and the general public felt that the Outcomes Project had fallen short of expectations. To develop a new evaluation method to track trainee progress throughout residency using benchmarks called milestones. A change in leadership at the Accreditation Council for Graduate Medical Education brought a new vision for the accreditation of training programs and a radically different approach to the evaluation of residents. The Pathology Milestones Working Group reviewed examples of developing milestones in other specialties, the literature, and the Accreditation Council for Graduate Medical Education program requirements for pathology to develop pathology milestones. The pathology milestones are a set of objective descriptors for measuring progress in the development of competency in patient care, procedural skill sets, medical knowledge, practice-based learning and improvement, interpersonal and communication skills, professionalism, and systems-based practice. The milestones provide a national standard for evaluation that will be used for the assessment of all residents in Accreditation Council for Graduate Medical Education-accredited pathology training programs.

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

USGS Publications Warehouse

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

2013-01-01

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

Lung and Intestine: A Specific Link in an Ulcerative Colitis Rat Model

PubMed Central

Liu, Yuan; Wang, Xin-Yue; Yang, Xue; Jing, Shan; Zhu, Li; Gao, Si-Hua

2013-01-01

Background. To investigate the link and mechanisms between intestine and lung in the ulcerative colitis (UC) rat model. Materials and Methods. We used the UC rat model by immunological sensitization combined with local 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol enema, observed dynamically animal general state and body weight, examined the histological and functional changes in the colon, lung, liver, and kidney tissues, and detected microvascular endothelium response towards inflammation characterized with the expression of iNOS, TXB2, P-selectin, ICAM-1, and vascular endothelial growth factor A (VEGF-A) in the colon and lung tissue. Results. Pulmonary function results suggested ventilator disorder, and pathological findings showed interstitial pneumonia. There were no significant changes in the liver and kidney function and histopathology. The colon and lung tissue iNOS, TXB2, P-selectin, ICAM-1, and VEGF-A expression of the model rats was significantly higher than the normal rats at both time points. Conclusions. Our study is the first to demonstrate the close association between the large intestine and lung in the immune-TNBS-ethanol-induced UC rat model. Different organs and tissues with the same embryonic origin may share the same pathological specificities in a disease. The present study provided a new way of thinking for pathological changes in clinical complex diseases manifested with multiorgan damage. PMID:23606829

Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States

PubMed Central

Xie, Rou-Gang; Chu, Wen-Guang; Hu, San-Jue; Luo, Ceng

2018-01-01

Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive. Here, by utilizing whole-cell patch clamp recordings, behavioral and pharmacological assays, we demonstrated that large dorsal root ganglion (DRG) neurons can be classified into three classes and four subclasses based on their excitability patterns, which is similar to mathematical models raised by Hodgkin. Analysis of hyperpolarization-activated cation current (Ih) revealed different magnitude of Ih in different excitability types of large DRG neurons, with higher Ih in Class 2-1 than that in Class 1, 2-2 and 3. This indicates a crucial role of Ih in the determination of excitability type of large DRG neurons. More importantly, this pattern of excitability displays plastic changes and transition under pathological pain states caused by peripheral nerve injury. This study sheds new light on the functional characteristics of large DRG neurons and extends functional classification of large DRG neurons by integration of transcriptomic and morphological characteristics. PMID:29303989

Comparison of Ferric Sulfate Combined Mineral Trioxide Aggregate Pulpotomy and Zinc Oxide Eugenol Pulpectomy of Primary Maxillary Incisors: An 18-month Randomized, Controlled Trial.

PubMed

Nguyen, Trang D; Judd, Peter L; Barrett, Edward J; Sidhu, Nicole; Casas, Michael J

2017-01-15

The purpose of this study was to compare outcomes and survival of ferric sulfate with mineral trioxide aggregate (FS+MTA) pulpotomy and root canal therapy (RCT) in carious vital primary maxillary incisors. In this parallel group noninferiority trial, asymptomatic carious vital primary incisors with pulp exposure in healthy 18- to 46-month-olds were allocated randomly to receive FS+MTA pulpotomy or RCT between September 2010 and September 2012. Each incisor was classified into one of the following radiographic outcomes: N (incisor without pathologic change); Po (pathologic change present, follow-up recommended); Px (pathologic change present, extract.) Clinical findings and incisor survival were secondary outcomes. Seventy subjects were enrolled with a total of 172 incisors. Twelve- and 18-month radiographic outcomes demonstrated no statistical difference between FS+MTA pulpotomy and RCT incisors for Px outcomes (P=0.38; odds ratio equals 0.60; 95 percent confidence interval equals 0.19 to 1.89; chi-square test). There was no statistical differences in clinical outcomes for FS+MTA pulpotomy and RCT at 12 and 18 months (P=0.51; Fisher's exact test) or survival for FS+MTA pulpotomy and RCT incisors (P=0.11; log-rank test). Ferric Sulfate with Mineral Trioxide Aggregate (FS+MTA) is an alternative to RCT for vital primary incisors.

Parallel appearance of compulsive behaviors and artistic creativity in Parkinson's disease.

PubMed

Joutsa, Juho; Martikainen, Kirsti; Kaasinen, Valtteri

2012-01-01

A 55-year-old male with idiopathic Parkinson's disease developed three behavioral changes under combination therapy with selegiline, cabergoline and levodopa. Co-existent behaviors included severe pathological gambling, punding and novel skills in writing poetry (published poetry books). Brain [(18)F]fluorodopa PET imaging showed decreased tracer uptake in the striatum contralateral to the predominant motor symptoms, consistent with the clinical diagnosis of Parkinson's disease. Uptake in the ventral striatum was markedly high. Brain MRI before and after behavioral changes showed no pathological findings. The patient was diagnosed as having Parkinson's disease together with DSM-IV criteria-fulfilling pathological gambling and punding-like stereotyped behavior. There are no established criteria for the classification of emerged artistic creativity, although there are descriptions of the phenomenon in the literature. Inspired by the case, we conducted a preliminary survey - including 290 patients with Parkinson's disease - exploring the possible relationship between creativity and impulsive-compulsive behaviors. The case, supported by the results of the survey, adds to the cumulative evidence of the association between dopaminergic medication and enhanced creativity, and suggests a possible linkage between increased artistic creativity and impulsive-compulsive behaviors in Parkinson's disease. Furthermore, it could be speculated that the high mesolimbic dopamine function might relate to the behavioral changes observed in this patient, and is suggestive of the overlapping neurobiological mechanisms of compulsive behaviors and artistic creativity.

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

PubMed

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

2013-07-22

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

Reduction of foveal bulges and other anatomical changes in fellow eyes of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes.

PubMed

Delas, Barbara; Julio, Gemma; Fernández-Vega, Álvaro; Casaroli-Marano, Ricardo P; Nadal, Jeroni

2017-11-01

To compare the foveal characteristics in fellow eyes (FE) of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes with eyes of healthy controls. Forty-seven FE and 52 eyes of 52 age- and sex-matched healthy controls were studied. Quantitative assessment of the dome-shaped appearance of the hyperreflective lines that represent external limiting membrane (ELM_bulge) and inner outer segment junctions (IS/OS_bulge) were made by optical coherence tomography (OCT) images. Inner retinal complex thickness (IRCT) was quantitatively assessed at 1000 and 2000 μm of the foveal center in nasal and temporal quadrants. Presence of alterations in the inner retinal outer layers and central foveal thickness (CFT) were also analyzed. Significantly lower ELM_bulge (p < 0.0001; Mann-Whitney test) and IS/OS_bulge (p < 0.001; student t test) and higher cases with COST alterations, expressed as a diffuse line (p < 0.006; Chi 2 test) were found in FE than control eyes. IRCT were significantly reduced in FE at all the studied locations when comparing to control eyes (p < 0.05; student t test), maintaining anatomical proportionality among locations. FE without pathologic vitreomacular interactions seems to present some central cone alterations that may be related to other causes than vitreomacular traction.

Parallel Appearance of Compulsive Behaviors and Artistic Creativity in Parkinson's Disease

PubMed Central

Joutsa, Juho; Martikainen, Kirsti; Kaasinen, Valtteri

2012-01-01

A 55-year-old male with idiopathic Parkinson's disease developed three behavioral changes under combination therapy with selegiline, cabergoline and levodopa. Co-existent behaviors included severe pathological gambling, punding and novel skills in writing poetry (published poetry books). Brain [18F]fluorodopa PET imaging showed decreased tracer uptake in the striatum contralateral to the predominant motor symptoms, consistent with the clinical diagnosis of Parkinson's disease. Uptake in the ventral striatum was markedly high. Brain MRI before and after behavioral changes showed no pathological findings. The patient was diagnosed as having Parkinson's disease together with DSM-IV criteria-fulfilling pathological gambling and punding-like stereotyped behavior. There are no established criteria for the classification of emerged artistic creativity, although there are descriptions of the phenomenon in the literature. Inspired by the case, we conducted a preliminary survey – including 290 patients with Parkinson's disease – exploring the possible relationship between creativity and impulsive-compulsive behaviors. The case, supported by the results of the survey, adds to the cumulative evidence of the association between dopaminergic medication and enhanced creativity, and suggests a possible linkage between increased artistic creativity and impulsive-compulsive behaviors in Parkinson's disease. Furthermore, it could be speculated that the high mesolimbic dopamine function might relate to the behavioral changes observed in this patient, and is suggestive of the overlapping neurobiological mechanisms of compulsive behaviors and artistic creativity. PMID:22679432

Transfer Technique Is Associated With Shoulder Pain and Pathology in People With Spinal Cord Injury: A Cross-Sectional Investigation.

