Sample records for atrophy diagnosed immunohistochemically

  1. Gastric atrophy, diagnosing and staging

    Institute of Scientific and Technical Information of China (English)

    Hala MT El-Zimaity


    H pylori is now accepted as the cause of gastritis and gastritis-associated diseases, such as duodenal ulcer,gastric ulcer, gastric carcinoma, and gastric MALT lymphoma. The natural history of H pylori gastritis includes inflammation progressing from the antrum into the adjacent corpus resulting in an atrophic front of advancing injury leading to a reduction in acid secretion and eventual loss of parietal cells and development of atrophy. Sub-typing intestinal metaplasia has no clinical value to the patient, the pathologist, or the endoscopist.The pattern, extent, and severity of atrophy, with or without intestinal metaplasia, is a far more important predictor than is intestinal metaplasia subtype. The challenge remains to identify a reliable marker that relates to pre-malignant potential.

  2. Subclassification of newly diagnosed glioblastomas through an immunohistochemical approach.

    Directory of Open Access Journals (Sweden)

    Siobhan Conroy

    Full Text Available Molecular signatures in Glioblastoma (GBM have been described that correlate with clinical outcome and response to therapy. The Proneural (PN and Mesenchymal (MES signatures have been identified most consistently, but others including Classical (CLAS have also been reported. The molecular signatures have been detected by array techniques at RNA and DNA level, but these methods are costly and cannot take into account individual contributions of different cells within a tumor. Therefore, the aim of this study was to investigate whether subclasses of newly diagnosed GBMs could be assessed and assigned by application of standard pathology laboratory procedures. 123 newly diagnosed GBMs were analyzed for the tumor cell expression of 23 pre-identified proteins and EGFR amplification, together allowing for the subclassification of 65% of the tumors. Immunohistochemistry (IHC-based profiling was found to be analogous to transcription-based profiling using a 9-gene transcriptional signature for PN and MES subclasses. Based on these data a novel, minimal IHC-based scheme for subclass assignment for GBMs is proposed. Positive staining for IDH1R132H can be used for PN subclass assignment, high EGFR expression for the CLAS subtype and a combined high expression of PTEN, VIM and/or YKL40 for the MES subclass. The application of the proposed scheme was evaluated in an independent tumor set, which resulted in similar subclass assignment rates as those observed in the training set. The IHC-based subclassification scheme proposed in this study therefore could provide very useful in future studies for stratification of individual patient samples.

  3. Optic atrophy differentially diagnosed as spinocerebellar ataxia from Leber hereditary optic neuropathy by gene mutation analysis. (United States)

    Song, Y P; Chen, Z S; Mo, G Y; Ding, Q; Zhu, L; Yan, M


    Optic atrophy describes a group of diseases of retinal ganglion cells and axons that eventually lead to loss of vision. Optic atrophy has both congenital and acquired causes, and its diagnosis (or differential diagnosis) is complicated. This case report describes a 20-year-old man who presented with a 1-year history of progressive vision loss in both eyes and no obvious systemic symptoms. Fundus examination revealed bilateral optic atrophy. Based on clinical characteristics, visual field analysis and pattern visual evoked potential examination, the presumptive diagnosis was Leber hereditary optic neuropathy (LHON). Analysis of mitochondrial DNA indicated the absence of all of three common mutations associated with LHON (m.3460G>A, m.11778G>A, m.14484T>C). Detailed questioning of the patient revealed a history of prolonged language development and poor balance. Neurological examination indicated abnormal co-ordination, suggesting the presence of inherited spinocerebellar ataxia (SCA). Analysis of the SCA7 gene revealed a high number of trinucleotide repeats [(CAG)(n), n > 64], confirming the diagnosis of SCA. The aetiology of optic atrophies is complicated and the molecular genetic detection approach provides the best information for diagnosing these diseases.

  4. Adult Onset of BRAFV600E-Mutated Langerhans Cell Histiocytosis with Cutaneous Involvement Successfully Diagnosed by Immunohistochemical Staining (United States)

    Tono, Hisayuki; Fujimura, Taku; Kakizaki, Aya; Furudate, Sadanori; Ishibashi, Masaya; Aiba, Setsuya


    Langerhans cell histiocytosis (LCH) is characterized by the clonal proliferation of Langerhans cells; it is categorized as a single-system disease with single or multifocal lesions, and as a multi-system disease with or without the risk of organ involvement. Although the skin is not categorized as a risk organ, the precise diagnosis of skin lesions is necessary to determine the protocol for the treatment of LCH. In this report, we describe a 28-year-old Japanese man with adult onset of BRAFV600E-mutated LCH with cutaneous involvement successfully diagnosed by immunohistochemical staining. Our report suggests that immunohistochemical staining for the BRAFV600E gene could be a diagnostic tool to determine the clinical type of LCH. PMID:26500535

  5. Adult Onset of BRAFV600E-Mutated Langerhans Cell Histiocytosis with Cutaneous Involvement Successfully Diagnosed by Immunohistochemical Staining

    Directory of Open Access Journals (Sweden)

    Hisayuki Tono


    Full Text Available Langerhans cell histiocytosis (LCH is characterized by the clonal proliferation of Langerhans cells; it is categorized as a single-system disease with single or multifocal lesions, and as a multi-system disease with or without the risk of organ involvement. Although the skin is not categorized as a risk organ, the precise diagnosis of skin lesions is necessary to determine the protocol for the treatment of LCH. In this report, we describe a 28-year-old Japanese man with adult onset of BRAFV600E-mutated LCH with cutaneous involvement successfully diagnosed by immunohistochemical staining. Our report suggests that immunohistochemical staining for the BRAFV600E gene could be a diagnostic tool to determine the clinical type of LCH.

  6. Leukocyte chemotactic factor 2 amyloidosis cannot be reliably diagnosed by immunohistochemical staining. (United States)

    Paueksakon, Paisit; Fogo, Agnes B; Sethi, Sanjeev


    We investigated the role of leukocyte chemotactic factor (LECT2) immunohistochemical staining in the diagnosis of type of renal amyloidosis. Fifty renal amyloidosis cases with available paraffin blocks in our 2002 to 2012 renal biopsy files were reviewed. Patients were designated as a defined amyloid, including amyloid light chain (AL) and amyloid-associated amyloid (AA), or a non-AL/non-AA amyloid group. LECT2-specific antibody immunohistochemistry was performed in all 50 cases. Laser microdissection and mass spectrometry (LMD/MS) were performed in 10 cases. Forty-five patients had amyloid classified as either AL (44) or AA (1), and 5 had undetermined amyloid. Three of the five non-AL/non-AA group patient biopsies showed positive LECT2 immunohistochemical staining, and of these, LECT2 was also identified by LMD/MS in 1 patient, fibrinogen-α was identified in 1 patient, and apolipoprotein IV was identified in 1 patient. Two of these non-AL/non-AA patients showed negative LECT2 staining, and LMD/MS showed apolipoprotein IV as a major protein component. Five of the 44 AL amyloid patients showed weakly positive LECT2 staining. However, LECT2 was not identified by LMD/MS in any of these 5 cases. The single patient with AA amyloid was negative for LECT2 by immunohistochemical staining. Among 5 non-AL and non-AA amyloidosis patients in our study, 1 had LECT2, 1 had fibrinogen-α, and 3 had apolipoprotein IV as a major protein component. The data from this study show that weak LECT2 staining should be regarded as indeterminate or a negative result and does not per se allow diagnosis of specific amyloid type. The diagnosis of LECT2 renal amyloidosis may require LMD/MS confirmation.

  7. Can patients without early, prominent visual deficits still be diagnosed of posterior cortical atrophy? (United States)

    Suárez-González, A.; Crutch, S.J.; Roldán Lora, F.; Franco-Macías, E.; Gil-Néciga, E.


    Background Early and progressive disabling visual impairment is a core feature for the diagnosis of posterior cortical atrophy (PCA). However, some individuals that fulfil criteria over time might initially present with an onset of prominent posterior dysfunction other than visuoperceptual. Methods The clinical profile of five patients with a predominantly ‘non-visual’ posterior presentation (PCA2) was investigated and compared with sixteen individuals with visually predominant PCA (PCA1) and eighteen with typical amnestic Alzheimer disease (tAD). Results PCA2 patients showed significantly better performance than PCA1 in one visuospatial task and were free of Balint's syndrome and visual agnosia. Compared to tAD, PCA2 showed trends towards significantly lower performance in visuoperceptual tasks, more severe apraxia and more symptoms of Gerstmann's syndrome. Conclusions Our sample of PCA2 patients did not present with clinically prominent visual symptoms but did show visual dysfunction on formal neuropsychological assessment (less pronounced than in PCA1 but more than in tAD) in addition to other posterior deficits. Broadening the definition of PCA to encompass individuals presenting with prominent ‘non-visual’ posterior dysfunction should be potentially considered in clinical and research contexts. PMID:27423559

  8. Vaginal Atrophy (United States)

    ... Body in Balance › Vaginal Atrophy Fact Sheet Vaginal Atrophy November, 2011 Download PDFs English Espanol Editors JoAnn ... MD Richard J. Santen, MD What is vaginal atrophy? Vaginal atrophy is a condition in which the ...

  9. How to diagnose muscular atrophy in children%小儿肌肉萎缩的诊断思路及鉴别诊断

    Institute of Scientific and Technical Information of China (English)



    在临床上,小儿肌肉萎缩较为常见,但由于皮下脂肪较厚不易发现.详细询问病史,仔细观察患儿的运动功能、哭声大小、卧位和坐立姿势,全面查体,合理的辅助检查等,均有助于早期诊断婴幼儿的肌肉萎缩疾病.%In clinical practice, muscular atrophy is a common sign in children. Because of relatively thick subcutaneous fat in children, muscular atrophy is not easy to be discovered. In order to confirm the diagnosis earlier, it is very important to take history in detail, to observe the motor function, cry, the posture of sitting and standing carefully, to do the physical examination thoroughly, and to use the assistant test reasonably.

  10. Solving a 50 year mystery of a missing OPA1 mutation: more insights from the first family diagnosed with autosomal dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Zrenner Eberhart


    Full Text Available Abstract Background Up to the 1950s, there was an ongoing debate about the diversity of hereditary optic neuropathies, in particular as to whether all inherited optic atrophies can be ascribed to Leber's hereditary optic neuropathy (LHON or represent different disease entities. In 1954 W. Jaeger published a detailed clinical and genealogical investigation of a large family with explicit autosomal dominant segregation of optic atrophy thus proving the existence of a discrete disease different from LHON, which is nowadays known as autosomal dominant optic atrophy (ADOA. Since the year 2000 ADOA is associated with genomic mutations in the OPA1 gene, which codes for a protein that is imported into mitochondria where it is required for mitochondrial fusion. Interestingly enough, the underlying mutation in this family has not been identified since then. Results We have reinvestigated this family with the aim to identify the mutation and to further clarify the underlying pathomechanism. Patients showed a classical non-syndromic ADOA. The long term deterioration in vision in the two teenagers examined 50 years later is of particular note 5/20 to 6/120. Multiplex ligation probe amplification revealed a duplication of the OPA1 exons 7-9 which was confirmed by long distance PCR and cDNA analysis, resulting in an in-frame duplication of 102 amino acids. Segregation was verified in 53 available members of the updated pedigree and a penetrance of 88% was calculated. Fibroblast cultures from skin biopsies were established to assess the mitochondrial network integrity and to qualitatively and quantitatively study the consequences of the mutation on transcript and protein level. Fibroblast cultures demonstrated a fragmented mitochondrial network. Processing of the OPA1 protein was altered. There was no correlation of the OPA1 transcript levels and the OPA1 protein levels in the fibroblasts. Intriguingly an overall decrease of mitochondrial proteins was observed

  11. An unusual cause of optic atrophy in a child

    Directory of Open Access Journals (Sweden)

    Nishant Kumar


    Full Text Available A 13-year-old child presenting with gross visual impairment was diagnosed as a case of optic atrophy. However, radiological investigations revealed osteopetrosis, which, though rare, can result in optic atrophy. The aim of this case report is to highlight this possibility while evaluating cases of optic atrophy in young patients.

  12. Learning about Spinal Muscular Atrophy (United States)

    ... News Release Fischbeck Group Learning About Spinal Muscular Atrophy What is spinal muscular atrophy? What are the ... for Spinal Muscular Atrophy What is spinal muscular atrophy? Spinal muscular atrophy is a group of inherited ...

  13. 四项免疫组化标志物在诊断甲状腺乳头状癌中的临床探讨%The Clinical Application of Diagnosing Papillary Thyroid Carcinoma by Four Items Immunohistochemical Markers

    Institute of Scientific and Technical Information of China (English)

    陈桂军; 董征


    Objective To approach expression of diagnosing papillary thyroid carcinoma by four items immunohistochemical markers.Method The 50 cases clinical data of papillary thyroid carcinoma patients in the center hospita of jinzhoul from February 2010 to March 2014, which was detection group. the benign thyroid nodules 200 cases were selected, which was to be control group.Result The Ki67, TTF-1, HBME-1 and HER-2/neu positive rate dection group were higher than control group,P<0.05, the difference statistical signiifcance. The sensitivity of the diagnosis of thyroid papillary carcinoma of HER-2/neu was 92%, speciifcity of TTF-1 was 96%.Conclusion Thyroid papillary carcinoma accuracy of HER-2/neu and TTF-1 are improved, which is to be used.%目的:探讨四项免疫组化标志物在诊断甲状腺乳头状癌中的表达情况。方法分析锦州市中心医院2010年2月至2014年3月收治的甲状腺乳头状癌患者50例临床资料,作为观察组,选取同期良性甲状腺结节患者200例作为对照组。结果观察组Ki67、TTF-1、HBME-1和HER-2/neu阳性率明显高于对照组,P<0.05,差异均有统计学意义。HER-2/neu诊断甲状腺乳头状癌的敏感性最高92%, TTF-1特异性最高96%。结论 HER-2/neu联合TTF-1可能明显的提高诊断甲状腺乳头状癌准确率,值得临床推广应用。

  14. Optic nerve atrophy (United States)

    Optic atrophy; Optic neuropathy ... There are many causes of optic atrophy. The most common is poor blood flow. This is called ischemic optic neuropathy. The problem most often affects older adults. The optic ...

  15. Multiple System Atrophy (MSA) (United States)

    Diseases and Conditions Multiple system atrophy (MSA) By Mayo Clinic Staff Multiple system atrophy (MSA) is a rare neurological disorder that impairs your body's involuntary (autonomic) functions, including blood ...

  16. Spinal Muscular Atrophy (SMA) (United States)

    ... Your 1- to 2-Year-Old Spinal Muscular Atrophy (SMA) KidsHealth > For Parents > Spinal Muscular Atrophy (SMA) A A A What's in this article? ... Outlook en español Atrofia muscular espinal Spinal muscular atrophy, or SMA, is an inherited condition that causes ...

  17. Dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Lenaers Guy


    Full Text Available Abstract Definition of the disease Dominant Optic Atrophy (DOA is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3 encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8 are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7 are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of

  18. Spinal Muscular Atrophy (United States)

    Spinal muscular atrophy (SMA) is a genetic disease that attacks nerve cells, called motor neurons, in the spinal cord. These cells communicate with your voluntary muscles - the ones you can control, like in your ...

  19. The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Babak Soltani


    Full Text Available ObjectiveA 4-month-old female with osteogenesis imperfecta (OI type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA type I was diagnosed.Keywords: Osteogenesis imperfecta; spinal muscular atrophy; hypotonia

  20. Bed Rest Muscular Atrophy (United States)

    Greenleaf, John E.


    A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

  1. Diagnosing MS (United States)

    ... a Local Support Group Ask an MS Navigator Edward M. Dowd Personal Advocate Program Connect with Peers ... Symptoms & Diagnosis Diagnosing MS Possible MS Clinically Isolated Syndrome (CIS) Newly Diagnosed Diagnosing Tools Other Conditions to ...

  2. Imaging of the Macula Indicates Early Completion of Structural Deficit in Autosomal-Dominant Optic Atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Milea, Dan; Larsen, Michael


    Optical coherence tomography (OCT) enables 3-dimensional imaging of the retina, including the layer of ganglion cells that supplies the optic nerve with its axons. We tested OCT as means of diagnosing and phenotyping autosomal-dominant optic atrophy (ADOA)....

  3. Progressive hemifacial atrophy with ciliary body atrophy and ocular hypotony

    Directory of Open Access Journals (Sweden)

    T Ashwini Kini


    Full Text Available Progressive hemifacial atrophy (PHA is a disease of unknown etiology affecting one-half of the face. Ocular involvement is uncommon. Atrophy of iris is rare, with only a few cases of partial atrophy being reported in the literature. We report a case of total atrophy of iris and ciliary body with associated ocular hypotony in a 16-year-old girl with PHA. We believe this is the first reported case of complete atrophy of iris and ciliary body in PHA. Ocular hypotony in PHA was thought to be due to intra-ocular inflammation. However in our case it appears to be secondary to severe atrophy of the ciliary body.

  4. The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Babak Soltani


    Full Text Available ObjectiveA 4-month-old female with osteogenesis imperfecta (OI type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA type I was diagnosed.

  5. Histopathological and immunohistochemical diagnosis of infectious bursal disease in poultry birds

    Directory of Open Access Journals (Sweden)

    J. Singh


    Full Text Available Aim: The aim of the present study was to diagnose infectious bursal disease (IBD using gross, histopathological, and immunopathological approaches and to compare efficacy of immunohistochemical techniques with conventional diagnostic techniques. Materials and Methods: A total of 33 samples were collected from the six different poultry farms from Ludhiana and the nearby districts. Upon gross analysis of the necropsied birds, the relevant tissue samples such as bursa, kidney, junction of proventriculus and gizzard, heart, and muscles were then processed for histopathological and immunohistochemical studies. Results: Varied macroscopic changes were noted in bursa, characterized as swollen, hemorrhages to atrophy in size. Nonetheless, hemorrhages over thigh muscles were rarely seen. Histologically, the bursa showed prominent fibrotic and atrophic changes. Rarefaction of bursal follicles with intermittent infiltration of lympho-mononuclear cells with chronic cystic changes was additional changes, considered to be paramount for IBD. Expression and localization of IBD specific viral antigens were noticed mainly intracellular to the rarefied areas of bursal follicle section(s, in conjunction to inner lining of the cystic cavities of affected follicles. In addition, the junction of proventriculus and gizzard, the heart muscle, respiratory ciliated epithelium, and proventriculus also revealed positive expression to IBD virus (IBDV antigen. Advanced immunopathological techniques, i.e., immunofluorescence further testified the evidence of antigen as positive green signal within affected follicles. Further consideration to the reliability of various techniques employed, positive correlation (r=0.64623 was emerged out with conventional pathological scoring. Conclusion: It is concluded that the bursa acts as an organ of choice for demonstrating IBDV antigen for specific diagnosis of disease using immunohistochemistry (IHC, and IHC staining is a precise

  6. Muscular atrophy in diabetic neuropathy

    DEFF Research Database (Denmark)

    Andersen, H; Gadeberg, P C; Brock, B


    Diabetic patients with polyneuropathy develop motor dysfunction. To establish whether motor dysfunction is associated with muscular atrophy the ankle dorsal and plantar flexors of the non-dominant leg were evaluated with magnetic resonance imaging in 8 patients with symptomatic neuropathy, in 8 non...... confirmed that the atrophy predominated distally. We conclude that muscular atrophy underlies motor weakness at the ankle in diabetic patients with polyneuropathy and that the atrophy is most pronounced in distal muscles of the lower leg indicating that a length dependent neuropathic process explains...

  7. Genetics Home Reference: optic atrophy type 1 (United States)

    ... Home Health Conditions optic atrophy type 1 optic atrophy type 1 Enable Javascript to view the expand/ ... Download PDF Open All Close All Description Optic atrophy type 1 is a condition that affects vision. ...

  8. Genetics Home Reference: multiple system atrophy (United States)

    ... Home Health Conditions multiple system atrophy multiple system atrophy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Multiple system atrophy is a progressive brain disorder that affects movement ...

  9. The inheritance of peripapillary atrophy

    NARCIS (Netherlands)

    Healey, Paul R.; Mitchell, Paul; Gilbert, Clare E.; Lee, Anne J.; Ge, Dongliang; Snieder, Harold; Spector, Timothy D.; Hammond, Christopher J.


    PURPOSE. To estimate the relative importance of genes and environment in peripapillary atrophy type beta (beta-PPA) in a classic twin study. METHODS. Female twin pairs (n = 506) aged 49 to 79 years were recruited from the St. Thomas' UK Adult Twin Registry. Peripapillary atrophy was identified from

  10. Antral atrophy, intestinal metaplasia, and preneoplastic markers in Mexican children with Helicobacter pylori-positive and Helicobacter pylori-negative gastritis. (United States)

    Villarreal-Calderon, Rodolfo; Luévano-González, Arturo; Aragón-Flores, Mariana; Zhu, Hongtu; Yuan, Ying; Xiang, Qun; Yan, Benjamin; Stoll, Kathryn Anne; Cross, Janet V; Iczkowski, Kenneth A; Mackinnon, Alexander Craig


    Chronic inflammation and infection are major risk factors for gastric carcinogenesis in adults. As chronic gastritis is common in Mexican children, diagnosis of Helicobacter pylori and other causes of gastritis are critical for the identification of children who would benefit from closer surveillance. Antral biopsies from 82 Mexican children (mean age, 8.3 ± 4.8 years) with chronic gastritis (36 H pylori+, 46 H pylori-) were examined for gastritis activity, atrophy, intestinal metaplasia (IM), and immunohistochemical expression of gastric carcinogenesis biomarkers caudal type homeobox 2 (CDX2), ephrin type-B receptor 4 (EphB4), matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, β-catenin, and E-cadherin. Atrophy was diagnosed in 7 (9%) of 82, and IM, in 5 (6%) of 82 by routine histology, whereas 6 additional children (7%) (3 H pylori+) exhibited aberrant CDX2 expression without IM. Significant positive correlations were seen between EphB4, MMP3, and MIF (Pgastritis.

  11. APOE ε4 is associated with disproportionate progressive hippocampal atrophy in AD.

    Directory of Open Access Journals (Sweden)

    Emily N Manning

    Full Text Available OBJECTIVES: To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD, mild cognitive impairment (MCI and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates. METHODS: MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls were used. MCI subjects were divided into "progressors" (MCI-P if diagnosed with AD within 36 months or "stable" (MCI-S if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated. RESULTS: Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P. CONCLUSIONS: These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD.

  12. Newly Diagnosed (United States)

    ... Sites Podcasts QR Codes RSS Feeds Social Bookmarking Social Network Sites Text Messaging Twitter Video Games Video Sharing ... in care is similar to that of HIV-negative individuals. Additional Resources AIDSinfo – Just Diagnosed: Next ...

  13. Multiple system atrophy. (United States)

    Peeraully, Tasneem


    Multiple system atrophy (MSA) is a rare adult-onset synucleinopathy associated with dysautonomia and the variable presence of poorly levodopa-responsive parkinsonism and/or cerebellar ataxia. Other clinical symptoms that can be associated with MSA include hyperreflexia, stridor, sleep apnea, and rapid eye movement sleep behavior disorder (RBD). Mean survival from time of diagnosis ranges between 6 to 10 years, and definitive diagnosis is made on autopsy with demonstration of oligodendroglial cytoplasmic inclusions consisting of fibrillar α-synuclein. Magnetic resonance imaging (MRI) may be positive for cruciform T2 hyperintensity within the pons (the "hot cross bun sign"), volume loss in the pons and cerebellum, and T2 signal loss in the dorsolateral putamen with hyperintense rim on fluid attenuated inversion recovery (FLAIR) sequencing. Although most cases are sporadic, genetic polymorphisms have been identified both in familial and sporadic cases of MSA, and influence observed phenotypes. Treatment is symptomatic, with both pharmacological and nonpharmacological strategies. There are currently no consensus guidelines on management. Current and future research is aimed at identifying biomarkers and developing disease-modifying therapies.


    Institute of Scientific and Technical Information of China (English)

    信明军; 施诚仁; 张忠德; 李敏; 陈方; 潘伟华


    Objective To evaluate the sensitivity and specificity of regularly used immunohistochemical markers, including Vimentin (Vim), Desmin (Des), Myoglobin (MG), Myosin (MS), Smooth-muscle actin(SMA) and Sarcomeric actin ( Sr-A), in the diagnosis of rhabdomyosarcoma (RMS). Methods After resection, 24 RMSs and other childhood tumor specimens were fixed in 10% neutral-buffered formalin and embeded in paraffin. The immunohistochemical staining was performed by LSAB procedure. Heat-induced epitope retrieval of Des, MS, Sr-A was processed in order to enhence positive rate and positive strength. Results Vim, MG, MS,Des, Sr-A, SMA were arranged in the order of sensitivity from higher to lower. About specificity, Sr-A, Des, SMA,MG, Vim standed in a sequence from higher to lower (the data of MS is insufficient); Des, MG, Sr-A possessed higher experimental efficiency, followed by SMA, Vim in a succession. Conclusion Vim and MG are of the higher sensitivity but lower specificity. On the reverse, Sr-A and Des hold the better specificity but lower sensitivity.So the combination of multiple antibody reactions should be considered to improve the diagnostic ability in poorly differentiated RMS. According to the result of experimental efficiency, we suggest that the combination of Des, MG and Sr-A can make it possible to diagnose the majority of RMS clearly.

  15. Scrub typhus hepatitis confirmed by immunohistochemical staining

    Institute of Scientific and Technical Information of China (English)

    Jong-Hoon Chung; Sung-Chul Lim; Na-Ra Yun; Sung-Heui Shin; Choon-Mee Kim; Dong-Min Kim


    Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi (O.tsutsugamushi).We report herein the case of a woman who presented with fever and elevated serum levels of liver enzymes and who was definitively diagnosed with scrub typhus by histopathological examination of liver biopsy specimens,serological tests and nested polymerase chain reaction.Immunohistochemical staining using a monoclonal anti-O.tsutsugamushi antibody showed focally scattered positive immunoreactions in the cytoplasm of some hepatocytes.This case suggests that scrub typhus hepatitis causes mild focal inflammation due to direct liver damage without causing piecemeal necrosis or interface hepatitis.Thus,scrub typhus hepatitis differs from acute viral hepatitis secondary to liver damage due to host immune responses,which causes severe Iobular disarray with diffuse hepatocytic degeneration,necrosis and apoptosis as well as findings indicative of hepatic cholestasis,such as hepatic bile plugs or brown pigmentation of hepatocytes.

  16. Fibrosis, adipogenesis, and muscle atrophy in congenital muscular torticollis. (United States)

    Chen, Huan-Xiong; Tang, Sheng-Ping; Gao, Fu-Tang; Xu, Jiang-Long; Jiang, Xian-Ping; Cao, Juan; Fu, Gui-Bing; Sun, Ke; Liu, Shi-Zhe; Shi, Wei


    In the traditional view, muscle atrophy and interstitial fibrosis were regarded as the basic pathological features of congenital muscular torticollis (CMT). But in the ultrastructure study, the mesenchyme-like cells, myoblasts, myofibroblasts, and fibroblasts were found in the proliferation of interstitium of CMT. To investigate the characteristics of pathological features and the mechanisms of muscle atrophy in CMT, we retrospectively reviewed the medical records of 185 CMT patients from July 2009 to July 2011 in Shenzhen Children's Hospital in China and performed pathological studies. According to age, the 185 CMT patients were divided into 4 groups. All resected surgical specimens were processed for hematoxylin and eosin staining and Masson trichromic staining. Sudan III staining was used for frozen sections, whereas immunohistochemical staining for S-100, calpain-1, ubiquitin, and 20S proteasome was carried out on 40 CMT specimens. Eight adductor muscle specimens from 8 patients with development dysplasia of the hip were taken as control group in the immunohistochemical staining. By Masson trichromic staining, the differences in the percent area of fibrous tissue in each CMT groups were significant. In Sudan III staining and immunostaining for S-100, adipocyte hyperplasia was the pathological feature of CMT. Moreover, compared with controls, most atrophic muscle fibers in CMT specimens were found to show strong immunoreactivity for calpain-1, ubiquitin, and 20S proteasome. With increasing age, fibrosis peaked at both sides and it was low in middle age group. Adipocytes increased with age. The characteristics of pathological features in CMT are changeable with age. The calpain and the ubiquitin-proteasome system may play a role in muscle atrophy of CMT. In the CMT, adipogenesis, fibrogenesis, and myogenesis may be the results of mesenchyme-like cells in SCM (sternocleidomastoid muscle). In conclusion, the present study furthermore supports maldevelopment of the

  17. Idiopathic atrophie blanche. (United States)

    Amato, Lauretta; Chiarini, Caterina; Berti, Samantha; Massi, Daniela; Fabbri, Paolo


    clinical, serologic, histopathologic, and immunopathologic findings, a diagnosis of idiopathic atrophie blanche was made. The patient was treated with dapsone (50 mg p.o. q.d.) and pentoxifylline (400 mg p.o. t.i.d.) with pain relief and complete resolution of the ulcerations after 6 weeks of therapy.

  18. Optic atrophy and glaucomatous cupping. (United States)

    Radius, R L; Maumenee, A E


    We reviewed 170 eyes of 112 patients with optic atrophy from various causes. Special attention was directed towards measured cup:disk ratios as well as presence of glaucomatous-like cupping of the optic nerve head. We observed a small but significant increase in nerve head cupping in eyes with optic atrophy when compared to contralateral eyes, as well as to eyes of 50 diabetic patients. No characteristic glaucomatous disk changes were documented. We evaluated these findings with respect to possible causes of glaucomatous disk and field changes.

  19. Types of SMA (Spinal Muscular Atrophy) (United States)

    ... genes other than the SMN1 gene. Spinal Muscular Atrophy Respiratory Distress (SMARD) SMARD is a very rare ... and 50. It causes muscle weakness and wasting (atrophy) throughout the body, which is most noticeable in ...

  20. Genetics Home Reference: dentatorubral-pallidoluysian atrophy (United States)

    ... Understand Genetics Home Health Conditions DRPLA dentatorubral-pallidoluysian atrophy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Dentatorubral-pallidoluysian atrophy , commonly known as DRPLA , is a progressive brain ...

  1. C4d staining as immunohistochemical marker in inflammatory myopathies. (United States)

    Pytel, Peter


    The diagnosis of an inflammatory myopathy is often established based on basic histologic studies. Additional immunohistochemical studies are sometimes required to support the diagnosis and the classification of inflammatory myopathies. Staining for major histocompatibility complex 1 (MHC1) often shows increased sarcolemmal labeling in inflammatory myopathies. Endomysial capillary staining C5b-9 (membrane attack complex) is a feature that is reported as frequently associated with dermatomyositis. Immunohistochemical staining for C4d is widely used for various applications including the assessment of antibody-mediated rejection after solid organ transplantation. In the context of dermatomyositis, C4d staining has been described in skin biopsies but not in muscle biopsies. A total of 32 muscle biopsy specimens were examined. The hematoxylin and eosin-stained slides were reviewed, and immunohistochemical studies for MHC1, C5b-9, and C4d were conducted. The staining observed for C5b-9 and C4d was compared. Overall, the staining pattern for C4d mirrored the one observed for C5b-9 in the examined muscle biopsy specimens. There was high and statistically significant (P<0.0001) correlation between the staining seen with these 2 antibodies. Both antibodies labeled the cytoplasm of degenerating necrotic myofibers. In addition, both antibodies showed distinct endomysial capillary labeling in a subset of dermatomyositis. Areas with perifascicular atrophy often exhibited the most prominent vascular labeling for C4d and C5b-9. In conclusion, C4d and C5b-9 show similar expression patterns in muscle biopsies of patients with inflammatory myopathies and both highlight the presence of vascular labeling associated with dermatomyositis. C4d antibodies are widely used and may offer an alternative for C5b-9 staining.

  2. Neuronal involvement in muscular atrophy

    Directory of Open Access Journals (Sweden)

    Bruno Alejandro Cisterna


    Full Text Available The innervation of skeletal myofibers exerts a crucial influence on the maintenance of muscle tone and normal operation. Consequently, denervated myofibers manifest atrophy, which is preceded by an increase in sarcolemma permeability. Recently, de novo expression of hemichannels formed by connexins and other none selective channels, including P2X7 receptors, TRPV2 channels were demonstrated in denervated fast skeletal muscles. The denervation-induced atrophy was drastically prevented in denervated muscles deficient in connexins 43 and 45. Nonetheless, the transduction mechanism by which the nerve represses the expression of the above mentioned none selective channels remains unknown. The paracrine action of extracellular signaling molecules including ATP, neurotrophic factors (i.e., BDNF, agrin/Lrp4/MuSK and acetylcholine are among the possible perpetrators of repression for connexin expression. This review discusses the possible role of relevant factors in maintaining the normal functioning of fast skeletal muscles and suppression of connexin hemichannel expression.

  3. Immunohistochemical differentiation of inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Jayalakshmi B Panicker


    Full Text Available Background: Idiopathic inflammatory myopathies are a heterogeneous group of acquired muscle disorders with considerable overlap in the histological features, making histological diagnosis difficult at times. Aims: To determine the immunohistochemical profile of clinically suspected cases of inflammatory myopathies, using monoclonal antibodies to HLA-1 and membrane attack complex (MAC, and to correlate the clinical, serological, and electromyographic profile and the histopathological picture, with the immunohistochemical profile. Settings and Design: This was a retrospective study analyzing the clinical and histopathological features in muscle of clinically suspected cases of inflammatory myopathy and correlating it to their HLA-1 and MAC immunostaining profiles. Material and Methods: The study subjects included 33 cases with suspected inflammatory myopathy and 59 with non-inflammatory muscle disease, as controls. Clinical data, electromyographic findings, serological profile, and details of therapy were obtained from patient records. Statistical Analysis: Student ′T′ test, Pearson′s Chi square test, and Kappa statistics were used appropriately. Results: Although HLA-1 and MAC immunostaining did not help to differentiate the individual subtypes of inflammatory myopathy, when either HLA-1 or MAC was positive, inflammatory myopathy could be ruled in with 86.5% certainty and when both HLA-1 and MAC were negative, it could be ruled out with 95% certainty. Conclusions: A combination of clinical presentation, serological profile, electromyographic and histopathological features, together with the immunoprofile for HLA-1 and MAC, contribute toward making a diagnosis of inflammatory myopathy.

  4. Massive retinal gliosis: An unusual case with immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Sanjay D Deshmukh


    Full Text Available Massive retinal gliosis (MRG is a rare, benign intraocular condition that results from the proliferation of well-differentiated glial cells. Immunohistochemically, these cells show positivity for glial fibrillary acid protein (GFAP, neuron specific enolase (NSE, and S-100 protein. We encountered a case of a 45-year-old female with loss of vision in the left eye. She had a history of trauma to that eye two years ago. Enucleation was carried out, because malignancy was suspected due to retinal calcification. On the basis of light microscopy and immunohistochemistry (IHC performed on the enucleated eye, it was diagnosed as massive retinal gliosis.

  5. Mitochondrial signaling contributes to disuse muscle atrophy


    Powers, Scott K.; Wiggs, Michael P.; Duarte, Jose A.; Zergeroglu, A. Murat; Demirel, Haydar A.


    It is well established that long durations of bed rest, limb immobilization, or reduced activity in respiratory muscles during mechanical ventilation results in skeletal muscle atrophy in humans and other animals. The idea that mitochondrial damage/dysfunction contributes to disuse muscle atrophy originated over 40 years ago. These early studies were largely descriptive and did not provide unequivocal evidence that mitochondria play a primary role in disuse muscle atrophy. However, recent exp...

  6. A Possible Link between Gastric Mucosal Atrophy and Gastric Cancer after Helicobacter pylori Eradication (United States)

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


    Background The effect of H. pylori eradication in gastric cancer prevention can be attributed to the improvement of atrophic gastritis, which is a known risk of gastric cancer. However, gastric cancer has also been diagnosed after long-term H. pylori eradication. This study aimed to clarify the association between gastric atrophy and gastric cancer after H. pylori eradication, including its clinicopathological features. Methods A total of 55 consecutive patients with 64 early gastric cancers (EGCs) diagnosed after H. pylori eradication were enrolled. The degree of endoscopic atrophy and the histological degrees of mononuclear cell infiltration, atrophy, and metaplasia in the corpus and adjacent mucosa of the EGCs were determined and scored. Results The majority of EGCs (63/64) were located within the endoscopically assessed atrophic mucosa or along the atrophic border. The adjacent mucosa of the EGCs presented significantly higher degrees of all histological parameters than in the corpus (mononuclear cell infiltration, 0.86+/-0.09 vs. 0.51+/-0.11, P = 0.016; atrophy, 1.77+/-0.13 vs. 0.65+/-0.14, Pgastric ulcers. Conclusions Severe gastric atrophy remained in the adjacent mucosa of the EGCs after H. pylori eradication, which may be linked to gastric carcinogenesis. PMID:27706195

  7. Histological and Immunohistochemical Revision of Hepatocellular Adenomas: A Learning Experience

    Directory of Open Access Journals (Sweden)

    S. Fonseca


    Full Text Available Light has been shed on the genotype/phenotype correlation in hepatocellular adenoma (HCA recognizing HNF1α-inactivated HCA (H-HCA, inflammatory HCA (IHCA, and β-catenin-activated HCA (b-HCA. We reviewed retrospectively our surgical HCA series to learn how to recognize the different subtypes histopathologically and how to interpret adequately their immunohistochemical staining. From January 1992 to January 2012, 37 patients underwent surgical resection for HCA in our institution. Nine had H-HCA (25% characterized by steatosis and loss of L-FABP expression; 20 had IHCA (55.5% showing CRP and/or SAA expression, sinusoidal dilatation, and variable inflammation; and 1 patient had both H-HCA and IHCA. In 5 patients (14%, b-HCA with GS and β-catenin nuclear positivity was diagnosed, two already with hepatocellular carcinoma. Two cases (5.5% remained unclassified. One of the b-HCA showed also the H-HCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/HNF1α-inactivated HCA, another b-HCA exhibited the IHCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/inflammatory HCA. Interestingly, three patients had underlying vascular abnormalities. Using the recently published criteria enabled us to classify histopathologically our retrospective HCA surgical series with accurate recognition of b-HCA for which we confirm the higher risk of malignant transformation. We also underlined the association between HCA and vascular abnormalities.

  8. Little effects of Insulin-like Growth Factor-I on testicular atrophy induced by hypoxia

    Directory of Open Access Journals (Sweden)

    Casares Amelia


    Full Text Available Abstract Background Insulin-like Growth Factor-I (IGF-I supplementation restores testicular atrophy associated with advanced liver cirrhosis that is a condition of IGF-I deficiency. The aim of this work was to evaluate the effect of IGF-I in rats with ischemia-induced testicular atrophy (AT without liver disease and consequently with normal serum level of IGF-I. Methods Testicular atrophy was induced by epinephrine (1, 2 mg/Kg intra-scrotal injection five times per week during 11 weeks. Then, rats with testicular atrophy (AT were divided into two groups (n = 10 each: untreated rats (AT receiving saline sc, and AT+IGF, which were treated with IGF-I (2 μg.100 g, sc. for 28d. Healthy controls (CO, n = 10 were studied in parallel. Animals were sacrificed on day 29th. Hypophyso-gonadal axis, IGF-I and IGFBPs levels, testicular morphometry and histopathology, immuno-histochemical studies and antioxidant enzyme activity phospholipid hydroperoxide glutathione peroxidase (PHGPx were assessed. Results Compared to controls, AT rats displayed a reduction in testicular size and weight, with histological testicular atrophy, decreased cellular proliferation and transferrin expression, and all of these alterations were slightly improved by IGF-I at low doses. IGF-I therapy increased signifincantly steroidogenesis and PHGPx activity (p Conclusion In testicular atrophy by hypoxia, condition without IGF-I deficiency, IGF-treatment induces only partial effects. These findings suggest that IGF-I therapy appears as an appropriate treatment in hypogonadism only when this is associated to conditions of IGF-I deficiency (such as Laron Syndrom or liver cirrhosis.

  9. Parvovirus infection: an immunohistochemical study using fetal and placental tissue. (United States)

    Li, Jing Jing; Henwood, Tony; Van Hal, Sebastian; Charlton, Amanda


    Parvovirus B19 infection causes 5% to 15% of cases of nonimmune hydrops fetalis. The aim of our study was to evaluate the use of immunohistochemistry in diagnosing parvovirus infection in fetal and placental tissue during routine fetal and perinatal autopsies. Histology slides of 20 cases of confirmed parvovirus infection were reviewed, and immunohistochemistry was applied to selected blocks of fetal and placental tissue. Immunohistochemistry was positive in all 20 cases, and histologic viral inclusions were seen in 19 cases. Immunohistochemical staining was closely correlated with histology and was more sensitive than histology in detecting virally infected cells, especially in autolyzed tissue. All cases also had confirmatory evidence of parvovirus infection by polymerase chain reaction of fetal liver and positive maternal serology, where it was available. We conclude that parvovirus immunohistochemistry is a reliable method for diagnosing parvovirus infection, especially in autolyzed tissue where histologic assessment may be suboptimal.

  10. Genetics Home Reference: spinal and bulbar muscular atrophy (United States)

    ... Kennedy spinal and bulbar muscular atrophy Kennedy's disease SBMA X-linked spinal and bulbar muscular atrophy Related ... Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. Brain. 2006 ...

  11. How Are Arrhythmias Diagnosed? (United States)

    ... page from the NHLBI on Twitter. How Are Arrhythmias Diagnosed? Arrhythmias can be hard to diagnose, especially the types ... symptoms every once in a while. Doctors diagnose arrhythmias based on medical and family histories, a physical ...

  12. Etiology and clinical profile of childhood optic nerve atrophy at a tertiary eye care center in South India

    Directory of Open Access Journals (Sweden)

    Supriya Chinta


    Full Text Available Background: Optic nerve atrophy is an important ophthalmological sign that may be associated with serious systemic conditions having a significant bearing on the overall morbidity of the child. Studies specific to etiology of childhood optic atrophy are scarce, this being the first such study from India to the best of our knowledge. Aim: The aim was to analyze the clinical features and etiology of diagnosed cases of optic nerve atrophy in children <16 years of age. Materials and Methods: Retrospective review of records of children diagnosed with optic nerve atrophy between the ages of 0 and 16 years from 2006 to 2011. Results: A total of 324 children (583 eyes were identified. Among these 160 (49% presented with defective vision, 71 (22% with strabismus, 18 (6% with only nystagmus. Rest had a combination of two or three of the above symptoms. Sixty-five patients (20% had a unilateral affection. Hypoxic ischemic encephalopathy seen in 133 patients (41% was the most frequent cause of childhood optic atrophy, followed by idiopathic in 98 (30%, hydrocephalus in 24 (7%, compressive etiology in 18 (5%, infective in 19 (6%, congenital in 6 (2%, inflammatory in 5 (2% patients, respectively. Conclusion: Hypoxic ischemic encephalopathy appears to be the most common cause of optic atrophy in children in this series. The most common presenting complaint was defective vision.

  13. Visualizing stages of cortical atrophy in progressive MCI from the ADNI cohort

    DEFF Research Database (Denmark)

    Eskildsen, Simon Fristed; Fonov, Vladimir; Coupé, Pierrick;

    Amnestic mild cognitive impairment (MCI) is considered a condition where patients are at risk of developing clinically definite Alzheimer’s disease (AD) with an annual conversion rate of approximately 15%[1]. AD is characterized by progressive brain atrophy with major impact on the cerebral cortex...... and medial temporal lobe structures such as hippocampus. Understanding the structural pattern of cortical atrophy at different stages of MCI, before AD can be diagnosed, may help in patient monitoring and prognosis. We used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to calculate...... and visualize the cortical atrophy at different stages in patients who eventually converted to clinically definite AD. We selected patients with a diagnosis of MCI from the ADNI database who converted to AD during the follow-up period. T1-weighted MRI scans were collected at time of conversion(n=140...

  14. Possible role of polyamines in gyrate atrophy.

    Directory of Open Access Journals (Sweden)

    Sulochana Konerirajapuram


    Full Text Available PURPOSE: Gyrate atrophy (GA is marked by hyperornithinemia and lowered ornithine amino transferase (OAT. However there are patients of GA without hyperornithinemia and those with hyperornithinemia without GA. Some cases of GA have been reported to have low lysine. The purpose of the study was to determine if polyamines, the metabolites of ornithine, and lysine have any diagnostic role in GA. METHODS: Ornithine in plasma was estimated by two-dimensional paper chromatography, with elution of the coloured spot, and the absorbance measured using a spectrophotometer at 560 nm. OAT assay in lymphocytes was done spectrophotometrically using ornithine as substrate. Blood and urinary polyamines were extracted with n-butanol, benzoylated and analysed with HPLC; putrescine, spermine, spermidine, and cadaverine were assayed individually at 254 nm with the UV detector using ODS, G18 column with 63% methanol as solvent. RESULTS: Of the 7 patients investigated, 6 had features typical of GA. One was diagnosed to have atypical retinitis pigmentosa (case 3. The first five cases had elevated ornithine and diminished OAT, but cases 6 and 7 had near-normal ornithine and case 7 had near-normal OAT. However, all 7 patients had increased levels of total polyamines in urine compared to normals. Five had increased putrescine and three had increased spermine. All the 7 had decreased cadaverine in urine. Thus, though there were inconsistencies with ornithine and OAT, all the 7 patients had elevated polyamines from ornithine and decreased cadaverine. CONCLUSION: In addition to estimating ornithine and OAT in GA, it is suggested that urinary polyamines may be analysed as the latter appears to correlate better with the clinical condition and help in the diagnosis to a greater extent. Moreover, while ornithine is an innocuous amino acid, polyamines are known to damage DNA and proteins.

  15. Hemangiopericytoma in a young dog: Evaluation of histopathological and immunohistochemical features

    Directory of Open Access Journals (Sweden)

    Fatemeh Namazi


    Full Text Available In the present study, we describe a subcutaneous mass between the left flank and hip in a 2-year-old male Great Dane dog. Histopathologically, cells appeared to be spindle shaped around a central capillary together with a fingerprint pattern. Immunohistochemical analysis presented that the neoplastic cells expressed vimentin, but did not stain for S-100 protein. On the basis of histopathology and immunohistochemical findings, the present tumor was diagnosed as canine hemangiopericytoma. Hemangiopericytoma could be considered in differential diagnosis list of any mass in the skin (even in young dogs and must be identified histopathologically.

  16. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kanoto, Masafumi, E-mail: [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Hosoya, Takaaki, E-mail: [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Toyoguchi, Yuuki, E-mail: [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Oda, Atsuko, E-mail: [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan)


    Purpose: Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. Materials and methods: The subjects consist of a CPNBD group (n = 4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n = 19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n = 23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Results: Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p < 0.05), and between the CPNBD group and the normal control group (p < 0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p < 0.001, p < 0.01 respectively), and between the CPNBD group and the normal control group (p < 0.001). Conclusions: Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis.

  17. Association between anti-endomysial antibody and total intestinal villous atrophy in children with coeliac disease.

    Directory of Open Access Journals (Sweden)

    Ozgenc F


    Full Text Available BACKGROUND: There is growing evidence to suggest that detection of anti-gliadin antibody (AGA and anti-endomysial antibody (EmA can serve as sensitive markers of the degree of histological abnormalities in patients with coeliac disease. AIM: To evaluate the association between the presence of AGA and EmA and villous atrophy in intestinal biopsies of children with suspected coeliac disease. SETTINGS AND DESIGN: Intestinal samples of 46 children with failure to thrive, chronic diarrhoea, malabsorption and short stature with either AGA and/or EmA positivity were evaluated, retrospectively. The diagnosis of coeliac disease was based on ESPGHAN criteria. METHODS AND MATERIAL: Patients with total villous atrophy who fulfilled the ESPGHAN criteria for the diagnosis of coeliac disease were diagnosed to have coeliac disease. Nine patients without villous atrophy were taken as negative controls for this study. AGA-IgA was measured both by immunoflourescence (IF and ELISA and EmA-IgA by IF while patients were on normal diet. Relationship between autoantibody positivity and intestinal total villous atrophy was evaluated. RESULTS: Overall positivity for AGA IgA was 85% (39/46 by IF+ELISA and EmA positivity was 85% (39/46 by IF within the study group. Histological examination revealed total villous atrophy with lymphocyte infiltration and crypt hyperplasia in 37 (80% patients. AGA IgA was positive in 14 (38% and 31 (84% of these children by ELISA and IF, respectively. EmA positivity was detected in 35/37 (95% cases with atrophy and 4/9 (44% without atrophy (p=0.002. Thirty out of 37 (81% patients with villous atrophy had both AGA IgA (IF and EmA positivity (p=0.186. All of the sixteen patients that had both positive AGA IgA (ELISA+IF and EmA had total villous atrophy (p=0.037. CONCLUSION: A significant association between total villous atrophy and EmA positivity has been documented in this study.

  18. Case of dentato-rubro-pallido-luysian atrophy. MRI findings and disturbance of ocular movement

    Energy Technology Data Exchange (ETDEWEB)

    Usui, Sadanari; Komiya, Tadatoshi


    A clinical case of dentato-rubro-pallido-luysian atrophy (DRPLA) was reported. We established several aspects on the basis of MRI findings and a neuro-otological study. A 47-year-old woman had gait disturbance, involuntary movements, speech disturbance, and memory disturbance at the age of 42. She was admitted to the hospital because of worsening of the gait disturbance. Neurological examinations showed choreo-athetosis of the face, neck and upper extremities, mental disturbance, and scanning speech. However, she had neither ocular disturbance nor epilepsy or myoclonus. On the MRI-CT, an atrophy of midbrain and pontine tegmentum was observed. The neuro-otological study showed gaze nystagmus at the horizontal gaze, rebound nystagmus, hypometria of the saccade, saccadic pursuit, reduction of the optokinetic nystagmus, and increase in caloric nystagmus by means of visual input. A severe atrophy of the brainstem tegmentum and a mild atrophy of the cerebellar hemisphere and cerebral cortex are regarded as neuro-radiological features of DRPLA. Moreover, tegmental atrophy is related to ocular disturbance as a clinical feature. Various neuro-otological findings reveal many systems of ocular movements, i.e., a smooth pursuit system, a saccade system, and a vestibulo-ocular reflex system, involving flocculus. DRPLA can be clinically diagnosed by means of clinical features, MRI findings, and neuro-otological findings. A variety of neuro-otological abnormalities may indicate a progression of the ocular disturbance and a variety of lesions.