PubMed

Hogaboom, Nathan S; Worobey, Lynn A; Boninger, Michael L

2016-10-01

To evaluate how transfer technique and subject characteristics relate to ultrasound measures of shoulder soft tissue pathology and self-reported shoulder pain during transfers in a sample of wheelchair users with spinal cord injury (SCI). Cross-sectional observational study. Research laboratory, national and local veterans' wheelchair sporting events. A convenience sample of wheelchair users (N=76) with nonprogressive SCI. Participants were aged >18 years, >1 year postinjury, and could complete repeated independent wheelchair transfers without the use of their leg muscles. Not applicable. Transfer pain items from the Wheelchair User's Shoulder Pain Index; transfer technique assessed using the Transfer Assessment Instrument (TAI); and shoulder pathology markers examined using the Ultrasound Shoulder Pathology Rating Scale (USPRS). Better transfer technique (higher TAI) correlated with less injury (lower USPRS) (partial η(2)=.062, P<.05) and less pain during transfers (partial η(2)=.049, P<.10). Greater age was the strongest predictor of greater pathology (USPRS total: partial η(2)=.225, supraspinatus grade: partial η(2)=.174, P<.01). An interaction between technique and weight was found (P<.10): participants with lower body weights showed a decrease in pathology markers with better transfer technique (low weight: R(2)=.422, P<.05; middle weight: R(2)=.200, P<.01), while those with higher weight showed little change with technique (R(2)=.018, P>.05). Participants with better transfer technique exhibited less shoulder pathology and reported less pain during transfers. The relationship between technique and pathology was strongest in lower-weight participants. While causation cannot be proven because of study design, it is possible that using a better transfer technique and optimizing body weight could reduce the incidence of shoulder pathology and pain. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Discordance in pathology report after central pathology review: Implications for breast cancer adjuvant treatment.

PubMed

Orlando, Laura; Viale, Giuseppe; Bria, Emilio; Lutrino, Eufemia Stefania; Sperduti, Isabella; Carbognin, Luisa; Schiavone, Paola; Quaranta, Annamaria; Fedele, Palma; Caliolo, Chiara; Calvani, Nicola; Criscuolo, Mario; Cinieri, Saverio

2016-12-01

Pathological predictive factors are the most important markers when selecting early breast cancer adjuvant therapy. In randomized clinical trials the variability in pathology report after central pathology review is noteworthy. We evaluated the discordance rate (DR) and inter-rater agreement between local and central histopathological report and the clinical implication on treatment decision. A retrospective analysis was conducted in a series of consecutive early breast cancer tumors diagnosed by local pathologists and subsequently reviewed at the Pathology Division of European Institute of Oncology. The inter-rater agreement (k) between local and central pathology was calculated for Ki-67, grading, hormone receptors (ER/PgR) and HER2/neu. The Bland-Altman plots were derived to determine discrepancies in Ki-67, ER and PgR. DR was calculated for ER/PgR and HER2. From 2007 to 2013, 187 pathology specimens from 10 Cancer Centers were reviewed. Substantial agreement was observed for ER (k0.612; 95% CI, 0538-0.686), PgR (k0.659; 95% CI, 0580-0.737), Ki-67 (k0.609; 95% CI, 0.534-0.684) and grading (k0.669; 95% CI, 0.569-0.769). Moderate agreement was found for HER2 (k0.546; 95% CI, 0444-0.649). DR was 9.5% (negativity to positivity) and 31.7% (positivity to negativity) for HER2 and 26.2% (negativity to positivity) and 12.5% (positivity to negativity) for ER/PgR. According to changes in Her2 and ER/PgR status, 23 (12.2%) and 33 (17.6%) systemic prescription were respectively modified. In our retrospective analysis, central pathological review has a significant impact in the decision-making process in early breast cancer, as shown in clinical trials. Further studies are warranted to confirm these provocative results. Copyright © 2016 Elsevier Ltd. All rights reserved.

The modern role of transoesophageal echocardiography in the assessment of valvular pathologies

PubMed Central

Bull, Sacha; Newton, James

2017-01-01

Despite significant advancements in the field of cardiovascular imaging, transoesophageal echocardiography remains the key imaging modality in the management of valvular pathologies. This paper provides echocardiographers with an overview of the modern role of TOE in the diagnosis and management of valvular disease. We describe how the introduction of 3D techniques has changed the detection and grading of valvular pathologies and concentrate on its role as a monitoring tool in interventional cardiology. In addition, we focus on the echocardiographic and Doppler techniques used in the assessment of prosthetic valves and provide guidance for the evaluation of prosthetic valves. Finally, we summarise quantitative methods used for the assessment of valvular stenosis and regurgitation and highlight the key areas where echocardiography remains superior over other novel imaging modalities. PMID:28096184

Acute glandular fever-like illness in a patient with HTLV-III antibody.

PubMed

McCaul, T F; Tovey, G; Farthing, C F; Gazzard, B; Zuckerman, A J

1985-10-01

A lymph node biopsy obtained from a patient with human T-cell lymphocytotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody, presenting with an acute glandular fever-like illness, was examined by electron microscopy. Numerous pathological changes were present in the biopsy, including hypertrophy of smooth endoplasmic reticulum, intracytoplasmic rod-like inclusions within the cisternae of endoplasmic reticulum, multivesicular bodies, test-tube and ring-shaped forms, and tubulo-reticular structures. Intranuclear and intracytoplasmic viral-like particles measuring 105-120 nm in diameter and small cytoplasmic particles measuring 50-70 nm in diameter were found in some degenerating lymph node cells. These pathological findings may reflect a host cell response to various pathological and viral stimuli resulting from immune deficiency owing to infection with HTLV-III/LAV.

The modern role of transoesophageal echocardiography in the assessment of valvular pathologies.

PubMed

Wamil, Malgorzata; Bull, Sacha; Newton, James

2017-01-17

Despite significant advancements in the field of cardiovascular imaging, transoesophageal echocardiography remains the key imaging modality in the management of valvular pathologies. This paper provides echocardiographers with an overview of the modern role of TOE in the diagnosis and management of valvular disease. We describe how the introduction of 3D techniques has changed detection and grading of valvular pathologies and concentrate on its role as a monitoring tool in interventional cardiology. In addition, we focus on the echocardiographic and Doppler techniques used in the assessment of prosthetic valves, and provide guidance for evaluation of prosthetic valves. Finally, we summarise quantitative methods used for the assessment of valvular stenosis and regurgitation and highlight the key areas where echocardiography remains superior over other novel imaging modalities. © 2017 The authors.

Can zero-hour cortical biopsy predict early graft outcomes after living donor renal transplantation?

PubMed

Rathore, Ranjeet Singh; Mehta, Nisarg; Mehta, Sony Bhaskar; Babu, Manas; Bansal, Devesh; Pillai, Biju S; Sam, Mohan P; Krishnamoorthy, Hariharan

2017-11-01

The aim of this study was to identify relevance of subclinical pathological findings in the kidneys of living donors and correlate these with early graft renal function. This was a prospective study on 84 living donor kidney transplant recipients over a period of two years. In all the donors, cortical wedge biopsy was taken and sent for assessment of glomerular, mesangial, and tubule status. The graft function of patients with normal histology was compared with those of abnormal histological findings at one, three, and six months, and one year post-surgery. Most abnormal histological findings were of mild degree. Glomerulosclerosis (GS, 25%), interstitial fibrosis (IF, 13%), acute tubular necrosis (ATN 5%), and focal tubal atrophy (FTA, 5%) were the commonly observed pathological findings in zero-hour biopsies. Only those donors who had histological changes of IF and ATN showed progressive deterioration of renal function at one month, three months, six months, and one year post-transplantation. In donors with other histological changes, no significant effect on graft function was observed. Zero-hour cortical biopsy gave us an idea of the general status of the donor kidney and presence or absence of subclinical pathological lesions. A mild degree of subclinical and pathological findings on zero-hour biopsy did not affect early graft renal function in living donor kidney transplantation. Zero-hour cortical biopsy could also help in discriminating donor-derived lesions from de novo alterations in the kidney that could happen subsequently.

Joint pathology and behavioral performance in autoimmune MRL-lpr Mice.

PubMed

Sakić, B; Szechtman, H; Stead, R H; Denburg, J A

1996-09-01

Young autoimmune MRL-lpr mice perform more poorly than age-matched controls in tests of exploration, spatial learning, and emotional reactivity. Impaired behavioral performance coincides temporally with hyperproduction of autoantibodies, infiltration of lymphoid cells into the brain, and mild arthritic-like changes in hind paws. Although CNS mechanisms have been suggested to mediate behavioral deficits, it was not clear whether mild joint pathology significantly affected behavioral performance. Previously we observed that 11-week-old MRL-lpr mice showed a trend for disturbed performance when crossing a narrow beam. The first aim of the present study was to test the significance of this trend by increasing the sample size and, second, to examine the possibility that arthritis-like changes interfere with performance in brief locomotor tasks. For the purpose of the second goal, 18-week-old mice that differ widely in severity of joint disease were selectively taken from the population and tested in beam walking and swimming tasks. It was expected that the severity of joint inflammation would be positively correlated with the degree of locomotor impairment. The larger sample size revealed that young MRL-lpr mice perform significantly more poorly than controls on the beam-walking test, as evidenced by more foot slips and longer traversing time. However, significant correlation between joint pathology scores and measures of locomotion could not be detected. The lack of such relationship suggests that mild joint pathology does not significantly contribute to impaired performance in young, autoimmune MRL-lpr mice tested in short behavioral tasks.

Micro-Raman spectroscopy on oral tissues

NASA Astrophysics Data System (ADS)

Zenone, F.; Lepore, M.; Perna, G.; Carmone, P.; Riccio, R.; Gaeta, G. M.; Capozzi, V.

2006-02-01

Micro-Raman Spectroscopy (μ-RS) provides a unique tool in medicine for a not invasive and real time analysis of biological tissue for biopsy and "in vivo" investigation. Based on the evaluation of molecular vibration frequencies, the μ-RS is able to detect the main molecular bonds of protein constituents, as the C-H and C-C ones. Changes in frequency or in the relative intensity of the vibration modes revealed by μ-RS can be related to changes of chemical bond and of protein structure induced by pathology. The μ-RS has been performed on samples of oral tissue from informed patients, affected by pemphigus vulgaris (an oral pathology) in an advanced regression state. The biopsies were thin slices (about 1mm thick) with 6mm diameter. The sample was measured through a 170 μm thick cover-glass. The experimental set-up was mainly composed by a He-Ne laser and a monochromator equipped with a Peltier cell and with a grating of 1800 grooves/mm. The laser light was focused on the sample surface by means of a long focal length 50X optical objective. The main protein bonds are clearly detectable in the considered samples and this give important information on the integrity and on the state of tissue components (lipids and proteins), and consequently on the occurrence of pathology. The potential application of this method for in vivo analysis is an invaluable alternative to biopsy and pathological examinations for many medical application as screening diagnostic, therapy progress examination, and surgical support.