  19. Infraspinatus muscle atrophy from suprascapular nerve compression. (United States)

    Cordova, Christopher B; Owens, Brett D


    Muscle weakness without pain may signal a nerve compression injury. Because these injuries should be identified and treated early to prevent permanent muscle weakness and atrophy, providers should consider suprascapular nerve compression in patients with shoulder muscle weakness.

  20. Hippocampal atrophy rates in Alzheimer disease (United States)

    Henneman, W J.P.; Sluimer, J D.; Barnes, J; van der Flier, W M.; Sluimer, I C.; Fox, N C.; Scheltens, P; Vrenken, H; Barkhof, F


    Objective: To investigate the added value of hippocampal atrophy rates over whole brain volume measurements on MRI in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls. Methods: We included 64 patients with AD (67 ± 9 years; F/M 38/26), 44 patients with MCI (71 ± 6 years; 21/23), and 34 controls (67 ± 9 years; 16/18). Two MR scans were performed (scan interval: 1.8 ± 0.7 years; 1.0 T), using a coronal three-dimensional T1-weighted gradient echo sequence. At follow-up, 3 controls and 23 patients with MCI had progressed to AD. Hippocampi were manually delineated at baseline. Hippocampal atrophy rates were calculated using regional, nonlinear fluid registration. Whole brain baseline volumes and atrophy rates were determined using automated segmentation and registration tools. Results: All MRI measures differed between groups (p < 0.005). For the distinction of MCI from controls, larger effect sizes of hippocampal measures were found compared to whole brain measures. Between MCI and AD, only whole brain atrophy rate differed significantly. Cox proportional hazards models (variables dichotomized by median) showed that within all patients without dementia, hippocampal baseline volume (hazard ratio [HR]: 5.7 [95% confidence interval: 1.5–22.2]), hippocampal atrophy rate (5.2 [1.9–14.3]), and whole brain atrophy rate (2.8 [1.1–7.2]) independently predicted progression to AD; the combination of low hippocampal volume and high atrophy rate yielded a HR of 61.1 (6.1–606.8). Within patients with MCI, only hippocampal baseline volume and atrophy rate predicted progression. Conclusion: Hippocampal measures, especially hippocampal atrophy rate, best discriminate mild cognitive impairment (MCI) from controls. Whole brain atrophy rate discriminates Alzheimer disease (AD) from MCI. Regional measures of hippocampal atrophy are the strongest predictors of progression to AD. GLOSSARY AD = Alzheimer disease; BET = brain

  1. Zika virus causes testicular atrophy (United States)

    Uraki, Ryuta; Hwang, Jesse; Jurado, Kellie Ann; Householder, Sarah; Yockey, Laura J.; Hastings, Andrew K.; Homer, Robert J.; Iwasaki, Akiko; Fikrig, Erol


    Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has recently been found to cause fetal infection and neonatal abnormalities, including microcephaly and neurological dysfunction. ZIKV persists in the semen months after the acute viremic phase in humans. To further understand the consequences of ZIKV persistence in males, we infected Ifnar1−/− mice via subcutaneous injection of a pathogenic but nonlethal ZIKV strain. ZIKV replication persists within the testes even after clearance from the blood, with interstitial, testosterone-producing Leydig cells supporting virus replication. We found high levels of viral RNA and antigen within the epididymal lumen, where sperm is stored, and within surrounding epithelial cells. Unexpectedly, at 21 days post-infection, the testes of the ZIKV-infected mice were significantly smaller compared to those of mock-infected mice, indicating progressive testicular atrophy. ZIKV infection caused a reduction in serum testosterone, suggesting that male fertility can be affected. Our findings have important implications for nonvector-borne vertical transmission, as well as long-term potential reproductive deficiencies, in ZIKV-infected males. PMID:28261663


    Directory of Open Access Journals (Sweden)

    Katarina Bevizova


    Full Text Available Malignant cancers of urinary bladder are the second most common malignancy of the urinary tract and the fourth most common malignancy in general, especially in men. The aim of this study was a retrospective analysis of selected markers (p53, Ki-67 and E-cadherin of urinary bladder cancers from the Department of Urology in Bratislava, Slovak Republic between years 2007 and 2009. We analysed 244 patients (202 males, 42 females with diagnosed bladder cancer via cystoscopy and subsequent transurethral resection. Patients’ age varied from 36 to 98 years. Obtained samples were fixed by 10% buffered formalin for 24 to 48 h. Subsequently, they were dehydrated in ascending ethanol series and embedded in paraffin. The parafin sections of 5 µm were prepared by microtome and they were stained by haematoxylin and eosin. The antibodies against to p53, Ki-67 and E-cadherin were used in immunohistochemical analysis. Statistical evaluation was performed via SPSS using non-parametric Kruskal-Wallis test and p values<0.05 were considered statistically significant. No significant differences in the expression of selected markers were found between genders. Expression of p53 and Ki-67, in G1 and G2 of low grade tumours was lower in comparison to their expression in G3 tumors. Expression of E-cadherin was the opposite in this case. The expression of p53 and Ki-67 positively correlated with tumor’s depth of invasion, while the expression of E-cadherin significantly decreased. In case of T4 tumors, the expression of all markers exhibited consistently high values. When analysing tumor multiplicity, the expression of p53 and Ki-67 significantly decreased, while the expression of E-cadherin significantly increased. Based on the obtained results it can be concluded that the analysis of p53, Ki-67 and E-cadherin expression is essential for diagnostics and prognostics of bladder cancer and should be routinely used in daily practise together with

  3. Convenient diagnosis of spinal and bulbar muscular atrophy using a microchip electrophoresis system


    Maruyama, Hirofumi; Morino, Hiroyuki; Izumi, Yuishin; Noda, Kouichi; Kawakami, Hideshi


    Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive motor neuron disease. Lower and primary sensory neuronopathy is one of the major neuropathological changes that occurs in SBMA. However, many sings are common to SBMA and amyotrophic lateral sclerosis (ALS), and SBMA patients are sometimes diagnosed with ALS. Leuprorelin may be used to treat SBMA, but an accurate diagnosis is necessary for treatment and care. Genetic diagnosis can be performed to detect the expansion of a CAG r...

  4. Occurrence of trichoepithelioma in a cat: Histopathologic and immunohistochemical study. (United States)

    Tavasoli, Abbas; Golshahi, Hannaneh; Rad, Maryam Nobakht; Taymouri, Afra


    Trichoepitheliomas are benign follicular appendage tumors with differentiation to all three segments of the hair follicle. A 2 years old female domestic short hair cat presented with a mass on the tail. The mass was surgically excised and for histopathologic and immunohistochemical studies, was sent to Department of Pathology. Histologically, the tumor was encapsulated and consisted of many islands of follicular epithelium and also cysts structures which varied in size and shape. The cells of epithelium islands were round to oval and had variable amounts of slightly, eosinophilic cytoplasm and euchromatic nuclei. The cystic structures were lined by a complex layer of squamous epithelium. Often, cells under went an abrupt transition between basal layers and keratinization without the development of a granular cell layer. No tendency of malignancy was seen in this case. According to mentioned characteristics, trichoepithelioma was diagnosed. By immunohistochemical study it was confirmed that this tumor had epithelial origin because squamous tumor cells reacted with the pan-cytokeratin antibody. The expression of β-catenin was predominately cytoplasmic and also together with numerous positive nuclei but membranous expression was inconsistenet. Distribution of neoplastic cells with β-catenin expression was more than 75% and labeling intensity was strong in both cytoplasm and nuclei. According to author's knowledge, this is the first report of trichoepithelioma in cat in Iran and also investigation of β-catenin expression in feline trichoepithelioma in veterinary literature.

  5. On the atrophy of the internal carotid artery in capybara. (United States)

    Steele, Caroline; Fioretto, Emerson T; Sasahara, Tais H C; Guidi, Wanderley L; de Lima, Ana R; Ribeiro, Antonio A C M; Loesch, Andrzej


    Capybara might be a useful model for studying changes in cerebral circulation as the natural atrophy of the internal carotid artery (ICA) occurs in this animal at maturation. In this study, confocal and electron microscopy combined with immunohistochemical techniques were applied in order to reveal the changes in morphology and innervation to the proximal part of ICA in young (6-month-old) and mature (12-month-old) capybaras. Some features of the basilar artery (BA) were also revealed. The ICA of young animals degenerated to a ligamentous cord in mature animals. Immunolabelling positive for pan-neuronal marker protein gene product 9.5 but negative for tyrosine hydroxylase was observed in the proximal part of ICA at both ages examined. Axon varicosities positive for synaptophysin were present in the adventitia of ICA of young animals but were absent in the ligamentous cord of mature animals. In the ICA of young animals, adventitial connective tissue invaded the media suggesting that the process of regression of this artery began within the first 6 months of life. An increase in size of the BA was found in mature animals indicating increased blood flow in the vertebro-basilar system, possibly making capybara susceptible to cerebrovascular pathology (e.g. stroke). Capybara may therefore provide a natural model for studying adaptive responses to ICA regression/occlusion.

  6. Currently available useful immunohistochemical markers of renal pathology for the diagnosis of renal allograft rejection. (United States)

    Kanzaki, Go; Shimizu, Akira


    Renal allograft dysfunction may be induced by various causes, including alloimmune rejection, viral infection, urinary tract obstruction, calcineurin inhibitor nephrotoxicity and/or recurrent renal disease. In order to determine the underlying cause, a renal biopsy is performed and the renal transplant pathology is diagnosed using the internationally consensus Banff classification. Although a progressive understanding of allograft rejection has provided numerous immunohistochemical markers, only the C4d is regarded to be a sufficiently useful marker for antibody-mediated allograft rejection according to the Banff classification. This review summarizes currently available useful immunohistochemical markers of renal transplant pathology, including C4d, with diagnostic implications for human renal allograft rejection. In particular, we discuss immunohistochemical markers in the following three categories: immunohistochemical markers of renal pathology used to (i) analyze the mechanisms of alloimmune rejection, (ii) monitor cell injury and/or inflammation associated with rejection and (iii) identify renal components in order to improve the diagnosis of rejection. In addition, recent progress in the field of renal transplant pathology includes the development of a new method for assessing molecular pathology using OMICS analyses. As the recent findings of various studies in patients undergoing renal transplantation are very encouraging, novel immunohistochemical markers must be also developed and combined with new technologies for the diagnosis of human renal allograft rejection.

  7. Type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog.

    Directory of Open Access Journals (Sweden)

    L Insabato


    Full Text Available The Silent Corticotroph Adenoma (SCA is a pituitary adenoma variant characterized by the immunoreactivity for adrenocorticotropic hormone (ACTH and related peptides, without the clinical signs of Cushing's disease. SCA has been postulated to either secrete structurally abnormal ACTH that is inactive but detectable by immunohistochemistry or radioimmunoassay, or to secrete ACTH intermittently or at low levels continuously. Excess of ACTH has been associated to type II muscle atrophy. We describe a case of type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog. The dog showed moderate to severe proximal muscle wasting and weakness with normal levels of muscle-associated enzymes. In the limb muscle biopsies, type II fibers were uniformly smaller than type I fibers. In temporalis muscles, there were few atrophic fibers, and several irregular areas of loss of enzymatic activity observed in NADH, SDH and COX stains. The tumour showed a trabecular growth pattern and immunohistochemical analysis demonstrated the presence of cytoplasmic immunoreactivity for ACTH. The muscle atrophy was considered to be related to an excess of inactive ACTH. Studying spontaneous occurring rare diseases in animals could help to understand the mechanism of similar diseases in human has well.

  8. Immunohistochemical investigations of genital ulcers caused by Haemophilus ducreyi. (United States)

    Abeck, D; Freinkel, A L; Korting, H C; Szeimis, R M; Ballard, R C


    To gain information on the specific composition of the inflammatory infiltrate of genital ulcers caused by Haemophilus ducreyi, biopsies of 6 genital ulcers which were diagnosed as chancroid on clinical and microbiological grounds were subjected to immunohistochemical investigations after conventional haematoxylineosin staining. A variety of antibodies reactive against B- and T-cells, plasma cells and granulocytes were used with each tissue sections. The lymphocytic infiltrate of chancroid ulcers consisted of both B- and T-lymphocytes and showed a cluster-like formation. B-lymphocytes were preferentially localized perivascularly in the middle layer, T-lymphocytes mainly in the deep layer of the inflamed oedematous tissue. Results stress the importance of both B- and T-cell mediated immune responses in Haemophilus ducreyi infection.

  9. How Is COPD Diagnosed? (United States)

    ... page from the NHLBI on Twitter. How Is COPD Diagnosed? Your doctor will diagnose COPD based on ... Rate This Content: NEXT >> Featured Video What is COPD? 05/22/2014 Describes how COPD, or chronic ...

  10. Diagnosing Tic Disorders (United States)

    ... Other Websites Information For... Media Policy Makers Diagnosing Tic Disorders Language: English Español (Spanish) Recommend on Facebook ... or postviral encephalitis). Persistent (Chronic) Motor or Vocal Tic Disorder For a person to be diagnosed with ...

  11. How Is Atherosclerosis Diagnosed? (United States)

    ... page from the NHLBI on Twitter. How Is Atherosclerosis Diagnosed? Your doctor will diagnose atherosclerosis based on ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  12. Ductal adenocarcinoma of the prostate: immunohistochemical findings and clinical significance

    Directory of Open Access Journals (Sweden)

    Sha JJ


    Full Text Available Jianjun Sha,1,2 Juanjie Bo,1 Jiahua Pan,1 Lianhua Zhang,1 Hanqing Xuan,1 Wei Chen,1 Dong Li,1 Zhaoliang Wang,1 Dongming Liu,1 Yiran Huang1,2 1Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 2School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai, People's Republic of China Introduction: To investigate the clinical features, diagnosis, treatment, and prognosis of ductal adenocarcinoma of the prostate. Methods: The clinicopathological and immunohistochemical data of seven patients with ductal adenocarcinoma of the prostate were retrospectively analyzed. All patients underwent physical examination, magnetic resonance imaging (MRI, bone scan, cystoscopy, and computed tomography (CT scan. The level of prostate-specific antigen (PSA before and after surgery was assessed. Different prostate cancer markers were used for immunohistochemical staining. Results: The mean age of the seven patients diagnosed with prostatic ductal adenocarcinoma in this study was 76.2 years (range 57–88. Five patients presented with intermittent and painless gross hematuria, one patient with progressive dysuria, and one patient with elevated serum PSA on routine health examination. The level of PSA before surgery ranged from 1.3 to 45.0 ng/mL. Immunohistochemical staining results of the prostatic ductal adenocarcinoma confirmed positivity for PSA, prostatic acid phosphatase, androgen receptor, and alpha-methyacyl co-enzyme A (CoA-reductase markers. Two of the patients underwent bilateral orchiectomy combined with anti-androgen therapy, three underwent transurethral resection of prostate, one received radical prostatectomy, and one received medical castration therapy. The clinical outcomes of all patients were satisfactory, based on follow-up data. The symptoms of hematuria and dysuria were ameliorated well, and the postoperative PSA level decreased below 4.0 ng/mL. Recurrence or metastasis of disease was

  13. Cytohistopathological and immunohistochemical correlation of soft tissue tumors

    Directory of Open Access Journals (Sweden)

    J. Chandralekha


    Full Text Available Background: Fine needle aspiration cytology has become an established tool in the diagnostic armamentarium of many clinical practices. The initial diagnosis of many mass lesions, both superficial and deep-seated, can often be readily and safely assessed by fine needle aspiration cytology. In our study, we assessed 361 cases of soft tissue tumors by fine needle aspiration cytology during a period of three years. We tried to follow up as many cases as possible to obtain corresponding excision biopsies for histopathological examination. Immunohistochemical studies were also performed on biopsy sections in some cases for confirmation of diagnoses. Aims and objectives: 1 To study the age, sex and site-wise distribution of soft tissue tumors. 2 To assess the utility of fine needle aspiration cytology in diagnosing various types of soft tissue tumors. 3 To assess the sensitivity, specificity, positive and negative predictive values, and overall histological correlation percentage of fine needle aspiration cytology in diagnosing soft tissue tumors. Methods: Aspirations were carried out using a 22 gauge disposable needle and a 10c.c disposable syringe for suction. Wet-fixed smears were stained with hematoxylin and eosin and pap stain. Dry-fixed smears were stained with May-Grunwald Giemsa stain. Periodic Acid Schiff stain was used in some cases of extraskeletal Ewing's sarcoma. Corresponding biopsy sections were stained with hematoxylin and eosin. Immunohistochemical stains were also used in some of the cases for confirmation of diagnosis. Results: Of the 361 cases recorded in our study, 320 patients could be successfully followed up and excision biopsies were obtained. The remaining 41 patients were excluded from the study due to inability to obtain biopsy. Of the 320 cases, 200 were diagnosed as benign soft tissue tumors, while 120 were diagnosed as malignant on cytological examination. The median age of occurrence of benign soft tissue tumors was 34

  14. Does gastric atrophy exist in children?

    Institute of Scientific and Technical Information of China (English)

    Georges Dimitrov; Frédéric Gottrand


    Several clinical reports confirmed that gastric atrophy is a pathology not only limited to adult patients. In pediatrics, it is most often described in association with a Hpylori infection but this bacteria does not seem to be the only etiological factor of this preneoplastic state in children. The frequency of gastric atrophy and intestinal metaplasia in children are unknown because they are not systematically sought during upper gastrointestinal endoscopy. The lack of specific histological classification of children's gastropathies makes their diagnosis difficult for pathologists. Based on our knowledge to date, we think that it is necessary to describe, in detail, the natural course of this lesion during childhood. A close and prolonged clinical and endoscopic follow-up is important for children with gastric atrophy.

  15. Mirror movements in progressive hemifacial atrophy

    Directory of Open Access Journals (Sweden)

    Rajesh Verma


    Full Text Available Mirror movements are simultaneous, involuntary, identical movements occurring during contralateral voluntary movements. These movements are considered as soft neurologic signs seen uncommonly in clinical practice. The mirror movements are described in various neurological disorders which include parkinsonism, cranio veretebral junction anamolies, and hemiplegic cerebral palsy. These movements are intriguing and can pose significant disability. However, no such observation regarding mirror movements in progressive hemifacial atrophy have been reported previously. We are reporting a teenage girl suffering from progressive hemifacial atrophy and epilepsy with demonstrable mirror movements in hand.

  16. Progressive cerebral atrophy in neuromyelitis optica. (United States)

    Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji


    We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients.

  17. Restless legs syndrome in multiple system atrophy. (United States)

    Ghorayeb, Imad; Dupouy, Sandrine; Tison, François; Meissner, Wassilios G


    The purpose of the study was to evaluate the frequency of restless legs syndrome in 30 patients with multiple system atrophy. Eight patients complained from restless legs syndrome, their severity score was 19.4 ± 4.1. Pittsburgh Sleep Quality Index scores were significantly higher in patients with restless legs syndrome than those without (9.3 ± 3.7 vs. 4.8 ± 2.9, p = 0.00165). Periodic limb movements were found in 75% of patients with restless legs syndrome. Restless legs syndrome is more prevalent in multiple system atrophy as compared to the acknowledged prevalence in the general population.

  18. Mirror movements in progressive hemifacial atrophy (United States)

    Verma, Rajesh; Dixit, Puneet Kumar; Lalla, Rakesh; Singh, Babita


    Mirror movements are simultaneous, involuntary, identical movements occurring during contralateral voluntary movements. These movements are considered as soft neurologic signs seen uncommonly in clinical practice. The mirror movements are described in various neurological disorders which include parkinsonism, cranio veretebral junction anamolies, and hemiplegic cerebral palsy. These movements are intriguing and can pose significant disability. However, no such observation regarding mirror movements in progressive hemifacial atrophy have been reported previously. We are reporting a teenage girl suffering from progressive hemifacial atrophy and epilepsy with demonstrable mirror movements in hand. PMID:26019431

  19. Posterior cortical atrophy: a brief review. (United States)

    Kirshner, Howard S; Lavin, Patrick J M


    Posterior cortical atrophy is a striking clinical syndrome in which a dementing illness begins with visual symptoms. Initially, the problem may seem to be loss of elementary vision, but over time the patient develops features of visual agnosia, topographical difficulty, optic ataxia, simultanagnosia, ocular apraxia (Balint's syndrome), alexia, acalculia, right-left confusion, and agraphia (Gerstmann's syndrome), and later a more generalized dementia. Occasional patients have visual hallucinations and signs of Parkinson's disease or Lewy body dementia. A number of different neuropathologic disorders are associated with posterior cortical atrophy.

  20. Bilingualism as a contributor to cognitive reserve: evidence from brain atrophy in Alzheimer's disease. (United States)

    Schweizer, Tom A; Ware, Jenna; Fischer, Corinne E; Craik, Fergus I M; Bialystok, Ellen


    Much of the research on delaying the onset of symptoms of Alzheimer's disease (AD) has focused on pharmacotherapy, but environmental factors have also been acknowledged to play a significant role. Bilingualism may be one factor contributing to 'cognitive reserve' (CR) and therefore to a delay in symptom onset. If bilingualism is protective, then the brains of bilinguals should show greater atrophy in relevant areas, since their enhanced CR enables them to function at a higher level than would be predicted from their level of disease. We analyzed a number of linear measurements of brain atrophy from the computed tomography (CT) scans of monolingual and bilingual patients diagnosed with probable AD who were matched on level of cognitive performance and years of education. Bilingual patients with AD exhibited substantially greater amounts of brain atrophy than monolingual patients in areas traditionally used to distinguish AD patients from healthy controls, specifically, the radial width of the temporal horn and the temporal horn ratio. Other measures of brain atrophy were comparable for the two groups. Bilingualism appears to contribute to increased CR, thereby delaying the onset of AD and requiring the presence of greater amounts of neuropathology before the disease is manifest.

  1. Grey matter hypometabolism and atrophy in Parkinson's disease with cognitive impairment: a two-step process. (United States)

    González-Redondo, Rafael; García-García, David; Clavero, Pedro; Gasca-Salas, Carmen; García-Eulate, Reyes; Zubieta, José L; Arbizu, Javier; Obeso, José A; Rodríguez-Oroz, María C


    The pathophysiological process underlying cognitive decline in Parkinson's disease is not well understood. Cerebral atrophy and hypometabolism have been described in patients with Parkinson's disease and dementia or mild cognitive impairment with respect to control subjects. However, the exact relationships between atrophy and hypometabolism are still unclear. To determine the extension and topographical distribution of hypometabolism and atrophy in the different cognitive states of Parkinson's disease, we examined 46 patients with Parkinson's disease (19 female, 27 male; 71.7 ± 5.9 years old; 14.6 ± 4.2 years of disease evolution; modified Hoehn and Yahr mean stage 3.1 ± 0.7). Cognitive status was diagnosed as normal in 14 patients, as mild cognitive impairment in 17 and as dementia in 15 patients. Nineteen normal subjects (eight female, 11 male; 68.1 ± 3.2 years old) were included as controls. (18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging scans were obtained, co-registered, corrected for partial volume effect and spatially normalized to the Montreal Neurological Institute space in each subject. Smoothing was applied to the positron emission tomography and magnetic resonance imaging scans to equalize their effective smoothness and resolution (10 mm and 12 mm full-width at half-maximum and Gaussian kernel, respectively). Z-score maps for atrophy and for hypometabolism were obtained by comparing individual images to the data set of control subjects. For each group of patients, a paired Student's t-test was performed to statistically compare the two Z-map modalities (P mild cognitive impairment, hypometabolism exceeded atrophy in the angular gyrus, occipital, orbital and anterior frontal lobes. In patients with dementia, the hypometabolic areas observed in the group with mild cognitive impairment were replaced by areas of atrophy, which were surrounded by extensive zones of hypometabolism. Areas where atrophy was more

  2. Collagenous gastritis: a morphologic and immunohistochemical study of 40 patients. (United States)

    Arnason, Thomas; Brown, Ian S; Goldsmith, Jeffrey D; Anderson, William; O'Brien, Blake H; Wilson, Claire; Winter, Harland; Lauwers, Gregory Y


    Collagenous gastritis is a rare condition defined histologically by a superficial subepithelial collagen layer. This study further characterizes the morphologic spectrum of collagenous gastritis by evaluating a multi-institutional series of 40 patients (26 female and 14 male). The median age at onset was 16 years (range 3-89 years), including 24 patients (60%) under age 18. Twelve patients (30%) had associated celiac disease, collagenous sprue, or collagenous colitis. Hematoxylin and eosin slides were reviewed in biopsies from all patients and tenascin, gastrin, eotaxin, and IgG4/IgG immunohistochemical stains were applied to a subset. The distribution of subepithelial collagen favored the body/fundus in pediatric patients and the antrum in adults. There were increased surface intraepithelial lymphocytes (>25 lymphocytes/100 epithelial cells) in five patients. Three of these patients had associated celiac and/or collagenous sprue/colitis, while the remaining two had increased duodenal lymphocytosis without specific etiology. An eosinophil-rich pattern (>30 eosinophils/high power field) was seen in 21/40 (52%) patients. Seven patients' biopsies demonstrated atrophy of the gastric corpus mucosa. Tenascin immunohistochemistry highlighted the subepithelial collagen in all 21 specimens evaluated and was a more sensitive method of collagen detection in biopsies from two patients with subtle subepithelial collagen. No increased eotaxin expression was identified in 16 specimens evaluated. One of the twenty-three biopsies tested had increased IgG4-positive cells (100/high power field) with an IgG4/IgG ratio of 55%. In summary, collagenous gastritis presents three distinct histologic patterns including a lymphocytic gastritis-like pattern, an eosinophil-rich pattern, and an atrophic pattern. Eotaxin and IgG4 were not elevated enough to implicate these pathways in the pathogenesis. Tenascin immunohistochemistry can be used as a sensitive method of collagen detection.

  3. Genetics Home Reference: spinal muscular atrophy with progressive myoclonic epilepsy (United States)

    ... Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes muscle weakness ... muscle jerks (myoclonic epilepsy). In individuals with SMA-PME, spinal muscular atrophy results from a loss of ...

  4. Grey matter atrophy in patients suffering from multiple sclerosis. (United States)

    Kincses, Zsigmond Tamás; Tóth, Eszter; Bankó, Nóra; Veréb, Dániel; Szabó, Nikoletta; Csete, Gergő; Faragó, Péter; Király, András; Bencsik, Krisztina; Vécsei, László


    White matter lesions are defining characteristics of multiple sclerosis (MS), whereas grey matter involvement is a less recognised attribute. Recent investigations using dedicated imaging approaches have made it possible to depict cortical lesions. Additionally, grey matter atrophy may be estimated using various methods. Several studies have suggested that grey matter atrophy closely correlates to clinical disability. In this review we have collected information on grey matter atrophy in MS and the effect of disease modifying therapies upon brain atrophy.

  5. Matrix metalloproteinase imbalance in muscle disuse atrophy. (United States)

    Giannelli, G; De Marzo, A; Marinosci, F; Antonaci, S


    Muscle atrophy commonly occurs as a consequence of prolonged muscle inactivity, as observed after cast immobilization, bed rest or space flights. The molecular mechanisms responsible for muscle atrophy are still unknown, but a role has been proposed for altered permeability of the sarcolemma and of the surrounding connective tissue. Matrix metallo-proteinases (MMPs) are a family of enzymes with proteolytic activity toward a number of extracellular matrix (ECM) components; they are inhibited by tissue inhibitors of MMPs (TIMPs). In a rat tail-suspension experimental model, we show that after fourteen days of non-weight bearing there is increased expression of MMP-2 in the atrophic soleus and gastrocnemius and decreased expression of TIMP-2. In the same experimental model the expression of Collagen I and Collagen IV, two main ECM components present in the muscles, was reduced and unevenly distributed in unloaded animals. The difference was more evident in the soleus than in the gastrocnemius muscle. This suggests that muscle disuse induces a proteolytic imbalance, which could be responsible for the breakdown of basal lamina structures such as Collagen I and Collagen IV, and that this leads to an altered permeability with consequent atrophy. In conclusion, an MMP-2/TIMP-2 imbalance could have a role in the mechanism underlying muscle disuse atrophy; more studies are needed to expand our molecular knowledge on this issue and to explore the possibility of targeting the proteolytic imbalance with MMP inhibitors.

  6. Redox control of skeletal muscle atrophy. (United States)

    Powers, Scott K; Morton, Aaron B; Ahn, Bumsoo; Smuder, Ashley J


    Skeletal muscles comprise the largest organ system in the body and play an essential role in body movement, breathing, and glucose homeostasis. Skeletal muscle is also an important endocrine organ that contributes to the health of numerous body organs. Therefore, maintaining healthy skeletal muscles is important to support overall health of the body. Prolonged periods of muscle inactivity (e.g., bed rest or limb immobilization) or chronic inflammatory diseases (i.e., cancer, kidney failure, etc.) result in skeletal muscle atrophy. An excessive loss of muscle mass is associated with a poor prognosis in several diseases and significant muscle weakness impairs the quality of life. The skeletal muscle atrophy that occurs in response to inflammatory diseases or prolonged inactivity is often associated with both oxidative and nitrosative stress. In this report, we critically review the experimental evidence that provides support for a causative link between oxidants and muscle atrophy. More specifically, this review will debate the sources of oxidant production in skeletal muscle undergoing atrophy as well as provide a detailed discussion on how reactive oxygen species and reactive nitrogen species modulate the signaling pathways that regulate both protein synthesis and protein breakdown.

  7. Cube propagation for focal brain atrophy estimation

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru; Sørensen, Lauge; Darkner, Sune;


    Precise and robust whole brain, ventricle, and hippocampal atrophy measurements are important as they serve as biomarkers for Alzheimer’s disease. They are used as secondary outcomes in drug trials, and they correlate with the cognitive scores. When two successive scans are non-linearly aligned...

  8. Genetics Home Reference: spinal muscular atrophy (United States)

    ... and abdomen, weakness in the leg muscles, involuntary muscle contractions, tremors, and a protrusion of the abdomen thought to be related to muscle weakness. Some affected individuals experience difficulty swallowing and problems with bladder and ... Frequency Spinal muscular atrophy affects 1 in 6,000 to 1 ...

  9. Diagnosing Sleep Disorders (United States)

    ... of this page please turn JavaScript on. Feature: Sleep Disorders Diagnosing Sleep Disorders Past Issues / Summer 2015 Table of Contents Depending ... several possible tests when trying to diagnose a sleep disorder: Sleep history and sleep log If you believe ...

  10. How Is Raynaud's Diagnosed? (United States)

    ... diagnose primary Raynaud's (Raynaud's disease) or secondary Raynaud's (Raynaud's phenomenon) based on your medical history, a physical exam, and test results. Specialists Involved Primary care doctors and internists often diagnose and treat Raynaud's. If you have the disorder, you also may ...

  11. Differential diagnoses to MS

    DEFF Research Database (Denmark)

    Horwitz, Henrik; Friis, Tina; Modvig, Signe;


    of 643 patients were included in the study. Apart from ON, the most frequent diagnoses were tumors (n = 15), ischemic or hypertensive neuropathies (n = 13), and retinal or choroid disorders (n = 9). Six patients were diagnosed with neuromyelitis optica. Rarer causes of visual loss were infections (n = 5...

  12. Pancreatic neuroendocrine tumor and solid-pseudopapillary neoplasm: Key immunohistochemical profiles for differential diagnosis (United States)

    Ohara, Yusuke; Oda, Tatsuya; Hashimoto, Shinji; Akashi, Yoshimasa; Miyamoto, Ryoichi; Enomoto, Tsuyoshi; Satomi, Kaishi; Morishita, Yukio; Ohkohchi, Nobuhiro


    AIM To reveal better diagnostic markers for differentiating neuroendocrine tumor (NET) from solid-pseudopapillary neoplasm (SPN), focusing primarily on immunohistochemical analysis. METHODS We reviewed 30 pancreatic surgical specimens of NET (24 cases) and SPN (6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pan-cytokeratin, E-cadherin, progesterone receptor, vimentin, α-1-antitrypsin, CD10, and β-catenin. RESULTS E-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles. CONCLUSION E-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.

  13. Anterior pituitary lobe atrophy as late complication of hemorrhagic fever with renal syndrome

    Directory of Open Access Journals (Sweden)

    Jovanović Dragan


    Full Text Available Introduction. Hemorrhagic fever with renal syndrome (HFRS is acute infective multisystemic disease followed by febrility, hemorrhages and acute renal insufficiency. Bleeding in the anterior pituitary lobe leading to tissue necrosis occurs in acute stage of severe clinical forms of HFRS, while atrophy of the anterior pituitary lobe with diminution of the gland function occurs after recovery stage. Case report. We presented a patient with the development of chronic renal insufficiency and hypopituitarism as complication that had been diagnosed six years after Hantavirus infection. Magnetic resonance of the pituitary gland revealed atrophy and empty sella turcica. Conclusion. Regarding frequency of this viral infection and its endemic character in some parts of our country partial and/or complete loss of pituitary function should be considered during the late stage of HFRS.

  14. Plantar fibromatosis: an immunohistochemical and ultrastructural study. (United States)

    de Palma, L; Santucci, A; Gigante, A; Di Giulio, A; Carloni, S


    The analogies between plantar fibromatosis and Dupuytren's disease (palmar fibromatosis) are well known. The latter is clinically more frequent and has been the object of extensive immunohistochemical and ultrastructural studies, with a view to investigating its pathogenesis. By contrast, such data on plantar fibromatosis are quite scarce. A histochemical, immunohistochemical, and ultrastructural study was performed on nodule tissue from six patients who were subjected to total fasciectomy for plantar fibromatosis. The study of myofibroblasts revealed features suggestive of their fibroblastic origin and evidenced a cytoskeleton and an extracellular filamentous system that could enable myofibroblasts to generate and exert the intracellular forces that contribute to the contraction of the aponeurosis. These aspects are similar to those observed in Dupuytren's disease and seem to lend support to the theory that the two diseases are expressions of the same disorder.

  15. HPV immunohistochemical testing and cervical dysplasia




    Background and aim HPV (Human Papilloma Virus) infection represents a necessary condition for cervical carcinogenesis. The purpose of this study was to evaluate the efficiency of HPV testing using an immunohistochemical staining kit with implications upon both diagnosis and treatment of cervical intraepithelial neoplasia (CIN). Methods Seventy-nine patients and eighty-six controls were enrolled in the study. Each patient had completed a physical examination, gynecological examination with cer...

  16. Histopathologic and immunohistochemical features of Hashimoto thyroiditis

    Directory of Open Access Journals (Sweden)

    H Kazem Amani


    Full Text Available Background: Intrathyroid lymphoid tissue is accrued in Hashimoto thyroiditis (HT. Histologically, this acquired lymphoid tissue bears a close resemblance to mucosa-associated lymphoid tissue (MALT and can evolve to lymphoma. Aim: To demonstrate the morphological, and immunohistochemical profiles of Hashimoto thyroiditis and to ascertain the importance of light chain restriction in distinguishing HT with extensive lymphoplasmacytoid infiltrate from MALT lymphoma. Materials and Methods: We studied histopathologically and immunohistochemically (CD20, CD3, Igk, Igl and cytokeratin 30 cases of HT for evaluation of the lymphoid infiltrate and the presence of lymphoepithelial lesions (LELs. Distinguishing between early thyroid lymphoma and HT was evaluated by light chain restriction. These findings were compared with two cases of primary thyroid lymphoma. Results: The histopathological findings were characteristic of HT. Immunohistochemistry confirmed inconspicuous, rare B-cell LELs as well as a prominent T-lymphocyte population. Testing for light chain restriction showed polyclonal population of plasma cells. The cases of MALT lymphoma had distinct destructive lymphoepithelial lesions, B-cell immunophenotyping and showed kappa light chain restriction in the plasmacytoid population. Conclusions: Hashimoto thyroiditis differs both histopathologically and immunohistochemically from thyroid lymphoma. In suspicious cases, immunohistochemistry could be helpful in reaching a definitive diagnosis.

  17. Differentiation in cutaneous adnexal tumors: Immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Figen BARUT


    Full Text Available Cutaneous adnexal neoplasms are rare tumors that display differentiation in different ways. The aim of this study is, to present embryonic developmental properties and to determine the way of differentiation of adnexal neoplasms by evaluating the immunohistochemical expression of various markers.Forty-seven cases with adnexal tumors enrolled in this study. Histopathologic groups of these 47 cases were: 15 (32% hair follicle tumors, 11 (23.4% sebaceous tumors, 8 (17% apocrine tumors, and 13 (27.6% eccrine tumors. CK5-6, CK6, CK7, CK8, CK10, CK19, GCDFP-15, carcinoembryonic antigen, epithelial membrane antigen and S100 protein expressions were examined by immunohistochemical methods.As a result of this immunohistochemical study it was concluded that the expression of CK5-6 and CK8 carries more importance than other markers in determining certain types of differentiation of hair follicle tumors. It was also determined that, epithelial membrane antigen expression is important for the diagnosis of sebaceous tumors and the markers like CK8, CK10 and carcinoembryonic antigen may aid for the same purpose as well. It was found that, GCDFP-15 as well as CK5-6 expressions are significant for apocrine tumors, and carcinoembryonic antigen reaction as well as CK8 positivity will aid in determining differentiation of eccrine tumors. The presence of similar CK6 expression in all kinds of adnexal tumors has demonstrated that this marker is useless in differential diagnosis.

  18. Research progress of posterior cortical atrophy

    Directory of Open Access Journals (Sweden)

    Li-jun PENG


    Full Text Available Posterior cotical atrophy (PCA is a kind of progressive dementia with main clinical manifestations of visual dysfunction as the starting symptom and associated with progressive cognitive disorder. The histopathology and imaging of PCA show visual dysfunction, neuritic plaques (NPs and neurofibrillary tangles (NFTs, which are the same as those in Alzheimer's disease (AD. Researches also showed that mutation of presenilin-1 (PS-1 gene and apolipoprotein E (ApoE genotype may participate in the occurrence and development of PCA. Parieto-occipital lobe atrophy, hypoperfusion and/or glucose metabolism reduction in the right posterior cerebrum can be seen in PCA. Cholinesterase inhibitors (ChEIs may improve the symptoms and postpone the progression of illness. No unified diagnostic criteria will reduce the comparability between different studies. Reasonable usage of the diagnostic criteria of PCA will be helpful in classifying and differentiating this disease. DOI: 10.3969/j.issn.1672-6731.2016.06.011

  19. How Is Hemophilia Diagnosed? (United States)

    ... page from the NHLBI on Twitter. How Is Hemophilia Diagnosed? If you or your child appears to ... have bleeding problems. However, some people who have hemophilia have no recent family history of the disease. ...

  20. Very severe spinal muscular atrophy (Type 0). (United States)

    Al Dakhoul, Suleiman


    This case report describes a rare phenotype of very severe spinal muscular atrophy (SMA) in a newborn who presented with reduced fetal movements in utero and significant respiratory distress at birth. The patient was homozygously deleted for exon 7 and exon 8 of the survival motor neuron gene 1. Very severe SMA should be considered in the differential diagnosis of respiratory distress at birth, and more research should be dedicated to investigate the genetic determinants of its widely variable phenotypes.

  1. Multiple system atrophy and cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Sen-yang LANG


    Full Text Available As the survival of patients with multiple system atrophy (MSA is prolonged, patients may present cognitive dysfunction or even dementia in addition to autonomic dysfunction, damage of extrapyramidal system and cerebellar ataxia. This article made a brief summary on the research progress of MSA combined with cognitive dysfunction reported at home and abroad. DOI: 10.3969/j.issn.1672-6731.2016.06.003

  2. Coeliac disease: more than villous atrophy. (United States)

    Wahab, Peter J; Meijer, Jos W R; Dumitra, Daniela; Goerres, Marije S; Mulder, Chris J J


    A continuing flow of new scientific developments concerning coeliac disease in the last decade asks for the formulation of a new concept of pathophysiology and clinical approach of the coeliac condition. Immunogenetic studies have shown a correlation of the disease to the HLA region on the short arm of chromosome 6. Immunological research has led to the concept of a T-cell driven immunologic response of the small intestine, with the identification of highly sensitive and specific antibodies, and in addition the understanding of the histopathology of coeliac disease has changed dramatically, initiated by the proposition of a spectrum of gluten sensitive enteropathy by Marsh in 1992. Clinical studies report a significant change in patient characteristics and epidemiology. The incidence of the disease has shifted to a majority of adult coeliacs and the disease may present with less severe symptoms of malabsorption while screening studies suggest an overall prevalence of up to 1 in 200-300. In the present paper (an update on histopathology) we specifically describe the work of our group in Arnhem, concerning the identification and validation of the spectrum of intestinal histopathology in gluten sensitive enteropathy, i.e. lymphocytic enteritis (Marsh I lesion), lymphocytic enteritis with crypthyperplasia (Marsh II lesion), and villous atrophy, subdivided in partial villous atrophy (Marsh IIIA), subtotal villous atrophy (Marsh IIIB) and total villous atrophy (Marsh IIIC). Special attention is given to a subgroup of "refractory coeliacs", including the identification of (pre-) malignant aberrant T-cells in the intestinal mucosa of these patients. The new data on immunogenetics, epidemiology, histo-pathology and patient characteristics point to a significant change of views on coeliac disease.

  3. Sensorimotor gating deficits in multiple system atrophy

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Biernat, Heidi Bryde; Nikolic, Miki


    Prepulse inhibition (PPI) of the auditory blink reflex is a measure of sensorimotor gating, which reflects an organism's ability to filter out irrelevant sensory information. PPI has never been studied in patients with multiple system atrophy (MSA), although sensorimotor deficits are frequently...... associated with synucleinopathies. We investigated whether alterations in PPI were more pronounced in MSA compared with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavior disorder (iRBD) and healthy controls....

  4. Granuloma faciale: clinical, morphological and immunohistochemical aspects in a series of 10 patients* (United States)

    Oliveira, Cristiano Claudino; Ianhez, Pedro Eugênio de Carvalho; Marques, Silvio Alencar; Marques, Mariângela Esther Alencar


    Granuloma faciale is a chronic, benign, cutaneous vasculitis with well-established clinical and morphological patterns, but with an unknown etiology. This study describes clinical and pathologic aspects of patients diagnosed with granuloma faciale. The authors analyzed demographic, clinical, morphological and immunohistochemical data from patients with a final diagnosis of granuloma faciale, confirmed between 1998 and 2012. There was a proportional and mixed inflammatory infiltrate, Grenz zones were present in almost all the samples. Immunophenotyping confirmed a higher intensity of T lymphocytes than B lymphocytes in thirteen samples, with a predominance of T CD8 lymphocytes in 64% of cases, in contrast to the literature, which indicates that the major component is T CD4 lymphocytes. All cases were positive for IgG4 but the majority (12/14) had less than 25% of stained cells. The pathogenesis of granuloma faciale remains poorly understood, making studies of morphological and immunohistochemical characterization important to better understand it. PMID:28099604

  5. Space travel directly induces skeletal muscle atrophy (United States)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.


    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  6. Proximal spinal muscular atrophy: current orthopedic perspective

    Directory of Open Access Journals (Sweden)

    Haaker G


    Full Text Available Gerrit Haaker, Albert Fujak Department of Orthopaedic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany Abstract: Spinal muscular atrophy (SMA is a hereditary neuromuscular disease of lower motor neurons that is caused by a defective "survival motor neuron" (SMN protein that is mainly associated with proximal progressive muscle weakness and atrophy. Although SMA involves a wide range of disease severity and a high mortality and morbidity rate, recent advances in multidisciplinary supportive care have enhanced quality of life and life expectancy. Active research for possible treatment options has become possible since the disease-causing gene defect was identified in 1995. Nevertheless, a causal therapy is not available at present, and therapeutic management of SMA remains challenging; the prolonged survival is increasing, especially orthopedic, respiratory and nutritive problems. This review focuses on orthopedic management of the disease, with discussion of key aspects that include scoliosis, muscular contractures, hip joint disorders, fractures, technical devices, and a comparative approach of conservative and surgical treatment. Also emphasized are associated complications including respiratory involvement, perioperative care and anesthesia, nutrition problems, and rehabilitation. The SMA disease course can be greatly improved with adequate therapy with established orthopedic procedures in a multidisciplinary therapeutic approach. Keywords: spinal muscular atrophy, scoliosis, contractures, fractures, lung function, treatment, rehabilitation, surgery, ventilation, nutrition, perioperative management

  7. Cellular and molecular mechanisms of muscle atrophy

    Directory of Open Access Journals (Sweden)

    Paolo Bonaldo


    Full Text Available Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.

  8. Congenital heart defects in spinal muscular atrophy type I : A clinical report of two siblings and a review of the literature

    NARCIS (Netherlands)

    Menke, Leonie A.; Poll-The, Bwee Tien; Clur, Sally-Ann; Bilardo, Catia M.; van der Wal, Allard C.; Lenunink, Henny H.; Cobben, Jan Maarten


    A newborn girl presented with asphyxia, joint contractures and diminished spontaneous movements. Echocardiography showed hypoplastic left heart. Spinal muscular atrophy type I (SMA I) was diagnosed by detecting a homozygous deletion in the survival motor neuron 1 gene (SMN1). In the first trimester

  9. A Case of Multiple System Atrophy-Cerebellar Type Preceded by Dementia

    Directory of Open Access Journals (Sweden)

    Eun Hye Jang


    Full Text Available Multiple system atrophy (MSA is a sporadic, adult-onset disease characterized by progressive degeneration of nervous systems including cerebellar, pyramidal, extrapyramidal, and autonomic system. Although a few recent studies reported that cognitive impairments could occur in patients with MSA, prominent dementia with progressive decline is not a typical clinical manifestation of MSA. In particular, dementia with MSA-cerebellar type is very rare. We have experienced a patient with 2-year history of severe cognitive impairment, who was finally diagnosed as MSA-cerebellar type.

  10. Spontaneous regression of a cystic hypoglossal schwannoma causing unilateral tongue atrophy. (United States)

    Durnford, Andrew J; Harrisson, Stuart E; Ditchfield, Adam; Shenouda, Emad


    A 60-year-old lady presented with intermittent headaches. Examination revealed striking marked unilateral tongue atrophy. Magnetic resonance imaging (MRI) revealed a cystic lesion in the hypoglossal canal and a provisional diagnosis of cystic hypoglossal schwannoma made. Annual surveillance scans showed stable appearances but surprisingly at 3 years they showed a significant reduction in the size of the lesion. Most patients with hypoglossal schwannomas present with ipsilateral hypoglossal nerve palsy; careful cranial nerve examination is vital in diagnosing such rare lesions. Little is known of their natural history, with most lesions undergoing surgery. This case highlights spontaneous regression following non-operative management.

  11. Phenotypic and immunohistochemical characterization of sarcoglycanopathies

    Directory of Open Access Journals (Sweden)

    Ana F. B. Ferreira


    Full Text Available INTRODUCTION: Limb-girdle muscular dystrophy presents with heterogeneous clinical and molecular features. The primary characteristic of this disorder is proximal muscular weakness with variable age of onset, speed of progression, and intensity of symptoms. Sarcoglycanopathies, which are a subgroup of the limb-girdle muscular dystrophies, are caused by mutations in sarcoglycan genes. Mutations in these genes cause secondary deficiencies in other proteins, due to the instability of the dystrophin-glycoprotein complex. Therefore, determining the etiology of a given sarcoglycanopathy requires costly and occasionally inaccessible molecular methods. OBJECTIVE: The aim of this study was to identify phenotypic differences among limb-girdle muscular dystrophy patients who were grouped according to the immunohistochemical phenotypes for the four sarcoglycans. METHODS: To identify phenotypic differences among patients with different types of sarcoglycanopathies, a questionnaire was used and the muscle strength and range of motion of nine joints in 45 patients recruited from the Department of Neurology - HC-FMUSP (Clinics Hospital of the Faculty of Medicine of the University of São Paulo were evaluated. The findings obtained from these analyses were compared with the results of the immunohistochemical findings. RESULTS: The patients were divided into the following groups based on the immunohistochemical findings: a-sarcoglycanopathies (16 patients, b-sarcoglycanopathies (1 patient, y-sarcoglycanopathies (5 patients, and nonsarcoglycanopathies (23 patients. The muscle strength analysis revealed significant differences for both upper and lower limb muscles, particularly the shoulder and hip muscles, as expected. No pattern of joint contractures was found among the four groups analyzed, even within the same family. However, a high frequency of tiptoe gait was observed in patients with a-sarcoglycanopathies, while calf pseudo-hypertrophy was most common in

  12. Severe spinal muscular atrophy variant associated with congenital bone fractures. (United States)

    Felderhoff-Mueser, Ursula; Grohmann, Katja; Harder, Anja; Stadelmann, Christine; Zerres, Klaus; Bührer, Christoph; Obladen, Michael


    Infantile autosomal recessive spinal muscular atrophy (type I) represents a lethal disorder leading to progressive symmetric muscular atrophy of limb and trunk muscles. Ninety-six percent cases of spinal muscular atrophy type I are caused by deletions or mutations in the survival motoneuron gene (SMNI) on chromosome 5q11.2-13.3. However, a number of chromosome 5q-negative patients with additional clinical features (respiratory distress, cerebellar hypoplasia) have been designated in the literature as infantile spinal muscular atrophy plus forms. In addition, the combination of severe spinal muscular atrophy and neurogenic arthrogryposis has been described. We present clinical, molecular, and autopsy findings of a newborn boy presenting with generalized muscular atrophy in combination with congenital bone fractures and extremely thin ribs but without contractures.