Comparison of magnetic resonance imaging and video capsule enteroscopy in diagnosing small-bowel pathology: localization-dependent diagnostic yield.

PubMed

Böcker, Ulrich; Dinter, Dietmar; Litterer, Caroline; Hummel, Frank; Knebel, Phillip; Franke, Andreas; Weiss, Christel; Singer, Manfred V; Löhr, J-Matthias

2010-04-01

New technology has considerably advanced the diagnosis of small-bowel pathology. However, its significance in clinical algorithms has not yet been fully assessed. The aim of the present analysis was to compare the diagnostic utility and yield of video-capsule enteroscopy (VCE) to that of magnetic resonance imaging (MRI) in patients with suspected or established Crohn's disease (Group I), obscure gastrointestinal blood loss (Group II), or suspected tumors (Group III). Forty-six out of 182 patients who underwent both modalities were included: 21 in Group I, 20 in Group II, and five in Group III. Pathology was assessed in three predetermined sections of the small bowel (upper, middle, and lower). The McNemar and Wilcoxon tests were used for statistical analysis. In Group I, lesions were found by VCE in nine of the 21 patients and by MRI in six. In five patients, both modalities showed pathology. In Group II, pathological changes were detected in 11 of the 20 patients by VCE and in eight patients by MRI. In five cases, pathology was found with both modalities. In Group III, neither modality showed small-bowel pathology. For the patient groups combined, diagnostic yield was 43% with VCE and 30% with MRI. The diagnostic yield of VCE was superior to that of MRI in the upper small bowel in both Groups I and II. VCE is superior to MRI for the detection of lesions related to Crohn's disease or obscure gastrointestinal bleeding in the upper small bowel.

Using Focused Laboratory Management and Quality Improvement Projects to Enhance Resident Training and Foster Scholarship

PubMed Central

Ford, Bradley A.; Klutts, J. Stacey; Jensen, Chris S.; Briggs, Angela S.; Robinson, Robert A.; Bruch, Leslie A.; Karandikar, Nitin J.

2017-01-01

Training in patient safety, quality, and management is widely recognized as an important element of graduate medical education. These concepts have been intertwined in pathology graduate medical education for many years, although training programs face challenges in creating explicit learning opportunities in these fields. Tangibly involving pathology residents in management and quality improvement projects has the potential to teach and reinforce key concepts and further fulfill Accreditation Council for Graduate Medical Education goals for pursuing projects related to patient safety and quality improvement. In this report, we present our experience at a pathology residency program (University of Iowa) in engaging pathology residents in projects related to practical issues of laboratory management, process improvement, and informatics. In this program, at least 1 management/quality improvement project, typically performed during a clinical chemistry/management rotation, was required and ideally resulted in a journal publication. The residency program also initiated a monthly management/informatics series for pathology externs, residents, and fellows that covers a wide range of topics. Since 2010, all pathology residents at the University of Iowa have completed at least 1 management/quality improvement project. Many of the projects involved aspects of laboratory test utilization, with some projects focused on other areas such as human resources, informatics, or process improvement. Since 2012, 31 peer-reviewed journal articles involving effort from 26 residents have been published. Multiple projects resulted in changes in ongoing practice, particularly within the hospital electronic health record. Focused management/quality improvement projects involving pathology residents can result in both meaningful quality improvement and scholarly output. PMID:28913416

Using Focused Laboratory Management and Quality Improvement Projects to Enhance Resident Training and Foster Scholarship.

PubMed

Krasowski, Matthew D; Ford, Bradley A; Klutts, J Stacey; Jensen, Chris S; Briggs, Angela S; Robinson, Robert A; Bruch, Leslie A; Karandikar, Nitin J

2017-01-01

Training in patient safety, quality, and management is widely recognized as an important element of graduate medical education. These concepts have been intertwined in pathology graduate medical education for many years, although training programs face challenges in creating explicit learning opportunities in these fields. Tangibly involving pathology residents in management and quality improvement projects has the potential to teach and reinforce key concepts and further fulfill Accreditation Council for Graduate Medical Education goals for pursuing projects related to patient safety and quality improvement. In this report, we present our experience at a pathology residency program (University of Iowa) in engaging pathology residents in projects related to practical issues of laboratory management, process improvement, and informatics. In this program, at least 1 management/quality improvement project, typically performed during a clinical chemistry/management rotation, was required and ideally resulted in a journal publication. The residency program also initiated a monthly management/informatics series for pathology externs, residents, and fellows that covers a wide range of topics. Since 2010, all pathology residents at the University of Iowa have completed at least 1 management/quality improvement project. Many of the projects involved aspects of laboratory test utilization, with some projects focused on other areas such as human resources, informatics, or process improvement. Since 2012, 31 peer-reviewed journal articles involving effort from 26 residents have been published. Multiple projects resulted in changes in ongoing practice, particularly within the hospital electronic health record. Focused management/quality improvement projects involving pathology residents can result in both meaningful quality improvement and scholarly output.

An eye witness perspective of the changing patterns of food allergy.

PubMed

Walker-Smith, John

2005-12-01

Food allergy may affect the gastrointestinal tract of children and adults too, albeit less commonly. The changing clinico-pathological expression of such food allergy in children over a 30 year period is related, from the eye witness perspective of a paediatric gastroenterologist in London. Tissue diagnosis by biopsy, related to dietary elimination and challenge has been the basis for the first clinico-pathological descriptions and accurate clinical diagnosis of these syndromes as they affect the gastrointestinal tract. In the 1970s cow's milk sensitive enteropathy presenting as chronic diarrhoea and failure to thrive in infancy often after infective gastroenteritis, especially with enteropathogenic Escherichia coli, was an important problem. By the late 1990s such presentations had become most uncommon in developed communities but they continue to occur in developing communities. By contrast in more recent times, multiple food allergy associated with minor small intestinal enteropathy and gastro-oesophageal reflux in older children has become an important clinical problem in children seen in developed communities. Accompanying these changes has been a dramatic fall in the number of children with clinically severe gastroenteritis with severe dehydration requiring hospital admission. Furthermore, the widespread diagnostic use of endoscopy of the upper and lower gastrointestinal tract in children with multiple biopsies has expanded gastroenterological diagnosis in children. This approach gives information about the oesophagus and ileo-colon not available in the earlier studies, which largely concentrated upon small intestinal biopsies, obtained by Crosby capsule biopsy. So, over this 30 year period clinico-pathological expression has altered but also the diagnostic approach has technically changed.

Cellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss – A Common Hereditary Deafness

PubMed Central

Wingard, Jeffrey C.; Zhao, Hong-Bo

2015-01-01

Hearing loss due to mutations in the connexin gene family, which encodes gap junctional proteins, is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2) mutations are responsible for ~50% of non-syndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate that congenital deafness mainly results from cochlear developmental disorders rather than hair cell degeneration and endocochlear potential reduction, while late-onset hearing loss results from reduction of active cochlear amplification, even though cochlear hair cells have no connexin expression. However, there is no apparent, demonstrable relationship between specific changes in connexin (channel) functions and the phenotypes of mutation-induced hearing loss. Moreover, new experiments further demonstrate that the hypothesized K+-recycling disruption is not a principal deafness mechanism for connexin deficiency induced hearing loss. Cx30 (GJB6), Cx29 (GJC3), Cx31 (GJB3), and Cx43 (GJA1) mutations can also cause hearing loss with distinct pathological changes in the cochlea. These new studies provide invaluable information about deafness mechanisms underlying connexin mutation-induced hearing loss and also provide important information for developing new protective and therapeutic strategies for this common deafness. However, the detailed cellular mechanisms underlying these pathological changes remain unclear. Also, little is known about specific mutation-induced pathological changes in vivo and little information is available for humans. Such further studies are urgently required. PMID:26074771

Ultrasound elastography: principles, techniques, and clinical applications.

PubMed

Dewall, Ryan J

2013-01-01

Ultrasound elastography is an emerging set of imaging modalities used to image tissue elasticity and are often referred to as virtual palpation. These techniques have proven effective in detecting and assessing many different pathologies, because tissue mechanical changes often correlate with tissue pathological changes. This article reviews the principles of ultrasound elastography, many of the ultrasound-based techniques, and popular clinical applications. Originally, elastography was a technique that imaged tissue strain by comparing pre- and postcompression ultrasound images. However, new techniques have been developed that use different excitation methods such as external vibration or acoustic radiation force. Some techniques track transient phenomena such as shear waves to quantitatively measure tissue elasticity. Clinical use of elastography is increasing, with applications including lesion detection and classification, fibrosis staging, treatment monitoring, vascular imaging, and musculoskeletal applications.

New paradigms in clonal evolution: punctuated equilibrium in cancer.