  13. Iritis and iris atrophy after eyebrow epilation with alexandrite laser

    Directory of Open Access Journals (Sweden)

    Elkin Z


    Full Text Available Zachary Elkin1, Milan P Ranka1, Eleanore T Kim1, Ronit Kahanowicz1, Wayne G Whitmore21Department of Ophthalmology, New York University; 2Department of Ophthalmology, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY, USAPurpose: To report a case of bilateral iritis and transillumination defects after laser hair removal of the eyebrows with an alexandrite laser.Methods: A 41-year-old male presented with bilateral eye pain and mild photophobia 2 days after receiving alexandrite (755 nm laser epilation of both eyebrows. Examination showed visual acuity of 20/20 in both eyes, 2+ conjunctival injection in both eyes, 1+ cells in the anterior chamber of right eye and trace cells in left eye, poor right pupil dilation, and left pupil without movement. Intraocular pressure and fundus examination were normal. He was diagnosed with iritis and iris atrophy, associated with laser epilation. Topical steroids and cycloplegic drops were prescribed for 1 month.Results: After 1 month of treatment, transillumination defects remained in both eyes, but greater in right. In dim light, the right pupil was 4 mm and oval and the left pupil was 6 mm and round. Visual acuity remained 20/20 in both eyes.Conclusion: Laser hair removal of the eyebrows can lead to permanent ocular damage even with eye protection, and should be avoided.Keywords: laser hair removal, transillumination defects, alexandrite laser

  14. Hypospadias as a novel feature in spinal bulbar muscle atrophy. (United States)

    Nordenvall, Anna Skarin; Paucar, Martin; Almqvist, Catarina; Nordenström, Anna; Frisén, Louise; Nordenskjöld, Agneta


    Spinal and bulbar muscle atrophy (SBMA) is an X-linked neuromuscular disorder caused by CAG repeat expansions in the androgen receptor (AR) gene. The SBMA phenotype consists of slowly progressive neuromuscular symptoms and undermasculinization features as the result of malfunction of the AR. The latter mainly includes gynecomastia and infertility. Hypospadias is also a feature of undermasculinization with an underdeveloped urethra and penis; it has not been described as part of the SBMA phenotype but has been suggested to be associated with a prolonged CAG repeat in the AR gene. This study includes the first epidemiologic description of the co-occurrence of hypospadias and SBMA in subjects and their male relatives in Swedish population-based health registers, as well as an additional clinical case. One boy with severe hypospadias was screened for mutations in the AR gene and was found to have 42 CAG repeats in it, which is in the full range of mutations causing SBMA later in life. We also detected a maximum of four cases displaying the combination of SBMA and hypospadias in our national register databases. This is the third case report with hypospadias in association with CAG repeat expansions in the AR gene in the full range known to cause SBMA later in life. Our findings suggest that hypospadias may be an under diagnosed feature of the SBMA phenotype and we propose that neurologists working with SBMA further investigate and report the true prevalence of hypospadias among patients with SBMA.

  15. [A case of spinal muscular atrophy type 0 in Japan]. (United States)

    Okamoto, Kentaro; Saito, Kayoko; Sato, Takatoshi; Ishigaki, Keiko; Funatsuka, Makoto; Osawa, Makiko


    The patient was a 2-month-old female infant born at 41 weeks and 2 days of gestation presenting multiple arthrogryposis, severe muscle hypotonia and respiratory distress with difficulty in feeding. She suffered from repeated complications with aspiration pneumonia. On admission to our hospital, she exhibited fasciculation and absence of deep tendon reflexes. Examination of the motor nerve conduction velocity (MCV) revealed no muscle contraction. Deletions of the SMN and NAIP genes were noted. Based on severe clinical course and disease development in utero, she was given a diagnosis of spinal muscular atrophy (SMA) type 0 (very severe type). Arthrogryposis and disappearance of MCV are exclusion criteria for SMA. However, the clinical course of the infant was very severe and included such exclusion items. Consequently, when an infant presents muscle hypotonia and respiratory distress, SMA must be considered as one of the differential diagnoses, even though arthrogryposis is an exclusion criterion for SMA. We discuss this case in relation to the few extant reports on SMA type 0 in Japanese infants in the literature.

  16. [Postoperative seizure in an epileptic patient with dentatorubral pallidoluysian atrophy]. (United States)

    Yanagidate, Fumi; Dohi, Shuji; Hamaya, Yoshihiro; Ueda, Norio


    A 28-year-old male with dentatorubral pallidoluysian atrophy (DRPLA) was scheduled for evulsion of bone marrow nail after tibia fracture. He was diagnosed as having DRPLA at the age of 12. Although he was receiving anticonvulsants, regular seizures had occurred occasionally and his symptoms were exacerbating. General anesthesia was induced and maintained with intravenous propofol supplemented with fentanyl, nitrous oxide, and oxygen. The operation was performed uneventfully. After the surgery, his breathing was depressed and naloxone was administered to reverse the depression. Thereafter, generalized tonic seizure associated with involuntary movement of the left arm occurred. These symptoms ceased soon after rapid injection of diazepam. Inhaled and intravenous anesthetics have been alleged to have both proconvulsant and anticonvulsant activities in humans. In the present patient with DRPLA, propofol, fentanyl, nitrous oxide, naloxone, and neostigmine administered might be factors, which could have lowered the threshold for seizure activity. Further, patients with DRPLA might have decreased GABA in the basal ganglia, and anesthetics would affect GABA receptors. Thus we should be aware of occurrence of convulsion in DRPLA patients during and after anesthesia.

  17. Head and Arm Tremor in X-linked Spinal and Bulbar Muscular Atrophy (United States)

    Aicua, Irene; Verhagen, Okker; Arenaza, Naroa; Cubo, Esther


    Background X-linked spinal and bulbar muscular atrophy (SBMA) is a rare adult-onset neuronopathy. Although tremor is known to occur in this disease, the number of reported cases of SBMA with tremor is rare, and the number with videotaped documentation is exceedingly rare. Our aim was to describe/document the characteristic signs of tremor in spinal and bulbar muscular atrophy. Case Report We report a case of a 58-year-old male with a positive family history of tremor. On examination, the patient had jaw and hand tremors but he also exhibited gynecomastia, progressive bulbar paresis, and wasting and weakness primarily in the proximal limb muscles. The laboratory tests revealed an elevated creatine phosphokinase. Genetic testing was positive for X-SBMA, with 42 CAG repeats. Discussion Essential tremor is one of the most common movement disorders, yet it is important for clinicians to be aware of the presence of other distinguishing features that point to alternative diagnoses. The presence of action tremor associated with muscle atrophy and gynecomastia should lead to a suspicion of SBMA. PMID:25374767

  18. How Is Testicular Cancer Diagnosed? (United States)

    ... Cancer Early Detection, Diagnosis, and Staging How Is Testicular Cancer Diagnosed? Testicular cancer is usually found as a ... the tumor might have returned. Surgery to diagnose testicular cancer Most types of cancer are diagnosed by removing ...

  19. How a Stroke Is Diagnosed (United States)

    ... News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis Stroke ... Diagnosis » How a Stroke is Diagnosed How a Stroke is Diagnosed How a Stroke is Diagnosed Lab ...

  20. Human vomeronasal epithelium development: An immunohistochemical overview. (United States)

    Dénes, Lóránd; Pap, Zsuzsanna; Szántó, Annamária; Gergely, István; Pop, Tudor Sorin


    The vomeronasal organ (VNO) is the receptor structure of the vomeronasal system (VNS) in vertebrates. It is found bilaterally in the submucosa of the inferior part of the nasal septum. There are ongoing controversies regarding the functionality of this organ in humans. In this study we propose the immunohistochemical evaluation of changes in components of the human vomeronasal epithelium during foetal development. We used 45 foetuses of different age, which were included in three age groups. After VNO identification immunohistochemical reactions were performed using primary antibodies against the following: neuron specific enolase, calretinin, neurofilament, chromogranin, synaptophysin, cytokeratin 7, pan-cytokeratin and S100 protein. Digital slides were obtained and following colorimetric segmentation, surface area measurements were performed. The VNO was found in less than half of the studied specimens (42.2%). Neuron specific enolase and calretinin immunoexpression showed a decreasing trend with foetal age, while the other neural/neuroendocrine markers were negative in all specimens. Cytokeratin 7 expression increased with age, while Pan-Ctk had no significant variations. S100 protein immunoexpression also decreased around the VNO. The results of the present work uphold the theory of regression of the neuroepithelium that is present during initial stages of foetal development.

  1. Corpus callosum atrophy in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Frederiksen, Kristian Steen; Garde, Ellen; Skimminge, Arnold


    Several studies have found atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD). However, it remains unclear whether callosal atrophy is already present in the early stages of AD, and to what extent it may be associated with other structural changes in the brain, such as ......Several studies have found atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD). However, it remains unclear whether callosal atrophy is already present in the early stages of AD, and to what extent it may be associated with other structural changes in the brain...

  2. The Impact of Gastric Atrophy on the Incidence of Diabetes (United States)

    Yu, Tse-Ya; Wei, Jung-Nan; Kuo, Chun-Heng; Liou, Jyh-Ming; Lin, Mao-Shin; Shih, Shyang-Rong; Hua, Cyue-Huei; Hsein, Yenh-Chen; Hsu, Ya-Wen; Chuang, Lee-Ming; Lee, Mei-Kuei; Hsiao, Ching-Hsiang; Wu, Ming-Shiang; Li, Hung-Yuan


    Gastric atrophy results in lower plasma ghrelin, higher gastrin secretion, a change in gut microbiota, and altered dietary nutrient absorption, which may be associated with the incidence of diabetes. Helicobacter pylori (H. pylori) infection is a major cause of gastric atrophy and is associated with diabetes in some reports. Since there is no study which investigates the impact of gastric atrophy on diabetes, we conduct a prospective cohort study to examine the relationship between H. pylori infection, gastric atrophy, and incident diabetes. In this study, subjects with gastric atrophy had a lower risk of incident diabetes, compared to those without gastric atrophy. The extent of gastric atrophy, measured by serum pepsinogen (PG) I/II ratio, was correlated with age, H. pylori IgG titer, HOMA2-IR, and HOMA2%B. When gastric atrophy is more extensive, presented as a lower serum PG I/II ratio, the risk of incident diabetes is lower. On the other hand, there was no significant association between H. pylori infection and the incidence of diabetes. In conclusion, the presence and the extent of gastric atrophy, but not H. pylori infection, are associated with incident diabetes. Further studies are needed to investigate the detailed mechanisms and the potential applications of the findings to guide diabetes screening and treatment strategies. PMID:28045079

  3. Circulating micrornas as potential biomarkers of muscle atrophy (United States)

    Wang, Fei


    Noninvasive biomarkers with diagnostic value and prognostic applications have long been desired to replace muscle biopsy for muscle atrophy patients. Growing evidence indicates that circulating microRNAs are biomarkers to assess pathophysiological status. Here, we show that the medium levels of six muscle-specific miRNAs (miR-1/23a/206/133/499/208b, also known as myomiRs) were all elevated in the medium of starved C2C12 cell (P atrophy patients, indicating that they might represent the degree of muscle atrophy. Collectively, our data indicated that circulating myomiRs could serve as promising biomarkers for muscle atrophy.

  4. Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis. (United States)

    Andrews, K Abigail; Frost, Chris; Modat, Marc; Cardoso, M Jorge; Rowe, Chris C; Villemagne, Victor; Fox, Nick C; Ourselin, Sebastien; Schott, Jonathan M


    Increased rates of brain atrophy measured from serial magnetic resonance imaging precede symptom onset in Alzheimer's disease and may be useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. Fifty-two healthy individuals (72.3 ± 6.9 years) from Australian Imaging, Biomarkers and Lifestyle Study of Aging had serial (0, 18 m, 36 m) magnetic resonance imaging, (0, 18 m) Pittsburgh compound B positron emission tomography, and clinical assessments. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over 3 years, rates of whole brain atrophy (p atrophy (p = 0.001, p = 0.023), and ventricular expansion (p atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p = 0.003). Acceleration of left hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p atrophy are associated with both baseline β-amyloid load and accumulation, and that there is presymptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the presymptomatic phase.

  5. Development of murine monoclonal antibodies for the immunohistochemical diagnosis of systemic bovine aspergillosis

    DEFF Research Database (Denmark)

    Jensen, H.E.; Aalbaek, B.; Lind, Peter


    Murine monoclonal antibodies (MAbs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Aspergillus fumigatus were produced by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. The supernatants of in vitro cultured hybridomas were in.......e., aspergillosis was diagnosed. The characteristics of the 2 MAbs (MAb-WF-AF-1 and-2) raised against the WF of A. fumigatus in ELISA and immunoblotting and immunohistochemical assays justify their application for the in situ diagnosis of systemic aspergillosis of cattle....

  6. CLADA: cortical longitudinal atrophy detection algorithm. (United States)

    Nakamura, Kunio; Fox, Robert; Fisher, Elizabeth


    Measurement of changes in brain cortical thickness is useful for the assessment of regional gray matter atrophy in neurodegenerative conditions. A new longitudinal method, called CLADA (cortical longitudinal atrophy detection algorithm), has been developed for the measurement of changes in cortical thickness in magnetic resonance images (MRI) acquired over time. CLADA creates a subject-specific cortical model which is longitudinally deformed to match images from individual time points. The algorithm was designed to work reliably for lower resolution images, such as the MRIs with 1×1×5 mm(3) voxels previously acquired for many clinical trials in multiple sclerosis (MS). CLADA was evaluated to determine reproducibility, accuracy, and sensitivity. Scan-rescan variability was 0.45% for images with 1mm(3) isotropic voxels and 0.77% for images with 1×1×5 mm(3) voxels. The mean absolute accuracy error was 0.43 mm, as determined by comparison of CLADA measurements to cortical thickness measured directly in post-mortem tissue. CLADA's sensitivity for correctly detecting at least 0.1mm change was 86% in a simulation study. A comparison to FreeSurfer showed good agreement (Pearson correlation=0.73 for global mean thickness). CLADA was also applied to MRIs acquired over 18 months in secondary progressive MS patients who were imaged at two different resolutions. Cortical thinning was detected in this group in both the lower and higher resolution images. CLADA detected a higher rate of cortical thinning in MS patients compared to healthy controls over 2 years. These results show that CLADA can be used for reliable measurement of cortical atrophy in longitudinal studies, even in lower resolution images.

  7. Being publicly diagnosed

    DEFF Research Database (Denmark)

    Konradsen, Hanne; Lillebaek, Troels; Wilcke, Torgny;


    . METHOD: A grounded theory design with field studies and qualitative interviews, following the recommendations from Glaser and Strauss. RESULT: A process of being publicly diagnosed was identified, which developed during the patient's trajectory from being on the way to becoming a patient, becoming...

  8. Diagnosing ADHD in Adolescence (United States)

    Sibley, Margaret H.; Pelham, William E., Jr.; Molina, Brooke S. G.; Gnagy, Elizabeth M.; Waschbusch, Daniel A.; Garefino, Allison C.; Kuriyan, Aparajita B.; Babinski, Dara E.; Karch, Kathryn M.


    Objective: This study examines adolescent-specific practical problems associated with current practice parameters for diagnosing attention-deficit/hyperactivity disorder (ADHD) to inform recommendations for the diagnosis of ADHD in adolescents. Specifically, issues surrounding the use of self- versus informant ratings, diagnostic threshold, and…

  9. Cardiac atrophy after bed rest and spaceflight (United States)

    Perhonen, M. A.; Franco, F.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.; Zerwekh, J. E.; Peshock, R. M.; Weatherall, P. T.; Levine, B. D.


    Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity

  10. [Susceptibility gene in multiple system atrophy (MSA)]. (United States)

    Tsuji, Shoji


    To elucidate molecular bases of multiple system atrophy (MSA), we first focused on recently identified MSA multiplex families. Though linkage analyses followed by whole genome resequencing, we have identified a causative gene, COQ2, for MSA. We then conducted comprehensive nucleotide sequence analysis of COQ2 of sporadic MSA cases and controls, and found that functionally deleterious COQ2 variants confer a strong risk for developing MSA. COQ2 encodes an enzyme in the biosynthetic pathway of coenzyme Q10. Decreased synthesis of coenzyme Q10 is considered to be involved in the pathogenesis of MSA through decreased electron transport in mitochondria and increased vulnerability to oxidative stress.

  11. A quantitative evaluation of pontine atrophy by MR imaging in patients with spinocerebellar degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Hirotomo; Tsukamoto, Hiroshi; Kawaguchi, Hiroshi [St. Marianna Univ., Kawasaki, Kanagawa (Japan). School of Medicine


    The purpose of this study is to evaluate if pontine measurement on MR images is capable of diagnosing spinocerebellar degeneration (SCD). The study population consists of 68 cases with SCD (34 males and 34 females with a mean age of 57.8 years ranging from 28 to 82 years) and 240 controls (120 males and 120 females with a mean age of 49.3 years ranging from 20 to 78 years). Patients with SCD were classified into three groups. Type I includes 23 cases with olivopontocerebellar atrophy (OPCA), 7 with spinocerebellar ataxia 2 (SCA2), one with SCA3, 3 with multiple system atrophy (MSA), and one with dentate-rubro-pallido-luysian atrophy (DRPLA) (total of 35 cases). Type II consists of 12 cases with late cortical cerebellar atrophy (LCCA) and 3 with SCA6 (total of 15 cases). The last group includes 18 cases with unclassified SCD. The pontine index was calculated using the following equation; transverse distance between bilateral trigeminal nerve root x AP distance of the pons between the pontine basilar sulcus and the median sulcus of the fourth ventricle. Measurement was performed at the level of the trigeminal nerve root on axial T1-weighted images. Pontine indexes were 699{+-}77.19 for the controls and 455{+-}134.23 for SCD groups (pERROR [Basic syntax error] in: <0ERROR [Basic syntax error] in:.0001; t-test). For SCD patients the pontine indexes were significantly Small for Type I in contrast to Type II (pERROR [Basic syntax error] in:<0ERROR [Basic syntax error] in:.001; t-test). Sensitivity of the Pontine indexes for SCD was 70.6% with a cutoff value of 540 (mean-2SD of controls). In agreement with the findings of the study it is proposed that the pontine index may be useful in diagnosis of SCD and OPCA in particular. (author)


    Directory of Open Access Journals (Sweden)

    Kanwardeep Singh


    Full Text Available BACKGROUND Primary central nervous system lymphoma (PCNSL is a rare form of extranodal non-Hodgkin lymphoma (NHL confined to the brain, spinal cord and/or eye, occurring in immunocompetent individuals. Histologically, they are diffuse large B-cell lymphomas. Over the last few decades there has been a gradual increase in their incidence. AIM To study the clinical, histopathological and immunohistochemical profile of primary central nervous system lymphoma. SETTING AND DESIGN Retrospective audit of seven cases of PCNSL diagnosed over a period of five years in a tertiary referral hospital of North India. MATERIAL AND METHODS The clinical, radiological and laboratory findings were retrieved from the hospital records. Histopathology slides were reviewed, studied in detail and a panel of immunohistochemical markers comprising of CD3, CD5, CD20, CD10, BCL6, BCL2, MUM1, CD30, EBV (LMP1, Ki-67 and p53 was done on all cases. RESULTS The male to female ratio was 3:4 with a median age of 60 years. The most common form of presentation was neurological deficits and altered sensorium. Imaging showed contrast enhancing, single or multiple, deep seated lesions within the cerebral hemispheres. Histologically, all were high-grade diffuse large B-cell lymphomas showing typical angiocentricity and a median Ki-67 proliferative index of 80%. Based on immunohistochemistry (Hans classifier three cases had germinal centre B-cell (GCB and four had non-germinal centre B-cell (non-GCB phenotype. p53 was expressed in all cases with strong expression in four of them. Four patients died before treatment could be initiated, one received palliative chemo-radiotherapy and two did not follow up after diagnosis. CONCLUSIONS Primary CNS lymphomas are high-grade diffuse large B-cell lymphomas which show high Ki-67 proliferative indices and frequent overexpression of p53. Irrespective of histological subtype, GCB or non-GCB, outcome is uniformly poor. Early and prompt diagnosis is

  13. Oats induced villous atrophy in coeliac disease (United States)

    Lundin, K E A; Nilsen, E M; Scott, H G; Løberg, E M; Gjøen, A; Bratlie, J; Skar, V; Mendez, E; Løvik, A; Kett, K


    The current trend is to allow coeliac disease (CD) patients to introduce oats to their gluten free diet. We sought further data from the clinical setting with regards to oats consumption by coeliac patients. Several oat products were tested for wheat contamination using a commercial enzyme linked immunoassay (ELISA) kit, and six samples were examined by an ELISA using a cocktail of monoclonal antibodies, mass spectrometry, and western blot analysis. Nineteen adult CD patients on a gluten free diet were challenged with 50 g of oats per day for 12 weeks. Serological testing and gastroduodenoscopy was performed before and after the challenge. Biopsies were scored histologically and levels of mRNA specific for interferon γ were determined by reverse transcription-polymerase chain reaction analysis. Oats were well tolerated by most patients but several reported initial abdominal discomfort and bloating. One of the patients developed partial villous atrophy and a rash during the first oats challenge. She subsequently improved on an oats free diet but developed subtotal villous atrophy and dramatic dermatitis during a second challenge. Five of the patients showed positive levels of interferon γ mRNA after challenge. Some concerns therefore remain with respect to the safety of oats for coeliacs. PMID:14570737

  14. Effects of muscle atrophy on motor control (United States)

    Stuart, D. G.


    As a biological tissue, muscle adapts to the demands of usage. One traditional way of assessing the extent of this adaptation has been to examine the effects of an altered-activity protocol on the physiological properties of muscles. However, in order to accurately interpret the changes associated with an activity pattern, it is necessary to employ an appropriate control model. A substantial literature exists which reports altered-use effects by comparing experimental observations with those from animals raised in small laboratory cages. Some evidence suggests that small-cage-reared animals actually represent a model of reduced use. For example, laboratory animals subjected to limited physical activity have shown resistance to insulin-induced glucose uptake which can be altered by exercise training. This project concerned itself with the basic mechanisms underlying muscle atrophy. Specifically, the project addressed the issue of the appropriateness of rats raised in conventional-sized cages as experimental models to examine this phenomenon. The project hypothesis was that rats raised in small cages are inappropriate models for the study of muscle atrophy. The experimental protocol involved: 1) raising two populations of rats, one group in conventional (small)-sized cages and the other group in a much larger (133x) cage, from weanling age (21 days) through to young adulthood (125 days); 2) comparison of size- and force-related characteristics of selected test muscles in an acute terminal paradigm.

  15. [Biochemical and immunohistochemical markers of brain injury]. (United States)

    Vajtr, D; Průsa, R; Houst'ava, L; Sámal, F; Kukacka, J; Pachl, J


    Proteins released to circulation from affected tissues during primary or secondary trauma brain injury might be used as serum markers of glial or ganglial cells damage (neuron specific enolasis and S100 B protein). Other markers of trauma can be proved as relatively specific of diffuse axonal injury by immunohistochemical detectoin (amyloid prekurzor protein, neuron specific enolasis, glial fibrilar acidic protein and superficial antigen receptor CD 68). Some markers are associated with blood brain barrier damage (matrix metaloproteinases (MMP-2, MMP-9) and synthase of nitric oxide (iNOS)). We aimed in our short communication on biomechanics of developed of trauma, primary or secondary kinds of trauma brain injury and use of trauma brain injury markers for clinical diagnostics and management of patients.

  16. Immunohistochemical demonstration of glial markers in retinoblastomas

    DEFF Research Database (Denmark)

    Schrøder, H D


    Twenty retinoblastomas were studied immunohistochemically in order to visualize glial cells. In the retina, the glial cells in the ganglion cell layer and the Müller cells were GFAP positive, while only the glial cells of the ganglion cell layer expressed S-100 reactivity. In the tumours S-100/GFAP...... positive glial cells were found in areas near the retina and along many tumour vessels. Some S-100 reactive cells previously interpreted as tumour cells were refound in a few tumours. In areas with Flexner-Winterstein rosettes and in areas with light cells showing photoreceptor-like differentiation, glial...... cells reactive for both S-100 and GFAP were demonstrated. The latter findings may represent differentiation in a glial direction in the more mature parts of retinoblastoma....

  17. Immunohistochemical detection of human intestinal spirochetosis. (United States)

    Ogata, Sho; Shimizu, Ken; Oda, Tomohiro; Tominaga, Susumu; Nakanishi, Kuniaki


    Human intestinal spirochetosis (HIS) is a colorectal infection by Brachyspira species of spiral bacteria. Immunohistochemical cross-reaction to an antibody for Treponema pallidum aids its histologic diagnosis. This study's aim was to analyze the immunohistochemical characteristics of HIS. In this analysis, on 223 specimens from 83 HIS cases, we focused on so-called fringe formation (a histologic hallmark of HIS), spiral organisms within mucus or within crypts, and strong immunopositive materials in the mucosa, together with their location and the types of lesions. Fringe formation was found in 81.6% of all specimens and spiral organisms within mucus or within crypts in 97.3% and 57.0%, respectively. Strong immunopositive materials were observed in the surface epithelial layer in 87.9%, in the subepithelial layer in 94.6%, and in deeper mucosa in 2.2% of all specimens. The positive rates in conventional adenomas (24.0%, n = 146) and hyperplastic nodules (100%, n = 17) were each different from that found in inflammation (70.8%, n = 24), and spiral organisms were seen more frequently in the right-side large intestine than in the left (within mucus, 100%, n = 104 versus 95.0%, n = 119; within crypts, 65.4%, n = 104 versus 49.6%, n = 119). Thus, immunohistochemistry was effective not only in supporting the diagnosis of HIS but also in highlighting spiral organisms within mucus or crypts that were invisible in routine histology. Possibly, these spiral organisms may spread throughout the entire large intestine, although there is a potential problem with antibody specificity.

  18. Cerebral atrophy after acute traumatic subdural orextradural hematomas in adults

    Institute of Scientific and Technical Information of China (English)

    冯海龙; 谭海斌; 黄光富; 廖晓灵


    @@ Cerebral atrophy is one of the serious sequelae ofsevere head injury. 1 Neuropathologicalinvestigation has revealed that cerebral atrophy iscaused by either diffuse axonal injury or cerebralhypoxia and ischemia. Secondary ipsilateral cerebralatrophy caused by acute subdural hematomas in infantshas been reported recently, but this unilateral cerebralatrophy after head injury in adult patients has rarelybeen reported.

  19. A case of spinocerebellar ataxia type 6 mimicking olivopontocerebellar atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, N.; Katayama, T.; Makita, Y.; Kuroda, K.; Aizawa, H.; Kikuchi, K. [First Dept. of Internal Medicine, Asahikawa Medical Coll. (Japan)


    Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant, slowly progressive cerebellar ataxia without multisystem involvement. We report a 57-year-old woman with genetically confirmed SCA6 who showed clinical features of olivopontocerebellar atrophy. Conventional T2-weighted and FLAIR MRI demonstrated high signal in the middle cerebellar peduncles, in addition to mild atrophy of the pons and cerebellum. (orig.)

  20. Multifocal motor neuropathy and progressive atrophy : Pathophysiological similarities and differences

    NARCIS (Netherlands)

    Vlam, L.


    Progressive muscular atrophy (PMA) and multifocal motor neuropathy (MMN) share many clinical similarities. They are both characterized by progressive asymmetric muscle weakness with atrophy and fasciculations. Tendon reflexes are normally low or absent, although in some patients with MMN normal or e

  1. Bone and muscle atrophy with suspension of the rat (United States)

    Leblanc, A.; Marsh, C.; Evans, H.; Johnson, P.; Schneider, V.; Jhingran, S.


    In order to identify a suitable model for the study of muscle atrophy due to suspension in space, a modified version of the Morey tail suspension model was used to measure the atrophic responses of rat bone and muscle to 14-30 days of unloading of the hindlimbs. The progress of atrophy was measured by increases in methylene diphosphonate (MDP) uptake. It is found that bone uptake of methylene diphosphonate followed a phasic pattern similar to changes in the bone formation rate of immobilized dogs and cats. Increased MDP uptake after a period of 60 days indicated an accelerated bone metabolism. Maximum muscle atrophy in the suspended rats was distinctly different from immobilization atrophy. On the basis of the experimental results, it is concluded that the tail suspension model is an adequate simulation of bone atrophy due to suspension.

  2. Indices of Regional Brain Atrophy: Formulae and Nomenclature (United States)

    Arias-Carrión, Oscar


    The pattern of brain atrophy helps to discriminate normal age-related changes from neurodegenerative diseases. Albeit indices of regional brain atrophy have proven to be a parameter useful in the early diagnosis and differential diagnosis of some neurodegenerative diseases, indices of absolute regional atrophy still have some important limitations. We propose using indices of relative atrophy for representing how the volume of a given region of interest (ROI) changes over time in comparison to changes in global brain measures over the same time. A second problem in morphometric studies is terminology. There is a lack of systematization naming indices and the same measure can be named with different terms by different research groups or imaging softwares. This limits the understanding and discussion of studies. In this technological report, we provide a general description on how to compute indices of absolute and relative regional brain atrophy and propose a standardized nomenclature. PMID:26261753

  3. [Prospects for using immunohistochemical methods in forensic medical thanatology]. (United States)

    Bogomolov, D V; Bogomolova, I N; Karavaeva, I E


    This review of Russian and foreign literature is focused on the use of immunohistochemical methods in forensic medical practice. It shows that forensic medical specialists not infrequently underestimate the value of these techniques. Recommendations are proposed for a more extensive application of immunohistochemical methods in practical and fundamental medico-legal thanatology.

  4. Integrins, muscle agrin and sarcoglycans during muscular inactivity conditions: an immunohistochemical study

    Directory of Open Access Journals (Sweden)

    G Anastasi


    Full Text Available Sarcoglycans are transmembrane proteins that seem to be functionally and pathologically as important as dystrophin. Sarcoglycans cluster together to form a complex, which is localized in the cell membrane of skeletal, cardiac, and smooth muscle. It has been proposed that the dystrophin-glycoprotein complex (DGC links the actin cytoskeleton with the extracellular matrix and the proper maintenance of this connection is thought to be crucial to the mechanical stability of the sarcolemma. The integrins are a family of heterodimeric cell surface receptors which play a crucial role in cell adhesion including cell-matrix and intracellular interactions and therefore are involved in various biological phenomena, including cell migration, and differentiation tissue repair. Sarcoglycans and integrins play a mechanical and signaling role stabilizing the systems during cycles of contraction and relaxation.Several studies suggested the possibility that integrins might play a role in muscle agrin signalling. On these basis, we performed an immunohistochemical analyzing sarcoglycans, integrins and agrin, on human skeletal muscle affected by sensitive-motor polyneuropathy, in order to better define the correlation between these proteins and neurogenic atrophy due to peripheral neuropathy. Our results showed the existence of a cascade mechanism which provoke a loss of regulatory effects of muscle activity on costameres, due to loss of muscle and neural agrin.This cascade mechanism could determine a quantitative modification of transmembrane receptors and loss of ?7B could be replaced and reinforced by enhanced expression of the ?7A integrin to restore muscle fiber viability. Second, it is possible that the reduced cycles of contraction and relaxation of muscle fibers, during muscular atrophy, provoke a loss of mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix. Consequently, these mechanical

  5. WRN protein as a novel erythroblast immunohistochemical marker with applications for the diagnosis of Werner syndrome. (United States)

    Sadahira, Yoshito; Sugihara, Takashi; Fujiwara, Hideyo; Nishimura, Hirotake; Suetsugu, Yoshimasa; Takeshita, Morishige; Okamura, Seiichi; Goto, Makoto


    Genetic testing for mutations in the WRN gene is critical for the diagnosis of Werner syndrome (WS); however, these tests cannot be performed in a clinical setting. Nearly all of the WRN mutations result in expression of truncated WRN proteins that are missing the C-terminal nuclear localization signal. We evaluated the use of WRN protein immunohistochemistry for diagnosing WS using paraffin-embedded bone marrow sections. Using a well-defined commercially available polyclonal antibody against the C terminus of WRN, we found that of all the cell types tested, bone marrow erythroid precursors showed the strongest nuclear expression of WRN. Immunohistochemical analysis of bone marrow samples from 120 patients with non-WS hematological disorders (age range, 7 days-90 years) revealed WRN staining of the nuclei of CD71-positive early and late erythroid precursors. Erythroblasts negative for WRN immunostaining were only observed in two patients, both of whom were diagnosed with WS: one with concomitant myelodysplastic syndrome and the other with erythroleukemia with overexpression of TP53. Western blot analysis and immunocytochemistry indicated WRN was localized in the nuclei of the four positive control cell lines from non-WS patients but not in the five cell lines from WS patients, who had three different types of WRN mutations. Thus, immunohistochemical detection of WRN in erythroblasts from bone marrow paraffin sections could be useful in screening of WS cases and worthy of further molecular confirmation.

  6. Extra-tongue oral granular cell tumor: Histological and immunohistochemical aspect (United States)

    Pigatti, Fernanda-Mombrini; Martins-Mussi, Maria-Carolina; Sedassari, Bruno-Tavares; Orsini-Machado de Sousa, Suzana-Cantanhede


    Background Granular cell tumor (GCT) is an uncommon benign tumor founded in any part of the body but mainly in the tongue. Extra-tongue oral granular cell tumor (ETOGCT) is rare with few cases reported. Here we describe seven cases of oral GCT located in sites other then the tongue and discuss histopathological and immunohistochemical differences between differential diagnoses. Material and Methods We retrieved all cases diagnosed with oral granular cell tumor, from the Oral Pathology Service at the School of Dentistry/ University of São Paulo, and excluded the ones sited in the tongue. Immunohistochemical staining anti-S100 was also performed. Results The presented cases of Extra-tongue Oral Granular Cell Tumor (ETOGT) are composed by granular cells with intimately association with the adjacent tissue. Atypia and mitoses were not seen, and in most cases, the typical pseudoepitheliomatous hyperplasia was not observed. Conclusions The importance of an adequate attention is to avoid misdiagnoses, since ETOGT is rare and the tricking histopathological findings could induce to it. All the cases can be differentiated from the tumors that has a granular cell proliferation through a morphological analysis and when needed, immunohistochemistry stain. Key words:Abrikossoff`s tumor, granular cell tumor, oral cavity. PMID:27918739

  7. Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: A retrospective study

    Directory of Open Access Journals (Sweden)

    Sen Seema


    Full Text Available Background: The extent of association of human papilloma virus (HPV in human conjunctival neoplasias has been debated in studies originating from different parts of the world, but no substantial evidence has been generated on Indian subjects. This prompted us to carry out a retrospective study on conjunctival neoplasias diagnosed over the past 12 years. Materials and Methods: Histopathological and immunohistochemical analysis of 65 specimens of ocular neoplasias and 30 normal controls diagnosed between 1991 and 2002 at a tertiary eye care hospital, was undertaken. Formalin-fixed, paraffin-embedded tissues were reviewed for confirming histopathological diagnosis, presence of koilocytosis and changes related to actinic keratosis. Immunohistochemical analysis was done using HPV-specific monoclonal antibodies. Clinicopathological correlation and the association of HPV antigen with the histopathological features were performed. Results: Out of the 65 cases analyzed, 35 were papillomas and 30 were ocular surface squamous neoplasias (OSSN. The mean age was 48 years with a male preponderance. Histologically, koilocytosis was observed in 17.1% of papillomas and 36.6% of OSSN. Actinic keratosis was present in 33% of OSSN. Immunohistochemically 17.1% conjunctival papillomas stained positive for HPV antigen, all cases of OSSN were negative for HPV. There was no correlation between koilocytosis or actinic keratosis and the detection of HPV antigen. Conclusions: The association between HPV and conjunctival neoplasias is variable in different geographical areas and also depends on the methods of detection used. This study warrants the need for applying more advanced techniques at a molecular level to determine the possible etiology of HPV in conjunctival neoplasias among Asian-Indians.

  8. Non-familial degenerative disease and atrophy of brainstem and cerebellum. Clinical and CT data in 47 patients. (United States)

    Staal, A; Meerwaldt, J D; van Dongen, K J; Mulder, P G; Busch, H F


    We studied the clinical features of 47 patients with a non-hereditary degenerative disease and with atrophy of brainstem or cerebellum or both in CT scanning. There was no relation between the CT findings and duration or severity of the disease, nor with the kind of the neurological signs which comprised ataxia, a hypokinetic rigid syndrome, oculomotor abnormalities, upper and lower motor neuron signs, orthostatic hypotension and dementia. The 2 main diagnoses were olivopontocerebellar atrophy (OPCA), or a combination of OPCA and striatonigral degeneration (SND). The differential diagnosis with Parkinson's disease and progressive supranuclear palsy was discussed. We concluded, that a CT scan is warranted in all cases of suspected Parkinson's disease, especially in those without tremor, and in cases of motoneuron disease with broad-based gait. In our patients with mainly hypokinesia and rigidity, levodopa treatment had no or brief beneficial effects. If ataxia predominated, OPCA appeared the most sensible diagnosis; if a hypokinetic-rigid syndrome predominated, the diagnoses SND plus OPCA appeared the most suitable. We assessed the degree of atrophy on CT subjectively, because an interobserver study of 60 normal CT scans, did not produce reliable measurements.

  9. Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge. (United States)

    Cash, David M; Frost, Chris; Iheme, Leonardo O; Ünay, Devrim; Kandemir, Melek; Fripp, Jurgen; Salvado, Olivier; Bourgeat, Pierrick; Reuter, Martin; Fischl, Bruce; Lorenzi, Marco; Frisoni, Giovanni B; Pennec, Xavier; Pierson, Ronald K; Gunter, Jeffrey L; Senjem, Matthew L; Jack, Clifford R; Guizard, Nicolas; Fonov, Vladimir S; Collins, D Louis; Modat, Marc; Cardoso, M Jorge; Leung, Kelvin K; Wang, Hongzhi; Das, Sandhitsu R; Yushkevich, Paul A; Malone, Ian B; Fox, Nick C; Schott, Jonathan M; Ourselin, Sebastien


    Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated "direct" measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the

  10. Fluid biomarkers in multiple system atrophy

    DEFF Research Database (Denmark)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy


    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...... engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood...... and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results...

  11. Diagnosis and therapy of multiple system atrophy

    Directory of Open Access Journals (Sweden)

    GU Wei-hong


    Full Text Available Multiple system atrophy (MSA is a sporadic and rapidly progressive neurodegenerative disorder characterised clinically by any combination of autonomic, cerebellar ataxia, parkinsonian, and pyramidal signs. Over the past 10 years, substantial progress has been achieved to establish MSA as an α-synucleinopathy along with other neurodegenerative diseases. Although the diagnosis of this disorder is largely based on clinical expertise, some investigations have been proposed to assist in early differential diagnosis, especially neuroimaging examination, which have resulted in revised diagnostic criteria. The UMSARS is a reliable and valid scale for semiquantitative clinical assessments of MSA patients. An outline of the rationale for managing symptomatic deterioration in MSA is provided including novel neuroprotective therapeutic approaches, together with the treatment of traditional Chinese medicine.

  12. Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Millino Caterina


    Full Text Available Abstract Background Spinal muscular atrophy (SMA is a neurodegenerative disorder associated with mutations of the survival motor neuron gene SMN and is characterized by muscle weakness and atrophy caused by degeneration of spinal motor neurons. SMN has a role in neurons but its deficiency may have a direct effect on muscle tissue. Methods We applied microarray and quantitative real-time PCR to study at transcriptional level the effects of a defective SMN gene in skeletal muscles affected by the two forms of SMA: the most severe type I and the mild type III. Results The two forms of SMA generated distinct expression signatures: the SMA III muscle transcriptome is close to that found under normal conditions, whereas in SMA I there is strong alteration of gene expression. Genes implicated in signal transduction were up-regulated in SMA III whereas those of energy metabolism and muscle contraction were consistently down-regulated in SMA I. The expression pattern of gene networks involved in atrophy signaling was completed by qRT-PCR, showing that specific pathways are involved, namely IGF/PI3K/Akt, TNF-α/p38 MAPK and Ras/ERK pathways. Conclusion Our study suggests a different picture of atrophy pathways in each of the two forms of SMA. In particular, p38 may be the regulator of protein synthesis in SMA I. The SMA III profile appears as the result of the concurrent presence of atrophic and hypertrophic fibers. This more favorable condition might be due to the over-expression of MTOR that, given its role in the activation of protein synthesis, could lead to compensatory hypertrophy in SMA III muscle fibers.

  13. Features of immunohistochemical diagnostic of melanocytic tumours

    Directory of Open Access Journals (Sweden)

    Shpon’ka I.S.


    Full Text Available Background. The malignant melanomas are the most important group of skin cancers. Although less common than the familiar basal and squamous cell tumours of the skin, they are much more frequently fatal, due to their intrinsic tendency to lymphatic and haematogenic metastasis. Objective. The article is devoted to parsing cases melanocytic tumours that were established through immunohistochemical study. Methods. In the study analyzed 236 patient material (150 women and 86 men aged 28 to 77 years during 2010-2013 turned out to clarify the histological diagnosis of skin tumors or metastases to lymph nodes (rare at other sites. The primary monoclonal antibodies used Сytokeratin, Рan Ab1 (clone AE1/AE3, S100 (clone 4C4.9, Ki-67 (clone SP6, Vimentin (clone V9, Melanoma gp100 (clone HMB-45. Results. Naevus proliferation rate showed a statistically significant difference with respect to proliferation rate of malignant melanomas (p<0,05. All samples (100% showed positive expression of high-intensity staining (+++ or moderate (++ intensity on the marker S100; 98,30% of samples (232 of 236 showed positive expression of marker HMB-45 at least in terms of tumor cells with intensity color from the high (+++ to weak (+ and 83.89% of the samples (198 of 236 were negative (– Сytokeratin, Рan Ab1 (other 38 cases showed weakly positive expression (+/– of tumor cells. Conclusions. 1. In the differential diagnosis of melanoma and naevus, we must bear in mind the uniformity immunophenotype of these tumors and consider only the cytological features of the tumor, changes in the structure of the epidermis and dermis (contour, symmetry, depth, inflammatory infiltration and proliferation rate. 2. Patients whose lymph nodes were the first clinical signs of cancer are always in need for additional immunohistochemical studies to avoid diagnostic errors. 3. The most common phenotype of melanocytic tumours responsible Сytokeratin, Рan–, Vimintin+, S100+, HMB-45

  14. White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy. (United States)

    Fiford, Cassidy M; Manning, Emily N; Bartlett, Jonathan W; Cash, David M; Malone, Ian B; Ridgway, Gerard R; Lehmann, Manja; Leung, Kelvin K; Sudre, Carole H; Ourselin, Sebastien; Biessels, Geert Jan; Carmichael, Owen T; Fox, Nick C; Cardoso, M Jorge; Barnes, Josephine


    This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5-T MRI. CSF Aβ42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

  15. Reviewing the options for local estrogen treatment of vaginal atrophy

    Directory of Open Access Journals (Sweden)

    Lindahl SH


    Full Text Available Sarah H Lindahl Sutter East Bay Medical Foundation, SEBMF – Diablo Division, Castro Valley, CA, USA Background: Vaginal atrophy is a chronic condition with symptoms that include vaginal dryness, pain during sex, itching, irritation, burning, and discharge, as well as various urinary problems. Up to 45% of postmenopausal women may be affected, but it often remains underreported and undertreated. This article aims to review the current recommendations for treatment of vaginal atrophy, and current data on the effectiveness and safety of local vaginal estrogen therapies. Methods: Literature regarding vaginal atrophy (2007–2012 was retrieved from PubMed and summarized, with emphasis on data related to the treatment of vaginal atrophy with local vaginal estrogen therapy. Results: Published data support the effectiveness and endometrial safety of low-dose local estrogen therapies. These results further support the general recommendation by the North American Menopause Society that a progestogen is not needed for endometrial protection in patients using low-dose local vaginal estrogen. Benefits of long-term therapy for vaginal atrophy include sustained relief of symptoms as well as physiological improvements (eg, decreased vaginal pH and increased blood flow, epithelial thickness, secretions. Conclusion: Currently available local vaginal estrogen therapies are well tolerated and effective in relieving symptoms of vaginal atrophy. Recent data support the endometrial safety of low-dose regimens for up to 1 year. Keywords: menopause, estrogen, local estrogen therapy, vaginal atrophy

  16. Transcriptional profile of a myotube starvation model of atrophy (United States)

    Stevenson, Eric J.; Koncarevic, Alan; Giresi, Paul G.; Jackman, Robert W.; Kandarian, Susan C.


    Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

  17. Immunohistochemical expression of p16 in lipoblastomas. (United States)

    Cappellesso, Rocco; d'Amore, Emanuele S G; Dall'Igna, Patrizia; Guzzardo, Vincenza; Vassarotto, Elisa; Rugge, Massimo; Alaggio, Rita


    Lipoblastoma (LB) is a rare benign adipocytic tumor of childhood occasionally showing histological similarities to myxoid liposarcoma (ML) or well-differentiated liposarcoma (WDL). p16 immunohistochemistry has proved to be useful in distinguishing various types of liposarcomas, in particular WDL from lipoma, with higher sensitivity and specificity than MDM2 and CDK4 immunohistochemistry. In this study, we reported the histologic features of a series of 30 LB with emphasis on the potential diagnostic pitfalls and investigated the immunohistochemical expression of p16. Moreover, p16 immunostaining was performed in 16 liposarcomas (11 WDL and 5 ML), 16 lipomas, and 16 cases of liponecrosis in order to evaluate its usefulness in the differential diagnosis of challenging lesions occurring in older children. Overall, p16 immunostaining was positive in 3 LBs and in 12 out of 16 liposarcomas (10 WDL and 2 ML), with a sensitivity of 75%, a specificity of 90%, a positive predictive value of 80%, and a negative predictive value of 87%. All lipomas were p16 negative, whereas 5 liponecroses were positive. Accounting altogether the benign lesions versus liposarcomas, p16 showed a sensitivity of 75%, a specificity of 87%, a positive predictive value of 60%, and a negative predictive value of 93%. Our data suggest that a negative p16 immunostaining may be helpful in excluding a liposarcoma when occurring in unusual clinical contexts, such as in adolescence or late recurrence. However, such finding should be interpreted with caution since also some liposarcomas lack p16 and occasional LBs are positive.

  18. Accuracy and cut-off values of pepsinogens I, II and gastrin 17 for diagnosis of gastric fundic atrophy: influence of gastritis.

    Directory of Open Access Journals (Sweden)

    Dariush Nasrollahzadeh

    Full Text Available BACKGROUND: To establish optimal cutoff values for serologic diagnosis of fundic atrophy in a high-risk area for oesophageal squamous cell carcinoma and gastric cancer with high prevalence of Helicobacter pylori (H. pylori in Northern Iran, we performed an endoscopy-room-based validation study. METHODS: We measured serum pepsinogens I (PGI and II (PGII, gastrin 17 (G-17, and antibodies against whole H. pylori, or cytotoxin-associated gene A (CagA antigen among 309 consecutive patients in two major endoscopy clinics in northeastern Iran. Updated Sydney System was used as histology gold standard. Areas under curves (AUCs, optimal cutoff and predictive values were calculated for serum biomarkers against the histology. RESULTS: 309 persons were recruited (mean age: 63.5 years old, 59.5% female. 84.5% were H. pylori positive and 77.5% were CagA positive. 21 fundic atrophy and 101 nonatrophic pangastritis were diagnosed. The best cutoff values in fundic atrophy assessment were calculated at PGI40 pmol/l was 81% sensitive and 73.3% specific for diagnosing fundic atrophy. At cutoff concentration of 11.8 µg/l, PGII showed 84.2% sensitivity and 45.4% specificity to distinguish nonatrophic pangastritis. Exclusion of nonatrophic pangastritis enhanced diagnostic ability of PGI/PGII ratio (from AUC = 0.66 to 0.90 but did not affect AUC of PGI. After restricting study samples to those with PGII<11.8, the sensitivity of using PGI<56 to define fundic atrophy increased to 83.3% (95%CI 51.6-97.9 and its specificity decreased to 88.8% (95%CI 80.8-94.3. CONCLUSIONS: Among endoscopy clinic patients, PGII is a sensitive marker for extension of nonatrophic gastritis toward the corpus. PGI is a stable biomarker in assessment of fundic atrophy and has similar accuracy to PGI/PGII ratio among populations with prevalent nonatrophic pangastritis.

  19. Giant cavernous hemangioma coexistent with diffuse hepatic hemangiomatosis presenting as portal vein thrombosis and hepatic lobar atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Bo Reum; Han, Hyun Young; Choi, So Young; Kim, Joo Heun [Eulji University Hospital, Daejeon(Korea, Republic of)


    A combination of giant hepatic hemangioma and diffuse hemangiomatosis is extremely rare in adults. Even when they are large, hemangiomas are soft and rarely compress adjacent structures. A 78-year-old man presented with abdominal pain and distension. Ultrasonography, computed tomography, and magnetic resonance imaging demonstrated a large expansile mass replacing the medial segment and caudate lobe with diffusely scattered nodules in the entire liver. The large hilar mass contained a central nonenhancing area and had a mass effect, leading to left portal vein occlusion. The image findings also revealed two unprecedented findings: left lateral segmental atrophy of the liver and recent portomesenteric vein thrombosis. The hepatic lesions were confirmed with hemangiomas by ultrasonography-guided biopsy. We diagnosed intrahepatic portal vein obstruction caused by a mass effect of giant hepatic hemangioma coexistent with diffuse hemangiomatosis, resulting in hepatic segmental atrophy and extrahepatic portal vein thrombosis.

  20. Giant cavernous hemangioma coexistent with diffuse hepatic hemangiomatosis presenting as portal vein thrombosis and hepatic lobar atrophy

    Directory of Open Access Journals (Sweden)

    Bo Reum Yoo


    Full Text Available

    A combination of giant hepatic hemangioma and diffuse hemangiomatosis is extremely rare in adults. Even when they are large, hemangiomas are soft and rarely compress adjacent structures. A 78-year-old man presented with abdominal pain and distension. Ultrasonography, computed tomography, and magnetic resonance imaging demonstrated a large expansile mass replacing the medial segment and caudate lobe with diffusely scattered nodules in the entire liver. The large hilar mass contained a central nonenhancing area and had a mass effect, leading to left portal vein occlusion. The image findings also revealed two unprecedented findings: left lateral segmental atrophy of the liver and recent portomesenteric vein thrombosis. The hepatic lesions were confirmed with hemangiomas by ultrasonography-guided biopsy. We diagnosed intrahepatic portal vein obstruction caused by a mass effect of giant hepatic hemangioma coexistent with diffuse hemangiomatosis, resulting in hepatic segmental atrophy and extrahepatic portal vein thrombosis.

  1. Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect. (United States)

    Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E


    While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter.

  2. How Is Pulmonary Hypertension Diagnosed? (United States)

    ... from the NHLBI on Twitter. How Is Pulmonary Hypertension Diagnosed? Your doctor will diagnose pulmonary hypertension (PH) ... To Look for the Underlying Cause of Pulmonary Hypertension PH has many causes, so many tests may ...

  3. How Is Lactose Intolerance Diagnosed? (United States)

    ... Information Clinical Trials Resources and Publications How is lactose intolerance diagnosed? Skip sharing on social media links ... people think that they or their children are lactose intolerant without being tested or diagnosed. 1 As ...

  4. How Is Kawasaki Disease Diagnosed? (United States)

    ... page from the NHLBI on Twitter. How Is Kawasaki Disease Diagnosed? Kawasaki disease is diagnosed based on your child's signs and ... are the first to suspect a child has Kawasaki disease. Pediatricians are doctors who specialize in treating children. ...

  5. How Is Pelvic Pain Diagnosed? (United States)

    ... Information Clinical Trials Resources and Publications How is pelvic pain diagnosed? Skip sharing on social media links Share ... needed to help diagnose the cause of the pelvic pain. These tests or procedures may include 1 , 2 : ...

  6. Diagnosing Dementia--Positive Signs (United States)

    ... Navigation Bar Home Current Issue Past Issues Diagnosing Dementia—Positive Signs Past Issues / Fall 2007 Table of ... easy, affordable blood test that could accurately diagnose Alzheimer's disease (AD)—even before symptoms began to show? Researchers ...

  7. Deformation-Based Atrophy Estimation for Alzheimer’s Disease

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru

    Alzheimer’s disease (AD) - the most common form of dementia, is a term used for accelerated memory loss and cognitive abilities enough to severely hamper day-to-day activities. One of the most globally accepted markers for AD is atrophy, in mainly the brain parenchyma. The goal of the PhD project...... and a new way to estimate atrophy from a deformation field. We demonstrate the performance of the proposed solution but applying it on the publicly available Alzheimer’s disease neuroimaging data (ADNI) initiative and compare to existing state-of-art atrophy estimation methods....

  8. Posterior cortical atrophy: an atypical variant of Alzheimer disease. (United States)

    Suárez-González, Aida; Henley, Susie M; Walton, Jill; Crutch, Sebastian J


    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by striking progressive visual impairment and a pattern of atrophy mainly involving posterior cortices. PCA is the most frequent atypical presentation of Alzheimer disease. The purpose of this article is to provide a summary of PCA's neuropsychiatric manifestations. Emotional and psychotic symptoms are discussed in the context of signal characteristic features of the PCA syndrome (the early onset, focal loss of visual perception, focal posterior brain atrophy) and the underlying cause of the disease. The authors' experience with psychotherapeutic intervention and PCA support groups is shared in detail.

  9. Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas


    Full Text Available ABSTRACT Multiple sclerosis (MS was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients.

  10. A new mouse allele of glutamate receptor delta 2 with cerebellar atrophy and progressive ataxia. (United States)

    Miyoshi, Yuka; Yoshioka, Yoshichika; Suzuki, Kinuko; Miyazaki, Taisuke; Koura, Minako; Saigoh, Kazumasa; Kajimura, Naoko; Monobe, Yoko; Kusunoki, Susumu; Matsuda, Junichiro; Watanabe, Masahiko; Hayasaka, Naoto


    Spinocerebellar degenerations (SCDs) are a large class of sporadic or hereditary neurodegenerative disorders characterized by progressive motion defects and degenerative changes in the cerebellum and other parts of the CNS. Here we report the identification and establishment from a C57BL/6J mouse colony of a novel mouse line developing spontaneous progressive ataxia, which we refer to as ts3. Frequency of the phenotypic expression was consistent with an autosomal recessive Mendelian trait of inheritance, suggesting that a single gene mutation is responsible for the ataxic phenotype of this line. The onset of ataxia was observed at about three weeks of age, which slowly progressed until the hind limbs became entirely paralyzed in many cases. Micro-MRI study revealed significant cerebellar atrophy in all the ataxic mice, although individual variations were observed. Detailed histological analyses demonstrated significant atrophy of the anterior folia with reduced granule cells (GC) and abnormal morphology of cerebellar Purkinje cells (PC). Study by ultra-high voltage electron microscopy (UHVEM) further indicated aberrant morphology of PC dendrites and their spines, suggesting both morphological and functional abnormalities of the PC in the mutants. Immunohistochemical studies also revealed defects in parallel fiber (PF)-PC synapse formation and abnormal distal extension of climbing fibers (CF). Based on the phenotypic similarities of the ts3 mutant with other known ataxic mutants, we performed immunohistological analyses and found that expression levels of two genes and their products, glutamate receptor delta2 (grid2) and its ligand, cerebellin1 (Cbln1), are significantly reduced or undetectable. Finally, we sequenced the candidate genes and detected a large deletion in the coding region of the grid2 gene. Our present study suggests that ts3 is a new allele of the grid2 gene, which causes similar but different phenotypes as compared to other grid2 mutants.

  11. A new mouse allele of glutamate receptor delta 2 with cerebellar atrophy and progressive ataxia.

    Directory of Open Access Journals (Sweden)

    Yuka Miyoshi

    Full Text Available Spinocerebellar degenerations (SCDs are a large class of sporadic or hereditary neurodegenerative disorders characterized by progressive motion defects and degenerative changes in the cerebellum and other parts of the CNS. Here we report the identification and establishment from a C57BL/6J mouse colony of a novel mouse line developing spontaneous progressive ataxia, which we refer to as ts3. Frequency of the phenotypic expression was consistent with an autosomal recessive Mendelian trait of inheritance, suggesting that a single gene mutation is responsible for the ataxic phenotype of this line. The onset of ataxia was observed at about three weeks of age, which slowly progressed until the hind limbs became entirely paralyzed in many cases. Micro-MRI study revealed significant cerebellar atrophy in all the ataxic mice, although individual variations were observed. Detailed histological analyses demonstrated significant atrophy of the anterior folia with reduced granule cells (GC and abnormal morphology of cerebellar Purkinje cells (PC. Study by ultra-high voltage electron microscopy (UHVEM further indicated aberrant morphology of PC dendrites and their spines, suggesting both morphological and functional abnormalities of the PC in the mutants. Immunohistochemical studies also revealed defects in parallel fiber (PF-PC synapse formation and abnormal distal extension of climbing fibers (CF. Based on the phenotypic similarities of the ts3 mutant with other known ataxic mutants, we performed immunohistological analyses and found that expression levels of two genes and their products, glutamate receptor delta2 (grid2 and its ligand, cerebellin1 (Cbln1, are significantly reduced or undetectable. Finally, we sequenced the candidate genes and detected a large deletion in the coding region of the grid2 gene. Our present study suggests that ts3 is a new allele of the grid2 gene, which causes similar but different phenotypes as compared to other grid2


    Institute of Scientific and Technical Information of China (English)

    张红梅; 樊小力; 周继斌


    Objective To compare the cross-section area (CSA) and the immunoreactivity of conjugated-ubiquitin in soleus extrafusal and intrafusal fibers after simulated-microgravity and to demonstrate the role of muscle spindle in muscle atrophy induced by simulated microgravity. Methods The immunohistochemical technique (ABC) and image analysis were used to assess the conjugated-ubiquitin immunostaining and the cross -sectional area of intrafusal and extrafusal fibers of soleus in simulated-microgravity rats. Results ①Tail-suspension caused a progressive loss of soleus mass. Mean fiber CSA of extrafusal fibers were (7±2)%, (21±4)% and (32±7)% smaller after 3 days, 7 days and 14 days suspension, respectively. While the CAS of intrafusal fibers (bag + chain fibers) were (14±3)% (P<0.05), (30±7)% (P<0.01) and (44±10)% (P<0.01) smaller after 3 days, 7 days and 14 days suspension. ② The immunoreactivity of conjugated-ubiquitin both in extrafusal and intrafusal fibers increased after tail-suspension. The immunoreactivity of intrafusal fibers increased 1 day after suspension and reached the hightest level at 3 days after tail-suspension. The immunoreactivity of extrafusal fibers increased after 3 days suspension and reached the highest level after 7 days tail-suspension, which was lower than that in intrafusal fibers after 3 days tail-suspension. Conclusion These results suggest that soleus atrophy of intrafusal fibers caused by tail-suspension is earlier and more severe than that in extrafusal fibers.

  13. Mechanisms of cisplatin-induced muscle atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Hiroyasu, E-mail: [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sato, Ken [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Chiba, Yoshihiko [Department of Biology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Yamazaki, Mitsuaki [Department of Anesthesiology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 9300194 (Japan); Matoba, Motohiro [Department of Palliative Medicine and Psychooncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 1040045 (Japan); Narita, Minoru, E-mail: [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan)


    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin.


    Directory of Open Access Journals (Sweden)

    Yu. G. KOLENKO


    Full Text Available In recent years, substantial changes have occurred in the structure of oral mucosa diseases, in particular an increased ratio of precancerous diseases, so that an effective non-invasive detection of any sign of malignancy appears as an urgent and most actual task of dentistry. Aim: To study the proliferative activity of epithelial cells in Ki-67 antigenin patients with leukoplakia of the oral mucosa. Materials and method: A complex clinical and laboratory examination was performed on 155 patients with oral leukoplakia, who addressed the Operative Dentistry Department of the “A.A.Bogomolets” National Medical University of Kiev between 2010 and 2014. All patients have been subjected to a careful clinical examination, which included: dental anamnesis, visual inspection, oral examination and digital palpation of oral mucosa and tongue mucosa, biopsy of leukoplakia lesions for cytological and histological examination. Results: Histological evaluation of the material has been performed according to the WHO (2005 classification of leukoplakia. 10 (14% sites of unaltered mucosa, 10 (14% samples of hyperkeratosis without atypia, 14 (19% biopsy specimens of hyperkeratosis SIN1, 15 (21% – hyperkeratosis SIN2, 10 (14% - SIN3 and 13 (18% cases of squamous cell carcinoma were evidenced. Immunohistochemical investigation evidenced the presence of protein Ki-67 in the nuclei of epithelial cells. In the unmodified epithelium of the oral mucosa, all epithelial cells with stained nuclei are virtually located in the basal layer. Conclusion: Against the general increase of the proliferative activity of epithelial cells with increasing SIN, a characteristic distribution of proliferating cells in the thickness of the epithelium was revealed for each studied group, as follows: in the control group and in leukoplakia without atypia, immunopositive cells are located in the basal layer, in leukoplakia (SIN1, SIN2 and SIN3 – in parabasal position while, in squamous

  15. Ingrown toenail: histopathologic and immunohistochemical study. (United States)

    Fernandez-Flores, Angel; Martínez-Nova, Alfonso; Salgado-Fernandez, Sara


    Although ingrown toenail (IT) is a common problem, the morphologic alterations presented in this condition have rarely been presented in literature. We have studied 14 cases from 12 different patients and studied the biopsies of all of them, not only with routine techniques but also with histochemical stains (Masson trichrome, periodic acid-Schiff, and Gram) and with immunohistochemical techniques mindbomb homolog-1 (MIB-1), p63, D2-40, and AE1-AE3). The patients were clinically classified into 4 stages (1, 2a, 2b, and 3). The main changes evidenced were ingrowing of the squamous epithelium (either from the matrix or mostly from the hyponichium) and chronic plasma-cell rich inflammation with prominent vascularization. The intensity of these changes varied depending on the stage: whereas they were mild in stages 1 and 2a, they were prominent in stages 2b and 3. In advanced stages, the epithelial nests showed certain dyskeratosis. The expression of MIB-1 was, nevertheless, only basal and parabasal. p63 was intensively expressed by the epithelial nests. We therefore conclude that (a) IT shows epithelial ingrowing with accompanying granulation tissue; (b) according to the clinical stage of the disease, this pattern can be more or less complex; (c) in advanced stages of IT, the pattern can mimic a well-differentiated squamous cell carcinoma; (d) MIB-1 is not helpful in distinguishing IT from squamous cell carcinoma; (e) the high expression of p63 by the ingrowing epithelium should not be the source of a misdiagnosis of malignancy.

  16. Immunohistochemical studies in equine recurrent uveitis (ERU). (United States)

    Romeike, A; Brügmann, M; Drommer, W


    Despite extensive clinical research, the etiology of equine recurrent uveitis (ERU) is still unknown. After an immunologic pathogenesis was established in recurrent uveitis in humans, a similar pathogenic mechanism was assumed to exist in ERU. To investigate whether immunopathologic mechanisms are involved in ERU, 20 eyes of 15 horses with ERU were examined immunohistochemically with a T cell marker, B cell marker, and anti-major histocompatibility complex (MHC) class II antibodies. Twenty-six eyes of 20 horses were used for investigation of MHC class II antigen expression in normal equine eyes. In 18 eyes of 14 horses, the number of T cells in the inflammatory cell population within the uvea was assessed. In 16/18 eyes (89%), the T lymphocyte fraction was > 70%. This cell population was distributed mostly in a diffuse manner throughout the uvea and also within the mantle zone of follicular lymphocytic aggregates. Foci of B lymphocytes could be found within the center of follicular aggregates in three eyes. The expression of MHC class II antigen on resident ocular cells was evaluated in 10 eyes of six horses with ERU. An increase of MHC class II antigen expression in the trabecular meshwork and on the nonpigmented ciliary epithelium was noted as was a deviant expression on proliferating Müller cells and retinal pigment epithelial cells. The predominance of T cells in the inflammatory infiltrates supports the central role of a cell-mediated immune response. Furthermore, the observation of a deviant MHC class II expression on resident ocular cells suggests that aberrant immune regulation may play a role in the pathogenesis of ERU.

  17. Primitive Neuro Ectodermal Tumor (PNET in infant diagnosed by histopathology and immunohistochemistry techniques

    Directory of Open Access Journals (Sweden)

    G. A. Artha


    Full Text Available Primitive Neuro Ectodermal Tumor (PNET is rare and difficult to diagnose. A case of PNET was diagnosed based on histopathological and immunohistochemical findings. A 4-month-old infant was admitted to the hospital with a tumor on the midline of his chest wall since he was 3 days old. The tumor was fixed on the chest wall and had ill-defined margin, enlarged over time and reached more than 10 cm in diameter when he was brought to a clinician. Two small ulcers were seen on the skin overlying the tumor. It was diagnosed as soft tissue tumor suggestive of a hemangioma. The tumor was 17 x 13 x 5.5 cm in size, white colored and firm to the touch. Microscopic examination revealed malignant small round cells with round to ovoid nuclei, coarse chromatin and scanty cytoplasm. Most cells were arranged in a solid pattern with scattered Homer-Wright rosettes. The mitotic count was 7/10 HPF, and necrosis was minimal (less than 25%. On immunohistochemical examination, the cells showed weak to moderate immunoreactivity to Vimentin and CD99, but showed negative to weak positive reactivity to NSE and Chromogranin. Based on the clinical features, gross findings, histopathologic and immunohistochemical examinations, the case was diagnosed as a malignant small round cell tumor consistent with PNET / ES (Ewing’s Sarcoma. To confirm the diagnosis, cytogenetic examination is suggested. (Med J Indones 2007; 16:108-12 Keywords: PNET, histopathology, immunohistochemistry

  18. Histopathological and Immunohistochemical Characterization of Methyl Eugenol-induced Nonneoplastic and Neoplastic Neuroendocrine Cell Lesions in Glandular Stomach of Rats. (United States)

    Janardhan, Kyathanahalli S; Rebolloso, Yvette; Hurlburt, Geoffrey; Olson, David; Lyght, Otis; Clayton, Natasha P; Gruebbel, Margarita; Picut, Catherine; Shackelford, Cynthia; Herbert, Ronald A


    Methyl eugenol induces neuroendocrine (NE) cell hyperplasia and tumors in F344/N rat stomach. Detailed histopathological and immunohistochemical (IHC) characterization of these tumors has not been previously reported. The objective of this study was to fill that data gap. Archived slides and paraffin blocks were retrieved from the National Toxicology Program Archives. NE hyperplasias and tumors were stained with chromogranin A, synaptophysin, amylase, gastrin, H(+)/K(+) adenosine triphosphatase (ATPase), pepsinogen, somatostatin, and cytokeratin 18 (CK18) antibodies. Many of the rats had gastric mucosal atrophy, due to loss of chief and parietal cells. The hyperplasias and tumors were confined to fundic stomach, and females were more affected than the males. Hyperplasia of NE cells was not observed in the pyloric region. Approximately one-third of the females with malignant NE tumors had areas of pancreatic acinar differentiation. The rate of metastasis was 21%, with liver being the most common site of metastasis. Immunohistochemically, the hyperplasias and tumors stained consistently with chromogranin A and synaptophysin. Neoplastic cells were also positive for amylase and CK18 and negative for gastrin, somatostatin, H(+)/K(+) ATPase, and pepsinogen. Metastatic neoplasms histologically similar to the primary neoplasm stained positively for chromogranin A and synaptophysin. Based on the histopathological and IHC features, the neoplasms appear to arise from enterochromaffin-like cells.

  19. Biochemical adaptations of antigravity muscle fibers to disuse atrophy (United States)

    Booth, F. W.


    Studies are presented in four parts of this report. The four parts include; (1) studies to gain information on the molecular basis of atrophy by antigravity muscle; (2) studies on the work capacity of antigravity muscles during atrophy and during recovery from atrophy; (3) studies on recovery of degenerated antigravity fibers after removal of hind-limb casts; and (4) studies on the atrophy and recovery of bone. The philosophy of these studies was to identify the time sequence of events in the soleus muscle of the rat following immobilization of the hind limbs, so that the length of the soleus muscle within the fixed limb is less than its resting length. In two separate studies, no decline in the weight of the soleus muscle could be detected during the first 72 hours of limb immobilization.

  20. Genetics Home Reference: gyrate atrophy of the choroid and retina (United States)

    ... newborn period. Gyrate atrophy usually does not affect intelligence; however, abnormalities may be observed in brain imaging ... the choroid and retina in a child with myopia. Indian Pediatr. 2001 Aug;38(8):914-8. ...

  1. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy. (United States)

    Shakespeare, Timothy J; Kaski, Diego; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Ryan, Natalie S; Schott, Jonathan M; Crutch, Sebastian J


    The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal 'visual dementia' and most common atypical Alzheimer's disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients' (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer's disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer's disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer's disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with 'sticky fixation'. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer's disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions

  2. Early and Degressive Putamen Atrophy in Multiple Sclerosis


    Julia Krämer; Meuth, Sven G.; Jan-Gerd Tenberge; Patrick Schiffler; Heinz Wiendl; Michael Deppe


    Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS). Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS). 68 patients with RRMS and 26 healthy controls (HC) were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (IC...

  3. Reversible "brain atrophy" in patients with Cushing's disease


    Gnjidić, Živko; Sajko, Tomislav; Kudelić, Nenad; Malenica, Maša; Vizner, Branka; Vrkljan, Milan; Hat, Josip; Rumboldt, Zoran


    During the past 25 years, we came across 60 patients with corticotroph pituitary adenomas and Cushing’s disease. Neuroradiological examination showed prominent volume loss of the brain parenchyma, unexpected for the patient’s age. This »brain atrophy« appeared to regress after surgical removal of pituitary adenoma and normalization of cortisol level. Observed difference between degree of »brain atrophy« in the Cushing’s disease group and in the control group was statistically sign...

  4. Steroid-induced Kager's fat pad atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Taneja, Atul K. [Hospital Israelita Albert Einstein, Musculoskeletal Radiology Division, Imaging Department, Sao Paulo (Brazil); Musculoskeletal Imaging, Diagnostic Center, Hospital do Coracao (HCor) and Teleimagem, Sao Paulo, SP (Brazil); Santos, Durval C.B. [Hospital Israelita Albert Einstein, Musculoskeletal Radiology Division, Imaging Department, Sao Paulo (Brazil)


    We report a rare case of Kager's fat pad atrophy and fibrosis in a 60-year-old woman 1 year after a steroid injection for Achilles tendinopathy. There are few published reports of steroid-induced atrophy affecting deeper layers of fat tissue. To our knowledge, this case report is the first to illustrate its features using magnetic resonance imaging. A review of the scientific literature is also presented. (orig.)

  5. Spinal Muscular Atrophy: Current Therapeutic Strategies (United States)

    Kiselyov, Alex S.; Gurney, Mark E.

    Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord. SMA is caused by deletion and/or mutation of the survival motor neuron gene (SMN1) on chromosome 5q13. There are variable numbers of copies of a second, related gene named SMN2 located in the proximity to SMN1. Both genes encode the same protein (Smn). Loss of SMN1 and incorrect splicing of SMN2 affect cellular levels of Smn triggering death of motor neurons. The severity of SMA is directly related to the normal number of copies of SMN2 carried by the patient. A considerable effort has been dedicated to identifying modalities including both biological and small molecule agents that increase SMN2 promoter activity to upregulate gene transcription and produce increased quantities of full-length Smn protein. This review summarizes recent progress in the area and suggests potential target product profile for an SMA therapeutic.

  6. Versatility of immunohistochemical reactions: comprehensive survey of detection systems. (United States)

    Mokrý, J


    The field of immunohistochemistry comprises histological methods enabling detection of tissue antigens via specific antibodies. Although all these techniques take an advantage of a large specificity of antibody to a particular tissue antigen there are many different approaches for enhancement and visualization of the signal. The aim of the present review article was to briefly outline the historical milestones that made the rapid progress of this discipline possible and give a comprehensive survey of immunohistochemical methods applicable to biomedical research. The survey starts with a description of the direct immunohistochemical method and then pays attention to a huge number of indirect methods. For better explanation of principles of individual techniques, the text is accompanied with graphical schemes. The highest attention is given to immunohistochemical methods that are most generally used, i.e. enzyme anti-enzyme complex methods (e.g. Peroxidase Anti-Peroxidase/PAP/ or Alkaline Phosphatase Anti-Alkaline Phosphatase /APAAP/) and methods based on avidin-biotin interactions (Bridged Avidin-Biotin/BRAB/, Avidin-Biotin Complex /ABC/, Labelled Avidin-Biotin/LAB/). Nevertheless, the principles of other immunohistochemical methods like two- or three-step indirect immunohistochemical methods, methods based on protein A-antibody interaction and Hapten Antibody Anti-Hapten method (HAAH), are also thoroughly characterized. Usefulness of each method for a specific utilization, its advantages and disadvantages are mentioned and compared with the latest immunohistochemical techniques, like Multi-Layered Peroxidase-Labelled Antibody (MLP) and water soluble polymer conjugates, e.g. Enhanced Polymer One-Step staining (EPOS) or EnVision. The last paragraphs are devoted to immunohistochemical amplification systems (Catalyzed Signal Amplification/CSA/ and label anti-label) that dramatically increase sensitivity of detection systems and enable to compare sensitivity of

  7. Diagnosing mucopolysaccharidosis IVA. (United States)

    Wood, Timothy C; Harvey, Katie; Beck, Michael; Burin, Maira Graeff; Chien, Yin-Hsiu; Church, Heather J; D'Almeida, Vânia; van Diggelen, Otto P; Fietz, Michael; Giugliani, Roberto; Harmatz, Paul; Hawley, Sara M; Hwu, Wuh-Liang; Ketteridge, David; Lukacs, Zoltan; Miller, Nicole; Pasquali, Marzia; Schenone, Andrea; Thompson, Jerry N; Tylee, Karen; Yu, Chunli; Hendriksz, Christian J


    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of biochemical genetics laboratory directors and clinicians involved in the diagnosis of MPS IVA, convened by BioMarin Pharmaceutical Inc., met to develop recommendations for diagnosis. The following conclusions were reached. Due to the wide variation and subtleties of radiographic findings, imaging of multiple body regions is recommended. Urinary glycosaminoglycan analysis is particularly problematic for MPS IVA and it is strongly recommended to proceed to enzyme activity testing even if urine appears normal when there is clinical suspicion of MPS IVA. Enzyme activity testing of GALNS is essential in diagnosing MPS IVA. Additional analyses to confirm sample integrity and rule out MPS IVB, multiple sulfatase deficiency, and mucolipidoses types II/III are critical as part of enzyme activity testing. Leukocytes or cultured dermal fibroblasts are strongly recommended for enzyme activity testing to confirm screening results. Molecular testing may also be used to confirm the diagnosis in many patients. However, two known or probable causative mutations may not be identified in all cases of MPS IVA. A diagnostic testing algorithm is presented which attempts to streamline this complex testing process.

  8. Diagnosing oceanic nutrient deficiency (United States)

    Moore, C. Mark


    The supply of a range of nutrient elements to surface waters is an important driver of oceanic production and the subsequent linked cycling of the nutrients and carbon. Relative deficiencies of different nutrients with respect to biological requirements, within both surface and internal water masses, can be both a key indicator and driver of the potential for these nutrients to become limiting for the production of new organic material in the upper ocean. The availability of high-quality, full-depth and global-scale datasets on the concentrations of a wide range of both macro- and micro-nutrients produced through the international GEOTRACES programme provides the potential for estimation of multi-element deficiencies at unprecedented scales. Resultant coherent large-scale patterns in diagnosed deficiency can be linked to the interacting physical-chemical-biological processes which drive upper ocean nutrient biogeochemistry. Calculations of ranked deficiencies across multiple elements further highlight important remaining uncertainties in the stoichiometric plasticity of nutrient ratios within oceanic microbial systems and caveats with regards to linkages to upper ocean nutrient limitation. This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.


    Directory of Open Access Journals (Sweden)

    Arockiasamy Babiya Infant


    Full Text Available BACKGROUND Primary adenocarcinoma of cervix constitutes 10-15% of all cases of carcinoma of cervix, which is the second most common carcinoma next to squamous cell carcinoma. Endocervical adenocarcinoma have a considerable morphological overlap with endometrial adenocarcinoma though they differ in their aetiologies, behaviour, and treatments. This makes their diagnosis very difficult particularly in biopsy or curetting specimens or when a fractional dilation and curettage specimens show adenocarcinoma in both components of it. This study was done in the aim to suggest the possible origin of the tumour with the help of immunohistochemistry. AIMS AND OBJECTIVES To identify the incidence, distribution, clinicopathological, histomorphological features of endocervical adenocarcinomas and to determine the immunohistochemical expression of CEA, Vimentin, ER and PR in endometrioid type of adenocarcinoma detected in endocervical biopsies, fractional dilation and curettage specimens (Both the components showing similar morphology, and in hysterectomy specimens to suggest the site of origin of tumour. MATERIALS AND METHODS It is a retrospective descriptive study of cervical adenocarcinomas conducted in the Institute of Obstetrics and Gynaecology, Madras Medical College, Chennai for a period of 4 years during the period between 2009 November to 2013 October. The statistical analysis was performed using statistical package for social science software version 11.5 the clinicopathological profile of the tumour were calculated using Student t-test and chi-square test. OBSERVATION AND RESULTS Among the total 13499 cases received during the study period, 2489 were cervical malignancies comprising 148 adenocarcinoma. It includes 101 mucinous (Endocervical type, 44 endometrioid type, 2 serous type, and 1 clear cell type. Among the 30 cases of endometrioid type, 16 cases showed definite immunophenotype of cervical origin, 9 cases of endometrial origin and in the

  10. Multiple system atrophy (MSA) with massive macrophage infiltration in the ponto-cerebellar afferent system. (United States)

    Yokoyama, Teruo; Hasegawa, Kazuko; Horiuchi, Emiko; Yagishita, Saburou


    Multiple system atrophy (MSA) is characterized pathologically by a systemic degeneration of the olivopontocerebellar (OPC), striatonigral (SN) and autonomic systems. Massive glial cytoplasmic inclusions (GCIs) are specific for this disease. Massive lipid-laden macrophage infiltration in the degenerating tracts has not been described up to now. We here report a case of MSA with this rare event in the ponto-cerebellar (cerebellopetal) fibers. The patient, 54-year-old housewife, developed ataxia. At the age of 55 years, she was diagnosed as having MSA by cerebellar ataxia, extrapyramidal signs, autonomic failure and Horner syndrome. She died from asphyxia at the age of 57. The autopsy revealed OPC and SN system atrophy, degeneration and numerous GCIs, compatible with MSA. Numerous lipid-laden macrophages were seen in the pontine nuclei and its transverse fibers including the white matter of the cerebellum, which has not been reported up to now. There was no macrophage infiltration in the other areas. Transient ischemia, infarction and wallerian degeneration do not account for this rare event. The ponto-cerebellar (cerebellopetal) tract pathology, as observed by postmortem neuropathological study, may occur in the context of MSA.

  11. Progressive brain atrophy in Schinzel-Giedion syndrome with a SETBP1 mutation. (United States)

    Takeuchi, Akihito; Okamoto, Nobuhiko; Fujinaga, Shoko; Morita, Hirosuke; Shimizu, Junya; Akiyama, Tomoyuki; Ninomiya, Shinsuke; Takanashi, Jun-ichi; Kubo, Toshihide


    Schinzel-Giedion syndrome is a rare congenital malformation syndrome. Recently, SETBP1 was identified as the causative gene. Herein, we present a Japanese boy with Schinzel-Giedion syndrome resulting from a novel mutation in SETBP1 in order to establish the clinical features and serial MRI findings associated with the syndrome. On the third day of life, the boy was referred to our hospital because of facial abnormalities and feeding difficulty. Midfacial retraction, frontal bossing, deep groove under the eyes, upturned nose, low-set ears, bilateral cryptorchidism, and generalized hypertrichosis were identified on admission. At the age of 7 months, epileptic spasms in series occurred. Based on characteristic facial and skeletal abnormalities and severe developmental delay, we clinically diagnosed him with Schinzel-Giedion syndrome. Direct sequencing of the SETBP1 gene revealed a heterozygous mutation (p.Ile871Ser) in exon 4. Although neither cardiac defect nor choanal stenosis were present in our case, the phenotype of our case was nearly identical to those of previously reported cases confirmed by genetic analysis. Serial MRI from the age of 1 month-3 years revealed progressive brain atrophy, especially in the white matter and basal ganglia. However, myelination was age-appropriate and no obvious abnormal signals in the white matter were seen. Diffusion weighted imaging revealed no abnormal findings. Accumulation of MRI data including diffusion weighted imaging from Schinzel-Giedion syndrome cases is needed to understand the mechanism underlying progressive brain atrophy in this syndrome.

  12. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model.

    Directory of Open Access Journals (Sweden)

    Simon Hauerslev

    Full Text Available Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.

  13. Calculation of brain atrophy using computed tomography and a new atrophy measurement tool (United States)

    Bin Zahid, Abdullah; Mikheev, Artem; Yang, Andrew Il; Samadani, Uzma; Rusinek, Henry


    Purpose: To determine if brain atrophy can be calculated by performing volumetric analysis on conventional computed tomography (CT) scans in spite of relatively low contrast for this modality. Materials & Method: CTs for 73 patients from the local Veteran Affairs database were selected. Exclusion criteria: AD, NPH, tumor, and alcohol abuse. Protocol: conventional clinical acquisition (Toshiba; helical, 120 kVp, X-ray tube current 300mA, slice thickness 3-5mm). Locally developed, automatic algorithm was used to segment intracranial cavity (ICC) using (a) white matter seed (b) constrained growth, limited by inner skull layer and (c) topological connectivity. ICC was further segmented into CSF and brain parenchyma using a threshold of 16 Hu. Results: Age distribution: 25-95yrs; (Mean 67+/-17.5yrs.). Significant correlation was found between age and CSF/ICC(r=0.695, patrophy among elderly VA patients is attributable to the presence of other comorbidities. Conclusion: Brain atrophy can be reliably calculated using automated software and conventional CT. Compared to MRI, CT is more widely available, cheaper, and less affected by head motion due to ~100 times shorter scan time. Work is in progress to improve the precision of the measurements, possibly leading to assessment of longitudinal changes within the patient.

  14. Immunohistochemical Study to Evaluate the Prognostic Significance of Four Biomolecular Markers in Radiotherapy of Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yeon Joo; Lee, Seung Hee; Wu, Hong Gyun; Go, Heoun Jeong; Jeon, Yoon Kyung [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    We performed an immunohistochemical study with pre-treatment biopsy specimens to evaluate the prognostic significance of four biomolecular markers which can be used as a predictive assay for radiotherapy (RT) treatment of nasopharyngeal carcinoma (NPC). From January 1998 through December 2006, 68 patients were histologically diagnosed as non-metastatic NPC and treated by RT. Only 38 patients had the paraffin block for the immunohistochemical study. Thirty-one patients had undifferentiated carcinoma and 7 patients had squamous cell carcinoma. Thirty two patients (84%) had advanced stage NPC (2002 AJCC Stage III{approx}IV). Immunohistochemical staining was performed for Met, COX-2, nm23-H1, and epidermal growth factor receptor (EGFR) expression using routine methods. The median follow-up time was 30 months (range, 11 to 83 months) for all patients, and 39 months (range, 19 to 83 months) for surviving patients. The 5-year overall survival (OS) rate of the patients with high Met extent ({>=}50%) was significantly lower than that of the patients with low Met extent (48% vs. 84%, p=0.02). In addition, Met extent was also a significant prognostic factor in multivariate analysis (p=0.01). No correlation was observed between Met extent and T stage, N stage, stage group, gender, age, and the response to chemotherapy or RT. Met extent showed moderate correlation with COX-2 expression (Pearson coefficient 0.496, p<0.01), but COX-2 expression did not affect OS. Neither nm23-H1 or EGFR expression was a prognostic factor for OS in this study. High Met extent ({>=}50%) might be an independent prognostic factor that predicts poor OS in NPC treated with RT.

  15. Visual neglect in posterior cortical atrophy

    Directory of Open Access Journals (Sweden)

    Andrade Katia


    Full Text Available Abstract Background In posterior cortical atrophy (PCA, there is a progressive impairment of high-level visual functions and parietal damage, which might predict the occurrence of visual neglect. However, neglect may pass undetected if not assessed with specific tests, and might therefore be underestimated in PCA. In this prospective study, we aimed at establishing the side, the frequency and the severity of visual neglect, visual extinction, and primary visual field defects in an unselected sample of PCA patients. Methods Twenty-four right-handed PCA patients underwent a standardized battery of neglect tests. Visual fields were examined clinically by the confrontation method. Results Sixteen of the 24 patients (66% had signs of visual neglect on at least one test, and fourteen (58% also had visual extinction or hemianopia. Five patients (21% had neither neglect nor visual field defects. As expected, left-sided neglect was more severe than right-sided neglect. However, right-sided neglect resulted more frequently in this population (29% than in previous studies on focal brain lesions. Conclusion When assessed with specific visuospatial tests, visual neglect is frequent in patients with PCA. Diagnosis of neglect is important because of its negative impact on daily activities. Clinicians should consider the routine use of neglect tests to screen patients with high-level visual deficits. The relatively high frequency of right-sided neglect in neurodegenerative patients supports the hypothesis that bilateral brain damage is necessary for right-sided neglect signs to occur, perhaps because of the presence in the right hemisphere of crucial structures whose damage contributes to neglect.

  16. In vivo models of multiple system atrophy. (United States)

    Fernagut, Pierre-Olivier; Ghorayeb, Imad; Diguet, Elsa; Tison, François


    Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disorder of unknown etiology clinically characterized by a combination of parkinsonian, pyramidal, and cerebellar signs. Levodopa-unresponsive parkinsonism is present in 80% of MSA cases, and this dominant clinical presentation (MSA-P) is associated with a combined degeneration of the substantia nigra pars compacta and the striatum in anatomically related areas. The limited knowledge of the pathophysiology of MSA and the lack of therapeutic strategies prompted the development of lesion models reproducing striatonigral degeneration, the substrate of levodopa-unresponsive parkinsonism in MSA-P. This method was carried out first in rats with two different stereotaxic strategies using either two neurotoxins ("double toxin-double lesion") or a single neurotoxin ("single toxin-double lesion"). Double-lesioned rat models showed severe motor impairment compared to those with a single nigral or striatal lesion and helped to mimic different stages of the disease. Systemic models were also developed in mice and primates using the nigral toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the striatal toxin 3-nitropropionic (3-NP). In mice, although MPTP reduced the subsequent sensitivity to 3-NP in a sequential lesion, simultaneous nigral and striatal insults were shown to exacerbate striatal damage. MPTP-treated monkeys displayed a significant worsening of parkinsonism and a loss of levodopa-responsiveness after the appearance of hindlimb dystonia and striatal lesion formation induced by subsequent 3-NP intoxication. The different species and intoxication paradigms used will be useful to investigate functional changes in substantia nigra and striatum and to define neuroprotective, neurorestorative, or symptomatic therapeutic strategies.

  17. Effects of baseline CSF α-synuclein on regional brain atrophy rates in healthy elders, mild cognitive impairment and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Niklas Mattsson

    Full Text Available BACKGROUND: Cerebrospinal fluid (CSF α-synuclein is reduced in synucleinopathies, including dementia with Lewy bodies, and some studies have found increased CSF α-synuclein in Alzheimer's disease (AD. No study has explored effects of CSF α-synuclein on brain atrophy. Here we tested if baseline CSF α-synuclein affects brain atrophy rates and if these effects vary across brain regions, and across the cognitive spectrum from healthy elders (NL, to patients with mild cognitive impairment (MCI and AD. METHODS: Baseline CSF α-synuclein measurements and longitudinal structural brain magnetic resonance imaging was performed in 74 NL, 118 MCI patients and 55 AD patients. Effects of baseline CSF α-synuclein on regional atrophy rates were tested in 1 four pre-hoc defined regions possibly associated with Lewy body and/or AD pathology (amygdala, caudate, hippocampus, brainstem, and 2 all available regions of interest. Differences across diagnoses were tested by assessing the interaction of CSF α-synuclein and diagnosis (testing NL versus MCI, and NL versus AD. RESULTS: The effects of CSF α-synuclein on longitudinal atrophy rates were not significant after correction for multiple comparisons. There were tendencies for effects in AD in caudate (higher atrophy rates in subjects with higher CSF α-synuclein, P=0.046 and brainstem (higher atrophy rates in subjects with lower CSF α-synuclein, P=0.063. CSF α-synuclein had significantly different effects on atrophy rates in NL and AD in brainstem (P=0.037 and caudate (P=0.006. DISCUSSION: With the possible exception of caudate and brainstem, the overall weak effects of CSF α-synuclein on atrophy rates in NL, MCI and AD argues against CSF α-synuclein as a biomarker related to longitudinal brain atrophy in these diagnostic groups. Any effects of CSF α-synuclein may be attenuated by possible simultaneous occurrence of AD-related neuronal injury and concomitant Lewy body pathology, which may elevate and

  18. Progressive retinal atrophy in Schapendoes dogs: mutation of the newly identified CCDC66 gene. (United States)

    Dekomien, Gabriele; Vollrath, Conni; Petrasch-Parwez, Elisabeth; Boevé, Michael H; Akkad, Denis A; Gerding, Wanda M; Epplen, Jörg T


    Canine generalized progressive retinal atrophy (gPRA) is characterized by continuous degeneration of photoreceptor cells leading to night blindness and progressive vision loss. Until now, mutations in 11 genes have been described that account for gPRA in dogs, mostly following an autosomal recessive inheritance mode. Here, we describe a gPRA locus comprising the newly identified gene coiled-coil domain containing 66 (CCDC66) on canine chromosome 20, as identified via linkage analysis in the Schapendoes breed. Mutation screening of the CCDC66 gene revealed a 1-bp insertion in exon 6 leading to a stop codon as the underlying cause of disease. The insertion is present in all affected dogs in the homozygous state as well as in all obligatory mutation carriers in the heterozygous state. The CCDC66 gene is evolutionarily conserved in different vertebrate species and exhibits a complex pattern of differential RNA splicing resulting in various isoforms in the retina. Immunohistochemically, CCDC66 protein is detected mainly in the inner segments of photoreceptors in mouse, dog, and man. The affected Schapendoes retina lacks CCDC66 protein. Thus this natural canine model for gPRA yields superior potential to understand functional implications of this newly identified protein including its physiology, and it opens new perspectives for analyzing different aspects of the general pathophysiology of gPRA.

  19. Cortical sensory loss in a patient with posterior cortical atrophy: a case report. (United States)

    Hsu, Jung-Lung; Chen, Wei-Hung; Chiu, Hou-Chang


    Patients with posterior cortical atrophy (PCA) who present with initial symptoms of higher visual function deficits eventually develop alexia, aphasia, and components of Balint's syndrome or Gerstmann's syndrome. Recently, pathological findings were reported for these patients that are generally suggestive of Alzheimer's disease even though Creutzfeldt-Jakob disease (CJD) was presumed as an alternative cause of some autopsy-diagnosed PCA cases. Here, we report a case with a four-year progression of cognitive and higher visual function deterioration, and with features not described in previously reported PCA cases (i.e., a distinct sensory complaint and early frontal lobe involvement). To summarize, this case belongs to perceptual-motor syndrome of asymmetric cortical degeneration and the underlying neuropathology is more suggestive of Alzheimer's disease than of Creutzfeldt-Jakob disease.

  20. Occurrence of trichoepithelioma in a cat:Histopathologic and immunohistochemical study

    Institute of Scientific and Technical Information of China (English)

    Abbas Tavasoli; Hannaneh Golshahi; Maryam Nobakht Rad; Afra Taymouri


    Trichoepitheliomas are benign follicular appendage tumors with differentiation to all three segments of the hair follicle. A 2 years old female domestic short hair cat presented with a mass on the tail. The mass was surgically excised and for histopathologic and immunohistochemical studies, was sent to Department of Pathology. Histologically, the tumor was encapsulated and consisted of many islands of follicular epithelium and also cysts structures which varied in size and shape. The cells of epithelium islands were round to oval and had variable amounts of slightly, eosinophilic cytoplasm and euchromatic nuclei. The cystic structures were lined by a complex layer of squamous epithelium. Often, cells under went an abrupt transition between basal layers and keratinization without the development of a granular cell layer. No tendency of malignancy was seen in this case. According to mentioned characteristics, trichoepithelioma was diagnosed. By immunohistochemical study it was confirmed that this tumor had epithelial origin because squamous tumor cells reacted with the pan-cytokeratin antibody. The expression of β-catenin was predominately cytoplasmic and also together with numerous positive nuclei but membranous expression was inconsistenet. Distribution of neoplastic cells with β-catenin expression was more than 75% and labeling intensity was strong in both cytoplasm and nuclei. According to author’s knowledge, this is the first report of trichoepithelioma in cat in Iran and also investigation of β-catenin expression in feline trichoepithelioma in veterinary literature.

  1. Papulo-pustulosis form rosacea – results of immunohistochemical research of the condition of the lesions

    Directory of Open Access Journals (Sweden)

    Sviatenko T.V.


    Full Text Available Studying and the analysis of links pathogenesis papulo-pus tulosis forms of rosacea by means of a wide spectrum of immunohistochemical markers became a research problem. For the decision of tasks in view by the author it is used biopsy a material of 11 diagnosed cases papulo-pus tulosis forms of rosacea at me at the age from 32 till 59 years. Use of immunohis-tochemical methods of research has allowed to reveal new links in pathogenesis of rosacea and to establish a role of some cellular populations of a skin and cages of immune system in progressing of disease and development papulo-pustulosis forms of rosacea. Authors have come to a conclusion that is possible, strengthening of pathological changes at papulo-pustulosis forms of rosacea is caused by presence of pincers which are capable to cause migration in skin CD68+ cages while quantity CD138+ plasmocytes was insignificant and didn't exceed 5-10 % in infiltrates. К i-67+ cages in a considerable quan-tity were as a part of sebaceous glands that specified in progressing hyperplastic changes in these appendages of a skin. Be-sides, the quantity of cages, pos itive on this marker, correlated wi th expressiveness of defeat of sebaceous glands in a greate r degree, than with a disease stage.

  2. Neural correlates of cognitive impairment in posterior cortical atrophy. (United States)

    Kas, Aurélie; de Souza, Leonardo Cruz; Samri, Dalila; Bartolomeo, Paolo; Lacomblez, Lucette; Kalafat, Michel; Migliaccio, Raffaella; Thiebaut de Schotten, Michel; Cohen, Laurent; Dubois, Bruno; Habert, Marie-Odile; Sarazin, Marie


    With the prospect of disease-modifying drugs that will target the physiopathological process of Alzheimer's disease, it is now crucial to increase the understanding of the atypical focal presentations of Alzheimer's disease, such as posterior cortical atrophy. This study aimed to (i) characterize the brain perfusion profile in posterior cortical atrophy using regions of interest and a voxel-based approach; (ii) study the influence of the disease duration on the clinical and imaging profiles; and (iii) explore the correlations between brain perfusion and cognitive deficits. Thirty-nine patients with posterior cortical atrophy underwent a specific battery of neuropsychological tests, mainly targeting visuospatial functions, and a brain perfusion scintigraphy with 99mTc-ethyl cysteinate dimer. The imaging analysis included a comparison with a group of 24 patients with Alzheimer's disease, matched for age, disease duration and Mini-Mental State Examination, and 24 healthy controls. The single-photon emission computed tomography profile in patients with posterior cortical atrophy was characterized by extensive and severe hypoperfusion in the occipital, parietal, posterior temporal cortices and in a smaller cortical area corresponding to the frontal eye fields (Brodmann areas 6/8). Compared with patients with Alzheimer's disease, the group with posterior cortical atrophy showed more severe occipitoparietal hypoperfusion and higher perfusion in the frontal, anterior cingulate and mesiotemporal regions. When considering the disease duration, the functional changes began and remained centred on the posterior lobes, even in the late stage. Correlation analyses of brain perfusion and neuropsychological scores in posterior cortical atrophy highlighted the prominent role of left inferior parietal damage in acalculia, Gerstmann's syndrome, left-right indistinction and limb apraxia, whereas damage to the bilateral dorsal occipitoparietal regions appeared to be involved in B

  3. A Leydig Cell Tumour in a Cat: Histological and Immunohistochemical Findings

    Directory of Open Access Journals (Sweden)

    Pietro Asproni


    Full Text Available A 13-year-old intact male cat was submitted to castration after the finding of the enlargement of the right testis during the clinical visit. Macroscopically, a nodule of 2 cm of diameter was observed on the cut surface of the enlarged testis. Histologically, the nodule was composed by polyhedral to elongated cells with a large, eosinophilic, and vacuolated cytoplasm and small, round, and dark nuclei. These cells were arranged in acinar structures and solid sheets. The tumour was diagnosed as a Leydig cell tumour. Immunohistochemical analysis revealed that neoplastic cells were vimentin, calretinin, and melan-A positive, whereas a lack of immunoreactivity to cytokeratins confirmed the diagnosis. To our knowledge, this is the first description of a feline Leydig cells tumour without any concurrent testicular neoplasm or in a nonretained testis.

  4. Epidemiological, clinical and immunohistochemical aspects of canine lymphoma in the region of Porto Alegre, Brazil

    Directory of Open Access Journals (Sweden)

    Elisa B. Neuwald


    Full Text Available This paper describes the epidemiological, clinical and immunohistochemical characteristics of canine lymphomas diagnosed in the region of Porto Alegre, Brazil. Thirty dogs were enrolled in the study; most of them were male (60%, mixed-breed (23% and middle-aged or older. The majority (87% of affected dogs showed the multicentric form. The B-cell phenotype was most frequently detected (62%; 37% of the animals were in clinical stage IV, and 83% were classified as sub-stage "b". Lymphadenopathy was observed in 67% of the cases, and dyspnea, prostration, decreased appetite and vomiting were the most common clinical signs encountered. Anemia was a frequently encountered laboratory alteration (57%, as were leukocytosis (40%, thrombocytopenia (33%, lymphopenia (30%, hyperglobulinemia (20% and hypercalcemia (13%. The results of this study indicate that the clinical features of dogs with lymphoma in the region of Porto Alegre are similar to those observed worldwide.