PubMed

Cross, William Ch; Graham, Trevor A; Wright, Nicholas A

2016-10-01

Evolutionary theories are themselves subject to evolution. Clonal evolution - the model that describes the initiation and progression of cancer - is entering a period of profound change, brought about largely by technological developments in genome analysis. A flurry of recent publications, using modern mathematical and bioinformatics techniques, have revealed both punctuated and neutral evolution phenomena that are poorly explained by the conventional graduated perspectives. In this review, we propose that a hybrid model, inspired by the evolutionary model of punctuated equilibrium, could better explain these recent observations. We also discuss the conceptual changes and clinical implications of variable evolutionary tempos. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Assessment of Reliable Change Using 95% Credible Intervals for the Differences in Proportions: A Statistical Analysis for Case-Study Methodology

ERIC Educational Resources Information Center

Unicomb, Rachael; Colyvas, Kim; Harrison, Elisabeth; Hewat, Sally

2015-01-01

Purpose: Case-study methodology studying change is often used in the field of speech-language pathology, but it can be criticized for not being statistically robust. Yet with the heterogeneous nature of many communication disorders, case studies allow clinicians and researchers to closely observe and report on change. Such information is valuable…

Three-dimensional confocal morphometry – a new approach for studying dynamic changes in cell morphology in brain slices

PubMed Central

Chvátal, Alexandr; Anděrová, Miroslava; Kirchhoff, Frank

2007-01-01

Pathological states in the central nervous system lead to dramatic changes in the activity of neuroactive substances in the extracellular space, to changes in ionic homeostasis and often to cell swelling. To quantify changes in cell morphology over a certain period of time, we employed a new technique, three-dimensional confocal morphometry. In our experiments, performed on enhanced green fluorescent protein/glial fibrillary acidic protein astrocytes in brain slices in situ and thus preserving the extracellular microenvironment, confocal morphometry revealed that the application of hypotonic solution evoked two types of volume change. In one population of astrocytes, hypotonic stress evoked small cell volume changes followed by a regulatory volume decrease, while in the second population volume changes were significantly larger without subsequent volume regulation. Three-dimensional cell reconstruction revealed that even though the total astrocyte volume increased during hypotonic stress, the morphological changes in various cell compartments and processes were more complex than have been previously shown, including swelling, shrinking and structural rearrangement. Our data show that astrocytes in brain slices in situ during hypotonic stress display complex behaviour. One population of astrocytes is highly capable of cell volume regulation, while the second population is characterized by prominent cell swelling, accompanied by plastic changes in morphology. It is possible to speculate that these two astrocyte populations play different roles during physiological and pathological states. PMID:17488344

Tracking Change in Children with Severe and Persisting Speech Difficulties

ERIC Educational Resources Information Center

Newbold, Elisabeth Joy; Stackhouse, Joy; Wells, Bill

2013-01-01

Standardised tests of whole-word accuracy are popular in the speech pathology and developmental psychology literature as measures of children's speech performance. However, they may not be sensitive enough to measure changes in speech output in children with severe and persisting speech difficulties (SPSD). To identify the best ways of doing this,…

Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice

USDA-ARS?s Scientific Manuscript database

Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric...

Longitudinal Cerebral Blood Flow Changes during Speech in Hereditary Ataxia

ERIC Educational Resources Information Center

Sidtis, John J.; Strother, Stephen C.; Naoum, Ansam; Rottenberg, David A.; Gomez, Christopher

2010-01-01

The hereditary ataxias constitute a group of degenerative diseases that progress over years or decades. With principal pathology involving the cerebellum, dysarthria is an early feature of many of the ataxias. Positron emission tomography was used to study regional cerebral blood flow changes during speech production over a 21 month period in a…

An entirely automated method to score DSS-induced colitis in mice by digital image analysis of pathology slides

PubMed Central

Kozlowski, Cleopatra; Jeet, Surinder; Beyer, Joseph; Guerrero, Steve; Lesch, Justin; Wang, Xiaoting; DeVoss, Jason; Diehl, Lauri

2013-01-01

SUMMARY The DSS (dextran sulfate sodium) model of colitis is a mouse model of inflammatory bowel disease. Microscopic symptoms include loss of crypt cells from the gut lining and infiltration of inflammatory cells into the colon. An experienced pathologist requires several hours per study to score histological changes in selected regions of the mouse gut. In order to increase the efficiency of scoring, Definiens Developer software was used to devise an entirely automated method to quantify histological changes in the whole H&E slide. When the algorithm was applied to slides from historical drug-discovery studies, automated scores classified 88% of drug candidates in the same way as pathologists’ scores. In addition, another automated image analysis method was developed to quantify colon-infiltrating macrophages, neutrophils, B cells and T cells in immunohistochemical stains of serial sections of the H&E slides. The timing of neutrophil and macrophage infiltration had the highest correlation to pathological changes, whereas T and B cell infiltration occurred later. Thus, automated image analysis enables quantitative comparisons between tissue morphology changes and cell-infiltration dynamics. PMID:23580198

Neurodegenerative disease and cognitive retest learning.

PubMed

Wilson, Robert S; Capuano, Ana W; Yu, Lei; Yang, Jingyun; Kim, Namhee; Leurgans, Sue E; Lamar, Melissa; Schneider, Julie A; Bennett, David A; Boyle, Patricia A

2018-06-01

Retest learning impacts estimates of cognitive aging, but its bases are uncertain. Here, we test the hypothesis that dementia-related neurodegeneration impairs retest learning. Older persons without cognitive impairment at enrollment (n = 567) had annual cognitive testing for a mean of 11 years, died, and had a neuropathologic examination to quantify 5 neurodegenerative pathologies. Change point models were used to divide cognitive trajectories into an early retest sensitive component and a later component less sensitive to retest. Performance on a global cognitive measure (baseline mean = 0.227, standard deviation = 0.382) increased an estimated mean of 0.142-unit per year for a mean of 1.5 years and declined an estimated mean of 0.123-unit per year thereafter. No pathologic marker was related to cognitive change before the change point; each was related to cognitive decline after the change point. Results were comparable in analyses that used specific cognitive outcomes, included 220 individuals with mild cognitive impairment at enrollment, or allowed a longer retest learning period. The findings suggest that neurodegeneration does not impact cognitive retest learning. Copyright © 2018 Elsevier Inc. All rights reserved.

Glucose Transporters in Cardiac Metabolism and Hypertrophy

PubMed Central

Shao, Dan; Tian, Rong

2016-01-01

The heart is adapted to utilize all classes of substrates to meet the high-energy demand, and it tightly regulates its substrate utilization in response to environmental changes. Although fatty acids are known as the predominant fuel for the adult heart at resting stage, the heart switches its substrate preference toward glucose during stress conditions such as ischemia and pathological hypertrophy. Notably, increasing evidence suggests that the loss of metabolic flexibility associated with increased reliance on glucose utilization contribute to the development of cardiac dysfunction. The changes in glucose metabolism in hypertrophied hearts include altered glucose transport and increased glycolysis. Despite the role of glucose as an energy source, changes in other nonenergy producing pathways related to glucose metabolism, such as hexosamine biosynthetic pathway and pentose phosphate pathway, are also observed in the diseased hearts. This article summarizes the current knowledge regarding the regulation of glucose transporter expression and translocation in the heart during physiological and pathological conditions. It also discusses the signaling mechanisms governing glucose uptake in cardiomyocytes, as well as the changes of cardiac glucose metabolism under disease conditions. PMID:26756635

[A study on pathology and immunoglobulin of orbital tissues from cases with Grave's ophthalmopathy].

PubMed

Zhou, X; Luo, Q; Xia, R

1999-07-01

To investigate pathological changes and the expression, localization of immunoglobulins (IgA & IgE) in orbital tissues from patients with Grave's ophthalmopathy. Orbital tissues were obtained at surgery from 19 patients with Grave's ophthalmopathy and 17 control subjects. Immunohistochemical studies were carried out by using anti-IgA, anti-IgE antibody and a streptavidin-biotin-peroxidase detection system. In addition, hematoxylin-eosin, alcian blue and Masson trichrome stains were employed to demonstrate the pathologic changes in the tissues. 12 of 17 samples from patients exhibited IgA positive staining for the connective tissue associated with the extraocular muscles and orbicularis oculi, however only 2 control muscles reacted minimally. IgE positive material was found in association with the majority of leukocytes and with muscle fibers in 13 patients, but only 4 control subjects displayed mild reactions. Significant expression of IgE was more often demonstrated in patients with eye disease of short course than in those of longer course. These results support the notion that the eye muscle fiber and fibroblast are important targets of the orbital autoimmune reaction in Graves' ophthalmopathy in which IgA and IgE both play important roles.

Effect of Cognitive Reserve Markers on Alzheimer Pathological Progression

PubMed Central

Lo, Raymond Y.; Jagust, William J.

2013-01-01

Education, occupation, premorbid intelligence and brain size are surrogate markers for cognitive reserve. Whether these markers have biological influence on Alzheimer disease (AD) pathology is not known. We thus aimed to investigate the effect of cognitive reserve proxies on longitudinal change of AD biomarkers. A total of 819 participants with normal cognition (NC), mild cognitive impairment (MCI) and mild AD were enrolled in the Alzheimer’s Disease Neuroimaging Initiative and followed up with repeated measures of CSF, PET and MRI biomarkers. Generalized estimating equations were employed to assess whether biomarker rates of change were modified by reserve proxies. CSF Aβ42 decline was slower in NC participants with higher cognitive reserve indexed by education, occupation and American National Adult Reading Test (ANART). The decline of [18F] fluorodeoxyglucose PET uptake was slower in AD participants with better performance on the ANART. Education, occupation and ANART did not modify the rates of MRI hippocampal atrophy in any group. These findings remained unchanged after accounting for APOE 4, longitudinal missing data and baseline cognitive performance. Higher levels of reserve markers may slow the rate of amyloid deposition before cognitive impairment and preserve glucose metabolism at the dementia stage over the course of AD pathological progression. PMID:23552443

Activity-based differentiation of pathologists' workload in surgical pathology.

PubMed

Meijer, G A; Oudejans, J J; Koevoets, J J M; Meijer, C J L M

2009-06-01

Adequate budget control in pathology practice requires accurate allocation of resources. Any changes in types and numbers of specimens handled or protocols used will directly affect the pathologists' workload and consequently the allocation of resources. The aim of the present study was to develop a model for measuring the pathologists' workload that can take into account the changes mentioned above. The diagnostic process was analyzed and broken up into separate activities. The time needed to perform these activities was measured. Based on linear regression analysis, for each activity, the time needed was calculated as a function of the number of slides or blocks involved. The total pathologists' time required for a range of specimens was calculated based on standard protocols and validated by comparing to actually measured workload. Cutting up, microscopic procedures and dictating turned out to be highly correlated to number of blocks and/or slides per specimen. Calculated workload per type of specimen was significantly correlated to the actually measured workload. Modeling pathologists' workload based on formulas that calculate workload per type of specimen as a function of the number of blocks and slides provides a basis for a comprehensive, yet flexible, activity-based costing system for pathology.

Drinking Patterns of Pathological Gamblers Before, During, and After Gambling Treatment

PubMed Central

Rash, Carla J.; Weinstock, Jeremiah; Petry, Nancy M.