  5. Delayed Diagnoses: Nonspecific Findings and Diagnostic Challenges in Eating Disorders

    Directory of Open Access Journals (Sweden)

    Dan Schwarz


    Full Text Available Objective. Eating disorders commonly present with nonspecific findings, masquerading as other, more common etiologies of malnutrition and wasting. In low-prevalence populations, these ambiguities can complicate clinicians’ diagnostic reasoning, resulting in delayed or missed diagnoses. Method. We report the atypical case of a 51-year-old male with a five-year history of unexplained weight loss despite extensive past medical evaluation. Previous documentation of profound lymphopenia and bone marrow atrophy had not been linked to a known association with eating disorders. Results. Evaluation for medical etiologies of wasting was negative. Following psychiatric evaluation, the patient was diagnosed with an eating disorder, not otherwise specified, and admitted to a specialized nutritional rehabilitation program. Conclusion. The nonspecific clinical history, physical exam, and laboratory abnormalities of eating disorders can make these diagnoses challenging and delay appropriate treatment. Clinicians should consider eating disorders in patients with malnutrition, severe lymphopenias, and gelatinous marrow transformation early in their workup, so as to avoid potentially negative outcomes.

  6. How Is Aplastic Anemia Diagnosed? (United States)

    ... from the NHLBI on Twitter. How Is Aplastic Anemia Diagnosed? Your doctor will diagnose aplastic anemia based on your medical and family histories, a ... your primary care doctor thinks you have aplastic anemia, he or she may refer you to a ...

  7. Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience. (United States)

    Gao, Yuping; Jiang, Jiyao; Liu, Qiang


    Primary central nervous system (CNS) germ cell tumors (GCTs) are a rare heterogeneous group of lesions, which the clinicopathological features have a marked degree of heterogeneity comparing with that of gonadal GCTs. Accurately diagnosing CNS GCTs might be extremely difficult and requires immunohistochemical verification. This study was to investigate the biological feature of CNS GCTs and diagnostic value of immunohistochemical markers OCT3/4, C-kit, PLAP, and CD30 in CNS GCTs. A retrospective study was performed on 34 patients with CNS germ cell tumors between 1990 and 2014. 34 CNS GCTs account for 9.2% of all primary CNS neoplasms. The sellar region (35.3%) and pineal gland (17.6%) were the most common sites of intracranial GCTs. Hydrocephalus (82.4%) and diplopia (46.9%) were the two most common clinical presentations. The most common histological subtypes were germinoma (67.6%). PLAP, c-kit, OCT3/4 were highly expressed in gernimomas. CD30 and CK AE1/3 stainings were positive in embryonal carcinoma. Yolk sac tumor component showed positive staining for AFP and CK AE1/3. β-HCG staining was positive in choriocarcinoma and STGC. Patients with mature teratomas and germinomas had a better prognosis (a 5-year survival rate) than those with embryonal carcinoma and choriocarcinoma (a 5-year survival rates were 0). Our finding suggest that the incidences of primary CNS GCTs are higher in South China than in the West, but mixed GCTs are uncommon in our study. The judicious use of a panel of selected markers is helpful in diagnosing and predicting the prognosis for CNS GCTs.

  8. Congenital segmental spinal muscular atrophy: a case report. (United States)

    Savaş, Tülin; Erol, Ilknur; Özkale, Yasemin; Saygi, Semra


    Spinal muscular atrophies are genetic disorders in which anterior horn cells in the spinal cord and motor nuclei of the brainstem are progressively lost. We present a patient with arthrogryposis due to congenital spinal muscular atrophy predominantly affecting the upper limbs. Spinal muscular atrophies with onset at birth may be a cause of arthrogryposis. Localized forms of neurogenic arthrogryposis have been divided into cervical and caudal forms. Our case is similar to the cases described by Hageman et al (J Neurol Neurosurg Psychiatry 1993;56:365-368): severe symmetric lower motor neuron deficit in the upper extremities at the time of birth, no history of injury to the cervical spinal cord or the brachial plexus during delivery, and severe muscle wasting suggesting chronic denervation in utero. Because there was improvement of our patient's situation, her disease was also possibly nonprogressive and sporadic. To our knowledge, this is the first reported case of a Turkish patient with congenital cervical spinal muscular atrophy. Congenital cervical spinal muscular atrophy affecting predominantly the upper limbs is a relatively rare form of motor neuron disease and should be considered in the differential diagnosis of infants with congenital contractures and severe muscle weakness by wasting mainly confined to the upper limbs.

  9. Early and Degressive Putamen Atrophy in Multiple Sclerosis. (United States)

    Krämer, Julia; Meuth, Sven G; Tenberge, Jan-Gerd; Schiffler, Patrick; Wiendl, Heinz; Deppe, Michael


    Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS). Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS). 68 patients with RRMS and 26 healthy controls (HC) were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (ICV). Patient's relative putamen volume (RPV), expressed in percent of ICV, was significantly reduced compared to HC. Based on the correlation between RPV and age, we computed the age-corrected RPV deviation (ΔRPV) from HC. Patients showed significantly negative ΔRPV. Interestingly, the age-corrected ΔRPV depended logarithmically on disease duration: Directly after first symptom manifestation, patients already showed a reduced RPV followed by a further degressive volumetric decline. This means that atrophy progression was stronger in the first than in later years of disease. Putamen atrophy starts directly after initial symptom manifestation or even years before, and progresses in a degressive manner. Due to its important role in neurological functions, early detection of putamen atrophy seems necessary. High-resolution structural MRI allows monitoring of disease course.

  10. Early and Degressive Putamen Atrophy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Julia Krämer


    Full Text Available Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS. Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS. 68 patients with RRMS and 26 healthy controls (HC were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (ICV. Patient’s relative putamen volume (RPV, expressed in percent of ICV, was significantly reduced compared to HC. Based on the correlation between RPV and age, we computed the age-corrected RPV deviation (ΔRPV from HC. Patients showed significantly negative ΔRPV. Interestingly, the age-corrected ΔRPV depended logarithmically on disease duration: Directly after first symptom manifestation, patients already showed a reduced RPV followed by a further degressive volumetric decline. This means that atrophy progression was stronger in the first than in later years of disease. Putamen atrophy starts directly after initial symptom manifestation or even years before, and progresses in a degressive manner. Due to its important role in neurological functions, early detection of putamen atrophy seems necessary. High-resolution structural MRI allows monitoring of disease course.

  11. Effect of the cognitive rehabilitation in patients with mild cognitive impairment and identified brain atrophy

    Directory of Open Access Journals (Sweden)

    Petr Nilius


    Full Text Available Aim: The main objective of this study was to analyse the development of cognitive functions and effect of cognitive rehabilitation on patients diagnosed with mild cognitive impairment (MCI, as a result of brain atrophy. Design: A quantitative non-randomized intervention study on a control sample of patients. Methods: The effect was observed in a group of patients ranging 59-91 years of age (N = 36. Only patients fulfilling the diagnostic criteria of mild cognitive disorder diagnosed by tomography (CT that had undergone 22 sessions, were involved in the clinical sample (n = 21. The control sample (n = 15 consisted of patients without any neurological diagnosis and who did not undergo cognitive sessions. Results: The effect of cognitive rehabilitation was measured by Addenbrooke's cognitive test, revised in 2010 (ACE-R; affective changes were measured by Beck´s scale of depression BDI-2 and by a scale used to detect anxiety and depression: the Hospital Anxiety and Depression Scale (HADS. Subjective change and improvement were observed using the Clinical Global Impression (CGI psychiatric scale. Changes in the functional state of patients were measured by means of the activities of daily living scale (ADL, including the instrumental version (IADL. The effect was examined in the form of entry and output tests, which were verified by statistical analysis, a significant level being p > 0.05. Conclusions: Significant differences in verbal tests and ACE-R were observed in the clinical sample of patients. Some significant changes were observed in the field of affective symptoms, according to the HADS and BDI-2. The clinical sample showed a significant improvement in subjective clinical state (CGI. The ADL and IADL questionnaires seem to have been inadequate for purpose due to their low sensitivity. The effect of cognitive rehabilitation in patients diagnosed with mild cognitive disorder can be seen and verified in comparison with the control sample

  12. Immunohistochemical diagnosis of myocarditis on (infantile) autopsy material: Does it improve the diagnosis? (United States)

    Grasmeyer, Sarah; Madea, Burkhard


    The standard for the histopathologic diagnosis of myocarditis has been the Dallas criteria. Recently, immunohistochemical studies that include the specification and quantification of interstitial inflammatory cells have been proposed as the diagnostic approach for myocarditis. Cut-off limits regarding inflammatory cell numbers for the positive diagnosis of myocarditis have been recommended. However, it is unclear whether these can be applied to postmortem tissues or to infants, as they were established from endomyocardial biopsies and for adults. Nevertheless, cut-off limits for the postmortem diagnosis of myocarditis in the first year of life have been proposed. Studies using these cut-off limits identified myocarditis in a high percentage of presumed sudden infant death syndrome (SIDS) cases. These results were re-evaluated by the present study, which examined heart specimens from infants less than 1 year of age. The study had a test group of 92 SIDS cases and a control group of 15. Myocardial tissue was examined from eight standardized locations, stained with hematoxylin-eosin and for three different immunohistochemical reagents (LCA for leukocytes, CD68 for macrophages, CD45-RO for T-lymphocytes). Histopathological assessment of the number of inflammatory cells was carried out on an aggregate of 80 mm(2) of myocardial tissue per case. Myocarditis, based on the Dallas criteria, was histologically diagnosed in only two cases. Immunohistochemical quantification revealed elevated cell counts in the SIDS group for LCA and CD45-RO. However, those differences were neither statistically significant nor clinically relevant as the mean cell counts per mm(2) were low. The density of inflammatory cells differed considerably from section to section and even within single sections. Therefore the commonly used arithmetic mean value was not diagnostically relevant, suggesting cut-off values based on the arithmetic mean value as recommended in the literature, cannot be regarded

  13. Apoptosis in skeletal muscle and its relevance to atrophy

    Institute of Scientific and Technical Information of China (English)

    Esther E Dupont-Versteegden


    Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less well defined. Apoptosis during muscle atrophy occurs in both myonuclei and other muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as -independent pathways have been implicated and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required for different causes of skeletal muscle loss.

  14. Can endurance exercise preconditioning prevention disuse muscle atrophy?

    Directory of Open Access Journals (Sweden)

    Michael P Wiggs


    Full Text Available Emerging evidence suggests that exercise training can provide a level of protection against disuse muscle atrophy. Endurance exercise training imposes oxidative, metabolic, and heat stress on skeletal muscle which activates a variety of cellular signaling pathways that ultimately leads to the increased expression of proteins that have been demonstrated to protect muscle from inactivity –induced atrophy. This review will highlight the effect of exercise-induced oxidative stress on endogenous enzymatic antioxidant capacity (i.e., superoxide dismutase, glutathione peroxidase, and catalase, the role of oxidative and metabolic stress on PGC1-α, and finally highlight the effect heat stress and HSP70 induction. Finally, this review will discuss the supporting scientific evidence that these proteins can attenuate muscle atrophy through exercise preconditioning.

  15. Immunohistochemical localization of epidermal growth factor in rat and man

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba


    Epidermal growth factor (EGF) is a peptide which stimulates cell mitotic activity and differentiation, has a cytoprotective effect on the gastroduodenal mucosa, and inhibits gastric acid secretion. The immunohistochemical localization of EGF in the Brunner's glands and the submandibular glands...... is well documented. The localization of EGF in other tissues is still unclarified. In the present study, the immunohistochemical localization of EGF in tissues from rat, man and a 20 week human fetus were investigated. In man and rat, immunoreaction was found in the submandibular glands, the serous glands...

  16. Villoglandular papillary adenocarcinoma of the uterine cervix with immunohistochemical characteristics. (United States)

    Polat, A; Düsmez, D; Pata, O; Aydin, O; Egilmez, R


    Villoglandular papillary adenocarcinoma of uterine cervix has been recently described and to date fewer than a hundred cases have been reported in the world literature. Here we present a 38-year-old woman who underwent radical hysterectomy combined bilateral pelvic lymphoadenectomy and after 28 months postoperatively no lymph node metastasis and no evidence of recurrent disease ocurred. Immunohistochemically Ki-67 overexpression was detected in the tumour, with no immunoreactivity with p53, estrogen and progesteron receptors and broadly-reactive human papilloma virus including types 6, 11, 16, 18, 31, 33, 42, 51, 52, 56, and 58. In this paper, clinical, macroscopical, microscopical and immunohistochemical characteristics of this tumour are reviewed.

  17. Atrophy of the corpus callosum correlates with white matter lesions in patients with cerebral ischaemia

    Energy Technology Data Exchange (ETDEWEB)

    Meguro, K.; Yamadori, A. [Section of Neuropsychology, Division of Disability Science, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, 980-8575 Sendai (Japan); Constans, J.M.; Courtheoux, P.; Theron, J. [MR Unit, University of Caen School of Medicine, Caen (France); Viader, F. [Department of Neuroradiology, University of Caen School of Medicine, Caen (France)


    Many studies of white matter high signal (WMHS) on T2-weighted MRI have disclosed that it is related to cerebral ischaemia and to brain atrophy. Atrophy of the corpus callosum (CC) has also been studied in relation to ischaemia. Our objective was to test the hypothesis that CC atrophy could be due to ischaemia. We therefore assessed CC, WMHS and brain atrophy in patients with risk factors without strokes (the risk factor group) and in those with infarcts (the infarct group), to investigate the relationships between these factors. We studied 30 patients in the infarct group, 14 in the risk factor group, and 29 normal subjects. Using axial T1-weighted MRI, cortical atrophy and ventricular enlargement (brain atrophy) were visually rated. Using axial T2-weighted MRI, WMHS was assessed in three categories: periventricular symmetrical, periventricular asymmetrical and subcortical. Using the mid-sagittal T1-weighted image, the CC was measured in its anterior, posterior, midanterior and midposterior portions. In the normal group, no correlations were noted between parameters. In the infarct group, there were significant correlations between CC and brain atrophy, and between CC atrophy and WMHS. After removing the effects of age, gender and brain atrophy, significant correlations were noted between some CC measures and subcortical WMHS. In the risk factor group, there were significant correlations between CC and brain atrophy and between CC atrophy and WMHS. After allowance for age, gender and brain atrophy, significant correlations between some CC measures and periventricular WMHS remained. The hypothesis that CC atrophy could be due to cerebral ischaemia was supported by other analyses. Namely, for correlations between the extent of infarcts and partial CC atrophy in patients with anterior middle cerebral artery (MCA) and with posterior MCA infarcts, there were significant correlations between the extent of infarct and midanterior CC atrophy in the former, and posterior

  18. Clinicopathological Features and Immunohistochemical Alterations of Keratinocyte Proliferation, Melanocyte Density, Smooth Muscle Hyperplasia and Nerve Fiber Distribution in Becker's Nevus (United States)

    Sheng, Ping; Cheng, Yun-Long; Cai, Chuan-Chuan; Guo, Wei-Jin; Zhou, Ying; Shi, Ge


    Background Although Becker's nevus (BN) is a relatively common disease, the systematic studies of clinicopathological and immunohistochemical results are poorly reported. Objective To investigate the clinicopathological features and immunohistochemical alterations of keratinocyte proliferation, melanocyte density, smooth muscle hyperplasia and nerve fiber distribution in BN. Methods Clinical and pathological data were collected in 60 newly-diagnosed BN cases. Immunohistochemical stain of Ki-67, Melan-A, keratin 15, smooth muscle actin and protein gene product 9.5 was performed in 21 cases. Results The median diagnostic and onset age was 17 and 12 years, respectively. Skin lesions usually appeared on the upper trunk and upper limbs. The pathological features included the rete ridge elongation and fusion and basal hyperpigmentation. Epidermal Ki-67, Melan-A and keratin 15 expression and dermal nerve fiber length were significantly higher in lesional and perilesional skin than in normal skin (p<0.05~0.01), while smooth muscle actin expression was upregulated only in skin lesion (p<0.05). Conclusion Although the clinical diagnosis of BN is often straightforward, histopathology is helpful to differentiate from other pigmentary disorders. The hyperproliferation of keratinocytes, melanocytes, arrector pili muscle and dermal nerve fibers could be involved in the pathogenesis of BN. PMID:27904268

  19. Accelerating regional atrophy rates in the progression from normal aging to Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Sluimer, Jasper D. [VU University Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Diagnostic Radiology and Alzheimer Centre, PO Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der; Scheltens, Philip [VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Neurology, Amsterdam (Netherlands); Karas, Giorgos B.; Barkhof, Frederik [VU University Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); Schijndel, Ronald van [VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Informatics, Amsterdam (Netherlands); Barnes, Josephine; Boyes, Richard G. [UCL, Institute of Neurology, Dementia Research Centre, London (United Kingdom); Cover, Keith S. [VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands); Olabarriaga, Silvia D. [University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam (Netherlands); Fox, Nick C. [VU University Medical Centre, Department of Neurology, Amsterdam (Netherlands); UCL, Institute of Neurology, Dementia Research Centre, London (United Kingdom); Vrenken, Hugo [VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands)


    We investigated progression of atrophy in vivo, in Alzheimer's disease (AD), and mild cognitive impairment (MCI). We included 64 patients with AD, 44 with MCI and 34 controls with serial MRI examinations (interval 1.8 {+-} 0.7 years). A nonlinear registration algorithm (fluid) was used to calculate atrophy rates in six regions: frontal, medial temporal, temporal (extramedial), parietal, occipital lobes and insular cortex. In MCI, the highest atrophy rate was observed in the medial temporal lobe, comparable with AD. AD patients showed even higher atrophy rates in the extramedial temporal lobe. Additionally, atrophy rates in frontal, parietal and occipital lobes were increased. Cox proportional hazard models showed that all regional atrophy rates predicted conversion to AD. Hazard ratios varied between 2.6 (95% confidence interval (CI) = 1.1-6.2) for occipital atrophy and 15.8 (95% CI = 3.5-71.8) for medial temporal lobe atrophy. In conclusion, atrophy spreads through the brain with development of AD. MCI is marked by temporal lobe atrophy. In AD, atrophy rate in the extramedial temporal lobe was even higher. Moreover, atrophy rates also accelerated in parietal, frontal, insular and occipital lobes. Finally, in nondemented elderly, medial temporal lobe atrophy was most predictive of progression to AD, demonstrating the involvement of this region in the development of AD. (orig.)

  20. From alveolar diffuse atrophy to aggressive periodontitis: a brief history. (United States)

    Guzeldemir, Esra; Toygar, Hilal Uslu


    Technologic advances in mechanics, electronics, physics, chemistry, and computer science have contributed to advances in dental medicine. Periodontology is not only a clinical science but is also directly related to the basic sciences. Research is conducted in laboratories rather than in clinics now. During the last century, aggressive periodontitis has received attention from numerous researchers because of its multifactorial features. This paper explores the long scientific journey of aggressive periodontitis, beginning with its first definition as alveolar diffuse atrophy. Perhaps in the future, "alveolar diffuse atrophy" will be referred to by another name or term. However, this journey will never end.

  1. Bilaterally impaired hand dexterity with posterior cortical atrophy

    Directory of Open Access Journals (Sweden)

    Nages Nagaratnam, MD, FRACP, FRCPA, FACC


    Full Text Available A 79-year- old man presented with bilaterally impaired hand movements pertaining to handling of objects although hand movements without the use of objects were preserved, findings consistent with tactile apraxia. His hand and finger movements were slow and clumsy. He had an isolated optic ataxia, a component of Balint's syndrome. The computed tomography scan showed enlargement of the posterior horns of the lateral ventricles. He had recurrent falls probably owing to visual attentional deficits, which may be present in patients with posterior cortical atrophy. The findings can be deemed to fall within the posterior cortical atrophy spectrum. The underlying mechanisms are discussed.

  2. Vulvar and Vaginal Atrophy: Physiology, Clinical Presentation, and Treatment Considerations. (United States)

    Lev-Sagie, Ahinoam


    Vulvovaginal atrophy is a common condition associated with decreased estrogenization of the vaginal tissue. Symptoms include vaginal dryness, irritation, itching, soreness, burning, dyspareunia, discharge, urinary frequency, and urgency. It can occur at any time in a woman's life cycle, although more commonly in the postmenopausal phase, during which the prevalence is approximately 50%. Despite the high prevalence and the substantial effect on quality of life, vulvovaginal atrophy often remains underreported and undertreated. This article aims to review the physiology, clinical presentation, assessment, and current recommendations for treatment, including aspects of effectiveness and safety of local vaginal estrogen therapies.

  3. Recommendations for the management of postmenopausal vaginal atrophy

    DEFF Research Database (Denmark)

    Sturdee, D W; Panay, N; Ulrich, Lian


    for hormone replacement therapy (HRT) over recent years that has suggested an increased risk of breast cancer, heart disease and stroke. But, regardless of whether these scares are justified, local treatment of vaginal atrophy is not associated with these possible risks of systemic HRT. Other reasons...... dryness can be helped by simple lubricants but the best and most logical treatment for urogenital atrophy is to use local estrogen. This is safe, effective and with few contraindications. It is hoped that these guidelines and recommendations, produced to coincide with World Menopause Day 2010, will help...

  4. How Is Thyroid Cancer Diagnosed? (United States)

    ... Cancer Early Detection, Diagnosis, and Staging Tests for Thyroid Cancer Thyroid cancer may be diagnosed after a person ... Health Care Team About Thyroid Cancer? More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...

  5. How Is Marfan Syndrome Diagnosed? (United States)

    ... common in many people. Doctors use a scoring system based on the number and type of Ghent criteria present to diagnose Marfan syndrome. Talk ... National Institutes of Health Department of Health and Human Services

  6. How to diagnose cardiac tamponade

    NARCIS (Netherlands)

    van Steijn, JHM; Sleijfer, DT; van der Graaf, WTA; van der Sluis, A; Nieboer, P


    Malignant pericardial effusion is a potentially fatal complication of malignancy unless recognised and treated promptly. Patients with this condition are often difficult to diagnose. Physical examination, chest radiography and electrocardiography have poor diagnostic values in identification of pati

  7. How Is Stomach Cancer Diagnosed? (United States)

    ... Cancer Early Detection, Diagnosis, and Staging How Is Stomach Cancer Diagnosed? Stomach cancers are usually found when a ... Ask Your Doctor About Stomach Cancer? More In Stomach Cancer About Stomach Cancer Causes, Risk Factors, and Prevention ...

  8. How Is Ovarian Cancer Diagnosed? (United States)

    ... Cancer Early Detection, Diagnosis, and Staging How Is Ovarian Cancer Diagnosed? If you have symptoms of ovarian cancer ... Ask Your Doctor About Ovarian Cancer? More In Ovarian Cancer About Ovarian Cancer Causes, Risk Factors, and Prevention ...

  9. Genetics Home Reference: spinal muscular atrophy with respiratory distress type 1 (United States)

    ... Home Health Conditions SMARD1 spinal muscular atrophy with respiratory distress type 1 Enable Javascript to view the expand/ ... All Close All Description Spinal muscular atrophy with respiratory distress type 1 ( SMARD1 ) is an inherited condition that ...

  10. Convenient diagnosis of spinal and bulbar muscular atrophy using a microchip electrophoresis system. (United States)

    Maruyama, Hirofumi; Morino, Hiroyuki; Izumi, Yuishin; Noda, Kouichi; Kawakami, Hideshi


    Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive motor neuron disease. Lower and primary sensory neuronopathy is one of the major neuropathological changes that occurs in SBMA. However, many sings are common to SBMA and amyotrophic lateral sclerosis (ALS), and SBMA patients are sometimes diagnosed with ALS. Leuprorelin may be used to treat SBMA, but an accurate diagnosis is necessary for treatment and care. Genetic diagnosis can be performed to detect the expansion of a CAG repeat in the androgen receptor gene in SBMA patients. To screen for this expansion, we used a microchip electrophoresis system. The discrepancy between the actual repeat length and that found by the microchip electrophoresis system was roughly dependent on the repeat length. The mean difference was -6.8 base pairs (bp) in SBMA patients, -0.30 bp in controls. The microchip electrophoresis results were approximately 2 CAG repeats shorter than the actual repeat length in SBMA patients. Using this method, we screened our ALS samples (31 were familial, 271 were sporadic): 4 subjects were diagnosed with SBMA; 2 had familial ALS, and 2 had sporadic ALS (0.7%). The microchip electrophoresis system is semi-quantitative, convenient and useful for screening a large number of samples.

  11. Posterior Cortical Atrophy Presenting with Superior Arcuate Field Defect

    Directory of Open Access Journals (Sweden)

    Sue Ling Wan


    Full Text Available An 80-year-old female with reading difficulty presented with progressive arcuate field defect despite low intraocular pressure. Over a 5-year period, the field defect evolved into an incongruous homonymous hemianopia and the repeated neuroimaging revealed progressive posterior cortical atrophy. Further neuropsychiatric assessment demonstrated symptoms and signs consistent with Benson’s syndrome.

  12. Pigmented paravenous chorioretinal atrophy with Coat′s like response

    Directory of Open Access Journals (Sweden)

    Manish Tandon


    Full Text Available Pigmented paravenous chorioretinal atrophy (PPCRA is an uncommon retinal disorder of unknown etiology that is neither well understood nor classified. We report an atypical case of PPCRA, associated with Coat′s like response (CLR in a 64-year-old man of Asian origin. Both the eyes were involved, though asymmetrically.

  13. CT findings of hereditary dentatorubral-pallidoluysian atrophy (DRPLA)

    Energy Technology Data Exchange (ETDEWEB)

    Tokiguchi, Susumu; Kurashima, Akihiko; Tsuchiya, Toshiaki; Ito, Jusuke; Naito, Haruhiko; Nagai, Hiroko; Wakabayashi, Masatoshi; Morita, Masahiro


    Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) has recently been recognized as a clinicopathological entity. It may be defined as a multisystem degenerative disease of dominant inheritance, and characterized clinically by a combination of epilepsy, myoclonus, ataxia, dementia, and choreo-athetosis. This paper reports on the CT findings of ten patients (in four families) with DRPLA. In two families, the diagnosis was established on the basis of the clinicopathological findings, while in the other two, the diagnosis was made clinically. Although the CT findings were not identical in all patients, some degree of atrophic change was always observed in the cerebellum, brainstem, and cerebral cortex. Cerebellar atrophy was always accompanied by a dilatation of the fourth ventricle. Midbrain atrophy was characterized by a prominent tegmental atrophy and aqueductal dilatation, such as is seen in progressive supranuclear palsy. Of the four patients over 40 years of age, three had a diffuse hypodensity of the cerebral white matter on CT. To our knowledge, there have been no previous reports on this hypodensity in patients with spino-cerebellar degeneration or Huntington's chorea. CT may be helpful in the differential diagnosis of progressive neuro-degenerative disorders.

  14. Reversible Altered Consciousness and Brain Atrophy Induced by Valproic Acid

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap


    Full Text Available A 5-year-old female child with valproic acid (VPA-related alteration of consciousness and brain atrophy that progressed over a 3 day period and resolved within 12 hours of discontinuing VPA is reported from Dokkyo University School of Medicine and Shimotsuga General Hospital, Tochigi, Japan.

  15. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice (United States)

    Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghreli...

  16. Atrophy of the Parietal Lobe in Preclinical Dementia (United States)

    Jacobs, Heidi I. L.; Van Boxtel, Martin P. J.; Uylings, Harry B. M.; Gronenschild, Ed H. B. M.; Verhey, Frans R.; Jolles, Jelle


    Cortical grey matter atrophy patterns have been reported in healthy ageing and Alzheimer disease (AD), but less consistently in the parietal regions of the brain. We investigated cortical grey matter volume patterns in parietal areas. The grey matter of the somatosensory cortex, superior and inferior parietal lobule was measured in 75 older adults…

  17. Skeletal muscle training for spinal muscular atrophy type 3

    NARCIS (Netherlands)

    Bartels, Bart; Montes, Jacqueline; van der Pol, W. Ludo; de Groot, Janke F.


    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of skeletal muscle training on functional performance in people with spinal muscular atrophy (SMA) type 3 and to identify any adverse effects.

  18. Benefits of Laser Therapy in Postmenopausal Vaginal Atrophy (United States)

    Brînzan, Daniela; Pǎiuşan, Lucian; Daşcǎu, Voicu; Furǎu, Gheorghe


    Maybe the worst aspect of menopause is the decline of the quality of the sexual life. The aim of the study is to demonstrate the beneficial effects of laser therapy in comparison with topical application of estrogen preparations, for the treatment of vaginal atrophy and sexual dysfunctions induced by menopause. A total of 50 menopausal patients were examined during a one year period. The methods used for objectifying vaginal atrophy and sexual dysfunctions were history taking, local clinical exam and PAP smear. From this group, 40 patients had vaginal atrophy with sexual dysfunctions. They have been treated differently, being included in four groups: patients treated with local estrogens, patients treated with intravaginal laser therapy, patients treated with both laser therapy and estrogens, patients treated with estrogens and placebo laser therapy. Therapeutic benefit, improvement of vaginal atrophy and quality of sexual life, were objectified by anamnesis (questionnaire), local and general clinical examination and PAP smear. The best results have been obtained, by far, in the 3rd group, followed by the women treated only with laser. In conclusion, we can say that laser therapy is the best way for solving the sexual inconveniences of menopause.

  19. Skeletal muscle training for spinal muscular atrophy type 3 (Protocol).

    NARCIS (Netherlands)

    Bartels, B.; Montes, J.; Pol, W.L. van der; Groot, J.F. de


    Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by a genetic mutation in the survival motor neuron 1 (SMN1) gene (5q11.2-q13.3) (Lefebvre 1995). With an incidence of one in 10,000 live births, it is the leading genetic cause of infant death (Lunn 2008; Mercur

  20. Tubular atrophy in the pathogenesis of chronic kidney disease progression. (United States)

    Schelling, Jeffrey R


    The longstanding focus in chronic kidney disease (CKD) research has been on the glomerulus, which is sensible because this is where glomerular filtration occurs, and a large proportion of progressive CKD is associated with significant glomerular pathology. However, it has been known for decades that tubular atrophy is also a hallmark of CKD and that it is superior to glomerular pathology as a predictor of glomerular filtration rate decline in CKD. Nevertheless, there are vastly fewer studies that investigate the causes of tubular atrophy, and fewer still that identify potential therapeutic targets. The purpose of this review is to discuss plausible mechanisms of tubular atrophy, including tubular epithelial cell apoptosis, cell senescence, peritubular capillary rarefaction and downstream tubule ischemia, oxidative stress, atubular glomeruli, epithelial-to-mesenchymal transition, interstitial inflammation, lipotoxicity and Na(+)/H(+) exchanger-1 inactivation. Once a a better understanding of tubular atrophy (and interstitial fibrosis) pathophysiology has been obtained, it might then be possible to consider tandem glomerular and tubular therapeutic strategies, in a manner similar to cancer chemotherapy regimens, which employ multiple drugs to simultaneously target different mechanistic pathways.

  1. Excessive daytime sleepiness in multiple system atrophy (SLEEMSA study)

    NARCIS (Netherlands)

    Moreno-Lopez, C.; Santamaria, J.; Salamero, M.; Del Sorbo, F.; Albanese, A.; Pellecchia, M.T.; Barone, P.; Overeem, S.; Bloem, B.R.; Aarden, W.C.C.A.; Canesi, M.; Antonini, A.; Duerr, S.; Wenning, G.K.; Poewe, W.; Rubino, A.; Meco, G.; Schneider, S.A.; Bhatia, K.P.; Djaldetti, R.; Coelho, M.; Sampaio, C.; Cochen, V.; Hellriegel, H.; Deuschl, G.; Colosimo, C.; Marsili, L.; Gasser, T.; Tolosa, E.


    BACKGROUND: Sleep disorders are common in multiple system atrophy (MSA), but the prevalence of excessive daytime sleepiness (EDS) is not well known. OBJECTIVE: To assess the frequency and associations of EDS in MSA. DESIGN: Survey of EDS in consecutive patients with MSA and comparison with patients

  2. Brain atrophy at onset and physical disability in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas


    Full Text Available The aim of this study was to investigate if brain atrophy in multiple sclerosis (MS patients during the disease onset predicts long term disability. METHODS: MS patients with follow-up time of at least 7 years from disease onset and with baseline and second magnetic resonance 12 months later were included to measure brain atrophy. Expanded Disability Status Scale (EDSS was categorized in three groups, EDSS=0, EDSS=1 and 2.5 and EDSS>2.5, and used as disability measure. RESULTS: Twenty-six patients were included. Mean atrophy during the first year in patients that reached an EDSS≥3 was -0.76±0.45 %, in patients with an EDSS between 1 and 2.5 was -0.59±0.56, while in patients with an EDSS of 0 it was -0.38±0.42 (p=0.003. DISCUSSION: Brain atrophy rates during the first year of disease were predictive of disease progression in our population.

  3. Prefrontal involvement related to cognitive impairment in progressive muscular atrophy

    NARCIS (Netherlands)

    Raaphorst, Joost; van Tol, Marie-José; Groot, Paul F C; Altena, Ellemarije; van der Werf, Ysbrand D; Majoie, Charles B; van der Kooi, Anneke J; van den Berg, Leonard H; Schmand, Ben; de Visser, Marianne; Veltman, Dick J


    OBJECTIVE: To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS). METHODS: fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in

  4. Prefrontal involvement related to cognitive impairment in progressive muscular atrophy

    NARCIS (Netherlands)

    J. Raaphorst; M.J. van Tol; P.F.C. Groot; E. Altena; Y.D. van der Werf; C.B. Majoie; A.J. van der Kooi; L.H. van den Berg; B. Schmand; M. de Visser; D.J. Veltman


    Objective: To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS). Methods: fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in

  5. Epidural anaesthesia in a child with possible spinal muscular atrophy

    NARCIS (Netherlands)

    Veen, A; Molenbuur, B; Richardson, FJ


    Spinal muscular atrophy (SMA) is a rare lower motor neurone disease in which anaesthetic management is often difficult as a result of muscle weakness and hypersensitivity to neuromuscular blocking agents. Neuraxial anaesthesia is controversial in these patients; however, some cases have been reporte

  6. [Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer]. (United States)

    Yamamoto, Mari; Ikeda, Masahiko; Kubo, Shinichiro; Tsukioki, Takahiro; Nakamoto, Shougo


    We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

  7. Longitudinal assessment of global and regional atrophy rates in Alzheimer's disease and dementia with Lewy bodies

    Directory of Open Access Journals (Sweden)

    Elijah Mak


    Conclusions: AD showed a faster rate of global brain atrophy compared to DLB, which had similar rates of atrophy to HC. Among dementia subjects, younger age was associated with accelerated atrophy, reflecting more aggressive disease in younger people. PBVC could aid in differentiating between DLB and AD, however its utility as an outcome marker in DLB is limited.

  8. Electromyogram and pathological features of adult spinal muscle atrophy:analysis of 46 cases%成人型脊髓性肌萎缩症46例电生理与病理变化

    Institute of Scientific and Technical Information of China (English)

    张平; 何晓军; 陈立晔


    AIM: To study the electromyogram and muscular pathological features of adult spinal muscular atrophy(SMA4). METHODS: 46 cases of SMA4 were evaluated based on clinical, histopathology, enzyme histochemistry and ultrastructure. RESULTS: A mean age of the patients with SMA4 was 38.7 years, clinical progressed was slowly. Clinic manifestations mainly appeared proximal muscular weakness and progressive muscular atrophy, and there was a relatively good prognosis. Laboratory found: one-fourth of the disease had elevated serum creatine kinase levels. Eletromyogram revealed neurogenic damages. The muscular pathological changes showed small groups of atrophy of denervation, ATPase reaction showed fibre-type grouping of renervation and hypertrophy in muscle fibers. CONCLUSION: Muscle biopsy was important; it could to help to establish to diagnose the disorder and provided available cases for gene study.

  9. Prevalence of brain atrophy in dogs submitted to cranial tomography in FMVZ - UNESP Botucatu: retrospective study; Prevalencia de atrofia cerebral em caes submetidos a tomografia craniana na FMVZ - UNESP Botucatu: estudo retrospectivo

    Energy Technology Data Exchange (ETDEWEB)

    Babicsak, Viviam Rocco; Belotta, Alexandra Frey; Oliveira, Hugo Salvador de; Zardo, Karen Maciel; Santos, Debora Rodrigues dos; Mamprim, Maria Jaqueline; Machado, Vania Maria de Vasconcelos; Vulcano, Luiz Carlos, E-mail: [Universidade Estadual Paulista Julio de Mesquita Filho (FMVZ/UNESP), Botucatu, SP (Brazil). Faculdade de Medicina Veterinaria e Zootecnia . Dept. de Reproducao Animal e Radiologia Veterinaria


    Brain atrophy is diagnosed by imaging methods that allow the verification of the widening of cerebral sulci and ventricular dilatation. In this retrospective study, in which the cranial CT scans of 150 dogs were evaluated, brain atrophy was identified in 16 animals. Mixed breed dogs were the most affected, followed by poodles, maltese, dachshunds, yorkshires, pinschers and cockers. Brain atrophy was observed in animals of all age groups, being more prevalent in middle aged dogs followed by elderly animals, in which this alteration can be commonly found. The identification of reduced brain volume, however, may not be the cause of neurological signs expressed by animals since in some dogs of this study it was considered a finding. (author)

  10. Choroidal atrophy in a patient with paraneoplastic retinopathy and anti-TRPM1 antibody

    Directory of Open Access Journals (Sweden)

    Ueno S


    Full Text Available Shinji Ueno,1 Yasuki Ito,1 Ruka Maruko,1 Mineo Kondo,2 Hiroko Terasaki1 1Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, 2Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Japan Abstract: The purpose of this paper is to report choroidal atrophy in a patient with cancer-associated retinopathy who had autoantibodies against the transient receptor potential cation channel, subfamily M, member 1 (TRPM1. A 69-year-old man visited our clinic in July 2010 with complaints of blurred vision and night blindness in both eyes. The full-field electroretinograms were negative type, indicating ON bipolar cell dysfunction. General physical examination revealed small cell carcinoma of the lung, and Western blot of the patient's serum showed autoantibodies against TRPM1. We diagnosed this patient with cancer-associated retinopathy and retinal ON bipolar dysfunction due to anti-TRPM1 autoantibody. We followed him for more than 2 years from the initial visit and his symptoms have not changed. However, consistent with the choroidal hypopigmentation of the fundus, spectral domain optical coherence tomography showed a decrease in choroidal thickness of about one third over a 2-year follow-up period. We suggest that this case of gradually progressive choroidal atrophy was caused by the autoantibody against TRPM1 directly, because TRPM1 is expressed not only on ON bipolar cells but also on melanocytes. These findings indicate that we should be aware of choroidal thickness in patients with paraneoplastic retinopathy who have retinal ON bipolar dysfunction with the anti-TRPM1 antibody. Keywords: choroidal thickness, melanocyte, TRPM1, cancer-associated retinopathy, paraneoplastic retinopathy

  11. Exercise training reverses skeletal muscle atrophy in an experimental model of VCP disease.

    Directory of Open Access Journals (Sweden)

    Angèle Nalbandian

    Full Text Available The therapeutic effects of exercise resistance and endurance training in the alleviation of muscle hypertrophy/atrophy should be considered in the management of patients with advanced neuromuscular diseases. Patients with progressive neuromuscular diseases often experience muscle weakness, which negatively impact independence and quality of life levels. Mutations in the valosin containing protein (VCP gene lead to Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD and more recently affect 2% of amyotrophic lateral sclerosis (ALS-diagnosed cases.The present investigation was undertaken to examine the effects of uphill and downhill exercise training on muscle histopathology and the autophagy cascade in an experimental VCP mouse model carrying the R155H mutation. Progressive uphill exercise in VCP(R155H/+ mice revealed significant improvement in muscle strength and performance by grip strength and Rotarod analyses when compared to the sedentary mice. In contrast, mice exercised to run downhill did not show any significant improvement. Histologically, the uphill exercised VCP(R155H/+ mice displayed an improvement in muscle atrophy, and decreased expression levels of ubiquitin, P62/SQSTM1, LC3I/II, and TDP-43 autophagy markers, suggesting an alleviation of disease-induced myopathy phenotypes. There was also an improvement in the Paget-like phenotype.Collectively, our data highlights that uphill exercise training in VCP(R155H/+ mice did not have any detrimental value to the function of muscle, and may offer effective therapeutic options for patients with VCP-associated diseases.

  12. Cobalt triggers necrotic cell death and atrophy in skeletal C2C12 myotubes

    Energy Technology Data Exchange (ETDEWEB)

    Rovetta, Francesca [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Stacchiotti, Alessandra [Institute of Human Anatomy, Department of Clinical and Experimental Sciences, University of Brescia, Brescia I-25123 (Italy); Faggi, Fiorella [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Catalani, Simona; Apostoli, Pietro [Unit of Occupational Health and Industrial Hygiene, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia I-25123 (Italy); Fanzani, Alessandro, E-mail: [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Aleo, Maria Francesca, E-mail: [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy)


    Severe poisoning has recently been diagnosed in humans having hip implants composed of cobalt–chrome alloys due to the release of particulate wear debris on polyethylene and ceramic implants which stimulates macrophagic infiltration and destroys bone and soft tissue, leading to neurological, sensorial and muscular impairments. Consistent with this premise, in this study, we focused on the mechanisms underlying the toxicity of Co(II) ions on skeletal muscle using mouse skeletal C2C12 myotubes as an in vitro model. As detected using propidium iodide incorporation, increasing CoCl{sub 2} doses (from 5 to 200 μM) affected the viability of C2C12 myotubes, mainly by cell necrosis, which was attenuated by necrostatin-1, an inhibitor of the necroptotic branch of the death domain receptor signaling pathway. On the other hand, apoptosis was hardly detectable as supported by the lack of caspase-3 and -8 activation, the latter resulting in only faint activation after exposure to higher CoCl{sub 2} doses for prolonged time points. Furthermore, CoCl{sub 2} treatment resulted in atrophy of the C2C12 myotubes which was characterized by the increased expression of HSP25 and GRP94 stress proteins and other typical 'pro-atrophic molecular hallmarks, such as early activation of the NF-kB pathway and down-regulation of AKT phosphorylation, followed by the activation of the proteasome and autophagy systems. Overall, these results suggested that cobalt may impact skeletal muscle homeostasis as an inducer of cell necrosis and myofiber atrophy. - Highlights: • The effects of cobalt on muscle myofibers in vitro were investigated. • Cobalt treatment mainly causes cell necrosis in skeletal C2C12 myotubes. • Cobalt impacts the PI3K/AKT and NFkB pathways and induces cell stress markers. • Cobalt induces atrophy of C2C12 myotubes through the activation of proteasome and autophagy systems. • Co treatment triggers NF-kB and PI3K/AKT pathways in C2C12 myotubes.

  13. Plasma clusterin concentration is associated with longitudinal brain atrophy in mild cognitive impairment. (United States)

    Thambisetty, Madhav; An, Yang; Kinsey, Anna; Koka, Deepthi; Saleem, Muzamil; Güntert, Andreas; Kraut, Michael; Ferrucci, Luigi; Davatzikos, Christos; Lovestone, Simon; Resnick, Susan M


    Recent genetic and proteomic studies demonstrate that clusterin/apolipoprotein-J is associated with risk, pathology, and progression of Alzheimer's disease (AD). Our main aim was to examine associations between plasma clusterin concentration and longitudinal changes in brain volume in normal aging and mild cognitive impairment (MCI). A secondary objective was to examine associations between peripheral concentration of clusterin and its concentration in the brain within regions that undergo neuropathological changes in AD. Non-demented individuals (N=139; mean baseline age 70.5 years) received annual volumetric MRI (912 MRI scans in total) over a mean six-year interval. Sixteen participants (92 MRI scans in total) were diagnosed during the course of the study with amnestic MCI. Clusterin concentration was assayed by ELISA in plasma samples collected within a year of the baseline MRI. Mixed effects regression models investigated whether plasma clusterin concentration was associated with rates of brain atrophy for control and MCI groups and whether these associations differed between groups. In a separate autopsy sample of individuals with AD (N=17) and healthy controls (N=4), we examined the association between antemortem clusterin concentration in plasma and postmortem levels in the superior temporal gyrus, hippocampus and cerebellum. The associations of plasma clusterin concentration with rates of change in brain volume were significantly different between MCI and control groups in several volumes including whole brain, ventricular CSF, temporal gray matter as well as parahippocampal, superior temporal and cingulate gyri. Within the MCI but not control group, higher baseline concentration of plasma clusterin was associated with slower rates of brain atrophy in these regions. In the combined autopsy sample of AD and control cases, representing a range of severity in AD pathology, we observed a significant association between clusterin concentration in the plasma and

  14. Comparative analysis of two and three marker immunohistochemical cocktails in the diagnosis of prostata carcinoma

    DEFF Research Database (Denmark)

    Dabir, Parag Deepak; Ottosen, Peter; Hamilton-Dutoit, Stephen Jacques;


    Comparative analysis of two and three marker immunohistochemical cocktails in the diagnosis of prostata carcinoma......Comparative analysis of two and three marker immunohistochemical cocktails in the diagnosis of prostata carcinoma...

  15. Comparative analysis of two and three marker immunohistochemical cocktails in the diagnosis of prostata carcinoma

    DEFF Research Database (Denmark)

    Dabir, Parag Deepak; Ottosen, Peter; Hamilton-Dutoit, Stephen Jacques;


    Comparative analysis of two and three marker immunohistochemical cocktails in the diagnosis of prostata carcinoma......Comparative analysis of two and three marker immunohistochemical cocktails in the diagnosis of prostata carcinoma...

  16. Challenges in diagnosing hepatic encephalopathy. (United States)

    Weissenborn, K


    The term "hepatic encephalopathy" (HE) covers the neuropsychiatric syndrome associated with acute, chronic and acute-on-chronic liver disease (CLD). This paper deals with clinical features and diagnosis of HE in patients with liver cirrhosis and portal hypertension or porto-systemic shunts. The possible impact of concomitant disorders and the cirrhosis underlying liver disease upon brain function is described emphasizing the need of a detailed diagnostic work up of every individual case before diagnosing HE. Currently used methods for diagnosing minimal or covert hepatic encephalopathy are compared with regard to their sensitivity and specificity for diagnosing HE against the background of a multitude of concomitant disorders and diseases that could contribute to brain dysfunction.

  17. Nursing diagnoses in overweight adolescents

    Directory of Open Access Journals (Sweden)

    Raphaela Santos do Nascimento Rodrigues


    Full Text Available This study aimed to identify nursing diagnoses in overweight adolescents from public schools, according to the International Classification for Nursing Practice. A population-based cross-sectional study that investigated the socio-demographic, behavioural and psychological characteristics of adolescents aged from 10 to 14 years. 11 nursing diagnoses were identified: "Risk of overweight", "Risk of impaired adolescent development", "Risk of insecurity in parental role performance", "Risk of the family impaired ability to manage diet regime", "Risk of impaired ability to manage diet regime", "Risk of lack of knowledge of dietary regime", "Risk of excess food intake", "Risk of negative self-image", "Risk of low self-esteem", "Risk of impaired social well-being" and "Impaired exercise pattern". These diagnoses reflect the multifactorial nature of obesity, highlighting the need for interdisciplinary and intersectoral articulation of nursing interventions for prevention and control of overweight.

  18. Factors Associated with Changes in Brain Atrophy during a Three-Year Observation in Elderly Diabetic Patients: Effect of Renal Impairment on Hippocampal Atrophy

    Directory of Open Access Journals (Sweden)

    Takahiko Kawamura


    Full Text Available Background/Aims: We conducted a 3-year longitudinal study concerning factors associated with changes in brain atrophy in elderly diabetic patients. Methods: We evaluated hippocampal and global brain atrophy using automatic voxel-based morphometry of structural magnetic resonance images, 4 cognitive function tests, and cerebral small vessel disease (SVD in 66 diabetic patients. Results: During the 3-year follow-up, hippocampal and global brain atrophy advanced, and cognitive functions worsened. For changes in hippocampal atrophy, changes in estimated glomerular filtration rate (eGFR, albuminuria, and being an ApoE ε4 carrier were independent factors; change in the number of silent brain infarctions was an independent factor for changes in global brain atrophy. A significant association of changes in eGFR and albuminuria with hippocampal atrophy remained after adjusting for confounders including SVD. Both types of brain atrophy at baseline were significantly correlated with cognitive impairment at baseline and especially associated with changes in delayed word recall during the follow-up after adjusting for confounders. Conclusion: Changes in eGFR and albuminuria during follow-up were independent risk factors for hippocampal atrophy, which was associated with decline in delayed word recall, suggesting that management of chronic kidney disease may prevent the progression of hippocampal atrophy.

  19. Immunological methods for diagnosing neurocysticercosis

    Energy Technology Data Exchange (ETDEWEB)

    Kuhn, R.E.; Estrada, J.J.; Grogl, M.


    A method is described for diagnosing active human neurocysticercosis by detecting the presence of at least one Taenia solium larval antigen in cerebrospinal fluid, which comprises: contacting cerebrospinal fluid from a human to be diagnosed with a solid support, wherein the support binds with a Taenia solium larval antigen if present, contacting the support with a first antibody, wherein the first antibody binds with a larval Taenia solium antigen if present in the cerebrospinal fluid, contacting the solid support with a detectable second antibody which will bind with the first antibody, and detecting the second antibody bound to the support.