2011-01-01

Despite the high co-occurrence of alcohol consumption and gambling, few studies have investigated alcohol use changes during gambling treatment. Using latent growth modeling, we examined weekly alcohol use trajectories of treatment-seeking pathological gamblers across 36 weeks, allowing rates of change to differ across the 12-week pre-treatment, during treatment, and post-treatment periods. For these secondary data analyses, we retained drinking gamblers (N = 163) from a combined sample of two randomized clinical trials for the treatment of pathological gambling. Results indicated a decrease in alcohol use corresponding with treatment entry and maintenance of less drinking during treatment and post-treatment. Despite these decreases in alcohol use overall, 31% (50 of 163) of participants exhibited risky drinking during the treatment or post-treatment periods. Gender, age, at-risk drinking (at any point in the 36-week interval), baseline gambling severity, treatment condition, and gambling during treatment predicted latent alcohol use growth factors. Although entry into gambling treatment was temporally associated with reductions in alcohol use in this retrospective analysis, a substantial portion of the sample exhibited at-risk drinking after treatment entry, suggesting that interventions targeting reductions in alcohol use may be useful for this population. PMID:21928867

Medical audit of rectal biopsy diagnosis of inflammatory bowel disease.

PubMed

Frei, J V; Morson, B C

1982-03-01

The records of the rectal biopsy diagnoses of ulcerative colitis and Crohn's disease in the Department of Pathology, St Mark's Hospital, London, were reviewed. The biopsy diagnoses were compared to subsequent resection diagnoses on the same patients, and annual and seasonal variations in the frequency of these and related diagnoses were studied. The accuracy rate for the biopsy diagnosis of ulcerative colitis was about 70% and for Crohn's disease about 40% each time a biopsy was read. The low figure for the accuracy rate for Crohn's disease could be attributed to sampling error inherent in the diagnosis of a disease which is essentially patchy, showing discontinuous pathology. Also, many patients with Crohn's disease have a normal rectum which is biopsied to demonstrate the distinction from ulcerative colitis. In practical terms therefore a 40% accuracy rate in Crohn's disease is probably adequate. The rate of "false-positive" diagnoses was about 5%. There was a seasonal variation in the frequency of these two diagnoses, but no variation attributable to changes in observers, as pathology trainees in the Department change regularly. The frequency of diagnoses of non-specific inflammation and of normal colon did show such non-random variations.

Sulforaphane Inhibits the Generation of Amyloid-β Oligomer and Promotes Spatial Learning and Memory in Alzheimer's Disease (PS1V97L) Transgenic Mice.

PubMed

Hou, Ting-Ting; Yang, He-Yun; Wang, Wei; Wu, Qiao-Qi; Tian, Yuan-Ruhua; Jia, Jian-Ping

2018-01-01

Abnormal amyloid-β (Aβ) aggregates are a striking feature of Alzheimer's disease (AD), and Aβ oligomers have been proven to be crucial in the pathology of AD. Any intervention targeting the generation or aggregation of Aβ can be expected to be useful in AD treatment. Oxidative stress and inflammation are common pathological changes in AD that are involved in the generation and aggregation of Aβ. In the present study, 6-month-old PS1V97L transgenic (Tg) mice were treated with sulforaphane, an antioxidant, for 4 months, and this treatment significantly inhibited the generation and aggregation of Aβ. Sulforaphane also alleviated several downstream pathological changes that including tau hyperphosphorylation, oxidative stress, and neuroinflammation. Most importantly, the cognition of the sulforaphane-treated PS1V97L Tg mice remained normal compared to that of wild-type mice at 10 months of age, when dementia typically emerges in PS1V97L Tg mice. Pretreating cultured cortical neurons with sulforaphane also protected against neuronal injury caused by Aβ oligomers in vitro. These findings suggest that sulforaphane may be a potential compound that can inhibit Aβ oligomer production in AD.

Microglial pathology.

PubMed

Streit, Wolfgang J; Xue, Qing-Shan; Tischer, Jasmin; Bechmann, Ingo

2014-09-26

This paper summarizes pathological changes that affect microglial cells in the human brain during aging and in aging-related neurodegenerative diseases, primarily Alzheimer's disease (AD). It also provides examples of microglial changes that have been observed in laboratory animals during aging and in some experimentally induced lesions and disease models. Dissimilarities and similarities between humans and rodents are discussed in an attempt to generate a current understanding of microglial pathology and its significance during aging and in the pathogenesis of Alzheimer dementia (AD). The identification of dystrophic (senescent) microglia has created an ostensible conflict with prior work claiming a role for activated microglia and neuroinflammation during normal aging and in AD, and this has raised a basic question: does the brain's immune system become hyperactive (inflamed) or does it become weakened (senescent) in elderly and demented people, and what is the impact on neuronal function and cognition? Here we strive to reconcile these seemingly contradictory notions by arguing that both low-grade neuroinflammation and microglial senescence are the result of aging-associated free radical injury. Both processes are damaging for microglia as they synergistically exhaust this essential cell population to the point where the brain's immune system is effete and unable to support neuronal function.

Histopathological changes in the pancreas of cattle with abdominal fat necrosis.

PubMed

Tani, Chikako; Pratakpiriya, Watanyoo; Tani, Mineto; Yamauchi, Takenori; Hirai, Takuya; Yamaguchi, Ryoji; Ano, Hitoshi; Katamoto, Hiromu

2017-01-20

The association between pancreatic disorder and abdominal fat necrosis in cattle remains unclear. The pancreases of 29 slaughtered cattle with or without fat necrosis were collected to investigate pathological changes. Japanese Black (JB) cattle were classified into the FN group (with abdominal fat necrosis; n=9) and N group (without fat necrosis; n=5). The pancreases were also collected from 15 Holstein Friesian (HF) cows. All JB cattle showed high body condition scores. Regarding the pathological findings, fatty pancreas which involves adipocyte infiltration into the pancreas and fat necrosis (saponification) were observed in 25 and 27 cases, respectively. Immunohistochemical staining with anti-Iba-1 antibody showed large numbers of macrophages surrounding the saponified fat in the pancreas. CD3-positive T cells were significantly more common in the pancreas of both the FN and N groups compared with the HF group (P<0.05). Furthermore, fibrosis in the pancreas exhibited a correlative tendency with the formation of necrotic fat mass in the peritoneal cavity (P<0.1). These results indicate that obesity leads to increased severity of pancreatic disorder, including fatty pancreas and pancreatitis. The pathological lesions in the pancreas may play a key role in abdominal fat necrosis through the inflammatory process.

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

PubMed

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

1992-09-01

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

Ultra-high magnetic resonance imaging (MRI): a potential examination for deep brain stimulation devices and the limitation study concerning MRI-related heating injury.

PubMed

Chen, Ying-Chuan; Li, Jun-Ju; Zhu, Guan-Yu; Shi, Lin; Yang, An-Chao; Jiang, Yin; Zhang, Xin; Zhang, Jian-Guo

2017-03-01

Nowadays, the patients with deep brain stimulation (DBS) devices are restricted to undertake 1.5T magnetic resonance imaging (MRI) according to the guideline. Nevertheless, we conducted an experiment to test pathological change near the leads in different field-strength MRI. Twenty-four male New Zealand rabbits were assigned to Group 1 (G1, n = 6, 7.0T, DBS), Group 2 (G2, n = 6, 3.0T, DBS), Group 3 (G3, n = 6, 1.5T, DBS), and Group 4 (G4, n = 6, 1.5T, paracentesis). DBS leads were implanted in G1, G2 and G3, targeting left nucleus ventralis posterior thalami. Paracentesis was performed in G4. 24 h after MRI scan, all animals were killed for examining pathological alternation (at different distance from lead) via transmission electron microscopy. Our results suggest that the severity of tissue injury correlates with the distance to electrode instead of field strength of MRI. Up to now, the reason for the restriction of MRI indicated no significantly different pathological change.

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

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

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

2013-11-01

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

Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice

PubMed Central

2009-01-01

To determine if nuclear factor-κB (NF-κB) activation may be a key factor in lung inflammation and respiratory dysfunction, we investigated whether NF-κB can be blocked by intratracheal administration of NF-κB decoy oligodeoxynucleotides (ODNs), and whether decoy ODN-mediated NF-κB inhibition can prevent smoke-induced lung inflammation, respiratory dysfunction, and improve pathological alteration in the small airways and lung parenchyma in the long-term smoke-induced mouse model system. We also detected changes in transcriptional factors. In vivo, the transfection efficiency of NF-κB decoy ODNs to alveolar macrophages in BALF was measured by fluorescein isothiocyanate (FITC)-labeled NF-κB decoy ODNs and flow cytometry post intratracheal ODN administration. Pulmonary function was measured by pressure sensors, and pathological changes were assessed using histology and the pathological Mias software. NF-κB and activator protein 1(AP-1) activity was detected by the electrophoretic motility shift assay (EMSA). Mouse cytokine and chemokine pulmonary expression profiles were investigated by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and lung tissue homogenates, respectively, after repeated exposure to cigarette smoke. After 24 h, the percentage of transfected alveolar macrophages was 30.00 ± 3.30%. Analysis of respiratory function indicated that transfection of NF-κB decoy ODNs significantly impacted peak expiratory flow (PEF), and bronchoalveolar lavage cytology displayed evidence of decreased macrophage infiltration in airways compared to normal saline-treated or scramble NF-κB decoy ODNs smoke exposed mice. NF-κB decoy ODNs inhibited significantly level of macrophage inflammatory protein (MIP) 1α and monocyte chemoattractant protein 1(MCP-1) in lung homogenates compared to normal saline-treated smoke exposed mice. In contrast, these NF-κB decoy ODNs-treated mice showed significant increase in the level of tumor necrosis factor-α(TNF-α) and pro-MMP-9(pro-matrix metalloproteinase-9) in mice BALF. Further measurement revealed administration of NF-κB decoy ODNs did not prevent pathological changes. These findings indicate that NF-κB activation play an important role on the recruitment of macrophages and pulmonary dysfunction in smoke-induced chronic lung inflammation, and with the exception of NF-κB pathway, there might be complex mechanism governing molecular dynamics of pro-inflammatory cytokines expression and structural changes in small airways and pulmonary parenchyma in vivo. PMID:19706153

Immunology of Gut-Bone Signaling.

PubMed

Collins, Fraser L; Schepper, Jonathan D; Rios-Arce, Naiomy Deliz; Steury, Michael D; Kang, Ho Jun; Mallin, Heather; Schoenherr, Daniel; Camfield, Glen; Chishti, Saima; McCabe, Laura R; Parameswaran, Narayanan

2017-01-01

In recent years a link between the gastrointestinal tract and bone health has started to gain significant attention. Dysbiosis of the intestinal microbiota has been linked to the pathology of a number of diseases which are associated with bone loss. In addition modulation of the intestinal microbiota with probiotic bacteria has revealed to have both beneficial local and systemic effects. In the present chapter, we discuss the intestinal and bone immune systems, explore how intestinal disease affects the immune system, and examine how these pathologic changes could adversely impact bone health.

Immunology of Gut Bone Signaling

PubMed Central

Collins, Fraser L.; Schepper, Jonathan; Rios-Arce, Naiomy Deliz; Steury, Michael; Kang, Ho Jun; Mallin, Heather; Schoenherr, Daniel; Camfield, Glen; Chishti, Saima; McCabe, Laura R; Parameswaran, Narayanan

2017-01-01

In recent years a link between the gastro-intestinal tract and bone health has started to gain significant attention. Dysbiosis of the intestinal microbiota has been linked to the pathology of a number of diseases which are associated with bone loss. In addition modulation of the intestinal microbiota with probiotic bacteria has revealed to have both beneficial local and systemic effects. In the present chapter we discuss the intestinal and bone immune systems, explore how intestinal disease affects the immune system and examine how these pathologic changes could adversely impact bone health. PMID:29101652

Pathology of orbital bones. The XXXII Edward Jackson Memorial Lecture.

PubMed

Blodi, F C

1976-01-01

The orbital bones may show nearly all the pathologic changes observed in the skull and in the face. The congenital anomalies in this area are numerous and involve various forms of craniostenoses. Among the benign osseous tumors the osteoma is most frequently encountered in the orbit. Fibrous dysplasia is a tumefaction of indeterminate behavior that often involves the orbit. Osteosarcoma or other malignant neoplasms are rarely seen in this area. Eosinophilic granuloma and Hand-Schüller-Christian disease are tumor-like lesions that may involve the orbit.

Clinical Applications for Exercise.

ERIC Educational Resources Information Center

Goldstein, David

1989-01-01

Patients with chronic conditions such as coronary artery disease, hypertension, diabetes, and obesity might benefit from prescribed exercise. Although exercise does not reverse pathologic changes, it may play a role in disease management. (JD)

Maternal Serum Lipid, Estradiol, and Progesterone Levels in Pregnancy, and the Impact of Placental and Hepatic Pathologies

PubMed Central

Pecks, U.; Rath, W.; Kleine-Eggebrecht, N.; Maass, N.; Voigt, F.; Goecke, T. W.; Mohaupt, M. G.; Escher, G.

2016-01-01

Objective: Lipids and steroid hormones are closely linked. While cholesterol is the substrate for (placental) steroid hormone synthesis, steroid hormones regulate hepatic lipid production. The aim of this study was to quantify circulating steroid hormones and lipid metabolites, and to characterize their interactions in normal and pathological pregnancies with a focus on hepatic and placental pathologies. Methods: A total of 216 serum samples were analyzed. Group A consisted of 32 patients with uncomplicated pregnancies who were analyzed at three different time-points in pregnancy (from the first through the third trimester) and once post partum. Group B consisted of 36 patients (24th to 42nd week of gestation) with pregnancy pathologies (IUGR n = 10, preeclampsia n = 13, HELLP n = 6, intrahepatic cholestasis n = 7) and 31 controls with uncomplicated pregnancies. Steroid profiles including estradiol, progesterone, and dehydroepiandrosterone were measured by GC-MS and compared with lipid concentrations. Results: In Group A, cholesterol and triglycerides correlated positively with estradiol (cholesterol ρ = 0.50, triglycerides ρ = 0.57) and progesterone (ρ = 0.49, ρ = 0.53) and negatively with dehydroepiandrosterone (ρ = − 0.47, ρ = − 0.38). Smoking during pregnancy affected estradiol concentrations, leading to lower levels in the third trimester compared to non-smoking patients (p < 0.05). In Group B, cholesterol levels were found to be lower in IUGR pregnancies and in patients with HELLP syndrome compared to controls (p < 0.05). Steroid hormone concentrations of estradiol (p < 0.05) and progesterone (p < 0.01) were lower in pregnancies with IUGR. Discussion: Lipid and steroid levels were affected most in IUGR pregnancies, while only minor changes in concentrations were observed for other pregnancy-related disorders. Each of the analyzed entities displayed specific changes. However, since the changes were most obvious in pregnancies complicated by IUGR and only minor changes were observed in pregnancies where patients had impaired liver function, our data suggests that placental rather than maternal hepatic function strongly determines lipid and steroid levels in pregnancy. PMID:27582578

Comprehensive proteomic profiles of mouse AApoAII amyloid fibrils provide insights into the involvement of lipoproteins in the pathology of amyloidosis.

PubMed

Miyahara, Hiroki; Sawashita, Jinko; Ishikawa, Eri; Yang, Mu; Ding, Xin; Liu, Yingye; Hachiya, Naomi; Kametani, Fuyuki; Yazaki, Masahide; Mori, Masayuki; Higuchi, Keiichi

2018-02-10

Amyloidosis is a disorder characterized by extracellular fibrillar deposits of misfolded proteins. The amyloid deposits commonly contain several non-fibrillar proteins as amyloid-associated proteins, but their roles in amyloidosis pathology are still unknown. In mouse senile amyloidosis, apolipoprotein A-II (ApoA-II) forms extracellular amyloid fibril (AApoAII) deposits with other proteins (AApoAII-associated proteins) in many organs. We previously reported that R1.P1-Apoa2 c mice provide a reproducible model of AApoAII amyloidosis. In order to investigate the sequential alterations of AApoAII-associated protein, we performed a proteomic analysis of amyloid fibrils extracted from mouse liver tissues that contained different levels of AApoAII deposition. We identified 6 AApoAII-associated proteins that constituted 20 of the top-ranked proteins in mice with severe AApoAII deposition. Although the amount of AApoAII-associated proteins increased with the progression of amyloidosis, the relative abundance of AApoAII-associated proteins changed little throughout the progression of amyloidosis. On the other hand, plasma levels of these proteins showed dramatic changes during the progression of amyloidosis. In addition, we confirmed that AApoAII-associated proteins were significantly associated with lipid metabolism based on functional enrichment analysis, and lipids were co-deposited with AApoAII fibrils from early stages of development of amyloidosis. Thus, these results demonstrate that lipoproteins are involved in AApoAII amyloidosis pathology. This study presented proteomic profiles of AApoAII amyloidosis during disease progression and it revealed co-deposition of lipids with AApoAII deposits based on functional analyses. The relative abundance of AApoAII-associated proteins in the amyloid fibril fractions did not change over the course of development of AApoAII amyloidosis pathology. However, their concentrations in plasma changed dramatically with progression of the disease. Interestingly, several AApoAII-associated proteins have been found as constituents of lipid-rich lesions of other degenerative diseases, such as atherosclerosis and age-related macular degeneration. The common protein components among these diseases with lipid-rich deposits could be accounted for by a lipoprotein retention model. Copyright © 2017 Elsevier B.V. All rights reserved.

Mouse model of plasma cell mastitis.

PubMed

Yu, Jian-jun; Bao, Shan-lin; Yu, Sheng-lin; Zhang, Da-Qing; Loo, Wings T Y; Chow, Louis W C; Su, Li; Cui, Zhen; Chen, Kai; Ma, Li-Qiong; Zhang, Ning; Yu, Hui; Yang, Yun-Zhen; Dong, Yu; Yip, Adrian Y S; Ng, Elizabeth L Y

2012-09-19

Plasma cell mastitis is distinct from the common form of mastitis and clinically resembles breast carcinoma. The lesion occurs in non-lactating young women, and the incidence rate is rising. Surgical resection is the main treatment, but cannot prevent recurrence of the disease. Disfigurement or removal of breast after the operations can cause marked physical and psychological distress. The etiology of plasma cell mastitis is unclear up till now. It is therefore necessary to investigate further the underlying immunological changes of the disease. The lesions of plasma cell mastitis removed from patients through aseptic operation were mixed with normal saline into homogenate tube machine (homogenate tubes were disinfected and sterilized prior to treatment). The mixture was homogenized at medium speed and grinded in ultrasonic cell disruptor. The homogenate obtained was made into oil emulsion with Freund's adjuvant. Thirty female BALB/c mice (6 weeks after sexual maturity) were divided into five groups A-E: group A was blank control; group B was normal saline control; group C was inoculated with 0.02 ml water-in-oil emulsion; group D was inoculated with 0.04 ml water-in-oil emulsion; group E was complete Freund's adjuvant control. Pathology results showed that mouse mammary gland acinar cells remained integral without any abnormal changes observed in control groups A and B. Experimental groups C and D showed dilation of mouse mammary ductal tissue with a large number of epithelial cells and debris in the lumen, and fibrosis around ducts accompanied by large duct cells, neutrophils, lymphocytes, and especially plasma cell infiltration. Pathological changes were observed in 3 (50%) mice and 5 (83.3%) mice in group C and D respectively. In group E, neutrophil infiltration in mammary gland was observed in 5 mice, but neither infiltration of plasma cells nor other abnormal pathological changes were observed. The lesions of patient with plasma cell mastitis could make the female BALB/c mice experience the similar clinical and pathological manifestation. High-dose group can successfully establish a mouse model of plasma cell mastitis.