  20. Retrospective canine skin peripheral nerve sheath tumors data with emphasis on histologic, immunohistochemical and prognostic factors

    Directory of Open Access Journals (Sweden)

    Gisele S. Boos


    Full Text Available Abstract: In this retrospective study was determined the frequency of canine skin peripheral nerve sheath tumors (PNST in cases diagnosed by the Setor de Patologia Veterinária of the Universidade Federal do Rio Grande do Sul (SPV-UFRGS, Brazil, between the years 2000 and 2012. The canine profiles, as well as histological, immunohistochemical and prognostic aspects of the tumors were based on 70 samples, comprising 40 females, 29 males and one unspecified sample. Between 2000 and 2012, 2,984 skin tumors of dogs were diagnosed in the SPV-UFRGS, totaling 2.34% of skin neoplasms in dogs. Animals that comprised the largest amount of samples (43% were those with no breed (SRD, followed by German Shepherds (10%. Females were more affected than males (40/70 - 57% and 29/70 - 41% respectively. Skin PNST of this research showed predominant localization on the limbs (40% in the forelimbs and 29% in the hindlimbs; affecting adult dogs, mostly aged between 8 and 11 years (54%. The samples were routinely processed for hematoxylin and eosin, and were also evaluated by toluidine blue and Masson's trichrome staining, and immunohistochemistry (IHC anti-vimentin, -S-100, -GFAP, -actin, von Willebrand factor and neurofilament. Anisocytosis and anisokaryosis, mitotic index, intratumoral necrosis, invasion of adjacent tissues, tumor location, local recurrence and metastasis were related to the diagnosis of benign (49/70 or malignant tumor (21/70. The Antoni A histological pattern was observed more frequently in benign tumors. The immunohistochemistry helped to diagnose PNST, and anti-vimentin and anti-protein S-100 showed the highest rates of immunostaining. Throughout statistical analysis of animals with tumor recurrence, it was found that the chance of an animal with a malignant peripheral nerve sheath tumor to develop recurrence is 4.61 times higher than in an animal that had a benign tumor.

  1. Papillary squamotransitional cell carcinoma of the uterine cervix: A histomorphological and immunohistochemical study of nine cases

    Directory of Open Access Journals (Sweden)

    Mani Anand


    Full Text Available Background: Papillary squamotransitional cell carcinoma (PSCC is a distinctive subcategory of squamous cell carcinoma of the uterine cervix. It has a propensity for local recurrence and late metastasis. Histologically, it can be misinterpreted as transitional cell carcinoma, or other papillary lesions of the cervix including squamous papilloma, verrucous carcinoma or cervical intraepithelial neoplasia grade 3 with papillary configuration. Materials and Methods: Nine cases of PSCC of the uterine cervix were diagnosed on a cervical biopsy specimen on routine hematoxylin and eosin (H and E stained sections. Their clinic-morphological features were analyzed. The cases were further evaluated immunohistochemically by cytokeratin 7 (CK7, cytokeratin 20 (CK20, p53 and Ki-67. Results: The patients ranged in age from 35 years to 75 years; with abnormal uterine bleeding being the most common clinical presentation. All the cases showed papillary architecture with fibrovascular cores lined by multilayered atypical epithelium. Three cell types were observed: Clear, intermediate and basaloid. Stromal invasion was seen in five cases, whereas in the remaining four cases, the biopsy specimen was too superficial to definitely assess invasion. Immunohistochemically, eight cases were CK7 + /CK20 - and one case was CK7 - /CK20 - . All nine cases showed nuclear accumulation of mutant p53. Moderate and high proliferative activity was observed in two and seven cases, respectively. Five of patients for whom follow-up information was available underwent radical hysterectomy and two of them were disease free 18 months following treatment. Conclusion: PSCC of the uterine cervix are a clinicomorphologically distinct group of cervical lesions that display a morphologic spectrum. They are potentially aggressive malignant tumors that should be distinguished from transitional cell carcinoma and other papillary lesions of the uterine cervix.

  2. Neuropsychological evaluation in an adolescent with cerebellar hypoplasia diagnosed with Asperger's Syndrome. (United States)

    Moss, Robert A


    There is a growing body of literature describing cases of cognitive impairment associated with both acquired and developmental damage to the cerebellum. The current case study describes such a case involving a 17-year-old male with cerebellar hypoplasia, having incomplete formation of the vermis and atrophy of the interior cerebellar hemispheres. He had previously been diagnosed as having Asperger's Syndrome. A full neuropsychological evaluation was performed, including effort testing. This is followed by a comparison of the current results to previously reported cases, with a discussion of the heterogeneity of deficits associated with developmental cerebellum malformation.

  3. Dynamic Foot Pressure as a Countermeasure to Muscle Atrophy (United States)

    Kyparos, A.; Layne, C. S.; Martinez, D. A.; Clarke, M. S. F.; Feeback, D. L.


    Mechanical unloading of skeletal muscle (SKM) as a consequence of space flight or ground-based analogues, such as human bedrest and rodent hindlimb suspension (HLS) models, induces SKM atrophy particularly affecting the anti-gravity musculature of the lower limbs. In the context of manned space flight, the subsequent loss of muscle strength and functionality will pose operational implications jeopardizing mission success. Exercise, currently the primary muscle degradation countermeasure, has not proven completely effective in preventing muscle atrophy. It is therefore imperative that some other forms of in- flight countermeasure be also developed to supplement the prescribed exercise regimen the astronauts follow during spaceflight. Previous work in both humans and rats has shown that mechanical stimulation of the soles of the feet increases neuromuscular activation in the lower limb musculature and that such stimulation results in the limited prevention of atrophy in the soleus muscle of unloaded rats. This study was designed to investigate the effect of cutaneous mechanoreceptor stimulation on hindlimb unloading- induced SKM atrophy in rats. It was hypothesized that mechanical stimulation of the plantar surface of the rat foot during hindlimb suspension (HLS), utilizing a novel stimulation paradigm known as Dynamic Foot Pressure (DFP), would attenuate unloading-induced SKM atrophy. Mature adult male Wistar rats were randomly assigned to four groups of 10 rats each as follows: sedentary controls (Ctrl), hindlimb suspended only (HLS), hindlimb suspended wearing an inflatable boot (HLS-IFL) and hindlimb suspended rats wearing a non-inflatable boot (HLS-NIFL). The stimulation of mechanoreceptors was achieved by applying pressure to the plantar surface of the foot during the 10-day period of HLS using a custom-built boot. The anti-atrophic effects of DFP application was quantified directly by morphological (muscle wet weight, myofiber cross-sectional area

  4. The role of immunohistochemical analysis in the diagnosis of parapsoriasis. (United States)

    Bordignon, Matteo; Belloni-Fortina, Anna; Pigozzi, Barbara; Saponeri, Andrea; Alaibac, Mauro


    Parapsoriasis is a chronic dermatosis whose biological distinction from early mycosis fungoides, the most frequent form of cutaneous T-cell lymphoma, is still not clearly defined. Two types of parapsoriasis have been delineated: large-plaque parapsoriasis and small-plaque parapsoriasis. The lack of clinical and histological features, which may allow distinguishing parapsoriasis from early mycosis fungoides has prompted several investigations to assess the role of immunohistochemistry in establishing a conclusive diagnosis of these conditions. However, the additional data obtained by immunohistochemical analysis concerning the CD4/CD8 ratio, the aberrant expression of T-cell antigens and the expression of proliferation markers has not generally helped establish a more definitive diagnosis. This review critically discusses these immunohistochemical markers and their use in diagnosis of parapsoriasis.

  5. Delineation of Chondroid Lipoma: An Immunohistochemical and Molecular Biological Analysis

    Directory of Open Access Journals (Sweden)

    Ronald S. A. de Vreeze


    Full Text Available Aims. Chondroid lipoma (CL is a benign tumor that mimics a variety of soft tissue tumors and is characterized by translocation t(11;16. Here, we analyze CL and its histological mimics. Methods. CL (n=4 was compared to a variety of histological mimics (n=83 for morphological aspects and immunohistochemical features including cyclinD1(CCND1. Using FISH analysis, CCND1 and FUS were investigated as potential translocation partners. Results. All CLs were strongly positive for CCND1. One of 4 myoepitheliomas, CCND1, was positive. In well-differentiated lipomatous tumors and in chondrosarcomas, CCND1 was frequently expressed, but all myxoid liposarcomas were negative. FISH analysis did not give support for direct involvement of CCND1 and FUS as translocation partners. Conclusions. Chondroid lipoma is extremely rare and has several and more prevalent histological mimics. The differential diagnosis of chondroid lipomas can be unraveled using immunohistochemical and molecular support.

  6. Cartilage canals in newborn dogs: histochemical and immunohistochemical findings

    Directory of Open Access Journals (Sweden)

    A. Di Giancamillo


    Full Text Available Cartilage canals (CCs are microscopic structures involved in secondary ossification centers (SOCs development. The features of CCs were investigated in the humeral and femoral proximal epiphyses of small-sized newborn dogs (from premature to 28 days after birth with histochemical and immunohistochemical approaches. Masson’s Trichrome revealed a ring-shaped area around CCs, which changes in colour from green (immature collagen to red (mature collagen as ossification progresses; perichondrium staining always matched the ring colour. Safranin-O was always negative. Immunohistochemical analysis revealed immunopositivity for both collagen type I and V around the CCs; collagen type II was negative. CCs count showed a tendency to be higher in the humerus than in the femur. This work enlightened for the first time changes in composition of CCs surrounding matrix during SOCs development in dogs, paving the way to further investigations.

  7. Pituitary carcinoma diagnosed on fine needle aspiration: Report of a case and review of pathogenesis

    Directory of Open Access Journals (Sweden)

    Yakoushina Tatiana


    Full Text Available Pituitary carcinoma (PC is a very rare entity (0.2% of all pituitary tumors, with only about 140 cases reported in English literature. There are no reliable histological, immunohistochemical or ultrastructural features distinguishing pituitary adenoma (PA from PC. By definition, a diagnosis of PC is made after a patient with PA develops non-contiguous central nervous system (CNS or systemic metastases. To date, only three cases of PC have been reportedly diagnosed on fine needle aspiration (FNA. Two of the reported cases were diagnosed on FNA of the cervical lymph nodes and one on FNA of the vertebral bone lesion. Herein, we present a case of PC, diagnosed on FNA of the liver lesion. In this case, we describe cytologic features of PC and compare them to histologic features of the tumor in the pituitary. Clinical behavior of tumor, pathogenesis of metastasis and immunochemical and prognostic markers will also be described.

  8. How Is Fanconi Anemia Diagnosed? (United States)

    ... from the NHLBI on Twitter. How Is Fanconi Anemia Diagnosed? People who have Fanconi anemia (FA) are born with the disorder. They may ... questions about: Any personal or family history of anemia Any surgeries you’ve had related to the ...

  9. The immunohistochemical characterization of sarcomatoid malignant mesothelioma of the pleura. (United States)

    Chirieac, Lucian R; Pinkus, Geraldine S; Pinkus, Jack L; Godleski, John; Sugarbaker, David J; Corson, Joseph M


    The immunohistochemical characteristics of epithelioid malignant mesothelioma are well described. However, immunohistochemical analyses of sarcomatoid mesothelioma, the less common type, are limited and its distinction from other tumors of the chest wall, lung and pleura is often problematic. We evaluated 24 patients with pleural sarcomatoid mesothelioma who had surgery (12 extrapleural pneumonectomies, 9 pleurectomies and 3 large biopsies) between 1989 and 2005. Clinicopathologic features and demographic data were recorded. We describe immunohistochemical results for 10 antibodies: AE1/AE3, CAM5.2 and MNF-116 keratins, calretinin, WT-1 protein, bcl-2, CD34, desmin, D2-40 and podoplanin. The patients were 23 men and one woman with a median age at diagnosis of 64.7 years (range 47 to 76). Tumor cells were positive for the keratin proteins AE1/AE3 in 18/24 cases, CAM 5.2 in 23/24 cases and MNF-116 in 21/21 cases. Calretinin was positive in 6/24 cases, WT-1 (nuclear) in 8/24 cases, bcl-2 in 0/24 cases, CD34 in 0/24 cases, desmin in 0/24 cases, D2-40 in 24/24 cases and podoplanin in 24/24 cases. This panel of antibodies may be helpful in establishing a pathologic diagnosis of sarcomatoid mesothelioma. In our study, D2-40 and podoplanin are highly sensitive immunohistochemical markers for sarcomatoid mesothelioma. Additional studies are required to define their role in the differential diagnosis of other spindle cell tumors.

  10. Epithelial ovarian tumors: Clinicopathological correlation and immunohistochemical study



    Background: Ovarian cancer is the third leading site of cancer among women, trailing behind cervix and breast cancer. Aim: This study was undertaken to analyze the immunohistochemical (IHC) profile of estrogen receptors (ER), progesterone receptors (PR), Ki-67, and p53 in various ovarian epithelial tumors and attempt correlation with clinical and histopathological findings. Materials and Methods: The present study was conducted over a period of 4 years. A technique of manual tissue ar...

  11. Endogenous avidin biotin activity (EABA in thyroid pathology: immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Nikiel Barbara


    Full Text Available Abstract Background Immunohistochemical methods based on the high affinity of avidin and biotin (e.g. ABC, LSAB are characterized by high sensitivity and are widely used for detection of immunologic reaction. However, a non-specific reaction, observed in frozen tissues and in paraffin-embedded material, increasing after heat induced epitope retrieval (HIER, and caused either by endogenous biotin or any another chemical compound with high affinity for avidin, may lead to diagnostic mistakes. The aim of our investigation is to study presence of endogenous avidin biotin activity (EABA in thyrocytes originating from various thyroid pathological lesions (neoplastic and non-neoplastic. Materials and methods The immunohistochemical study was performed on paraffin-embedded specimens of surgically resected thyroid tissue from 97 patients with thyroid diseases: 65 patients with papillary carcinoma (PTC, 11 patients with nodular goiter in whom features of benign papillary hyperplasia were found, 9 with lymphocytic thyroiditis (LT, 8 with follicular adenoma, and 4 patients with follicular carcinoma. In PTC immunohistochemical study was performed both in primary tumors and in lymph node metastases. After HIER, incubation with streptavidin from LSAB+ (DakoCytomation kit was done. Results Strong cytoplasmic EABA was observed in 56 of 65 (87.5% PTC and in oxyphilic cells in 8 of 9 cases of LT. Significant correlation between EABA in primary PTC tumor and EABA in lymph node metastases was stated. Normal surrounding thyroid tissues showed absence or weak EABA. Aberrant intranuclear localization of biotin was noted in morules of cribriform-morular variant of PTC. No statistically significant correlation between patient's age, sex, metastases presence and EABA was observed. Conclusion Among thyroid lesions, false positive reactions are highly probable in papillary thyroid carcinoma and in lymphocytic thyroiditis if immunohistochemical detection is used on systems

  12. Dendritic cells in melanoma - immunohistochemical study and research trends. (United States)

    Nedelcu, Roxana Ioana; Ion, Daniela Adriana; Holeab, Cosmin Adrian; Cioplea, Mirela Daniela; Brînzea, Alice; Zurac, Sabina Andrada


    Cutaneous dendritic cells play multiple physiological roles and are involved in various pathophysiological processes. Research studies of dendritic cells abound in the medical literature. Nevertheless, the role of dendritic cells in melanoma regression phenomenon is not completely understood. We conducted a scientometric analysis in order to highlight the current state on research regarding dendritic cells and melanoma. We also performed an immunohistochemical study, using specific markers for dendritic cells (CD1a, langerin). We evaluated the frequency and distribution of dendritic cells in areas of tumor regression compared to the areas of inflammatory infiltrate of melanoma without regression. The immunohistochemical study we performed revealed that dendritic cells are more frequent in the regressed areas, comparing with non-regressed ones. In regressed areas, dendritic cells have a predominant nodular pattern (19 cases), followed by diffuse isolate pattern (eight cases) and mixed pattern (diffuse and nodular) (three cases). In melanoma without regression, most cases presented a diffuse pattern (27 cases) of dendritic cells distribution. In conclusion, our immunohistochemical study stressed differences between frequency and distribution of dendritic cells located in the melanoma with regression and melanoma without regression. These data suggest that dendritic cells are involved in the regression phenomenon. Following the literature analysis we obtained, we observed that dendritic cells profile in melanoma with regression was poorly studied. Insights into antitumor immune response and dendritic cells may be essential for the understanding of the potential prognostic role of dendritic cells in melanoma and for the development of new promising therapeutic strategies for melanoma.


    Institute of Scientific and Technical Information of China (English)

    朱雪琼; 石一复; 陈晓端; 吴裕中


    Objective: To evaluate the diagnostic implications of immunohistochemical markers in uterine smooth muscle tumors. Methods: Formalin-fixed paraffin-embedded tissue blocks were selected from 17 uterine leiomyosarcomas, 40 uterine unusual leiomyomas and 25 uterine usual leiomyomas. Utilizing immunohistochemical techniques with antigen retrieval, serial sections of each tumor for immunoreactivity with myogenic markers, ovarian steroid receptors, CD44v3, proliferating cell nuclear antigen and mast cells were assessed. Results: Although the myogenic markers and CD44v3 showed less frequent positivity in uterine leiomyosarcomas than those in unusual leiomyomas, they were not reliable markers for differentiating leiomyosarcoma from leiomyoma. Uterine leiomyosarcoma tended to have lower ovarian steroid receptors immunoreactivity rates than leiomyoma. Leiomyoma tended to have a higher quantity of intratumoral mast cells than leiomyosarcoma, while the expression of proliferating cell nuclear antigen was lower in them. Conclusion: Because the estimation of mitotic count was subject to significant variation, the immunohistochemical expression of ovarian steroid receptors, mast cells and proliferating cell nuclear antigen seemed to be helpful for the discrimination of unusual leiomyoma from leiomyosarcoma.

  14. Immunohistochemical investigation of the coma blister and its pathogenesis. (United States)

    Kashiwagi, Masayuki; Ishigami, Akiko; Hara, Kenji; Matsusue, Aya; Waters, Brian; Takayama, Mio; Tokunaga, Itsuo; Nishimura, Akiyoshi; Kubo, Shin-ichi


    The erythematous patches and vesicles that are observed in coma patients, usually from an overdose of medication, are known as coma blisters. However, it is unknown whether the degenerated sweat gland is a necrosis or apoptosis. We immunohistochemically examined such skin lesions to investigate the characteristics and pathogenesis of the coma blister. Skin lesions were obtained from a forensic autopsy case, a woman in her thirties, of caffeine intoxication. Those lesions were observed in the left femoral, the lower left thigh, and the right knee. Histologically, the skin lesions showed that the keratinocytes had necrosed and the epidermis was thin in some areas. Eccrine sweat gland degeneration was observed. Obvious inflammatory cell infiltrations were not detected. Immunohistochemically, we stained each skin lesion against CD3, CD8, CD45RO, cytokeratin, 70 kD heat shock protein, ubiquitin, 150 kD oxygen regulated protein, and caspase-cleaved keratin 18 neo-epitope M30. They were also stained with an in situ apoptosis detection kit. Degenerated sweat glands featured CD45RO and M30 immunoreactivity. Immunohistochemical staining for CD45RO, CK-L, and M30 might be useful to observe sweat gland degeneration in the coma blister. Therefore, the apoptosis might be related to coma blisters and sweat gland degenerations.

  15. A simplified immunohistochemical classification of skeletal muscle fibres in mouse

    Directory of Open Access Journals (Sweden)

    M. Kammoun


    Full Text Available The classification of muscle fibres is of particular interest for the study of the skeletal muscle properties in a wide range of scientific fields, especially animal phenotyping. It is therefore important to define a reliable method for classifying fibre types. The aim of this study was to establish a simplified method for the immunohistochemical classification of fibres in mouse. To carry it out, we first tested a combination of several anti myosin heavy chain (MyHC antibodies in order to choose a minimum number of antibodies to implement a semi-automatic classification. Then, we compared the classification of fibres to the MyHC electrophoretic pattern on the same samples. Only two anti MyHC antibodies on serial sections with the fluorescent labeling of the Laminin were necessary to classify properly fibre types in Tibialis Anterior and Soleus mouse muscles in normal physiological conditions. This classification was virtually identical to the classification realized by the electrophoretic separation of MyHC. This immunohistochemical classification can be applied to the total area of Tibialis Anterior and Soleus mouse muscles. Thus, we provide here a useful, simple and time-efficient method for immunohistochemical classification of fibres, applicable for research in mouse

  16. Reduced immunohistochemical expression of adhesion molecules in vitiligo skin biopsies. (United States)

    Reichert Faria, Adriane; Jung, Juliana Elizabeth; Silva de Castro, Caio César; de Noronha, Lucia


    Because defects in adhesion impairment seem to be involved in the etiopathogenesis of vitiligo, this study aimed to compare the immunohistochemical expression of several adhesion molecules in the epidermis of vitiligo and non lesional vitiligo skin. Sixty-six specimens of lesional and non lesional skin from 33 volunteers with vitiligo were evaluated by immunohistochemistry using anti-beta-catenin, anti-E-cadherin, anti-laminin, anti-beta1 integrin, anti-collagen IV, anti-ICAM-1 and anti-VCAM-1 antibodies. Biopsies of vitiligo skin demonstrated a significant reduction in the expression of laminin and integrin. The average value of the immunohistochemically positive reaction area of the vitiligo specimens was 3053.2μm(2), compared with the observed value of 3431.8μm(2) in non vitiligo skin (p=0.003) for laminin. The immuno-positive area was 7174.6μm(2) (vitiligo) and 8966.7μm(2) (non lesional skin) for integrin (p=0.042). A reduction in ICAM-1 and VCAM-1 expression in the basal layer of the epidermis in vitiligo samples was also observed (p=0.001 and pskin. Our results suggest that an impairment in adhesion exists in vitiligo skin, which is supported by the diminished immunohistochemical expression of laminin, beta1 integrin, ICAM-1 and VCAM-1.

  17. Prostatic tissue in testicular teratoma. A clinicopathologic and immunohistochemical study. (United States)

    Roma, Andres A; Humphrey, Peter A


    The presence of prostatic differentiation as part of teratoma is very unusual and has been reported less than 20 times in the literature; however, all but 1 case were described in ovarian teratomas. We reviewed 45 specimens of germ cell tumors with teratoma component in postpuberal male patients. Original hematoxylin and eosin review failed to identify glands morphologically consistent with prostatic differentiation. Immunohistochemical stains performed on 10 specimens from 10 patients with small glandular and/or tubular structures revealed 1 case with glands positive for prostatic-specific antigen, prostatic-specific acid phosphatase, and prostein/P501S, whereas high-molecular-weight cytokeratin and p63 highlighted only basal cells. The glands were irregular in size and shape and contained mostly cuboidal to columnar luminal-type cells with occasional basal-type cells. Re-review of all the specimens revealed a second block from the same testis as well as 1 retroperitoneal lymph node with metastatic teratoma in the same patient, also immunohistochemically confirmed. These glands were seen in a smooth muscle stromal background, adjacent to classic gastrointestinal and tracheobronchial teratoma components. Our findings show immunohistochemically confirmed prostatic differentiation in 2 specimens from 1 patient with teratoma. This study raises the possibility that prostatic differentiation, difficult to recognize on morphology alone, might not be that unusual and that immunostains can help detect it over the several different epithelial components of teratoma.

  18. Spinal muscular atrophy: development and implementation of potential treatments. (United States)

    Arnold, W David; Burghes, Arthur H M


    In neurodegenerative disorders, effective treatments are urgently needed, along with methods to determine whether treatment worked. In this review, we discuss the rapid progress in the understanding of recessive proximal spinal muscular atrophy and how this is leading to exciting potential treatments of the disease. Spinal muscular atrophy is caused by loss of the survival motor neuron 1 (SMN1) gene and reduced levels of SMN protein. The critical downstream targets of SMN deficiency that result in motor neuron loss are not known. However, increasing SMN levels has a marked impact in mouse models, and these therapeutics are rapidly moving toward clinical trials. Promising preclinical therapies, the varying degree of impact on the mouse models, and potential measures of treatment effect are reviewed. One key issue discussed is the variable outcome of increasing SMN at different stages of disease progression.

  19. Neuro-Behcet's disease showing severe atrophy of the cerebrum. (United States)

    Miyakawa, T; Murayama, E; Deshimaru, M; Shikai, I; Kozuma, S


    A 38-year-old female died 6 years after the onset of what was, clinically and histopathologically, consistent with neuro-Behcet's disease. Pathologically the cerebrum showed severe atrophy. The main changes were observed in the grey and white matter, the diencephalon and the basal ganglia by light microscopy. All these changes originated in softenings around blood vessels, especially small vessels or capillaries. These foci fused together to form large regions of softening. Glial or mesenchymal reactions were minimal. In the white matter there was slight perivascular-infiltration, mainly consisting of lymphocytes. In view of these findings, it is suggested that these changes were caused by an allergic vasculitis. The present case of Neuro-Behcet's disease is the first one showing general atrophy of the cerebrum. It is very important in relation to demyelinating encephalitis.

  20. Neuroelectrophysiological indexes and clinical characteristics of patients with peroneal muscular atrophy: Retrospective analysis of 24 cases

    Institute of Scientific and Technical Information of China (English)

    Changchun Su; Qinbao Qin


    BACKGROUND: Peroneal muscular atrophy (PMA) is characterized by insidious onset, gradually progressive course of disease, very mild disability degree and easily subjecting to missed diagnosis and misdiagnosis.Nerve conductive velocity is helpful in the diagnosis of atypical cases.OBJECTIVE: To retrospectively analyze the characteristics of clinical manifestation, electromyogram (EMG),motor and sensory nerve conduction velocity of patients with PMA.DESIGN: Retrospective case analysis.SETTING: Department of Neurology, Guangzhou First People's Hospital.PARTICIPANTS: Twenty-four patients with PMA, including 16 males and 8 females, aged 5-68 years old,admitted to Guangzhou First People's Hospital between March 1996 and January 2006 were recruited.Informed consents were obtained from all the patients.METHODS: All the patients subjected to EMG and detection of nerve conduction velocity at distal end of four extremities with a Keypoint evoked potential/ EMG instrument (Denmark). Sensory and motor conduction velocity, EMG changes of upper and lower extremities were observed, and relationship of neuroelectrophysiological characteristics and clinical symptoms was analyzed.MAIN OUTCOME MEASURES: Changes in sensory and motor conduction velocity, EMG and clinical manifestations of 24 patients.RESULTS: ① All the patients suffered from insidious onset and gradually progressive course of PMA.Muscular atrophy of lower extremity was found in 14 patients, and that of upper extremity in 5 patients. ② Routine nerve conduction study showed that sensory and motor conduction velocity were stepped down,especially in 16 patients with type Ⅰ PMA (demyelinating pattern, nerve conduction velocity below normal level 50%). Motor nerve conduction velocity of median nerve, ulnar nerve, common peroneal nerve and tibial nerve averaged 34.8 m/s, 37.2 m/s, 16.5 m/s and 17.4 m/s, respectively; Sensory nerve conduction velocity of median nerve, ulnar nerve and sural nerve averaged 27.9%, 24.6 m

  1. Pathological and immunohistochemical studies of subclinical infection of chicken anemia virus in 4-week-old chickens. (United States)

    Haridy, Mohie; Sasaki, Jun; Ikezawa, Mitsutaka; Okada, Kosuke; Goryo, Masanobu


    Subclinical infection of chicken anemia virus (CAV) at 4 to 6 weeks of age, after maternal antibodies have waned, is implicated in several field problems in broiler flocks. In order to understand the pathogenesis of subclinical infection with CAV, an immunopathological study of CAV-inoculated 4-week-old SPF chickens was performed. Sixty 4-week-old SPF chickens were equally divided into CAV and control groups. The CAV group was inoculated intramuscularly with the MSB1-TK5803 strain of CAV. Neither mortality nor anemia was detected in the CAV and control groups. In the CAV group, no signs were observed, except that some chickens were grossly smaller compared with the control group. Sporadic thymus lobes appeared to be reddening and atrophied. Within the first two weeks p.i. of CAV, there was a mild to moderate depletion of lymphocytes in the thymus cortex and spleen in some chickens. Moreover, lymphoid depletion of the bursa of Fabricius, proventriculus and cecal tonsils was observed. Hyperplastic lymphoid foci were observed in the liver, lungs, kidneys and heart at the 4th week p.i. of CAV. Immunohistochemically, a moderate lymphoid depletion of CD4(+)and CD8(+) T cells in the thymus cortex and spleen was observed in some chickens within two weeks p.i. of CAV. CAV inclusions and antigens were detected infrequently in the thymus cortex and spleen. It could be concluded that the immunosuppression in subclinical infection with CAV occurs as a result of reduction of cellular immunity.

  2. [Association of post-radiation focal muscular atrophy and hypertrophy]. (United States)

    Serratrice, G; Sangla, I; Pouget, J; Azulay, J P


    We report a 48 year old woman who had radiotherapy for uterine carcinoma and who developed amyotrophy and muscle hypertrophy in one lower limb. Very few cases of post-radiation monomelic amyotrophy have been reported. On the other hand denervation hypertrophy was presumed to be well known. The seat of the lesions was presumed to be radicular and spinal. The mechanism of atrophy and hypertrophy is discussed.

  3. Serological assessment of gastric mucosal atrophy in gastric cancer

    Directory of Open Access Journals (Sweden)

    Bornschein Jan


    Full Text Available Abstract Background Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1 (PG1, pepsinogen 2 (PG2 and gastrin 17 (G17 offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia. Methods Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Laurén type, localisation, degree of mucosal abnormalities (intestinal metaplasia, atrophy and serological parameters (PG1, PG2, PG1/2-ratio, G17, H. pylori IgG, CagA status. Association of the general factors to the different serological values have been statistically analyzed. Results Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (p = 0.003. The serum levels of PG2 itself and G17 were not significantly altered. H. pylori infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (p = 0.058. The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p Conclusions Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer.

  4. Regulation of muscle atrophy in aging and disease. (United States)

    Vinciguerra, Manlio; Musaro, Antonio; Rosenthal, Nadia


    Muscle aging is characterized by a decline in functional performance and restriction of adaptability, due to progressive loss of muscle tissue coupled with a decrease in strength and force output. Together with selective activation ofapoptotic pathways, a hallmark of age-related muscle loss or sarcopenia is the progressive incapacity of regeneration machinery to replace damaged muscle. These characteristics are shared by pathologies involving muscle wasting, such as muscular dystrophies or amyotrophic lateral sclerosis, cancer and AIDS, all characterized by alterations in metabolic and physiological parameters, progressive weakness in specific muscle groups. Modulation ofextracellular agonists, receptors, protein kinases, intermediate molecules, transcription factors and tissue-specific gene expression collectively compromise the functionality of skeletal muscle tissue, leading to muscle degeneration and persistent protein degradation through activation ofproteolytic systems, such as calpain, ubiquitin-proteasome and caspase. Additional decrements in muscle growth factors compromise skeletal muscle growth, differentiation, survival and regeneration. A better understanding of the mechanisms underlying the pathogenesis of muscle atrophy and wasting associated with different diseases has been the objective of numerous studies and represents an important first step for the development of therapeutic approaches. Among these, insulin-like growth factor-1 (IGF-1) has emerged as a growth factor with a remarkably wide range of actions and a tremendous potential as a therapeutic in attenuating the atrophy and frailty associated with muscle aging and diseases. In this chapter we provide an overview of current concepts in muscle atrophy, focusing specifically on the molecular basis of IGF-1 action and survey current gene and cell therapeutic approaches to rescue muscle atrophy in aging and disease.

  5. Interactive segmentation for geographic atrophy in retinal fundus images


    Lee, Noah; SMITH, R. THEODORE; Laine, Andrew F.


    Fundus auto-fluorescence (FAF) imaging is a non-invasive technique for in vivo ophthalmoscopic inspection of age-related macular degeneration (AMD), the most common cause of blindness in developed countries. Geographic atrophy (GA) is an advanced form of AMD and accounts for 12–21% of severe visual loss in this disorder [3]. Automatic quantification of GA is important for determining disease progression and facilitating clinical diagnosis of AMD. The problem of automatic segmentation of patho...

  6. Photoreceptor atrophy in acute zonal occult outer retinopathy

    DEFF Research Database (Denmark)

    Zibrandtsen, N.; Munch, I.C.; Klemp, K.;


    PURPOSE: To assess retinal morphology in acute zonal occult outer retinopathy (AZOOR) without ophthalmoscopically visible fundus changes. METHODS: Retrospective case series. Two consecutive patients with bilateral AZOOR with photopsia corresponding to areas of visual field loss and a normal fundus...... appearance were examined using optical coherence tomography (OCT), automated perimetry and electroretinography (ERG). RESULTS: Both patients demonstrated photoreceptor atrophy corresponding to partial or complete scotomata with reduced or extinct electroretinographic responses. Attenuation or complete loss...

  7. Olmesartan-Induced Enteropathy: An Unusual Cause of Villous Atrophy

    Directory of Open Access Journals (Sweden)

    Marta Eusébio


    Olmesartan is an angiotensin receptor blocker commonly prescribed for the management of hypertension. Spruelike enteropathy associated with this drug is a recently described entity with few cases reported. It presents with chronic diarrhea and intestinal villous atrophy and should be included in its differential diagnosis. This case intends to alert clinicians for the possibility of this event in a patient on treatment with this drug.

  8. Phenytoin-induced cerebellar atrophy in an epileptic boy

    Directory of Open Access Journals (Sweden)

    Nithin Kumar


    Full Text Available Epilepsy is an important health problem due to its high prevalence and potential for causing long-term morbidity. It is commonly treated in children with phenytoin sodium. It has wide pharmacokinetic variability and a narrow therapeutic range that leads to toxicity. Here, we report a case of phenytoin-induced cerebellar atrophy in a 16-year-old epileptic boy who presented to the hospital with a viral infection.

  9. Patterns of regional cerebellar atrophy in genetic frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Martina Bocchetta


    Conclusion: There appears to be a differential pattern of cerebellar atrophy in the major genetic forms of FTD, being relatively spared in GRN, localized to the lobule VIIa-Crus I in the superior-posterior region of the cerebellum in C9orf72, the area connected via the thalamus to the prefrontal cortex and involved in cognitive function, and localized to the vermis in MAPT, the ‘limbic cerebellum’ involved in emotional processing.

  10. Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach Distrofia muscular de Duchenne e Becker: abordagem molecular e imuno-histoquímica

    Directory of Open Access Journals (Sweden)

    Aline Andrade Freund


    Full Text Available Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are caused by mutations in the dystrophin gene. We studied 106 patients with a diagnosis of probable DMD/BMD by analyzing 20 exons of the dystrophin gene in their blood and, in some of the cases, by immunohistochemical assays for dystrophin in muscle biopsies. In 71.7% of the patients, deletions were found in at least one of the exons; 68% of these deletions were in the hot-spot 3' region. Deletions were found in 81.5% of the DMD cases and in all the BMD cases. The cases without deletions, which included the only woman in the study with DMD, had dystrophin deficiency. The symptomatic female carriers had no deletions but had abnormal dystrophin distribution in the sarcolemma (discontinuous immunostains. The following diagnoses were made for the remaining cases without deletions with the aid of a muscle biopsy: spinal muscular atrophy, congenital myopathy; sarcoglycan deficiency and unclassified limb-girdle muscular dystrophy. Dystrophin analysis by immunohistochemistry continues to be the most specific method for diagnosis of DMD/BMD and should be used when no exon deletions are found in the dystrophin gene in the blood.As distrofias musculares de Duchenne (DMD e de Becker (DMB são doenças causadas por mutação no gene da distrofina. Foram estudados 106 casos com a suspeita diagnóstica de DMD/BMD com a analise de 20 exons do gene da distrofina no sangue e biópsia muscular com imuno-histoquímica para distrofina em alguns casos. Em 71,7% dos casos foi encontrada deleção em pelo menos um dos exons, sendo que 68% das deleções localizam-se na região 3' hot spot. Foram encontradas deleções em 81,5% dos DMD e em todos os BMD, sendo que os sem deleção tinham deficiência de distrofina, incluindo a mulher com DMD. As portadoras sintomáticas não tinham deleções mas anormalidades na distribuição da distrofina no sarcolema. Os outros casos sem deleção, com auxilio da

  11. Masticatory muscles of mouse do not undergo atrophy in space. (United States)

    Philippou, Anastassios; Minozzo, Fabio C; Spinazzola, Janelle M; Smith, Lucas R; Lei, Hanqin; Rassier, Dilson E; Barton, Elisabeth R


    Muscle loading is important for maintaining muscle mass; when load is removed, atrophy is inevitable. However, in clinical situations such as critical care myopathy, masticatory muscles do not lose mass. Thus, their properties may be harnessed to preserve mass. We compared masticatory and appendicular muscles responses to microgravity, using mice aboard the space shuttle Space Transportation System-135. Age- and sex-matched controls remained on the ground. After 13 days of space flight, 1 masseter (MA) and tibialis anterior (TA) were frozen rapidly for biochemical and functional measurements, and the contralateral MA was processed for morphologic measurements. Flight TA muscles exhibited 20 ± 3% decreased muscle mass, 2-fold decreased phosphorylated (P)-Akt, and 4- to 12-fold increased atrogene expression. In contrast, MAs had no significant change in mass but a 3-fold increase in P-focal adhesion kinase, 1.5-fold increase in P-Akt, and 50-90% lower atrogene expression compared with limb muscles, which were unaltered in microgravity. Myofibril force measurements revealed that microgravity caused a 3-fold decrease in specific force and maximal shortening velocity in TA muscles. It is surprising that myofibril-specific force from both control and flight MAs were similar to flight TA muscles, yet power was compromised by 40% following flight. Continued loading in microgravity prevents atrophy, but masticatory muscles have a different set point that mimics disuse atrophy in the appendicular muscle.

  12. Counteracting Muscle Atrophy using Galvanic Stimulation of the Vestibular System (United States)

    Fox, Robert A.; Polyakov, Igor


    The unloading of weight bearing from antigravity muscles during space flight produces significant muscle atrophy and is one of the most serious health problems facing the space program. Various exercise regimens have been developed and used either alone or in combination with pharmacological techniques to ameliorate this atrophy, but no effective countermeasure exists for this problem. The research in this project was conducted to evaluate the potential use of vestibular galvanic stimulation (VGS) to prevent muscle atrophy resulting from unloading of weight bearing from antigravity muscles. This approach was developed based on two concepts related to the process of maintaining the status of the anti-gravity neuromuscular system. These two premises are: (1) The "tone," or bias on spinal motorneurons is affected by vestibular projections that contribute importantly to maintaining muscle health and status. (2) VGS can be used to modify the excitability, or 'tone' of motorneuron of antigravity muscles. Thus, the strategy is to use VGS to modify the gain of vestibular projections to antigravity muscles and thereby change the general status of these muscles.

  13. Hippocampal complex atrophy in poststroke and mild cognitive impairment. (United States)

    Selnes, Per; Grambaite, Ramune; Rincon, Mariano; Bjørnerud, Atle; Gjerstad, Leif; Hessen, Erik; Auning, Eirik; Johansen, Krisztina; Almdahl, Ina S; Due-Tønnessen, Paulina; Vegge, Kjetil; Bjelke, Börje; Fladby, Tormod


    To investigate putative interacting or distinct pathways for hippocampal complex substructure (HCS) atrophy and cognitive affection in early-stage Alzheimer's disease (AD) and cerebrovascular disease (CVD), we recruited healthy controls, patients with mild cognitive impairment (MCI) and poststroke patients. HCSs were segmented, and quantitative white-matter hyperintensity (WMH) load and cerebrospinal fluid (CSF) amyloid-β concentrations were determined. The WMH load was higher poststroke. All examined HCSs were smaller in amyloid-positive MCI than in controls, and the subicular regions were smaller poststroke. Memory was reduced in amyloid-positive MCI, and psychomotor speed and executive function were reduced in poststroke and amyloid-positive MCI. Size of several HCS correlated with WMH load poststroke and with CSF amyloid-β concentrations in MCI. In poststroke and amyloid-positive MCI, neuropsychological function correlated with WMH load and hippocampal volume. There are similar patterns of HCS atrophy in CVD and early-stage AD, but different HCS associations with WMH and CSF biomarkers. WMHs add to hippocampal atrophy and the archetypal AD deficit delayed recall. In line with mounting evidence of a mechanistic link between primary AD pathology and CVD, these additive effects suggest interacting pathologic processes.

  14. The pathogenesis and treatment of cardiac atrophy in cancer cachexia. (United States)

    Murphy, Kate T


    Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. In addition to a loss of skeletal muscle mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia is described as cardiac cachexia. The cardiac alterations may be due to underlying heart disease, the cancer itself, or problems initiated by the cancer treatment and, unfortunately, remains largely underappreciated by clinicians and basic scientists. Despite recent major advances in the treatment of cancer, little progress has been made in the treatment of cardiac cachexia in cancer, and much of this is due to lack of information regarding the mechanisms. This review focuses on the cardiac atrophy associated with cancer cachexia, describing some of the known mechanisms and discussing the current and future therapeutic strategies to treat this condition. Above all else, improved awareness of the condition and an increased focus on identification of mechanisms and therapeutic targets will facilitate the eventual development of an effective treatment for cardiac atrophy in cancer cachexia.

  15. Selective loss of alpha motor neurons with sparing of gamma motor neurons and spinal cord cholinergic neurons in a mouse model of spinal muscular atrophy. (United States)

    Powis, Rachael A; Gillingwater, Thomas H


    Spinal muscular atrophy (SMA) is a neuromuscular disease characterised primarily by loss of lower motor neurons from the ventral grey horn of the spinal cord and proximal muscle atrophy. Recent experiments utilising mouse models of SMA have demonstrated that not all motor neurons are equally susceptible to the disease, revealing that other populations of neurons can also be affected. Here, we have extended investigations of selective vulnerability of neuronal populations in the spinal cord of SMA mice to include comparative assessments of alpha motor neuron (α-MN) and gamma motor neuron (γ-MN) pools, as well as other populations of cholinergic neurons. Immunohistochemical analyses of late-symptomatic SMA mouse spinal cord revealed that numbers of α-MNs were significantly reduced at all levels of the spinal cord compared with controls, whereas numbers of γ-MNs remained stable. Likewise, the average size of α-MN cell somata was decreased in SMA mice with no change occurring in γ-MNs. Evaluation of other pools of spinal cord cholinergic neurons revealed that pre-ganglionic sympathetic neurons, central canal cluster interneurons, partition interneurons and preganglionic autonomic dorsal commissural nucleus neuron numbers all remained unaffected in SMA mice. Taken together, these findings indicate that α-MNs are uniquely vulnerable among cholinergic neuron populations in the SMA mouse spinal cord, with γ-MNs and other cholinergic neuronal populations being largely spared.

  16. Diagnosing GORD in respiratory medicine

    Directory of Open Access Journals (Sweden)

    Chris James Timms


    Full Text Available Gastroesophageal reflux disease is increasing in prevalence and is associated with several lung diseases such as asthma and COPD. Current diagnostic methods are imperfect, being insensitive, nonspecific, expensive or invasive. An accurate diagnosis of GORD can aid effective treatment with a significant clinical impact. Novel methods such as exhaled breath condensate analysis and electronic nose technology have the potential to improve the accuracy of diagnosing GORD.

  17. Analysis of voxel-based rCBF in patients with olivopontocerebellar atrophy of multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young Jin; Kang, Do Young; Park, Kyung Won; Kim, Sang Ho; Kim, Jae Woo [School of Medicine, Dong-A University, Busan (Korea, Republic of)


    Olivopontocerebellar Atrophy (OPCA) is one phenotype of multiple system atrophy (MSA) and is characterized neuropathologically by neuronal degeneration in the inferior olives, pons and cerebellar cortex. The diagnosis of OPCA requires clinical evaluation to exclude other diseases. And it's usually supported by atrophy of the cerebellum and brainstem visualized on CT or MRI. But there are some reports that the disease can occur without demonstrable atrophy in these anatomic studies. There are only a few reports about perfusion SPECT imaging in patients with OPCA. The aim of this study was to describe voxel-based rCBF of OPCA in comparison of healthy volunteers. We studied 5 patients with OPCA (1 men, 4 women: age 50.4{+-}9.6y) and age matched 13 healthy volunteers (4 men, 9 women: age 54.9{+-}6.6y). All subjects injected 20mCi of Tc-99m HMPAO and scanning was initiated 20 min after injection. Images were analyzed using SPM (SPM99) with Matlab 5.3. On visual analysis, in 3 patients with OPCA, SPECT image showed significant hypoperfusion in the cerebellum. In another 2 patients, diffuse hypoperfusion was found in the both cerebro-cerebellar hemispheres, untypical perfusion pattern in OPCA. So there is existed limitation to diagnosis by only visual analysis. On SPM analysis, in OPCA patients significantly decreased perfusion was present in culmen, tonsil, tuber in Lt. cerebellum and declive, tonsil, pyramid and inf. Semi-lunar lobule in Rt. cerebellum, Rt. inf. frontal gyrus and Rt. temporal lobe (p<0.001, uncorrected). We also performed individual analysis with SPM. Two of 5 patients have additional hypoperfusion brain lesions. In one patient, decreased perfusion found in Lt. temporal, both occipital lobe, Lt. parahippocampal gyrus. In another patient, decreased perfusion found in both frontal and parietal lobe. This study is one of a few trials analysis with SPM for OPCA. We defined the specific location of decreased perfusion in patients with OPCA.

  18. Feasibility of the Medial Temporal lobe Atrophy index (MTAi and derived methods for measuring atrophy of the medial temporal lobe

    Directory of Open Access Journals (Sweden)

    Francisco eConejo Bayón


    Full Text Available Introduction: the Medial Temporal-lobe Atrophy index (MTAi, 2D-Medial Temporal Atrophy (2D-MTA, yearly rate of MTA (yrRMTA and yearly rate of relative MTA (yrRMTA are simple protocols for measuring the relative extent of atrophy in the MTL in relation to the global brain atrophy. Albeit preliminary studies showed interest of these methods in the diagnosis of AD, FTLD and correlation with cognitive impairment in PD, formal feasibility and validity studies remained pending. As a first step, we aimed to assess the feasibility. Mainly, we aimed to assess the reproducibility of measuring the areas needed to compute these indices. We also aimed to assess the efforts needed to start using these methods correctly. Methods: a series of 290 1.5T-MRI studies from 230 subjects ranging 65-85 years old who had been studied for cognitive impairment were used in this study. Six inexperienced tracers (IT plus one experienced tracer (ET traced the three areas needed to compute the indices. Finally, tracers underwent a short survey on their experience learning to compute the MTAi and experience of usage, including items relative to training time needed to understand and apply the MTAi, time to perform a study after training and overall satisfaction. Results: learning to trace the areas needed to compute the MTAi and derived methods is quick and easy. Results indicate very good intrarater ICC for the MTAi, good intrarater ICC for the 2D-MTA, yrMTA and yrRMTA and also good interrater ICC for the MTAi, 2D-MTA, yrMTA and yrRMTA.Conclusion: our data support that MTAi and derived methods (2D-MTA, yrMTA and yrRTMA have good to very good intrarater and interrater reproducibility and may be easily implemented in clinical practice even if new users have no experience tracing the area of regions of interest.

  19. Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer's disease. (United States)

    Chételat, Gaël; Ossenkoppele, Rik; Villemagne, Victor L; Perrotin, Audrey; Landeau, Brigitte; Mézenge, Florence; Jagust, William J; Dore, Vincent; Miller, Bruce L; Egret, Stéphanie; Seeley, William W; van der Flier, Wiesje M; La Joie, Renaud; Ames, David; van Berckel, Bart N M; Scheltens, Philip; Barkhof, Frederik; Rowe, Christopher C; Masters, Colin L; de La Sayette, Vincent; Bouwman, Femke; Rabinovici, Gil D


    See O'Sullivan and Vann (doi:10.1093/aww166) for a scientific commentary on this article.About 15% of patients clinically diagnosed with Alzheimer's disease do not show high tracer retention on amyloid positon emission tomography imaging. The present study investigates clinical and demographic features, patterns of brain atrophy and hypometabolism and longitudinal clinical trajectories of these patients. Forty amyloid-negative patients carrying a pre-scan diagnosis of Alzheimer's disease dementia from four centres were included (11/29 females/males; mean age = 67 ± 9). Detailed clinical histories, including the clinical diagnoses before and after the amyloid scan and at follow-up, were collected. Patients were classified according to their pre-scan clinical phenotype as amnestic (memory predominant), non-amnestic (predominant language, visuospatial or frontal symptoms), or non-specific (diffuse cognitive deficits). Demographic, clinical, neuropsychological, magnetic resonance imaging and (18)F-fluorodeoxyglucose positon emission tomography data were compared to 27 amyloid-positive typical Alzheimer's disease cases (14/13 females/males; mean age = 71 ± 10) and 29 amyloid-negative controls (15/14 females/males; mean age = 69 ± 12) matched for age, gender and education. There were 21 amnestic, 12 non-amnestic, and seven non-specific amyloid-negative Alzheimer's disease cases. Amyloid-negative subgroups did not differ in age, gender or education. After the amyloid scan, clinicians altered the diagnosis in 68% of amyloid-negative patients including 48% of amnestic versus 94% of non-amnestic and non-specific cases. Amnestic amyloid-negative cases were most often reclassified as frontotemporal dementia, non-amnestic as frontotemporal dementia or corticobasal degeneration, and non-specific as dementia with Lewy bodies or unknown diagnosis. The longer-term clinical follow-up was consistent with the post-scan diagnosis in most cases (90%), including in amnestic amyloid

  20. Acute onset of brain atrophy and dementia in a patient with small cell lung cancer: a case report. (United States)

    Asano, Michiko; Fujimoto, Nobukazu; Gemba, Kenichi; Wada, Sae; Ono, Katsuichiro; Ozaki, Shinji; Adachi, Yoshiaki; Yamamoto, Hiromichi; Kishimoto, Takumi


    A 59-year-old man who was diagnosed with small cell lung cancer (SCLC), achieved a complete response to the induction chemoradiotherapy and received prophylactic cranial irradiation (PCI) (25 Gy at 250 cGy per fraction) in October 2008. Three months later, he complained of anorexia, weight loss, fatigue, and short-term memory loss and developed dementia and systemic muscle weakness. Magnetic resonance imaging in April and July 2009 revealed the progression of the diffuse brain atrophy without evidence of the metastasis of SCLC. Paraneoplastic neurological syndrome was suspected because anti-Hu antibody was detected in his serum and cerebrospinal fluid, but the adverse effects of chemotherapy and/or radiotherapy were also suspected as the cause of his neurological disorder.