Pre-amyloid oligomers budding:a metastatic mechanism of proteotoxicity

NASA Astrophysics Data System (ADS)

Bernini, Fabrizio; Malferrari, Daniele; Pignataro, Marcello; Bortolotti, Carlo Augusto; di Rocco, Giulia; Lancellotti, Lidia; Brigatti, Maria Franca; Kayed, Rakez; Borsari, Marco; Del Monte, Federica; Castellini, Elena

2016-10-01

The pathological hallmark of misfolded protein diseases and aging is the accumulation of proteotoxic aggregates. However, the mechanisms of proteotoxicity and the dynamic changes in fiber formation and dissemination remain unclear, preventing a cure. Here we adopted a reductionist approach and used atomic force microscopy to define the temporal and spatial changes of amyloid aggregates, their modes of dissemination and the biochemical changes that may influence their growth. We show that pre-amyloid oligomers (PAO) mature to form linear and circular protofibrils, and amyloid fibers, and those can break reforming PAO that can migrate invading neighbor structures. Simulating the effect of immunotherapy modifies the dynamics of PAO formation. Anti-fibers as well as anti-PAO antibodies fragment the amyloid fibers, however the fragmentation using anti-fibers antibodies favored the migration of PAO. In conclusion, we provide evidence for the mechanisms of misfolded protein maturation and propagation and the effects of interventions on the resolution and dissemination of amyloid pathology.

[Pathological changes in rat model of urinary calculus induced by melamine].

PubMed

Shen, Ying; Sun, Ning; Wang, Guan-nan; He, Le-jian; Jia, Li-qun; Wang, Yu; Xiao, Hong-zhan; Lü, Rui-fen

2011-09-01

To investigate melamine-induced pathological changes in the kidney. Wistar rats were fed with a diet containing 0, 1% and 2% melamine for 15 weeks. After melamine feeding was stopped, various outcome measures were observed for 4 weeks. Rats fed with melamine showed reduced caloric intake, slower weight gain and impaired renal function. The blood urea nitrogen of group A and B [(13.23 ± 5.10) mmol/L and (18.30 ± 5.90) mmol/L, respectively] and serum creatinine levels of group B [(19.90 ± 2.90) mmol/L] were higher than that of group C [(8.23 ± 2.30) mmol/L and (10.04 ± 1.73) mmol/L](P < 0.01, respectively). Additionally, the kidney coefficients of group A and B were higher than that of group C (P < 0.01, respectively). Crystals, tubular ectasia and interstitial inflammation and fibrosis were found in the kidneys of melamine fed rats. Four weeks after discontinuation of feeding with melamine-contained diet, the caloric intake and weight of the rats increased, the coefficients of the kidney decreased, and the blood urea nitrogen of group A and B [(17.96 ± 2.04) mmol/L and (19.20 ± 3.36) mmol/L, respectively] and serum creatinine levels of group B [(24.20 ± 5.28) mmol/L], which became worse than 4 weeks before (P < 0.01;P < 0.05, respectively), and were still higher than that of group C [(8.30 ± 1.79) mmol/L and (9.87 ± 2.71) mmol/L, P < 0.01, respectively]. Crystals remained inside the kidney, changes in the renal interstitium did not improve. (1) Melamine-induced urinary calculus rat model can be established by feeding 3-week old male Wistar rats with a diet containing 2% melamine for 15 weeks. The main constituent of the urinary calculus was melamine (> 90%), with a little uric acid and traces of cyanuric acid. (2) Melamine damaged the renal function, formed renal crystals, and led to the pathological changes of kidneys. All the influences seemed to be dose-depended and was related with the obstruction of the crystals or calculus in the kidney. (3) The renal function and the pathological changes did not improve 4 weeks after discontinuation of feeding with melamine-contained diet.

Dissecting the pathobiology of altered MRI signal in amyotrophic lateral sclerosis: A post mortem whole brain sampling strategy for the integration of ultra-high-field MRI and quantitative neuropathology.

PubMed

Pallebage-Gamarallage, Menuka; Foxley, Sean; Menke, Ricarda A L; Huszar, Istvan N; Jenkinson, Mark; Tendler, Benjamin C; Wang, Chaoyue; Jbabdi, Saad; Turner, Martin R; Miller, Karla L; Ansorge, Olaf

2018-03-13

Amyotrophic lateral sclerosis (ALS) is a clinically and histopathologically heterogeneous neurodegenerative disorder, in which therapy is hindered by the rapid progression of disease and lack of biomarkers. Magnetic resonance imaging (MRI) has demonstrated its potential for detecting the pathological signature and tracking disease progression in ALS. However, the microstructural and molecular pathological substrate is poorly understood and generally defined histologically. One route to understanding and validating the pathophysiological correlates of MRI signal changes in ALS is to directly compare MRI to histology in post mortem human brains. The article delineates a universal whole brain sampling strategy of pathologically relevant grey matter (cortical and subcortical) and white matter tracts of interest suitable for histological evaluation and direct correlation with MRI. A standardised systematic sampling strategy that was compatible with co-registration of images across modalities was established for regions representing phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) patterns that were topographically recognisable with defined neuroanatomical landmarks. Moreover, tractography-guided sampling facilitated accurate delineation of white matter tracts of interest. A digital photography pipeline at various stages of sampling and histological processing was established to account for structural deformations that might impact alignment and registration of histological images to MRI volumes. Combined with quantitative digital histology image analysis, the proposed sampling strategy is suitable for routine implementation in a high-throughput manner for acquisition of large-scale histology datasets. Proof of concept was determined in the spinal cord of an ALS patient where multiple MRI modalities (T1, T2, FA and MD) demonstrated sensitivity to axonal degeneration and associated heightened inflammatory changes in the lateral corticospinal tract. Furthermore, qualitative comparison of R2* and susceptibility maps in the motor cortex of 2 ALS patients demonstrated varying degrees of hyperintense signal changes compared to a control. Upon histological evaluation of the same region, intensity of signal changes in both modalities appeared to correspond primarily to the degree of microglial activation. The proposed post mortem whole brain sampling methodology enables the accurate intraindividual study of pathological propagation and comparison with quantitative MRI data, to more fully understand the relationship of imaging signal changes with underlying pathophysiology in ALS.

The changes of serum proteome and tissular pathology in mouse induced by botulinum toxin E injection.

PubMed

Wang, J F; Mao, X Y; Zhao, C

2014-01-01

The experiment were performed to investigate the poisoning-related proteins and main pathological changes after mouse suffered from injection of botulinum toxin serotype E. Dose of 0.75 LD50 botulinum toxin serotype E per mice were administrated by intraperitoneal injection. Survival mouse were picked as experimental group. The blood were collected from orbital blood and serum sample was separated by centrifugation. The heart, liver, spleen, lung, kidney were fixed in 10 % neutral buffered formalin and then developed paraffin sections. Serum protein components were analyzed by SDS-PAGE gel electrophoresis coupled with 2-DE SDS-PAGE gel electrophoresis. Differentially expressed proteins were analyzed by PDQUest8.0 software and subjected to ion trap mass spectrometry equipped with a high performance liquid chromatography system. The observation of pathological section showed that heart, liver, spleen, lung, kidney exhibited pathological changes in different degree, especially in heart, liver and lung tissues. Heart muscle tissue display serious inflammatory response, heart muscle fiber compulsively expanded and filled with erythrocyte and inflammatory exudates, some heart muscle fiber ruptured, even necrosis; hepatic cell in edge of liver occur apoptosis and some hepatic cell have disintegrated, and even died; pulmonary alveoli broken and partial vein filled with blood. Serum proteins component present a significant changes between control serum and botulism in 24 h by SDS-PAGE gel electrophoresis and 2-DE-SDS-PAGE gel electrophoresis. Twenty differentially expressed protein spots were observed in 2-DE profiles, in which 14 protein spots were undetectable in serum proteome under botulism, 3 protein spots exclusively expressed in state of botulism, 3 protein spots were low-expressed in serum proteome under botulism. Fourteen proteins have been identified among 20 spots elected on two-dimensional electrophoresis gels. Crystal proteins family exclusively expressed in control group serum. Haptoglobin were low-expressed under botulism in serum protein components, however, serum amyloid A only expressed in serum sample under botulism in 24 h, which were verified by Western-blot. Identified proteins involved in energy metabolism, cellular stress response, transcription, body defense and cell proliferation. These findings represent the first report of BoNT-induced changes in serum proteome and histopathology, and reinforce the utility of applying proteomic tools to the study of system-wide biological processes in normal and botulism.

Dynamic Changes in Striatal mGluR1 But Not mGluR5 during Pathological Progression of Parkinson's Disease in Human Alpha-Synuclein A53T Transgenic Rats: A Multi-PET Imaging Study.

PubMed

Yamasaki, Tomoteru; Fujinaga, Masayuki; Kawamura, Kazunori; Furutsuka, Kenji; Nengaki, Nobuki; Shimoda, Yoko; Shiomi, Satoshi; Takei, Makoto; Hashimoto, Hiroki; Yui, Joji; Wakizaka, Hidekatsu; Hatori, Akiko; Xie, Lin; Kumata, Katsushi; Zhang, Ming-Rong

2016-01-13

Parkinson's disease (PD) is a prevalent degenerative disorder affecting the CNS that is primarily characterized by resting tremor and movement deficits. Group I metabotropic glutamate receptor subtypes 1 and 5 (mGluR1 and mGluR5, respectively) are important targets for investigation in several CNS disorders. In the present study, we investigated the in vivo roles of mGluR1 and mGluR5 in chronic PD pathology by performing longitudinal positron emission tomography (PET) imaging in A53T transgenic (A53T-Tg) rats expressing an abnormal human α-synuclein (ASN) gene. A53T-Tg rats showed a dramatic decline in general motor activities with age, along with abnormal ASN aggregation and striatal neuron degeneration. In longitudinal PET imaging, striatal nondisplaceable binding potential (BPND) values for [(11)C]ITDM (N-[4-[6-(isopropylamino) pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[(11)C]methylbenzamide), a selective PET ligand for mGluR1, temporarily increased before PD symptom onset and dramatically decreased afterward with age. However, striatal BPND values for (E)-[(11)C]ABP688 [3-(6-methylpyridin-2-ylethynyl)-cyclohex-2-enone-(E)-O-[(11)C]methyloxime], a specific PET ligand for mGluR5, remained constant during experimental terms. The dynamic changes in striatal mGluR1 BPND values also showed a high correlation in pathological decreases in general motor activities. Furthermore, declines in mGluR1 BPND values were correlated with decreases in BPND values for [(18)F]FE-PE2I [(E)-N-(3-iodoprop-2E-enyl)-2β-carbo-[(18)F]fluoroethoxy-3β-(4-methylphenyl) nortropane], a specific PET ligand for the dopamine transporter, a biomarker for dopaminergic neurons. In conclusion, our results have demonstrated for the first time that dynamic changes occur in mGluR1, but not mGluR5, that accompany pathological progression in a PD animal model. Synaptic signaling by glutamate, the principal excitatory neurotransmitter in the brain, is modulated by group I metabotropic glutamate receptors, including the mGluR1 and mGluR5 subtypes. In the brain, mGluR1 and mGluR5 have distinct functional roles and regional distributions. Their roles in brain pathology, however, are not well characterized. Using longitudinal PET imaging in a chronic rat model of PD, we demonstrated that expression of mGluR1, but not mGluR5, dynamically changed in the striatum accompanying pathological PD progression. These findings imply that monitoring mGluR1 in vivo may provide beneficial information to further understand central nervous system disorders. Copyright © 2016 the authors 0270-6474/16/360376-10$15.00/0.