  1. Myeloid sarcomas: a histologic, immunohistochemical, and cytogenetic study

    Directory of Open Access Journals (Sweden)

    Rodgers William H


    Full Text Available Abstract Context. - Myeloid sarcoma (MS is a neoplasm of immature granulocytes, monocytes, or both involving any extramedullary site. The correct diagnosis of MS is important for adequate therapy, which is often delayed because of a high misdiagnosis rate. Objective. - To evaluate the lineage differentiation of neoplastic cells in MS by immunohistochemistry, and to correlate the results with clinicopathologic findings and cytogenetic studies. Design. - Histologic and immunohistochemical examinations were performed on formalin-fixed paraffin-embedded tissue samples from 13 cases of MS. They were classified according to the World Health Organization criteria. Chromosomal analysis data were available in 11 cases. Clinical, pathological, and cytogenetic findings were analyzed. Results. - The study included six male and seven female patients with an age range of 25 to 72 years (mean, 49.3 years and a male to female ratio of 1:1.2. MS de novo occurred in 4/13 (31% of cases examined. The most sensitive immunohistochemical markers were CD43 and lysozyme present in all cases with MS (13/13, 100%. All de novo MS showed a normal karyotype, monoblastic differentiation, and lack of CD34. The most common chromosomal abnormalities in MS associated with a hematopoietic disorder were trisomy 8 and inv(16 (2/11, 18%. Conclusion. - An immunohistochemical panel including CD43, lysozyme, myeloperoxidase (MPO, CD68 (or CD163, CD117, CD3 and CD20 can successfully identify the vast majority of MS variants in formalin-fixed paraffin-embedded tissue sections. The present report expands the spectrum of our knowledge showing that de novo MS has frequent monoblastic differentiation and frequently carries a normal karyotype.

  2. β-amyloid, hippocampal atrophy and their relation to longitudinal brain change in cognitively normal individuals. (United States)

    Fletcher, Evan; Villeneuve, Sylvia; Maillard, Pauline; Harvey, Danielle; Reed, Bruce; Jagust, William; DeCarli, Charles


    Recent literature has examined baseline hippocampal volume and extent of brain amyloidosis to test potential synergistic effects on worsening cognition and extent of brain atrophy. Use of hippocampal volume in prior studies was based on the notion that limbic circuit degeneration is an early manifestation of the Alzheimer's Disease (AD) pathophysiology. To clarify these interactions early in the AD process, we tested the effects of amyloid and baseline normalized hippocampal volume on longitudinal brain atrophy rates in a group of cognitively normal individuals. Results showed that the combination of elevated β-amyloid and baseline hippocampal atrophy is associated with increased rates specific to the limbic circuit and splenium. Importantly, this atrophy pattern emerged from a voxelwise analysis, corroborated by regression models over region of interests in native space. The results are broadly consistent with previous studies of the effects of amyloid and baseline hippocampal atrophy in normals, while pointing to accelerated atrophy of AD-vulnerable regions detectable at the preclinical stage.

  3. Histomorphological and immunohistochemical characterization of 172 cutaneous round cell tumours in dogs

    Directory of Open Access Journals (Sweden)

    Marina Rios Araújo


    Full Text Available This paper describes the use of a panel of antibodies (CD117, CD3, CD79a, CD45, cytokeratin, vimentin and E-cadherin on formalin-fixed, paraffin-embedded sections of canine cutaneous round cell tumours. Neoplastic tumours were diagnosed by histology and histochemical stains and included 107 mast cell tumours, 31 cutaneous histiocytomas, two localized histiocytic sarcomas, 21 cutaneous lymphomas, three plasma cell tumours, one transmissible venereal tumour and seven unclassified round cell tumours. The histologic diagnosis was modified in 39.5% of the total 172 neoplasms. The staining for CD45 and Ecadherin were variable, and therefore, the final diagnoses of cutaneous histiocytoma and localized histiocytic sarcoma were made based on histology in association with negative results for CD3, CD79a, CD117 and cytokeratin. The cellular origin of unclassified round cell tumours was defined in all cases. Cutaneous B-cell lymphoma and plasma cell tumours were CD79a-positive and could be distinguished from each other by the morphological characteristics. Mast cell tumours and T cell lymphoma were CD117 and CD3 positive, respectively. The positive staining for vimentin and the negative staining for CD3, CD79a, CD117 and cytokeratin favoured the diagnosis of transmissible venereal tumours. Thus, the final diagnosis of cutaneous round cell tumours should be based on the interpretation of immunohistochemical results together with the cellular morphology observed by histology. Therefore, more studies to optimize the specific markers in formalin-fixed, paraffinembedded tissues (especially for histiocytes are required for definitive diagnosis of round cell tumours in dogs.

  4. Calcifying Odontogenic Cyst with Complex Odontoma: Histological and Immunohistochemical Features

    Directory of Open Access Journals (Sweden)

    Nooshin Mohtasham


    Full Text Available The calcifying odontogenic cyst (COC is a rare odontogenic cyst. Only 2% of all odontogenic cysts and tumors are COC. COC associated with odontoma (COCaO reported in 24% of COCs. COCaO presents a greater incidence in female, with a ratio of 2 to 1. The highest incidence of COCaO occurs during the second decade with a mean age of 16 years, most frequently occurring in the maxilla (61.5%. Here, we describe a classic case of COCaO of the maxillary incisor-canine region in 17-year-old girl, and discuss the clinicopathological features and immunohistochemical finding of this tumor.

  5. Calcifying Odontogenic Cyst with Complex Odontoma: Histological and Immunohistochemical Features

    Directory of Open Access Journals (Sweden)

    Mohsen Merati


    Full Text Available The calcifying odontogenic cyst (COC is a rare odontogenic cyst. Only 2% of all odontogenic cysts and tumors are COC. COC associated with odontoma (COCaO reported in 24% of COCs. COCaO presents a greater incidence in female, with a ratio of 2 to 1. The highest incidence of COCaO occurs during the second decade with a mean age of 16 years, most frequently occurring in the maxilla (61.5%. Here, we describe a classic case of COCaO of the maxillary incisor-canine region in 17-year-old girl, and discuss the clinicopathological features and immunohistochemical finding of this tumor.

  6. Diagnostic value of 18F-FDG PET and 11C-PIB PET on early stage posterior cortical atrophy

    Directory of Open Access Journals (Sweden)

    Shuai LIU


    Full Text Available Background  Posterior cortical atrophy (PCA is a kind of progressive neurodegenerative disease with cortical visual impairment as the first symptom. Because of rare clinical incidence, early onset age, special clinical symptoms and unobvious MRI abnormality, the definitive diagnosis of PCA is difficult. This study used 18F-fluoro-2-deoxy-D-glucose (18F-FDG PET and 11C-Pittsburgh compound B (11C-PIB PET for PCA patients with unobvious MRI abnormality, so as to discuss the value of PET in the early diagnosis of PCA.  Methods  Five patients diagnosed as PCA in our hospital between April 2012 and March 2015 were enrolled in this study. Cognitive function was measured by Mini-Mental State Examination (MMSE, Montreal Cognitive Assessment (MoCA, Activities of Daily Living (ADL and Clock Drawing Test (CDT. Brain MRI, 18F-FDG PET and 11C-PIB PET were performed to analyze glucose metabolism and perfusion of posterior cortex.  Results Neuropsychological tests revealed that the ability of writing, calculating, visuospatial and executive function of all these patients were impaired. Color vision tests showed abnormal results. MRI showed that the posterior atrophy (PA scores were 0-2 (average 1 on the left side and 0-1 (average 0.80 on the right side. The medial temporal atrophy (MTA scores were 1-3 (average 1.80 on the left side and 1-4 (average 2 on the right side. The ventricular enlargement (VE scores were 1-2 (average 1.80 on the left side and 1-2 (average 1.60 on the right side. 18F-FDG PET showed glucose metabolism decreased obviously on bilateral temporo-parieto-occipital cortex, precuneus and cingulate gyrus, and slightly on frontal lobes and subcortical structure. 11C-PIB PET showed radioactive 11C-PIB deposition on bilateral frontal, temporal, parietal and occipital cortex, and the outline of cerebellar cortex was clear.  Conclusions  For PCA patients whose parietal and occipital cortical atrophy is not obvious on MRI, 18F-FDG PET

  7. Genomic deletions in OPA1 in Danish patients with autosomal dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Larsen Michael


    Full Text Available Abstract Background Autosomal dominant optic atrophy (ADOA, Kjer disease, MIM #165500 is the most common form of hereditary optic neuropathy. Mutations in OPA1 located at chromosome 3q28 are the predominant cause for ADOA explaining between 32 and 89% of cases. Although deletions of OPA1 were recently reported in ADOA, the frequency of OPA1 genomic rearrangements in Denmark, where ADOA has a high prevalence, is unknown. The aim of the study was to identify copy number variations in OPA1 in Danish ADOA patients. Methods Forty unrelated ADOA patients, selected from a group of 100 ADOA patients as being negative for OPA1 point mutations, were tested for genomic rearrangements in OPA1 by multiplex ligation probe amplification (MLPA. When only one probe was abnormal results were confirmed by additional manually added probes. Segregation analysis was performed in families with detected mutations when possible. Results Ten families had OPA1 deletions, including two with deletions of the entire coding region and eight with intragenic deletions. Segregation analysis was possible in five families, and showed that the deletions segregated with the disease. Conclusion Deletions in the OPA1 gene were found in 10 patients presenting with phenotypic autosomal dominant optic neuropathy. Genetic testing for deletions in OPA1 should be offered for patients with clinically diagnosed ADOA and no OPA1 mutations detected by DNA sequencing analysis.

  8. An investigation of diffusion imaging techniques in the evaluation of spinocerebellar ataxia and multisystem atrophy. (United States)

    Rozenfeld, Michael N; Nemeth, Alexander J; Walker, Matthew T; Mohan, Prasoon; Wang, Xue; Parrish, Todd B; Opal, Puneet


    Multisystem system atrophy and spinocerebellar ataxia are rare neurodegenerative ataxias that can be difficult to diagnose, with important prognostic and treatment implications. The purpose of this study is to evaluate various methods of diffusion imaging and tractography in their effectiveness at differentiating these diseases from control subjects. Our secondary aim is determining whether diffusion abnormalities correspond with clinical disease severity. Diffusion imaging and tractography were performed on five patients and seven age-matched controls. Fractional anisotropy, generalized fractional anisotropy, and apparent diffusion coefficient values and corticospinal tract volumes were measured within various diffusion and probabilistic tractography models, including standard diffusion tensor and Q-ball tractography. Standard diffusion based fractional anisotropy and apparent diffusion coefficient values were significantly altered in patients versus controls in the middle cerebellar peduncles and central pons. Tractography based fractional anisotropy and generalized fractional anisotropy values were significantly lower in patients versus controls when corticospinal tracts were drawn in a craniocaudal direction (bilaterally using Q-ball imaging, only on the right using diffusion tensor imaging). The right corticospinal tract volume was significantly smaller in patients versus controls when created using Q-ball imaging in a caudocranial direction. There was no correlation between diffusion alteration and clinical symptomatology. In conclusion, various diffusion-based techniques can be effective in differentiating ataxic patients from control subjects, although the selection of diffusion algorithm and tract growth technique and direction is non-trivial.

  9. [Olivo-ponto-cerebellar atrophy with personality changes and slight disturbance of intelligence]. (United States)

    Deshimaru, M; Miyakawa, T; Suzuki, T


    H. I., a housewife aged 55 years, began feeling a gait disturbance at 48 years old. After this she had incoordination of arms, dysarthria and tremor of hands. Aged 54 years, she could not stand up by herself. In addition to these neurological signs she had a change of character, such as losing control of herself, unreservedness and unceremoniousness, and slight disturbance of intelligence. She died at the age of 55 years about seven years after the onset. Histopathologically, noticeable changes were observed on the medulla oblongata, pons and cerebellum; the severe neuronal loss of the pontine nuclei and the olivary nuclei with demyelination and gliosis of the cerebellopetal fibers. Especially a great deal of lipofuscin granules in the nerve cells of the frontal and temporal lobe were observed. In the substantia nigra some pigmented cells were deleted. This case was diagnosed as olivo-ponto-cerebellar atrophy clinico-histopathologically. We discussed conserning the etiology of the changes of personality and slight disturbance of intelligence in relation to histopathological changes. It is speculated that the mental disorders are due to the degeneration of the nerve cells in the frontal and temporal lobes.

  10. [A Patient with Early-Stage Multiple System Atrophy Showing Augmented Nystagmus in Light]. (United States)

    Oguri, Masayoshi; Nakamura, Yousuke; Hara, Ayako; Kitano, Hiroya; Motokura, Toru


    The ability to fix the eyes on a target, visual fixation, is important for the maintenance of equilibrium. The visual suppression (VS) test is one method of measuring the function of visual fixation. The test records caloric nystagmus by electrooculography, and the maximum slow phase velocity of caloric nystagmus in darkness is compared with the slow phase velocity in light with eyes fixed. Lesions of the cerebellum, brain stem, and cerebrum cause abnormalities of VS. We report a patient whose VS became a clue in the diagnosis of a disorder of the central nervous system. A 54-year-old man complained of dizziness, which gradually increased in frequency over 5 months. He visited several clinics, where vestibular neutritis and cervical spondylosis were suspected and treated without improvement. Although a pure-tone auditory test revealed bilateral normal hearing, a caloric test showed a weak response and VS was lost with augmentation of caloric nystagmus in light on both sides. Both eye tracking and optokinetic nystagmus tests were abnormal. Although magnetic resonance imaging showed no abnormalities, single photon emission computed tomography revealed decreased blood flow in the parietal area. VS of caloric nystagmus towards the side of a lesion is reduced or abolished after unilateral flocculus damage, and is abolished bilaterally after bilateral flocculus damage. In the case of a parietal lobe or pontine lesion, VS is strongly abolished, and even augmentation of caloric nystagmus may be observed. In the present case, the patient was diagnosed with multiple-system atrophy after onset of dizziness.

  11. Immunohistochemical study of genital and extragenital forms of canine transmissible venereal tumor in Brazil

    Directory of Open Access Journals (Sweden)

    Mariana B. Mascarenhas


    Full Text Available Aiming to provide insight and discussing the problems related to the diagnosis and differential diagnosis of canine transmissible venereal tumor (CTVT, especially in its extragenital form, immunohistochemical evaluation was performed and a comparison was established by analysis of the microscopic appearance of 10 genital CTVTs and 13 exclusively extragenital CTVTs previously diagnosed by cytology and histopathology. CTVTs samples were incubated with biotinylated antibodies raised against specific membrane (anti-macrophage and cytoplasmic antigens (anti-lysozyme, anti-S-100 protein, anti-vimentin and anti-CD18 and subsequently developed using streptavidin-biotin peroxidase and streptavidin-biotin-alkaline phosphatase methods. A strong reactivity with the anti-vimentin antibody was found in 100% of the tumors tested (22/22. No reactivity was found for the anti-lysozyme, anti-macrophage, anti-S-100 protein and anti-CD18. No histopathological or immunoreactivity differences between genital and extragenital CTVTs were found. These findings do not corroborate the hypothesis of histiocytic origin of CTVT (no reactivity to anti-lysozyme, anti-macrophage and anti-CD 18 antibodies. In addition, the antibody panel used is useful to narrow the differential diagnosis for lymphomas, histiocytic tumors, amelanotic melanomas, and poorly differentiated epithelial neoplasias, among others.

  12. Expression of Selected Markers in Immunohistochemical Diagnosis of Canine and Human Testicular Tumours

    Directory of Open Access Journals (Sweden)

    Ciaputa Rafał


    Full Text Available Immunohistochemical profiles of the most common canine testicular tumours, including the Leydig cell tumours, seminomas, and Sertoli cell tumours were analysed, and the results were compared with those obtained in the corresponding types of human testicular neoplasms. The expressions of vimentin, von Willebrand factor (FVIII, chromogranin A, synaptophysin, and MCM3 were quantified. In the case of Sertoli cell tumours, only canine ones were analysed, since this type of tumour is very rarely diagnosed in men. The expression of the analysed proteins in the testicular tumours was similar. The von Willebrand factor exhibited the strongest expression in Leydig cell tumours in dogs and men, while vimentin was expressed more strongly in dogs (96.7% had an intensity at +++ than in men (62.5% had +++ in the Leydigioma. The immunoexpression of MCM3 in seminomas was high in both men and dogs – 90% +++ and 100% +++ respectively. The lack of chromogranin A and synaptophysin was observed in almost 100% of seminomas in men and dogs. This differed from the results obtained for Leydigioma, where chromogranin A was expressed in 70% of dogs at +++ and in 100% of men at ++++. The results may indicate that the antibodies were selected correctly. Their analysis and interpretation provides valuable information concerning the nature of the studied tumours.

  13. Odontogenic myxoma: clinico-pathological, immunohistochemical and ultrastructural findings of a multicentric series. (United States)

    Martínez-Mata, Guillermo; Mosqueda-Taylor, Adalberto; Carlos-Bregni, Roman; de Almeida, Oslei Paes; Contreras-Vidaurre, Elisa; Vargas, Pablo Agustin; Cano-Valdéz, Ana María; Domínguez-Malagón, Hugo


    The aim of this study was to analyze the clinico-pathological and immunohistochemical features of 62 cases of odontogenic myxoma (OM) diagnosed in three Oral Pathology Diagnostic Services in Latin America, as well as to describe the ultrastructural features of three of these cases. OM showed a wide age range (9-71 years), with a mean of 27.97 yr (SD: 11.01) and a male to female ratio of 1:2.2. Mandible was affected in 37 cases (59.6%) and maxilla in 25 (40.4%), with 61.3% located in the posterior region. Thirty-nine cases (62.9%) were multilocular and 23 (37.1%) unilocular. Size ranged from 1 to 13 cm, (mean: 5.2 cm). Thirty-seven multilocular (54.8%) and 6 unilocular lesions (26%) were larger than 4 cm (pNSE and CD68, and showed a low index of expression of Bcl2 and ki-67 proteins (products. However, further investigations are needed to better understand the participation of these elements in this particular neoplasm.

  14. Cytokeratin expression in gastrointestinal stromal tumor: a clinicopathologic and immunohistochemical study of 687 cases. (United States)

    Lopes, Lisandro F; Bacchi, Carlos E


    Gastrointestinal stromal tumor is the most common clinically significant mesenchymal neoplasm of the gastrointestinal tract. The expression of the intermediate filament cytokeratin in gastrointestinal stromal tumor is not frequently reported in the literature. The aim of this study was to investigate the immunohistochemical expression of several types of cytokeratin in a large number of cases (n=687), including a pan-cytokeratin marker (AE1/AE3 cocktail antibodies), high-molecular weight cytokeratins (34ßE12 antibody), and individual cytokeratins 8 (35ßH11 and CAM5.2 antibodies), 7, 14, and 20. Ki-67 antigen was used for the determination of cell proliferation index, and the correlation between Ki-67 and cytokeratin expression was evaluated. Cytokeratin expression was also correlated with several clinicopathologic parameters. The expression of pan-cytokeratin was observed in 24 (3.5%) cases, with variable intensity. Only 1 of 687 (0.1%) cases showed cytokeratin 14 expression. All 687 cases revealed no expression of high-molecular weight cytokeratins, cytokeratins 7, 8, and 20. No significant statistical association was found between AE1/AE3 immunoreactivity and several clinicopathologic parameters, including sex, tumor location and size, cell morphology, mitotic count, risk of aggressive behavior, and Ki-67 antigen cell proliferation index. However, statistical correlation between AE1/AE3 immunoreactivity and a higher age at diagnosis was detected. These results show that cytokeratin expression is not frequent in gastrointestinal stromal tumor, but caution is necessary to avoid erroneous diagnoses.

  15. Prognostic significance of new immunohistochemical markers in refractory classical Hodgkin lymphoma: a study of 59 cases.

    Directory of Open Access Journals (Sweden)

    Danielle Canioni

    Full Text Available Although most classical Hodgkin lymphoma patients are cured, a significant minority fail after primary therapy and may die as result of their disease. To date, there is no consensus on biological markers that add value to usual parameters (which comprise the International Prognostic Score used at diagnosis to predict outcome. We evaluated 59 patients (18 with primary refractory or early relapse disease and 41 responders for bcl2, Ki67, CD20, TiA1 and c-kit expression by semi-quantitative immunohistochemical study and correlated the results with the response to treatment.The results showed that expression of bcl2 and CD20 in Hodgkin and Reed Sternberg cells, and expression of TiA1 in micro-environmental lymphocytes, and c-kit positive mast cells in microenvironment, were independent prognostic markers. These novel cHL markers could be used in association with clinical parameters to identify newly diagnosed patients with favorable or unfavorable prognosis and to better tailor treatment for different risk groups.

  16. Prostatic stromal tumor with fatal outcome in a young man: histopathological and immunohistochemical case presentation

    Directory of Open Access Journals (Sweden)

    Massimo Roncalli


    Full Text Available Stromal tumors of the prostate are rare and only a few cases have been described in the literature, including exceptional cases of stromal tumors with unknown malignant potential (STUMP and a fatal outcome in young patients. Morphologically distinguishing a STUMP from a stromal sarcoma of the prostate (PSS is still a challenge. We describe the histopathological and immunohistochemical findings in a 34-year-old man with a malignant specialized cell stromal tumor of the prostate that was diagnosed initially as STUMP, and he developed lung metastases within a few months. The patient attended our hospital because of lower urinary tract symptoms, after having excreted tissue through the urethra a few months before. Ultrasonography and urethrocystoscopy examinations showed a mass arising from the verumontanum, and a transurethral resection (TUR revealed a high-grade spindle cell sarcoma reminiscent of a phyllode tumor of the breast. The tumor cells were immunoreactive for vimentin, progesterone receptor and, focally, CD34. The preliminary histo­logical findings were subsequently confirmed after radical prostatectomy. The patient developed bilateral lung metastases and died 25 months after the initial diagnosis. Although rare in young patients, the challenging differential diagnosis of STUMP and PSS means that a prostate STUMP diagnosis made on the basis of biopsy or TUR specimens also requires urethrocystoscopic monitoring for the early detection of any progression to PSS. Radical prostatectomy should also be carefully considered.

  17. Diagnosability issues in multiprocessor systems

    Energy Technology Data Exchange (ETDEWEB)

    Raghavan, V.


    In a seminal paper on fault diagnosis, Preparata, Metze, and Chien introduced a graph-theoretical model. Barsi, Grandoni, and Maestrini relaxed some constraints in this model to create a different model for fault diagnosis. Both these models have become the subject of intense research in the past two decades. A major open problem for these models is the question of sequential t-diagnosability-Given an arbitrary system of units and that there are no more than t faulty units in it, can we always identify at least one faulty unit The author shows that this problem is co-NP complete in both models. Recent research has shown that there are polynomial time algorithms to find the maximum number of faulty units a system can withstand and still identify all of them from a single collection of test results. He presents improved algorithms to solve this problem in both models. Using the letters n,m, and {tau} to denote the number of units, the number of tests, and the maximum number of faulty units respectively, our results can be summarized as follows: in the model of Barsi, Grandoni, and Maestrini, the algorithm has a time complexity of O(n{tau}{sup 2}/log{tau}) improving on the currently known O(n{tau}{sup 2}); in the model of Preparata, Metze, and Chien, the algorithm has a complexity of O(n{tau}{sup 2.5}) improving on the currently known O(mn{sup 1.5}). He also presents related results in the latter model, which suggest the possibility of reducing the complexity even further. Finally, he develops a general scheme for characterizing diagnosable systems. Using this scheme, he solves the open problem of characterizing t/s and sequentially t-diagnosable systems. The characterizations are then used to rederive some known results.

  18. TP53 Staining in Tissue Samples of Chronic Lymphocytic Lymphoma Cases: An Immunohistochemical Survey of 51 Cases

    Directory of Open Access Journals (Sweden)

    İbrahim Kulaç


    Full Text Available Objective: Chronic lymphocytic leukemia (CLL is the most common lymphoproliferative disease in adults. The aim of this study is to find out if the extent of proliferation centers or the immunohistochemical expression of p53 is related to disease prognosis. Materials and Methods: In the scope of this study, 54 biopsy specimens from 51 patients (50 of lymph nodes; the others of spleen, tonsil, orbit, and liver diagnosed with CLL at the Hacettepe University Department of Pathology in 2000-2013 were reevaluated. The clinical and demographic data of the patients were obtained from our patient database. Biopsy samples were assessed semi-quantitatively for the percentage of proliferation center/total biopsy area (PC/TBA and an immunohistochemical study was performed on representative blocks of tissues for p53 expression. Results: When the patients were divided into two categories according to Rai stage as high and low (stages 0, 1, and 2 vs. stages 3 and 4, it was seen that patients with low Rai stage had a better prognosis than those with high stages (p=0.030. However, there was no statistically significant correlation between overall survival and PC/TBA ratio or p53 expression levels. Conclusion: In our cohort, PC/TBA ratio and immunopositivity of p53 did not show correlations with overall survival.

  19. How to diagnose acute appendicitis

    DEFF Research Database (Denmark)

    Mostbeck, Gerhard; Adam, E Jane; Nielsen, Michael Bachmann;


    Acute appendicitis (AA) is a common abdominal emergency with a lifetime prevalence of about 7 %. As the clinical diagnosis of AA remains a challenge to emergency physicians and surgeons, imaging modalities have gained major importance in the diagnostic work-up of patients with suspected AA in order...... appendicitis (AA). • Primary US for AA diagnosis will decrease ionizing radiation and cost. • Sensitivity of US to diagnose AA is lower than of CT/MRI. • Non-visualization of the appendix should lead to clinical reassessment. • Complementary MRI or CT may be performed if diagnosis remains unclear....

  20. Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD and Alzheimer's disease (AD

    Directory of Open Access Journals (Sweden)

    Dong Seok Yi

    Full Text Available ABSTRACT Behavioural disturbances in frontotemporal dementia (FTD are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. Objective: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. Methods: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R and Frontal System Behaviour Scale (FrSBe. Atrophy in prefrontal (VMPFC, DLPFC and striatal (caudate, putamen regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. Results: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. Conclusion: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

  1. Testicular atrophy secondary to a large long standing incarcerated inguinal hernia

    Directory of Open Access Journals (Sweden)

    Nikolaos S Salemis


    Full Text Available Testicular atrophy is a rare but distressing complication of inguinal hernia repair. Apart from the postsurgical etiology, ischemic orchitis and subsequent testicular atrophy may occur secondary to compression of the testicular vessels by chronically incarcerated hernias. We present a rare case of testicular atrophy secondary to a large long standing incarcerated inguinal hernia of 2-decade duration in a 79-year-old man. Testicular atrophy should be always considered in long standing incarcerated inguinal hernias and patients should be adequately informed of this possibility during the preoperative work-up. Preoperative scrotal ultrasonography can be used to determine testicular status in this specific group of patients.


    Directory of Open Access Journals (Sweden)

    D. Tamiolakis


    Full Text Available Bone marrow is infrequently implicated in early stages of Hodgkin’s disease. We studied the immunohistochemical bone marrow tissue of 7 out of 20 cases with early stage Hodgkin’s disease of the mixed cellularity variant, diagnosed by lymph node biopsy at initial presentation, not responding to radiotherapy alone, in order to examine possible marrow attack. A statistically significant prevalence of CD45, CD45RO, and CD4 positive infiltrates, to the advantage of unremitting hosts, was found. The predominance of CD4-positive cells in the bone marrow space might be suggestive of involvement in the process and could explain the abnormal cytokine production leading to reduced T-cell immunity and inefficient antitumor response despite the existence of a vast majority of reactive infiltrating immune cells.

  3. Distal DVT: worth diagnosing? Yes. (United States)

    Schellong, S M


    Much of the argument for or against diagnosis of distal deep vain thrombosis (DVT) depends on the extra effort that has to be spent on it. This review presents the data on ultrasound of paired calf veins and calf muscle veins (distal ultrasound) in terms of protocols, feasibility, reliability and expected findings. In summary, provided there is adequate and anatomically sound training of sonographers, distal ultrasound is a valid, 4-minute procedure, which can easily be added to the examination of proximal veins. The second part of the review refers to the pathophysiology of ascending DVT, which is the most common type. Adequate patient care in terms of benefit, harm and cost includes a single non-invasive examination followed by risk adopted treatment allocation. This concept ideally should be valid for any type of DVT. The data extending this concept to distal DVT can only be derived from studies that look closely at this entity (i.e. in fact diagnose distal DVT). Even before these data are available, diagnosing distal DVT at least doubles the number of symptomatic patients in which signs and symptoms can be ascribed to a definitive diagnosis, which in itself is a benefit for patient care.

  4. System-wide immunohistochemical analysis of protein co-localization.

    Directory of Open Access Journals (Sweden)

    Minjung Kim

    Full Text Available The analysis of co-localized protein expression in a tissue section is often conducted with immunofluorescence histochemical staining which is typically visualized in localized regions. On the other hand, chromogenic immunohistochemical staining, in general, is not suitable for the detection of protein co-localization. Here, we developed a new protocol, based on chromogenic immunohistochemical stain, for system-wide detection of protein co-localization and differential expression.In combination with a removable chromogenic stain, an efficient antibody stripping method was developed to enable sequential immunostaining with different primary antibodies regardless of antibody's host species. Sections were scanned after each staining, and the images were superimposed together for the detection of protein co-localization and differential expression. As a proof of principle, differential expression and co-localization of glutamic acid decarboxylase67 (GAD67 and parvalbumin proteins was examined in mouse cortex.All parvalbumin-containing neurons express GAD67 protein, and GAD67-positive neurons that do not express parvalbumin were readily visualized from thousands of other neurons across mouse cortex. The method provided a global view of protein co-localization as well as differential expression across an entire tissue section. Repeated use of the same section could combine assessments of co-localization and differential expression of multiple proteins.

  5. Immunohistochemical expression of type VI collagen in superficial fibromatoses. (United States)

    Magro, G; Colombatti, A; Lanzafame, S


    The expression of type VI collagen was studied immunohistochemically in 26 cases of superficial fibromatoses (palmar, plantar and penile) using an immunoperoxidase method for light microscopic visualization. The polyclonal antibody against type VI collagen used in this study was isolated from human placenta and its specifity was tested by immunoblotting assay. All cases consisted of multiple nodules showing a variable degree of cellularity and fibrosis. Depending on the predominant histological appearance of these nodules, each case was assigned to the three following phases: proliferative, involutional and residual. Morphologically normal palmar and plantar aponeuroses were included as controls. Immunohistochemical findings showed that type VI collagen was present as longitudinal thin fibers in normal palmar and plantar aponeuroses. A differential expression of this collagen was found in the different stages of superficial fibromatoses. Type VI collagen was markedly expressed as a distinct fibrillar network in the extracellular matrix (ECM) surrounding proliferating stromal cells in proliferative and involutional phases. Its expression completely disappeared from the connective tissue undergoing fibrotic transformation during involutional and residual phases. The results of the present study suggest that type VI collagen is an extracellular marker of stromal tissue proliferation and is involved in the early phases of tissue remodelling occurring in the superficial fibromatoses.

  6. Histochemical and Immunohistochemical Study of Peripolar Cells in Sheep

    Directory of Open Access Journals (Sweden)

    Passos Joana


    Full Text Available Peripolar cells are granulated cells located in the vascular pole of the renal corpuscle. Even though these cells have already been described, there are still many unknown histological and physiological characteristics. We carried out histochemical and immunohistochemical analyses of peripolar cells in sheep and compared their number in both normal and injured kidneys, discriminating according to the age of the animal. We tested HE, Toluidine Blue, PAS, and Masson's Trichrome stains to select the best stain for identification and quantification. Masson Trichrome yielded the best results and was selected for this purpose. We identified the cells by the presence of cytoplasmatic granules and by their position in the vascular pole. We found no statistically significant association between the number of peripolar cells and the age of the animal or the occurrence of lesions. In the immunohistochemical analysis, we found that the cells were positive to α-smooth muscle actin and less consistently positive to NSE and S100 protein. Chromogranin A, cyclooxygenase-2, AE1/AE3, and Wide Spectrum Cytokeratin and desmin yielded negative results. We conclude that although there was evidence of a contractile function, there was no evidence to support that peripolar cells have either a neuroendocrine or an epithelial nature.

  7. Hepatocellular Tumors: Immunohistochemical Analyses for Classification and Prognostication

    Institute of Scientific and Technical Information of China (English)

    Regina Cheuk-Lam Lo; Irene Oi-Lin Ng


    Following the classification of hepatocellular nodules by the International Working Party in 1995 and further elaboration by the International Consensus Group for Hepatocellular Neoplasia in 2009,entities under the spectrum of hepatocellular nodules have been better characterized.Research work hence has been done to answer questions such as distinguishing high-grade dysplastic nodules from early hepatocellular carcinoma (HCC),delineating the tumor cell origin of HCC,identifying its prognostic markers,and subtyping hepatocellular adenomas.As a result,a copious amount of data at immunohistochemical and molecular levels has emerged.A panel of immunohistochemical markers including glypican-3,heat shock protein 70 and glutamine synthetase has been found to be of use in the diagnosis of small,well differentiated hepatocellular tumors and particularly of HCC.The use of liver fatty acid binding protein (L-FABP),β-catenin,glutamine synthetase,serum amyloid protein and C-reactive protein is found to be helpful in the subtyping of hepatocellular adenomas.The role of tissue biomarkers for prognostication in HCC and the use of biomarkers in subclassifying HCC based on tumor cell origin are also discussed.

  8. Immunohistochemical demonstration of airway epithelial cell markers of guinea pig. (United States)

    Li, Yong; Wang, Jing; He, Hai Yan; Ma, Ling Jie; Zeng, Jin; Deng, Guang Cun; Liu, Xiaoming; Engelhardt, John F; Wang, Yujiong


    The guinea pig (Cavea porcellus) is a mammalian non-rodent species in the Caviidae family. The sensitivity of the respiratory system and the susceptibility to infectious diseases allows the guinea pig to be a useful model for both infectious and non-infectious lung diseases such as asthma and tuberculosis. In this report, we demonstrated for the first time, the major cell types and composition in the guinea pig airway epithelium, using cell type-specific markers by immunohistochemical staining using the commercial available immunological reagents that cross-react with guinea pig. Our results revealed the availability of antibodies cross-reacting with airway epithelial cell types of basal, non-ciliated columnar, ciliated, Clara, goblet and alveolar type II cells, as well as those cells expressing Mucin 5AC, Mucin 2, Aquaporin 4 and Calcitonin Gene Related Peptide. The distribution of these various cell types were quantified in the guinea pig airway by immunohistochemical staining and were comparable with morphometric studies using an electron microscopy assay. Moreover, this study also demonstrated that goblet cells are the main secretory cell type in the guinea pig's airway, distinguishing this species from rats and mice. These results provide useful information for the understanding of airway epithelial cell biology and mechanisms of epithelial-immune integration in guinea pig models.

  9. Collagenase-3 expression in periapical lesions: an immunohistochemical study. (United States)

    Bhalla, G; Astekar, M S; Ramesh, G; Kaur, P; Sowmya, G V


    Collagenase-3 (matrix metalloproteinase-13) is a metalloproteinase (MMP) that is associated with bone lesions and exhibits variable expression patterns in odontogenic cysts; it may play a role in regulating focal proliferation and maturation of jaw cyst epithelium. We studied the localization, staining intensity and distribution of collagenase-3 in 13 periapical granulomas with epithelium, 16 periapical granulomas without epithelium and 10 radicular cysts using archived formalin fixed, paraffin embedded tissues. A monoclonal antibody against human collagenase-3 was used to evaluate its expression. Immunohistochemical staining intensities of collagenase-3 in all periapical lesions were (-), 4 (10%); (+), 1 (3%); (++), 22 (56%) and (+++), 12 (31%); differences were not statistically significant. Immunohistochemical distribution of collagenase-3 in epithelial cells was (-), 17 (44%); (+), 17 (44%); (++), 5 (13%); in fibroblasts it was (-), 8 (20%); (+), 23 (59%); (++), 8 (21%); in plasma cells it was (-), 7 (18%); (+), 22 (56%); (++), 10 (26%); in macrophages it was (-), 7 (18%); (+), and 15 (38%); and (++), 17 (44%). Statistically significant differences were found in epithelial cells (p = 0.00) and fibroblasts (p = 0.02), whereas differences were not statistically significant for plasma cells and macrophages. Collagenase-3 may play a role in the conversion of a periapical granuloma with epithelium to radicular cyst. MMP's influence not only epithelial rest cell migration, but also invasion of various stromal cells into granulomatous tissue.

  10. Recommendations for the management of postmenopausal vaginal atrophy

    DEFF Research Database (Denmark)

    Sturdee, D W; Panay, N; Ulrich, Lian


    itching, burning and dyspareunia, and sexual activity is often compromised. But, despite the various safe and effective options, only a minority (about 25% in the Western world and probably considerably less in other areas) will seek medical help. Some of this reluctance is due to the adverse publicity...... dryness can be helped by simple lubricants but the best and most logical treatment for urogenital atrophy is to use local estrogen. This is safe, effective and with few contraindications. It is hoped that these guidelines and recommendations, produced to coincide with World Menopause Day 2010, will help...

  11. Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials.

    Directory of Open Access Journals (Sweden)

    K Abigail Andrews

    Full Text Available There is considerable interest in designing therapeutic studies of individuals at risk of Alzheimer disease (AD to prevent the onset of symptoms. Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET, and several studies have shown that ~1/3 of healthy elderly have significant β-amyloid deposition. Here we assessed whether asymptomatic amyloid-PET-positive controls have increased rates of brain atrophy, which could be harnessed as an outcome measure for AD prevention trials. We assessed 66 control subjects (age = 73.5±7.3 yrs; MMSE = 29±1.3 from the Australian Imaging Biomarkers & Lifestyle study who had a baseline Pittsburgh Compound B (PiB PET scan and two 3T MRI scans ~18-months apart. We calculated PET standard uptake value ratios (SUVR, and classified individuals as amyloid-positive/negative. Baseline and 18-month MRI scans were registered, and brain, hippocampal, and ventricular volumes and annualized volume changes calculated. Increasing baseline PiB-PET measures of β-amyloid load correlated with hippocampal atrophy rate independent of age (p = 0.014. Twenty-two (1/3 were PiB-positive (SUVR>1.40, the remaining 44 PiB-negative (SUVR≤1.31. Compared to PiB-negatives, PiB-positive individuals were older (76.8±7.5 vs. 71.7±7.5, p<0.05 and more were APOE4 positive (63.6% vs. 19.2%, p<0.01 but there were no differences in baseline brain, ventricle or hippocampal volumes, either with or without correction for total intracranial volume, once age and gender were accounted for. The PiB-positive group had greater total hippocampal loss (0.06±0.08 vs. 0.02±0.05 ml/yr, p = 0.02, independent of age and gender, with non-significantly higher rates of whole brain (7.1±9.4 vs. 4.7±5.5 ml/yr and ventricular (2.0±3.0 vs. 1.1±1.0 ml/yr change. Based on the observed effect size, recruiting 384 (95%CI 195-1080 amyloid-positive subjects/arm will provide 80% power to detect 25

  12. Imaging geographic atrophy in age-related macular degeneration. (United States)

    Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G


    Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized.

  13. Neuropathology and Therapeutic Intervention in Spinal and Bulbar Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Haruhiko Banno


    Full Text Available Spinal and bulbar muscular atrophy (SBMA is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR. The histopathological finding in SBMA is loss of lower motor neurons in the anterior horn of the spinal cord as well as in the brainstem motor nuclei. Animal studies have revealed that the pathogenesis of SBMA depends on the level of serum testosterone, and that androgen deprivation mitigates neurodegeneration through inhibition of nuclear accumulation of the pathogenic AR. Heat shock proteins, ubiquitin-proteasome system and transcriptional regulation are also potential targets of therapy development for SBMA.

  14. Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy (United States)

    Konagaya, Masaaki; Konagaya, Yoko; Max, Stephen R.


    The effects are studied of the oral administration of RU38486, a potent selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose 6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose 6-phosphate dehydrogernase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids.

  15. Axonal loss occurs early in dominant optic atrophy

    DEFF Research Database (Denmark)

    Milea, Dan; Sander, Birgit; Wegener, Marianne


    Purpose: This study set out to investigate retinal nerve fibre layer (RNFL) thickness and best corrected visual acuity (BCVA) in relation to age in healthy subjects and patients with OPA1 autosomal dominant optic atrophy (DOA). Methods: We carried out a cross-sectional investigation of RNFL...... thickness and ganglion cell layer density in 30 healthy subjects and 10 patients with OPA1 DOA using optical coherence tomography (OCT). We then performed a regression analysis of RNFL thickness and BCVA versus age. Results: Both healthy subjects and DOA patients demonstrated a gradual reduction in RNFL...

  16. How Is Diabetic Heart Disease Diagnosed? (United States)

    ... page from the NHLBI on Twitter. How Is Diabetic Heart Disease Diagnosed? Your doctor will diagnose diabetic ... have diabetes, protein in the urine is a risk factor for DHD. Other Tests and Procedures Your doctor ...

  17. Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies. (United States)

    Sarro, Lidia; Senjem, Matthew L; Lundt, Emily S; Przybelski, Scott A; Lesnick, Timothy G; Graff-Radford, Jonathan; Boeve, Bradley F; Lowe, Val J; Ferman, Tanis J; Knopman, David S; Comi, Giancarlo; Filippi, Massimo; Petersen, Ronald C; Jack, Clifford R; Kantarci, Kejal


    Alzheimer's disease pathology frequently coexists with Lewy body disease at autopsy in patients with probable dementia with Lewy bodies. More than half of patients with probable dementia with Lewy bodies have high amyloid-β deposition as measured with (11)C-Pittsburgh compound B binding on positron emission tomography. Biomarkers of amyloid-β deposition precede neurodegeneration on magnetic resonance imaging during the progression of Alzheimer's disease, but little is known about how amyloid-β deposition relates to longitudinal progression of atrophy in patients with probable dementia with Lewy bodies. We investigated the associations between baseline (11)C-Pittsburgh compound B binding on positron emission tomography and the longitudinal rates of grey matter atrophy in a cohort of clinically diagnosed patients with dementia with Lewy bodies (n = 20), who were consecutively recruited to the Mayo Clinic Alzheimer's Disease Research Centre. All patients underwent (11)C-Pittsburgh compound B positron emission tomography and magnetic resonance imaging examinations at baseline. Follow-up magnetic resonance imaging was performed after a mean (standard deviation) interval of 2.5 (1.1) years. Regional grey matter loss was determined on three-dimensional T1-weighted magnetic resonance imaging with the tensor-based morphometry-symmetric normalization technique. Linear regression was performed between baseline (11)C-Pittsburgh compound B standard unit value ratio and longitudinal change in regional grey matter volumes from an in-house modified atlas. We identified significant associations between greater baseline (11)C-Pittsburgh compound B standard unit value ratio and greater grey matter loss over time in the posterior cingulate gyrus, lateral and medial temporal lobe, and occipital lobe as well as caudate and putamen nuclei, after adjusting for age (P < 0.05). Greater baseline (11)C-Pittsburgh compound B standard unit value ratio was also associated with greater

  18. Baseline and longitudinal grey matter changes in newly diagnosed Parkinson's disease: ICICLE-PD study. (United States)

    Mak, Elijah; Su, Li; Williams, Guy B; Firbank, Michael J; Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Owen, Adrian M; Khoo, Tien K; Brooks, David J; Rowe, James B; Barker, Roger A; Burn, David J; O'Brien, John T


    Mild cognitive impairment in Parkinson's disease is associated with progression to dementia (Parkinson's disease dementia) in a majority of patients. Determining structural imaging biomarkers associated with prodromal Parkinson's disease dementia may allow for the earlier identification of those at risk, and allow for targeted disease modifying therapies. One hundred and five non-demented subjects with newly diagnosed idiopathic Parkinson's disease and 37 healthy matched controls had serial 3 T structural magnetic resonance imaging scans with clinical and neuropsychological assessments at baseline, which were repeated after 18 months. The Movement Disorder Society Task Force criteria were used to classify the Parkinson's disease subjects into Parkinson's disease with mild cognitive impairment (n = 39) and Parkinson's disease with no cognitive impairment (n = 66). Freesurfer image processing software was used to measure cortical thickness and subcortical volumes at baseline and follow-up. We compared regional percentage change of cortical thinning and subcortical atrophy over 18 months. At baseline, cases with Parkinson's disease with mild cognitive impairment demonstrated widespread cortical thinning relative to controls and atrophy of the nucleus accumbens compared to both controls and subjects with Parkinson's disease with no cognitive impairment. Regional cortical thickness at baseline was correlated with global cognition in the combined Parkinson's disease cohort. Over 18 months, patients with Parkinson's disease with mild cognitive impairment demonstrated more severe cortical thinning in frontal and temporo-parietal cortices, including hippocampal atrophy, relative to those with Parkinson's disease and no cognitive impairment and healthy controls, whereas subjects with Parkinson's disease and no cognitive impairment showed more severe frontal cortical thinning compared to healthy controls. At baseline, Parkinson's disease with no cognitive impairment

  19. Progressive cerebellar atrophy: hereditary ataxias and disorders with spinocerebellar degeneration. (United States)

    Wolf, Nicole I; Koenig, Michel


    The hereditary ataxias with onset in childhood are a group of heterogeneous disorders, usually with autosomal recessive inheritance. In many of them, magnetic resonance imaging (MRI) shows cerebellar atrophy. The most prominent exception to this is Friedreich's ataxia, where MRI shows normal cerebellar volume, but sometimes spinal cord atrophy. In several of the hereditary ataxias, the causative gene plays an important role in DNA repair: ataxia telangiectasia and ataxia telangiectasia-like disorder, and ataxia with oculomotor apraxia type I and II. Mitochondrial metabolism is impaired in another group of inherited ataxias including the emergent group of defects in coenzyme Q10 synthesis. Few of these disorders are amenable to effective treatment, the most important of these being vitamin E-responsive ataxia. The autosomal dominant spinocerebellar ataxias are rare in childhood. Some of them, especially SCA7 and SCA2, may begin in childhood or even infancy, family history being positive in these cases. Additional clinical clues such as presence or absence of neuropathy or oculomotor apraxia still help in making a definitive diagnosis albeit there are still many unsolved cases. In pontocerebellar hypoplasia, a neurodegenerative disease with prenatal onset, the genetic basis of the different subtypes has recently been elucidated and involves genes with different functions.

  20. Memory Impairment at Initial Clinical Presentation in Posterior Cortical Atrophy. (United States)

    Ahmed, Samrah; Baker, Ian; Husain, Masud; Thompson, Sian; Kipps, Christopher; Hornberger, Michael; Hodges, John R; Butler, Christopher R


    Posterior cortical atrophy (PCA) is characterized by core visuospatial and visuoperceptual deficits, and predominant atrophy in the parieto-occipital cortex. The most common underlying pathology is Alzheimer's disease (AD). Existing diagnostic criteria suggest that episodic memory is relatively preserved. The aim of this study was to examine memory performance at initial clinical presentation in PCA, compared to early-onset AD patients (EOAD). 15 PCA patients and 32 EOAD patients, and 34 healthy controls were entered into the study. Patients were tested on the Addenbrooke's Cognitive Examination (ACE-R), consisting of subscales in memory and visuospatial skills. PCA and EOAD patients were significantly impaired compared to controls on the ACE total score (p skills (p skills compared to EOAD patients (p presentation. The findings suggest that memory impairment must be considered in assessment and management of PCA. Further study into memory in PCA is warranted, since the ACE-R is a brief screening tool and is likely to underestimate the presence of memory impairment.

  1. Interactive segmentation for geographic atrophy in retinal fundus images. (United States)

    Lee, Noah; Smith, R Theodore; Laine, Andrew F


    Fundus auto-fluorescence (FAF) imaging is a non-invasive technique for in vivo ophthalmoscopic inspection of age-related macular degeneration (AMD), the most common cause of blindness in developed countries. Geographic atrophy (GA) is an advanced form of AMD and accounts for 12-21% of severe visual loss in this disorder [3]. Automatic quantification of GA is important for determining disease progression and facilitating clinical diagnosis of AMD. The problem of automatic segmentation of pathological images still remains an unsolved problem. In this paper we leverage the watershed transform and generalized non-linear gradient operators for interactive segmentation and present an intuitive and simple approach for geographic atrophy segmentation. We compare our approach with the state of the art random walker [5] algorithm for interactive segmentation using ROC statistics. Quantitative evaluation experiments on 100 FAF images show a mean sensitivity/specificity of 98.3/97.7% for our approach and a mean sensitivity/specificity of 88.2/96.6% for the random walker algorithm.

  2. Current Status of Treatment of Spinal and Bulbar Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Fumiaki Tanaka


    Full Text Available Spinal and bulbar muscular atrophy (SBMA is the first member identified among polyglutamine diseases characterized by slowly progressive muscle weakness and atrophy of the bulbar, facial, and limb muscles pathologically associated with motor neuron loss in the spinal cord and brainstem. Androgen receptor (AR, a disease-causing protein of SBMA, is a well-characterized ligand-activated transcription factor, and androgen binding induces nuclear translocation, conformational change and recruitment of coregulators for transactivation of AR target genes. Some therapeutic strategies for SBMA are based on these native functions of AR. Since ligand-induced nuclear translocation of mutant AR has been shown to be a critical step in motor neuron degeneration in SBMA, androgen deprivation therapies using leuprorelin and dutasteride have been developed and translated into clinical trials. Although the results of these trials are inconclusive, renewed clinical trials with more sophisticated design might prove the effectiveness of hormonal intervention in the near future. Furthermore, based on the normal function of AR, therapies targeted for conformational changes of AR including amino-terminal (N and carboxy-terminal (C (N/C interaction and transcriptional coregulators might be promising. Other treatments targeted for mitochondrial function, ubiquitin-proteasome system (UPS, and autophagy could be applicable for all types of polyglutamine diseases.