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

PubMed

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

1995-01-01

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

Digital image analysis in pathology: benefits and obligation.

PubMed

Laurinavicius, Arvydas; Laurinaviciene, Aida; Dasevicius, Darius; Elie, Nicolas; Plancoulaine, Benoît; Bor, Catherine; Herlin, Paulette

2012-01-01

Pathology has recently entered the era of personalized medicine. This brings new expectations for the accuracy and precision of tissue-based diagnosis, in particular, when quantification of histologic features and biomarker expression is required. While for many years traditional pathologic diagnosis has been regarded as ground truth, this concept is no longer sufficient in contemporary tissue-based biomarker research and clinical use. Another major change in pathology is brought by the advancement of virtual microscopy technology enabling digitization of microscopy slides and presenting new opportunities for digital image analysis. Computerized vision provides an immediate benefit of increased capacity (automation) and precision (reproducibility), but not necessarily the accuracy of the analysis. To achieve the benefit of accuracy, pathologists will have to assume an obligation of validation and quality assurance of the image analysis algorithms. Reference values are needed to measure and control the accuracy. Although pathologists' consensus values are commonly used to validate these tools, we argue that the ground truth can be best achieved by stereology methods, estimating the same variable as an algorithm is intended to do. Proper adoption of the new technology will require a new quantitative mentality in pathology. In order to see a complete and sharp picture of a disease, pathologists will need to learn to use both their analogue and digital eyes.

Pathological diagnosis is maybe non-essential for special gastric cancer: case reports and review.

PubMed

Song, Wu; Chen, Chun-Yu; Xu, Jian-Bo; Ye, Jin-Ning; Wang, Liang; Chen, Chuang-Qi; Zhang, Xin-Hua; Cai, Shi-Rong; Zhan, Wen-Hua; He, Yu-Long

2013-06-28

Histopathological results are critical for the diagnosis and surgical decision regarding gastric cancer. However, opposite opinions from radiology and pathology can sometimes affect clinical decisions. The two cases reported in this article were both highly suspected as gastric cancer by clinical manifestations and radiologic findings, although both showed negative results in the first biopsy examination. One was confirmed as gastric cancer by the time of the 6(th) biopsy, while the other was still negative even after 8 biopsies. With a definite pathologic result and the agreement of the patient for the latter case, both of them finally received surgery. Postoperative pathological examination revealed findings that were the same as Borrmann type IV gastric cancer. We believed that duplicate biopsies under radiologic guidance were necessary for highly suspected gastric cancer cases in the absence of a definite pathology result, and patients should be under close follow-up. We propose that, if gastric cancer is highly suspected when typical radiology changes of widely diffuse gastric parietal lesions suffice to exclude lymphoma and other similar situations, and even in absence of a positive biopsy result, a diagnostic laparotomy under laparoscopy and even radical gastrectomy may be reasonably performed by an experienced gastric cancer center with the agreement of the patient after being decided by a multidisciplinary discussion team.

Predicting Problematic Alcohol Use with the DSM-5 Alternative Model of Personality Pathology

PubMed Central

Creswell, Kasey G.; Bachrach, Rachel L.; Wright, Aidan G.C.; Pinto, Anthony; Ansell, Emily

2015-01-01

There is high comorbidity between personality disorders and alcohol use disorders, which appears related to individual differences in underlying personality dimensions of behavioral undercontrol and affective dysregulation. Very little is known about how the DSM-5 Section III trait model of personality pathology relates to alcohol problems, however, or how the strength of the relationship between personality pathology and alcohol problems changes with age and across gender. The current study examined these questions in a sample of 877 participants using the General Assessment of Personality Disorder to assess general personality dysfunction, the Personality Inventory for DSM-5 to measure specific traits, and the Alcohol Use Disorder Identification Test to assess problematic alcohol use. Results demonstrated that general personality pathology (Criterion A) was significantly related to problematic alcohol use after controlling for age and gender effects. Further, two of the five higher-order personality trait domains (Criterion B), Antagonism and Disinhibition, remained significant predictors of problematic alcohol use after accounting for the influence of general personality pathology; however, general personality pathology no longer predicted hazardous alcohol use once Antagonism and Disinhibition were added into the model. Finally, these two specific traits interacted with age, such that Antagonism was a stronger predictor of AUDIT scores among older individuals and Disinhibition was a stronger predictor of alcohol problems among younger individuals. Findings support the general validity of this new personality disorder diagnostic system and suggest important age effects in the relationship between traits and problematic alcohol use. PMID:26389625

The Takei Handheld Dynamometer: An Effective Clinical Outcome Measure Tool for Hand and Wrist Function in Boxing.

PubMed

Gatt, Ian; Smith-Moore, Sophie; Steggles, Charlie; Loosemore, Mike

2018-05-01

The aim of this article was to explore retrospectively the Takei dynamometer as a valid and reliable outcome measure tool for hand and wrist pathology in the Great Britain amateur boxing squad between 2010 and 2014. Longitudinal retrospective injury surveillance of the Great Britain boxing squad was performed from 2010 to 2014. The location, region affected, description, and duration of each injury were recorded by the team doctor and team physiotherapists. For each significant injury, we recorded hand grip scores using the Takei handheld dynamometer and compared the scores with baseline measures. At the hand, fractures and dislocations were highly detected with an average difference of 40.2% ( P < .05) when comparing postinjury to baseline measures. At the wrist, carpometacarpal and carpal joint injuries were highly detected with an average difference of 32.6% ( P < .05). Other injuries provided varied results. In the absence of pathology, up to 15% difference between left and right scores can be considered normal with a predominance observed below 10%. A difference of 20% can be indicative of a form of pathology, although pathologies can also be present with lower difference or no apparent changes. A difference of >20% should be highly considered for significant pathology. The Takei dynamometer is a valid and reliable outcome measure tool for hand and wrist pathologies in boxing. Our study highlights the importance of appropriate clinical tools to guide injury management in this sport.

Functional Assays for Neurotoxicity Testing

EPA Science Inventory

Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

Functional Assays for Neurotoxicity Testing*

EPA Science Inventory

Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

Dietary Protection Against Pulmonary Oxygen Poisoning.

DTIC Science & Technology

1980-12-31

hyperoxia produces pathological changes in lung which can be fatal. With an interest in delineating dietary factors which might affect the pulmonary response...by dietary fat type (6,7). This study was conducted to investigate any changes in pulmonary PG synthetic capacity following treatment with diets...at 1 atmosphere in controlled environment chambers (9). In our mc3Rl system oxygen exposure produces discernible pulmonary biochem-cal changes after 24

Pathology of deaths associated with "ecstasy" and "eve" misuse.

PubMed

Milroy, C M; Clark, J C; Forrest, A R

1996-02-01

To study the postmortem pathology associated with ring substituted amphetamine (amphetamine derivatives) misuse. The postmortem findings in deaths associated with the ring substituted amphetamines 3,4-methylenedioxymethyl-amphetamine (MDMA, ecstasy) and 3,4-methylenedioxyethylamphetamine (MDEA, eve) were studied in seven young white men aged between 20 and 25 years. Striking changes were identified in the liver, which varied from foci of individual cell necrosis to centrilobular necrosis. In one case there was massive hepatic necrosis. Changes consistent with catecholamine induced myocardial damage were seen in five cases. In the brain perivascular haemorrhagic and hypoxic changes were identified in four cases. Overall, the changes in four cases were the same as those reported in heart stroke, although only two cases had a documented history of hyperthermia. Of these four cases, all had changes in their liver, three had changes in their brains, and three in their heart. Of the other three cases, one man died of fulminant liver failure, one of water intoxication and one probably from a cardiac arrhythmia associated with myocardial fibrosis. These data suggest that there is more than one mechanism of damage in ring substituted amphetamine misuse, injury being caused by hyperthermia in some cases, but with ring substituted amphetamines also possibly having a toxic effect on the liver and other organs in the absence of hyperthermia.

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

NASA Technical Reports Server (NTRS)

Furukawa, S.

1975-01-01

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

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

PubMed

Seemann, Sophie

2016-01-01

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

Is synaptic loss a unique hallmark of Alzheimer's disease?

PubMed Central

Scheff, Stephen W.; Neltner, Janna H.; Nelson, Peter T.

2014-01-01

Synapses may represent a key nidus for dementia including Alzheimer's disease (AD) pathogenesis. Here we review published studies and present new ideas related to the question of the specificity of synapse loss in AD. Currently, AD is defined by the regional presence of neuritic plaques and neurofibrillary tangles in the brain. The severity of involvement by those pathological hallmarks tends to correlate both with antemortem cognitive status, and also with synapse loss in multiple brain areas. Recent studies from large autopsy series have led to a new standard of excellence with regard to clinical–pathological correlation and to improved comprehension of the numerous brain diseases of the elderly. These studies have provided evidence that it is the rule rather than the exception for brains of aged individuals to demonstrate pathologies (often multiple) other than AD plaques and tangles. For many of these comorbid pathologies, the extent of synapse loss is imperfectly understood but could be substantial. These findings indicate that synapse loss is probably not a hallmark specific to AD but rather a change common to many diseases associated with dementia. PMID:24412275