  3. Transgenic mouse models of spinal and bulbar muscular atrophy (SBMA). (United States)

    Katsuno, M; Adachi, H; Inukai, A; Sobue, G


    Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by proximal muscle atrophy, weakness, contraction fasciculations, and bulbar involvement. Only males develop symptoms, while female carriers usually are asymptomatic. A specific treatment for SBMA has not been established. The molecular basis of SBMA is the expansion of a trinucleotide CAG repeat, which encodes the polyglutamine (polyQ) tract, in the first exon of the androgen receptor (AR) gene. The pathologic hallmark is nuclear inclusions (NIs) containing the mutant and truncated AR with expanded polyQ in the residual motor neurons in the brainstem and spinal cord as well as in some other visceral organs. Several transgenic (Tg) mouse models have been created for studying the pathogenesis of SBMA. The Tg mouse model carrying pure 239 CAGs under human AR promoter and another model carrying truncated AR with expanded CAGs show motor impairment and nuclear NIs in spinal motor neurons. Interestingly, Tg mice carrying full-length human AR with expanded polyQ demonstrate progressive motor impairment and neurogenic pathology as well as sexual difference of phenotypes. These models recapitulate the phenotypic expression observed in SBMA. The ligand-dependent nuclear localization of the mutant AR is found to be involved in the disease mechanism, and hormonal therapy is suggested to be a therapeutic approach applicable to SBMA.

  4. Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA). (United States)

    Katsuno, Masahisa; Tanaka, Fumiaki; Adachi, Hiroaki; Banno, Haruhiko; Suzuki, Keisuke; Watanabe, Hirohisa; Sobue, Gen


    Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by slowly progressive muscle weakness and atrophy. During the last two decades, basic and clinical research has provided important insights into the disease phenotype and pathophysiology. The cause of SBMA is the expansion of a trinucleotide CAG repeat encoding a polyglutamine tract within the first exon of the androgen receptor (AR) gene. SBMA exclusively affects adult males, whereas females homozygous for the AR mutation do not manifest neurological symptoms. The ligand-dependent nuclear accumulation of the polyglutamine-expanded AR protein is central to the gender-specific pathogenesis of SBMA, although additional steps, e.g., DNA binding, inter-domain interactions, and post-translational modification of AR, modify toxicity. The interactions with co-regulators are another requisite for the toxic properties of the polyglutamine-expanded AR. It is also shown that the polyglutamine-expanded AR induces diverse molecular events, such as transcriptional dysregulation, axonal transport disruption, and mitochondrial dysfunction, which play causative roles in the neurodegeneration in SBMA. The pathogenic AR-induced myopathy also contributes to the non-cell autonomous degeneration of motor neurons. Pre-clinical studies using animal models show that the pathogenic AR-mediated neurodegeneration is suppressed by androgen inactivation, the efficacy of which has been tested in clinical trials. Pharmacological activation of cellular defense machineries, such as molecular chaperones, ubiquitin-proteasome system, and autophagy, also exerts neuroprotective effects in experimental models of SBMA.

  5. Development and Translation of Therapies for Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Hannah K. Shorrock


    Full Text Available Spinal muscular atrophy (SMA is an autosomal recessive neuromuscular disorder characterised by widespread loss of lower motor neurons from the spinal cord, leading to progressive weakness and muscle atrophy. SMA is largely caused by homozygous loss of the survival motor neuron (SMN 1 gene, resulting in reduced levels of full-length SMN protein. Although no approved treatment is currently available for SMA, several clinical trials investigating different approaches to increase SMN levels are showing promising early results. Trials investigating the use of therapies targeting muscle strength and neuroprotective pathways are also in progress, generating the possibility of delivering combination therapies utilising both SMN-dependent and SMN-independent targets. Due to an increased understanding of the cellular and molecular consequences of SMN depletion, a second wave of therapies targeted at pathways downstream of SMN are currently undergoing preclinical development. As these therapies move forward towards the clinic, new treatment options are likely to become available, raising the potential to generate an effective ‘cure’ for SMA.

  6. Carbocalcitonin treatment in Sudeck's atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Nuti, R.; Vattimo, A.; Martini, G.; Turchetti, V.; Righi, G.A.


    The efficacy of new calcitonin, the amino analog of eel calcitonin (carboCT) on Sudeck's atrophy of the foot was investigated in 14 patients. CarboCT was administered at the dose of 40 Medical Research Council (MRC) units per day, and the duration of treatment was two to ten months. No adverse effects were noted. Bone pain and local edema decreased associated with improvement of motility. CarboCT induced a slight decrease in plasma calcium, plasma phosphate, and 24-hour urinary calcium excretion. An increase in cAMP/Cr ratio, an index of parathyroid function, was also observed (probably a manifestation of the hypocalcemic effect of calcitonin and secondary parathyroid stimulation). The whole body retention of 99mTc-MDP represents a valuable index of bone turnover, it decreased progressively and significantly on treatment. A dynamic study of local bone uptake of 99mTC-MDP was performed in eight patients. After carboCT therapy, statistically significant decreases in local blood flow, early uptake, and delayed uptake were appreciated in the involved foot. These findings lead to the conclusion that carboCT is effective in the treatment of Sudeck's atrophy.

  7. Connectivity network measures predict volumetric atrophy in mild cognitive impairment. (United States)

    Nir, Talia M; Jahanshad, Neda; Toga, Arthur W; Bernstein, Matt A; Jack, Clifford R; Weiner, Michael W; Thompson, Paul M


    Alzheimer's disease (AD) is characterized by cortical atrophy and disrupted anatomic connectivity, and leads to abnormal interactions between neural systems. Diffusion-weighted imaging (DWI) and graph theory can be used to evaluate major brain networks and detect signs of a breakdown in network connectivity. In a longitudinal study using both DWI and standard magnetic resonance imaging (MRI), we assessed baseline white-matter connectivity patterns in 30 subjects with mild cognitive impairment (MCI, mean age 71.8 ± 7.5 years, 18 males and 12 females) from the Alzheimer's Disease Neuroimaging Initiative. Using both standard MRI-based cortical parcellations and whole-brain tractography, we computed baseline connectivity maps from which we calculated global "small-world" architecture measures, including mean clustering coefficient and characteristic path length. We evaluated whether these baseline network measures predicted future volumetric brain atrophy in MCI subjects, who are at risk for developing AD, as determined by 3-dimensional Jacobian "expansion factor maps" between baseline and 6-month follow-up anatomic scans. This study suggests that DWI-based network measures may be a novel predictor of AD progression.

  8. Periorbital muscle atrophy associated with topical bimatoprost therapy

    Directory of Open Access Journals (Sweden)

    Wang PX


    Full Text Available Priscilla Xinhui Wang, Victor Teck Chang Koh, Jin Fong ChengDepartment of Ophthalmology, National University Health System, SingaporeAbstract: Topical Bimatoprost is a common and popular prostaglandin analog used as an ocular hypotensive agent in the treatment of glaucoma. Side effects include ocular hyperaemia, ocular pruritus, and periocular and iris pigmentary changes. Perioribital lipodystrophy is another well-documented outcome associated with chronic use of topical bimatoprost, which results in periorbital hallowing, upper eyelid sulcus deepening, eyelid retraction and enophthalmos. We report an unusual case of periocular muscle atrophy and weakness from unilateral topical bimatoprost use. Our patient had primary angle closure and experienced a right upper eyelid ptosis 2 months after she started to use topical bimatoprost in that eye. Clinical measurements of her eyelids clearly showed reduction in the function of her right levator muscle, suggesting that effects of topical bimatoprost may not be limited to periorbital fat. She was advised to stop topical bimatoprost and right ptosis correction surgery with levator muscle advancement was performed successfully. Ophthalmologists and patients should be aware of this potential rare side effect of topical bimatoprost, as it may be potentially disfiguring, especially with monocular use. However, its exact mechanism of action needs to be clarified further.Keywords: prostaglandin analog, levator, muscle atrophy, muscle weakness, ptosis, side effects

  9. Brain atrophy in patients with arterial disease. The SMART-MR study

    NARCIS (Netherlands)

    Appelman, A.P.A.


    Brain atrophy is often observed on magnetic resonance imaging (MRI) in the elderly. This is of clinical importance since the extent and rate of progression of brain atrophy are associated with future cognitive deterioration and conversion to Alzheimer’s dementia. The overall aim of this thesis was t

  10. Dominant inherited distal spinal muscular atrophy with atrophic and hypertrophic calves

    NARCIS (Netherlands)

    Groen, R J; Sie, O G; van Weerden, T W


    The clinical, electrophysiological, radiological and morphological data of 3 members of a family with autosomal dominant distal spinal muscular atrophy (DSMA) are reported. One patient has the clinical picture of peroneal muscular atrophy with atrophic calves. His father and sister suffer from cramp

  11. Toll-like Receptor 4 Signaling in Ventilator-induced Diaphragm Atrophy.

    NARCIS (Netherlands)

    Schellekens, W.J.M.; Hees, H.W.H. van; Vaneker, M.; Linkels, M.; Dekhuijzen, P.N.R.; Scheffer, G.J.; Hoeven, J.G. van der; Heunks, L.M.A.


    BACKGROUND:: Mechanical ventilation induces diaphragm muscle atrophy, which plays a key role in difficult weaning from mechanical ventilation. The signaling pathways involved in ventilator-induced diaphragm atrophy are poorly understood. The current study investigated the role of Toll-like receptor

  12. Association between blood pressure levels over time and brain atrophy in the elderly

    NARCIS (Netherlands)

    den Heijer, T; Skoog, [No Value; Oudkerk, M; de Leeuw, FE; de Groot, JC; Hofman, A; Breteler, MMB


    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  13. Association between blood pressure levels over time and brain atrophy in the elderly.

    NARCIS (Netherlands)

    Heijer, T.; Skoog, I.; Oudkerk, M.; Leeuw, H.F. de; Groot, J.C. de; Hofman, A.W.I.M.; Breteler, M.H.M.


    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  14. Relating Cortical Atrophy in Temporal Lobe Epilepsy with Graph Diffusion-Based Network Models. (United States)

    Abdelnour, Farras; Mueller, Susanne; Raj, Ashish


    Mesial temporal lobe epilepsy (TLE) is characterized by stereotyped origination and spread pattern of epileptogenic activity, which is reflected in stereotyped topographic distribution of neuronal atrophy on magnetic resonance imaging (MRI). Both epileptogenic activity and atrophy spread appear to follow white matter connections. We model the networked spread of activity and atrophy in TLE from first principles via two simple first order network diffusion models. Atrophy distribution is modeled as a simple consequence of the propagation of epileptogenic activity in one model, and as a progressive degenerative process in the other. We show that the network models closely reproduce the regional volumetric gray matter atrophy distribution of two epilepsy cohorts: 29 TLE subjects with medial temporal sclerosis (TLE-MTS), and 50 TLE subjects with normal appearance on MRI (TLE-no). Statistical validation at the group level suggests high correlation with measured atrophy (R = 0.586 for TLE-MTS, R = 0.283 for TLE-no). We conclude that atrophy spread model out-performs the hyperactivity spread model. These results pave the way for future clinical application of the proposed model on individual patients, including estimating future spread of atrophy, identification of seizure onset zones and surgical planning.

  15. COTA (colon-ovarian tumor antigen). An immunohistochemical study. (United States)

    Pant, K D; Fenoglio-Preiser, C M; Berry, C O; Zamora, P O; Ram, M D; Fulks, R M; Rhodes, B A


    A goat anti-serum was prepared against mucinous ovarian cyst fluid and absorbed with normal colon and a variety of normal tissues until the only residual immunoreactivity was directed against colon cancer and ovarian tumor mucin. The set of antigenic determinants defined by this anti-serum has been called COTA, standing for colon-ovarian-tumor-antigen. This highly absorbed anti-serum (anti-COTA) was used for immunohistochemical staining of 42 different tissues in parallel with staining with a goat anti-CEA, which was also highly absorbed. The results suggest that COTA is a highly sensitive and specific antigen for colon carcinoma and may have potential for the early detection of malignant changes predictive of cancer of the colon.

  16. A Histopathological and Immunohistochemical Analysis of Ameloblastic Fibrodentinoma

    Directory of Open Access Journals (Sweden)

    Ronell Bologna-Molina


    Full Text Available Ameloblastic fibrodentinoma (AFD is considered a mixed odontogenic tumor that is characterized by conserved epithelial and ectomesenchymal neoplastic components. AFD is composed of long narrow cords and islands of odontogenic epithelium; the epithelial strands lie in a myxoid cell-rich ectomesenchymal tissue with stellate-shaped fibroblasts that exhibit long slender cytoplasmic extensions that resemble dental papilla. The lesions show the presence of dysplastic dentin. Although AFD is a rare entity and its very existence is not completely accepted, based on the extent of histodifferentiation, it is considered to represent a stage between ameloblastic fibroma and ameloblastic fibroodontoma. This study aimed to provide a histopathological and immunohistochemical characterization of this infrequent tumor. A large panel of antibodies including amelogenin, Ck 19, calretinin, syndecan-1, E-cadherin, MSH2, histone H3, and Ki-67 was used to illustrate the nature of the tumor.

  17. Immunohistochemical Characteristics of Bone Forming Cells in Pleomorphic Adenoma

    Directory of Open Access Journals (Sweden)

    Keisuke Nakano, Takehiro Watanabe, Takako Shimizu, Toshiyuki Kawakami


    Full Text Available Histopathological and immunohistochemical examinations were carried out in a case of pleomorphic adenoma with bone formation, occurring in the chin of a 34-year-old Japanese man. Examination results showed the modified neoplastic myoepithelial cells reacted positively to S-100 protein. The S-100-positive modified neoplastic myoepithelial cells were proliferated in the closely related area of the bone tissue. Furthermore, positive reaction was detected in the bone forming cells: osteoblasts and osteocytes. These cells also reacted positively to Runx2 as a marker of bone forming cells. These results suggest that the origin of the bone forming cells in this case of pleomorphic adenoma was modified neoplastic myoepithelial cells.

  18. Immunohistochemical detection of brain tissue in heated meat products. (United States)

    Tersteeg, M H G; Koolmees, P A; van Knapen, F


    Immunohistochemical methods were used to determine whether brain tissue could be detected in test batches of meat products prepared with known levels of this tissue (0, 1, 5, 10, or 20% bovine brain tissue or 5% porcine brain tissue). Four different, commercially-available antibodies were examined: anti-Neurofilament (anti-NF), anti-MyelinBasicProtein (anti-MBP), anti-NeuronSpecificEnolase (anti-NSE) and anti-GlialFibrillaryAcidicProtein (anti-GFAP). Results obtained with the four antibodies differed with the heat treatment applied to the products (pasteurisation or sterilisation). The amount of immunoreaction product in the raw meat product varied with the antibody, even when the sample contained the same amount of brain tissue. The staining pattern also varied with the antibody. Overall, the anti-MBP antibody proved to be most useful in detecting brain tissue in finely comminuted heated meat products.

  19. Immunohistochemical studies of the periodontal membrane in primary teeth

    DEFF Research Database (Denmark)

    Bille, Marie-Louise Bastholm; Nolting, Dorrit; Kjær, Inger


    Objectives. To describe the periodontal membrane of human primary teeth immunohistochemically, while focusing on the epithelial layer of Malassez, fibers, and peripheral nerves, and to compare the findings with those of a previous study of human permanent teeth. Material and methods. Nineteen human...... primary teeth extracted in late childhood in connection with treatment were fixed, decalcified, dehydrated, and embedded in paraffin. Paraffin sections were stained with wide spectrum screening (WSS), Vimentin, and NeuN in order to mark the epithelial layer of Malassez, fibers, and peripheral nerves...... could be identical to those in regions with no resorption. Conclusion. In regions without resorption, spatial organization of the periodontal membrane of primary teeth was similar to that of permanent teeth, although the number and distribution of epithelial cells and fibers differed. In regions...

  20. Clinical, pathological, immunohistochemical and molecular characterization of feline chronic gingivostomatitis. (United States)

    Rolim, Veronica Machado; Pavarini, Saulo Petinatti; Campos, Fabrício Souza; Pignone, Viviam; Faraco, Cláudia; Muccillo, Marcelo de Souza; Roehe, Paulo Michel; da Costa, Fernanda Viera Amorim; Driemeier, David


    Objectives This study presents the clinical, pathological, immunohistochemical and molecular characterization of 26 cats with feline chronic gingivostomatitis (FCG). Methods Oral mucosal biopsies, blood and swabs were collected from cats presenting with oral lesions. The tissue sections were submitted for histopathology and immunohistochemical analysis for feline calicivirus (FCV), feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). The swabs were subjected to PCR analysis for FCV, and blood for FeLV and FIV. Results The main clinical findings were dysphagia (88.2%), halitosis (76.5%), sialorrhea (47.1%), weight loss (41.2%), intense oral discomfort (35.3%), oral hemorrhage (17.6%), and lackluster and fragile coat (11.8%). Gross inspection revealed bilateral lesions across the palatoglossal fold to the lateral tongue base. The lesions were diffuse, proliferative, intensely red and friable, and bled easily upon examination in 80.8% of cases. In 23.1% of cases, the lesions were multifocal to coalescent, at times forming multiple vesicles on a reddened, edematous palatoglossal fold. Microscopic examination showed that 15.4% of lesions had moderate (grade 2) and 84.6% had severe (grade 3) inflammation. Immunohistochemistry revealed the presence of FeLV antigens in the epithelium and the inflammatory infiltrate of 30.8% of the cats with FCG. FCV antigens were not detected in the FCG lesions. Conclusions and relevance The FCG cases analyzed could not be correlated with FCV. It is possible that FeLV plays a role as a causal agent of lesions in cases where the presence of the virus has been confirmed by immunohistochemistry in epithelial samples.

  1. Morphological and immunohistochemical characterisation of seminomas in Norwegian dogs

    Directory of Open Access Journals (Sweden)

    Thorvaldsen Tor


    Full Text Available Abstract Background Seminomas in the dog have traditionally been assumed to resemble human spermatocytic seminomas, based on their low malignancy and high occurrence in old individuals. However, recently published studies indicate that canine seminomas can be classified as classical and spermatocytic seminomas in a similar way as in man, and that classical seminomas comprise a substantial proportion of seminomas in the dog. These two factors both contribute to increasing the potential of canine seminoma as a relevant model for human testicular cancer. The aim of the present study was to characterise seminoma in Norwegian dogs using morphology and immunohistochemistry, and determine whether these tumours are comparable with human classical seminoma. Methods By applying diagnostic criteria from human pathology, 45 seminomas from the Norwegian Canine Cancer Register were examined histologically with hematoxylin and eosin (HE and periodic acid-Schiff (PAS stains. All sections were stained immunohistochemically with antibodies against human placental alkaline phosphatase (PLAP and the transmembrane receptor c-KIT. Results Although two of the seminomas showed immunohistochemical staining characteristics indicative of classical seminoma (PLAP+/c-KIT+, all 45 examined seminomas were morphologically consistent with spermatocytic seminoma. Conclusions The value of canine seminoma as a model for SE in man remains unclear. Among the 45 investigated tumours from Norwegian dogs, none were classified as classical seminoma based on morphological criteria consistent with human seminomas. Regional or breed differences in the occurrence of classical seminoma in the dog, as well as the lack of uniform diagnostic criteria, might explain the discrepancy between the findings in the current study and the results presented by other authors.

  2. Parapapillary atrophy and optic disc region assessment (PANDORA): retinal imaging tool for assessment of the optic disc and parapapillary atrophy (United States)

    Lu, Cheng-Kai; Tang, Tong Boon; Laude, Augustinus; Dhillon, Baljean; Murray, Alan F.


    We describe a computer-aided measuring tool, named parapapillary atrophy and optic disc region assessment (PANDORA), for automated detection and quantification of both the parapapillary atrophy (PPA) and the optic disc (OD) regions in two-dimensional color retinal fundus images. The OD region is segmented using a combination of edge detection and ellipse fitting methods. The PPA region is identified by the presence of bright pixels in the temporal zone of the OD, and it is segmented using a sequence of techniques, including a modified Chan-Vese approach, thresholding, scanning filter, and multiseed region growing. PANDORA has been tested with 133 color retinal images (82 with PPA; 51 without PPA) drawn randomly from the Lothian Birth Cohort (LBC) database, together with a "ground truth" estimate from an ophthalmologist. The PPA detection rate is 89.47% with a sensitivity of 0.83 and a specificity of 1. The mean accuracy in defining the OD region is 81.31% (SD=10.45) when PPA is present and 95.32% (SD=4.36) when PPA is absent. The mean accuracy in defining the PPA region is 73.57% (SD=11.62). PANDORA demonstrates for the first time how to quantify the OD and PPA regions using two-dimensional fundus images, enabling ophthalmologists to study ocular diseases related to PPA using a standard fundus camera.

  3. Large deletions within the spinal muscular atrophy gene region in a patient with spinal muscular atrophy type 3

    Institute of Scientific and Technical Information of China (English)

    Wei Wei; Chunyue Chen; Wenting Liu; Zhenfang Du; Xiaoling Chen; Xianning Zhang


    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration and loss of anterior horn cells in the spinal cord and brain stem nuclei, leading to progressive limb and trunk paralysis and muscular atrophy. Depending on the age of onset and maximum muscular function achieved, SMA is recognized as SMA1, SMA2, SMA3 or SMA4, and most patients have a deletion or truncation of the survival motor neuron 1 (SMN1) gene. In this report, we present a patient with a mild SMA phenotype, SMA3, and define his genetic abnormality. Tetra-primer amplification refractory mutation system PCR combined with restriction fragment length polymorphism analysis and array comparative genomic hybridization were used to determine the genetic variations in this patient. A 500 kb deletion in chromosome 5q13.2, including homozygous deletion of neuronal apoptosis inhibitory protein, and heterozygous deletion of occludin and B-double prime 1 was identified. This SMA region deletion did not involve SMN, indicating that SMN was likely to function normally. The phenotype was dependent of the large deletion and neuronal apoptosis inhibitory protein, occludin and B-double prime 1 may be candidate genes for SMA3.

  4. Quantitative analysis of the muscle atrophy in osteoarthritis of the hip by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Tajiri, Masahiro; Hieda, Hiroshi (Kurume Univ., Fukuoka (Japan). School of Medicine)


    Twenty normal hips and 30 cases of the unilateral osteoarthritic hips were examined by computed tomography in order to measure the atrophy of the muscles around the hip. We discussed the relationship among the muscle atrophy, stages of the osteoarthritic hip, and the clinical score of the JOA's criteria. The results were as follows: 1. There is no difference between the muscle volume of both sides in normal hips. 2. Atrophy of the gluteus maximus and the gluteus medius were already observed at the preosteoarthritic stage and the gluteus minimus, the tensor fasciae latae, iliopsoas revealed atrophy at the late stage. 3. There was a negative correlation between the percentage of atrophy of the gluteus maximus and the clinical score of the JOA's criteria. 4. In cases of normal position of the greater trochanter, artophy of the gluteus medius was more distinguished in cases of abductors of grade 4 by MMT than in those of normal grade.

  5. [Left pulmonary agenesis diagnosed late]. (United States)

    Deleanu, Oana; Pătraşcu, Natalia; Nebunoiu, Ana-Maria; Vintilă, V; Ulmeanu, Ruxandra; Mihălţan, F D


    We present the case of a 51 years old female-patient, with severe dextroscoliosis, having like unique symptom progressive dyspnea. The blood samples reveals polycythemia, the radiological exam shows the opacification of 2/3 of the left thorax, the absence of the lung structure in the other 1/3, the deviation of the mediastinum, and dextroscoliosis; the computed tomography reveals the absence of the left lung artery and the left airways, compensatory hyperinflation of the right lung and dilatation of the trunk and right pulmonary artery; the bronchoscopy does not visualize the carina or the left main bronchus, typical for pulmonary agenesis. Echocardiography confirmed the absence of left pulmonary artery and shows mild pulmonary hypertension (systolic pressure in the pulmonary artery of 33 mmHg) with dilatation of the right cavities, but good cinetics. We face a case of pulmonary agenesis lately diagnosed, with modest functional cardiologic implications, limited therapeutic options and good survival, justified by the late appearance of the pulmonary hypertension of low severity and without worsening in time.

  6. Immunohistochemical classification and prognosis of diffuse large B-cell lymphoma in China

    Institute of Scientific and Technical Information of China (English)



    Objective To study the immunohistochemical classification and prognosis of diffuse large B-cell lymphoma(DLBCL).Methods A total of 148 cases of DLBCL were classified into germinal center B-cell-like(GCB)and non-GCB/activated B-cell-like(ABC)subtypes by Hans,Choi and Tally immunohistochemical stain algorithms.The clinical features and survival data of GCB

  7. Strategies for treating scoliosis in children with spinal muscular atrophy. (United States)

    Tobert, Daniel G; Vitale, Michael G


    Progressive pulmonary dysfunction is a major complication of spinal muscular atrophy (SMA). Growing constructs are a well-established alternative to spinal arthrodesis to maximize pulmonary growth. We describe patients who demonstrated sustained pulmonary function and improved quality of life following hybrid growing construct implantation. The purpose of this article is to demonstrate a range of approaches for managing scoliosis in children with SMA by utilizing vertical expandable prosthetic titanium rib implantation or growing rods with lateral rib fixation to improve clinical and patient-reported outcomes. Pulmonary compromise and quality of life decline are leading concerns in the SMA population. This case series highlights important surgical strategies that can be utilized to treat scoliosis in patients with SMA.

  8. Exercise Therapy in Spinobulbar Muscular Atrophy and Other Neuromuscular Disorders

    DEFF Research Database (Denmark)

    Dahlqvist, Julia Rebecka; Vissing, John


    There is no curative treatment for most neuromuscular disorders. Exercise, as a treatment for these diseases, has therefore received growing attention. When executed properly, exercise can maintain and improve health and reduce the risk of cardiovascular disease, obesity, and diabetes. In persons...... in patients with neuromuscular diseases associated with weakness and wasting. We review studies that have investigated different types of exercise in both myopathies and motor neuron diseases, with particular emphasis on training of persons affected by spinobulbar muscular atrophy (SBMA). Finally, we provide...... with muscle wasting due to neuromuscular conditions, however, a common belief has been that physical activity could accelerate degeneration of the diseased muscle and a careful approach to training has therefore been suggested. In this review, we describe the current knowledge about physical training...

  9. The nature of the autonomic dysfunction in multiple system atrophy (United States)

    Parikh, Samir M.; Diedrich, Andre; Biaggioni, Italo; Robertson, David


    The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

  10. [Development of therapeutics for spinal and bulbar muscular atrophy (SBMA)]. (United States)

    Sobue, Gen


    Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a hereditary motor neuron disease that affects males, caused by the expansion of a polyglutamine (polyQ) tract in androgen receptor (AR). Female carriers are usually asymptomatic. The transgenic mouse (Tg) model carrying a full-length human AR with expanded polyQ has significant gender-related motor impairment. This phenotype is inhibited by castration, which prevents nuclear translocation of mutant AR. Leuprorelin, an LHRH agonist that reduces testosterone release from the testis, also rescues motor dysfunction and nuclear accumulation of mutant AR in the male Tg. Over-expression of a molecular chaperone HSP70, which renatures misfolded mutant AR, ameliorates neuromuscular phenotypes of the Tg by reducing nuclear-localized mutant AR. HSP70 appears to enhance the degradation of mutant AR via ubiquitin-proteasome pathway. These experimental approaches indicate the possibility of clinical application of drugs, such as leuprorelin, for SBMA patients.

  11. Unusual association of sporadic olivopontocerebellar atrophy and motor neuron disease. (United States)

    Testa, D; Tiranti, V; Girotti, F


    Sporadic olivopontocerebellar atrophy (OPCA) is a neurodegenerative disorder that presents a wide clinical spectrum. Motor neuron disease (MND) is characterized by a selective degeneration of motor neurons. A 60-year-old man developed slurred speech and unsteadiness of gait. He had also noticed difficulty in holding his head upright and shoulder weakness. The disease had a rapid progression. At the age of 63 years, magnetic resonance imaging supported a diagnosis of OPCA, and a diagnosis of MND was suggested by clinical and electrophysiological findings. He also had upward gaze palsy. A muscular biopsy showed sporadic ragged red and Cox deficient fibers. The present case could define a unique disorder, as the occasional occurrence of two degenerative disorders appears unlikely.

  12. LHON and other optic nerve atrophies: the mitochondrial connection. (United States)

    Howell, Neil


    The clinical, biochemical and genetic features of Leber's hereditary optic neuropathy (LHON) are reviewed. The etiology of LHON is complex, but the primary risk factor is a mutation in one of the seven mitochondrial genes that encode subunits of respiratory chain complex I. The pathogenesis of LHON is not yet understood, but one plausible model is that increased or altered mitochondrial ROS production renders the retinal ganglion cells vulnerable to apoptotic cell death. In addition to LHON, there are a large number of other optic nerve degenerative disorders including autosomal dominant optic atrophy, the toxic/nutritional optic neuropathies and glaucoma. A review of the recent scientific literature suggests that these disorders also involve mitochondrial dysfunction or altered mitochondrial signaling pathways in their pathogenesis. This mitochondrial link provides new avenues of experimental investigation to these major causes of loss of vision.

  13. Alexander disease with mild dorsal brainstem atrophy and infantile spasms. (United States)

    Torisu, Hiroyuki; Yoshikawa, Yoko; Yamaguchi-Takada, Yui; Yano, Tamami; Sanefuji, Masafumi; Ishizaki, Yoshito; Sawaishi, Yukio; Hara, Toshiro


    We present the case of a Japanese male infant with Alexander disease who developed infantile spasms at 8 months of age. The patient had a cluster of partial seizures at 4 months of age. He presented with mild general hypotonia and developmental delay. Macrocephaly was not observed. Brain magnetic resonance imaging (MRI) findings fulfilled all MRI-based criteria for the diagnosis of Alexander disease and revealed mild atrophy of the dorsal pons and medulla oblongata with abnormal intensities. DNA analysis disclosed a novel heterozygous missense mutation (c.1154 C>T, p.S385F) in the glial fibrillary acidic protein gene. At 8 months of age, tonic spasms occurred, and electroencephalography (EEG) revealed hypsarrhythmia. Lamotrigine effectively controlled the infantile spasms and improved the abnormal EEG findings. Although most patients with infantile Alexander disease have epilepsy, infantile spasms are rare. This comorbid condition may be associated with the distribution of the brain lesions and the age at onset of Alexander disease.

  14. Spinal muscular atrophy: Factors that modulate motor neurone vulnerability. (United States)

    Tu, Wen-Yo; Simpson, Julie E; Highley, J Robin; Heath, Paul R


    Spinal muscular atrophy (SMA), a leading genetic cause of infant death, is a neurodegenerative disease characterised by the selective loss of particular groups of motor neurones in the anterior horn of the spinal cord with concomitant muscle weakness. To date, no effective treatment is available, however, there are ongoing clinical trials are in place which promise much for the future. However, there remains an ongoing problem in trying to link a single gene loss to motor neurone degeneration. Fortunately, given successful disease models that have been established and intensive studies on SMN functions in the past ten years, we are fast approaching the stage of identifying the underlying mechanisms of SMA pathogenesis Here we discuss potential disease modifying factors on motor neurone vulnerability, in the belief that these factors give insight into the pathological mechanisms of SMA and therefore possible therapeutic targets.

  15. Neocortical Neuronal Loss in Patients with Multiple System Atrophy

    DEFF Research Database (Denmark)

    Salvesen, Lisette; Winge, Kristian; Brudek, Tomasz


    To determine the extent of neocortical involvement in multiple system atrophy (MSA), we used design-based stereological methods to estimate the total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the frontal, parietal, temporal, and occipital cortex of brains from 11 patients...... with MSA and 11 age- and gender-matched control subjects. The stereological data were supported by cell marker expression analyses in tissue samples from the prefrontal cortex. We found significantly fewer neurons in the frontal and parietal cortex of MSA brains compared with control brains. Significantly...... more astrocytes and microglia were observed in the frontal, parietal, and temporal cortex of MSA brains, whereas no change in the total number of oligodendrocytes was seen in any of the neocortical regions. There were significantly fewer neurons in the frontal cortex of MSA patients with impaired...

  16. Optic atrophy 1-dependent mitochondrial remodeling controls steroidogenesis in trophoblasts. (United States)

    Wasilewski, Michał; Semenzato, Martina; Rafelski, Susanne M; Robbins, Jennifer; Bakardjiev, Anna I; Scorrano, Luca


    During human pregnancy, placental trophoblasts differentiate and syncytialize into syncytiotrophoblasts that sustain progesterone production [1]. This process is accompanied by mitochondrial fragmentation and cristae remodeling [2], two facets of mitochondrial apoptosis, whose molecular mechanisms and functional consequences on steroidogenesis are unclear. Here we show that the mitochondria-shaping protein Optic atrophy 1 (Opa1) controls efficiency of steroidogenesis. During syncytialization of trophoblast BeWo cells, levels of the profission mitochondria-shaping protein Drp1 increase, and those of Opa1 and mitofusin (Mfn) decrease, leading to mitochondrial fragmentation and cristae remodeling. Manipulation of the levels of Opa1 reveal an inverse relationship with the efficiency of steroidogenesis in trophoblasts and in mouse embryonic fibroblasts where the mitochondrial steroidogenetic pathway has been engineered. In an in vitro assay, accumulation of cholesterol is facilitated in the inner membrane of isolated mitochondria lacking Opa1. Thus, Opa1-dependent inner membrane remodeling controls efficiency of steroidogenesis.

  17. OCT Minimum Intensity as a Predictor of Geographic Atrophy Enlargement (United States)

    Stetson, Paul F.; Yehoshua, Zohar; Garcia Filho, Carlos Alexandre A.; Portella Nunes, Renata; Gregori, Giovanni; Rosenfeld, Philip J.


    Purpose. We determined whether the minimum intensity (MI) of the optical coherence tomography (OCT) A-scans within the retina can predict locations of growth at the margin of geographic atrophy (GA) and the growth rate outside the margin. Methods. The OCT scans were analyzed at baseline and 52 weeks. Expert graders manually segmented OCT images of GA. The 52-week follow-up scans were registered to the baseline scan coordinates for comparison. The OCT MI values were studied within a 180-μm margin around the boundary of GA at baseline. Baseline MI values were compared in areas of progression and nonprogression of the GA, and sensitivity and specificity were assessed for prediction of growth at the margin. Average MI values in the margins were compared to overall growth rates to evaluate the prediction of growth outside the margins. Results. A statistically significant increase in MI (P < 0.05) was seen in areas of growth in 21/24 cases (88%), and 22/24 cases (92%) when the foveal subfield was excluded. Locations of growth within the margins at 52 weeks were predicted with 61% sensitivity and 61% specificity. The MI values correlated significantly with overall growth rate, and high and low growth rate subjects were identified with 80% sensitivity and 64% specificity. Conclusions. The MI may be increased at the margins of GA lesions before enlargement, which may indicate disruption or atrophy of the photoreceptors in these areas before GA becomes apparent. Increased MI may help predict areas of enlargement of GA, and may relate to overall growth rate and be a useful screening tool for GA. ( number, NCT00935883.) PMID:24408973

  18. White matter atrophy and cognitive dysfunctions in neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Frederic Blanc

    Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain and VBM for focal brain volume (GM and WM, NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54% had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in

  19. Luminal B tumors are the most frequent molecular subtype in breast cancer of North African women: an immunohistochemical profile study from Morocco

    Directory of Open Access Journals (Sweden)

    El Fatemi Hinde


    Full Text Available Abstract Background Breast cancer may be classified into luminal A, luminal B, HER2+/ER-, basal-like and normal-like subtypes based on gene expression profiling or immunohistochemical (IHC characteristics. The aim of our study is to show the molecular profile characteristic of breast cancer in the North African population of Morocco. This work showed preliminary results and correlations with clinicopathological and histological parameters. Three hundred and ninety primary breast carcinomas tumor tissues were immunostained for ER, PR, HER2, CK5/6, CK8/18 and Ki67 using paraffin tissue. Methods We reviewed 390 cases of breast cancer diagnosed on January 2008 to December 2011 at the Department of pathology, Hassan II teaching hospital, Fez, Morocco. Age, size tumor, metastatic profile, node involvement profile, histological type and immunohistochemical profile were studied. Results The average age was 46 years; our patients were diagnosed late with a high average tumor size. Luminal B subtype was more prevalent (41.8%, followed by luminal A (30.5%, basal-like (13, 6%, Her2-overexpressing (9, 2%, and unclassified subtype (4.9%. Conclusion This study showed that molecular classification and biological profile may be different according to geographical distribution, to encourage further studies to know the genomic profile of tumors and the environment. Virtual slide

  20. Immunohistochemical comparison of CD5, lambda, and kappa expression in primary and recurrent buccal mucosa-associated lymphoid tissue (MALT) lymphomas. (United States)

    Tanaka, Toshiaki; Kitabatake, Kenichirou; Iino, Mituyoshi; Goto, Kaoru


    Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal marginal zone B-cell lymphoma and is a distinct subtype of non-Hodgkin's lymphoma.Primary MALT lymphomas can also occur in the oral cavity, although their appearance in this location is rare. The neoplastic cells of which MALT lymphomas are composed express B-cell antigens and show monotypic immunoglobulin expression with light-chain restriction.Although neoplastic MALT lymphoma cells do not express CD5, previous studies have shown that CD5 positive MALT lymphomas are more prone to dissemination than those that do not express CD5. Moreover, there are some reports that describe kappa- and lambda- dual light chain expression in B cell malignant neoplasms.A 66-year-old Japanese woman with swelling of the right buccal mucosa was referred to our hospital. The lesion was excised and was pathologically diagnosed as a MALT lymphoma tumor with a t(11;18)(q21;q21) chromosome translocation.Swelling of the right buccal mucosa recurred 2 years later. The recurrent tumor was then excised and pathologically diagnosed as MALT lymphoma.Immunohistochemical examination of CD5, lambda, and kappa expressions revealed that the primary tumor was positive for CD5, kappa, and lambda, but the recurrent tumor was weakly positive for CD5 and kappa.With respect to lambda positivity, the recurrent tumor showed negativity.Our study suggests that immunohistochemical expression of CD5, kappa, and lambda in oral MALT lymphoma have the risk of recurrence.We first described the recurrence of CD5 positive MALT lymphoma in the oral cavity and compared the immunohistochemical expressions of CD5, lambda, and kappa between the primary and recurrent tumors.

  1. Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease. (United States)

    Lambert, Christian; Benjamin, Philip; Zeestraten, Eva; Lawrence, Andrew J; Barrick, Thomas R; Markus, Hugh S


    Cerebral small vessel disease is a common condition associated with lacunar stroke, cognitive impairment and significant functional morbidity. White matter hyperintensities and brain atrophy, seen on magnetic resonance imaging, are correlated with increasing disease severity. However, how the two are related remains an open question. To better define the relationship between white matter hyperintensity growth and brain atrophy, we applied a semi-automated magnetic resonance imaging segmentation analysis pipeline to a 3-year longitudinal cohort of 99 subjects with symptomatic small vessel disease, who were followed-up for ≥1 years. Using a novel two-stage warping pipeline with tissue repair step, voxel-by-voxel rate of change maps were calculated for each tissue class (grey matter, white matter, white matter hyperintensities and lacunes) for each individual. These maps capture both the distribution of disease and spatial information showing local rates of growth and atrophy. These were analysed to answer three primary questions: first, is there a relationship between whole brain atrophy and magnetic resonance imaging markers of small vessel disease (white matter hyperintensities or lacune volume)? Second, is there regional variation within the cerebral white matter in the rate of white matter hyperintensity progression? Finally, are there regionally specific relationships between the rates of white matter hyperintensity progression and cortical grey matter atrophy? We demonstrate that the rates of white matter hyperintensity expansion and grey matter atrophy are strongly correlated (Pearson's R = -0.69, P atrophy occurs annually (P atrophy rates, in the medial-frontal, orbito-frontal, parietal and occipital regions. Conversely, increased rates of global grey matter atrophy are significantly associated with faster white matter hyperintensity growth in the frontal and parietal regions. Together, these results link the progression of white matter hyperintensities

  2. Are Pediatricians Diagnosing Obese Children? (United States)

    Thomas, Katharine; Urrego, Fernando


    Background: Pediatric obesity is the most prevalent nutritional disorder in American children. The detrimental social, psychological, and physiological effects of obesity call for pediatricians to address this health concern. The literature demonstrates that clinicians are underreporting the diagnosis of obesity in the pediatric setting. The primary purpose of this study was to determine if pediatricians at one pediatrics clinic in the Ochsner Health System are documenting the presence of an overweight or obese body mass index (BMI) as a diagnosis in the medical record. A secondary purpose of this study was to determine the demographics of all pediatric patients in the Ochsner Health System to be used for program development. Methods: A retrospective medical record review was conducted. Records from April 1, 2012 to April 1, 2016, were reviewed for the presence of the diagnosis of BMI classified as obese or overweight. Results: We analyzed a total of 175,066 records in this study. Of these records, 1.32% documented a diagnosis of obesity, and 0.5% documented a BMI score indicating overweight. The percentages of patient visits that met the Centers for Disease Control and Prevention criteria to be classified as obese or overweight were 28.66% and 30.41%, respectively. The majority of our pediatric patients were male (51.76%), white (43.31%), and 5-12 years old (43.80%). Conclusion: This study demonstrates that pediatricians at Ochsner Health Center for Children are not diagnosing patients who have unhealthy BMI scores as overweight or obese. Interventions are needed to increase the identification of children who may benefit from receiving resources that encourage a healthy lifestyle and optimal weight maintenance. PMID:28331453

  3. Novel approaches in diagnosing tuberculosis (United States)

    Kolk, Arend H. J.; Dang, Ngoc A.; Kuijper, Sjoukje; Gibson, Tim; Anthony, Richard; Claassens, Mareli M.; Kaal, Erwin; Janssen, Hans-Gerd


    The WHO declared tuberculosis (TB) a global emergency. An estimated 8-9 million new cases occur each year with 2-3 million deaths. Currently, TB is diagnosed mostly by chest-X ray and staining of the mycobacteria in sputum with a detection limit of 1x104 bacteria /ml. There is an urgent need for better diagnostic tools for TB especially for developing countries. We have validated the electronic nose from TD Technology for the detection of Mycobacterium tuberculosis by headspace analysis of 284 sputum samples from TB patients. We used linear discriminant function analysis resulting in a sensitivity of 75% a specificity of 67% and an accuracy of 69%. Further research is still required to improve the results by choosing more selective sensors and sampling techniques. We used a fast gas chromatography- mass spectrometry method (GC-MS). The automated procedure is based on the injection of sputum samples which are methylated inside the GC injector using thermally assisted hydrolysis and methylation (THM-GC-MS). Hexacosanoic acid in combination with tuberculostearic acid was found to be specific for the presence of M. tuberculosis. The detection limit was similar to microscopy. We found no false positives, all microscopy and culture positive samples were also found positive with the THM-GC-MS method. The detection of ribosomal RNA from the infecting organism offers great potential since rRNA molecules outnumber chromosomal DNA by a factor 1000. It thus may possible to detect the organism without amplification of the nucleic acids (NA). We used a capture and a tagged detector probe for the direct detection of M. tuberculosis in sputum. So far the detection limit is 1x106 bacteria / ml. Currently we are testing a Lab-On-A-Chip Interferometer detection system.

  4. Immunohistochemical expression of p16ink4a in inflammatory, preneoplastic and neoplastic cervical lesions

    Directory of Open Access Journals (Sweden)

    Gajanin Radoslav


    Full Text Available Introduction. High-risk human papilloma viruses play a main role in the development of cervical dysplasias and carcinomas. p16INK4a can be considered as a surrogate marker of active highrisk human papillomaviruses infection in dysplastic and neoplastic cells of the cervix. This study was aimed at determining the presence and level of p16INK4a expression in inflammatory, preneoplastic and neoplastic lesions of the cervix. Material and Methods. The study was performed on 109 samples of cervical biopsy. Cervical cancer was diagnosed in 36 patients, 34 patients had a preneoplastic change (dysplasia in stratified squamous cervix epithelium and a nonspecific inflammatory process was found in 39 patients. In all samples, immunohistochemical analysis using antibodies to p16INK4a was performed. Results. The expression of p16INK4a was verified in all cases of cervical cancer (100%, in 67.65% of dysplastic cervical lesions and in 38.5% of inflammatory lesions. A statistically highly significant difference was found in the presence and level of expression among neoplasic, dysplastic and inflammatory lesions of the cervix (χ² = 76.02, p < 0.001. The expression was more frequent and had a higher level in neoplastic and high grade dysplastic lesions compared to expression in inflammatory lesions and low grade dysplasias. Conclusion. The analysis of the presence of p16INK4a can differentiate non-neoplastic, high grade preneoplastic and neoplastic changes of the cervix. The use of p16INK4a in interpreting borderline lesions of the cervix can enable a rational therapeutic treatment of patients.

  5. A clinicopathological and immunohistochemical study of clinically non-functioning pituitary adenomas: A single institutional experience

    Directory of Open Access Journals (Sweden)

    Rishi Arvind


    Full Text Available Background : Non-functioning pituitary adenomas (NFPA are characterized by the lack of clinical syndrome as compared to functioning adenomas (FA but not all functioning adenomas have clinical effects. Their exact incidence varies in different series. Materials and Methods : This study was undertaken to analyze the hormonal profile of NFPA at the immunohistochemical level in the Indian population and to see if any differences exist from the earlier studies. Their biological aggressiveness was also studied by MIB-1 labeling index (MIB-! LI and Epidermal Growth Factor Receptor (EGFR expression. These parameters along with their clinical behavior were correlated with radiological features of invasiveness and size. Results : Of the 151 pituitary adenomas diagnosed during a period of one and half years, 77 (51% were NFPA with a male predominance. There was increase in the incidence of NFPA with increase in age. Immunopositivity for various hormones was observed in 64 (83% cases, either singly or in various combinations. On the basis of immunohistochemistry, NFPA were classified into three subtypes; gonadotroph adenomas, silent adenomas, and null cell adenomas. Gonadotroph adenomas were the commonest subtype. In general, NFPA showed low MIB-1LI but invasive NFPA had LI on the higher side, however, this difference was not significant. We observed EGFR positivity in two cases only; therefore the tumorigenesis mechanism may be different in NFPA. Conclusion : Although non-functional at the clinical level immunohistochemistry showed reactivity for various hormones. If a battery of immunostains including seven hormones is studied, a significant number of cases are shifted to the functional group.

  6. Optic nerve atrophy and retinal nerve fibre layer thinning following optic neuritis: evidence that axonal loss is a substrate of MRI-detected atrophy. (United States)

    Trip, S Anand; Schlottmann, Patricio G; Jones, Stephen J; Li, Wai-Yung; Garway-Heath, David F; Thompson, Alan J; Plant, Gordon T; Miller, David H


    Magnetic resonance imaging (MRI) measures of brain atrophy are often considered to be a marker of axonal loss in multiple sclerosis (MS) but evidence is limited. Optic neuritis is a common manifestation of MS and results in optic nerve atrophy. Retinal nerve fibre layer (RNFL) imaging is a non-invasive way of detecting axonal loss following optic neuritis. We hypothesise that if the optic nerve atrophy that develops following optic neuritis is contributed to by axonal loss, it will correlate with thinning of the RNFL. Twenty-five patients were studied at least 1 year after a single unilateral attack of optic neuritis without recurrence, with a selection bias towards incomplete recovery. They had MR quantification of optic nerve cross-sectional area and optic nerve lesion length, as well as optical coherence tomography (OCT) measurement of mean RNFL thickness and macular volume, quantitative visual testing, and visual evoked potentials (VEPs). Fifteen controls were also studied. Significant optic nerve atrophy (mean decrease 30% versus controls), RNFL thinning (mean decrease 33% versus controls), and macular volume loss occurred in patients' affected eyes when compared with patients' unaffected eyes and healthy controls. The optic nerve atrophy was correlated with the RNFL thinning, macular volume loss, visual acuity, visual field mean deviation, and whole field VEP amplitude but not latency. These findings suggest that axonal loss contributes to optic nerve atrophy following a single attack of optic neuritis. By inference, axonal loss due to other post-inflammatory brain lesions is likely to contribute to the global MRI measure of brain atrophy in multiple sclerosis.

  7. 萎缩性花斑糠疹%Atrophying pityriasis versicolor

    Institute of Scientific and Technical Information of China (English)

    胡燕; 朱小红; 陈浩; 张海平; 吉津; 杨莉佳


    A 26-year-old woman presented with scaly atrophic erythema on the chest and abdomen for nearly 2 years.Direct microscopic examination of the lesion scrapings revealed numerous stubby hyphae and clustered spores.Periodic acid-Schiff (PAS) staining of the biopsy tissue showed the presence of numerous hyphae and spores in the horny layer.The stain for elastic fibers revealed that the number of elastic fibers decreased,and some elastic fibers became fine and disrupted.The patient was diagnosed with atrophying pityriasis versicolor.The lesions subsided and direct microscopic examination was negative after 1-week treatment with oral itraconazole of 200 mg once daily and 4-week treatment with topical 2% sertaconazole cream.%患者女,26岁.因胸腹部鳞屑性红斑伴萎缩近2年就诊.取皮屑直接镜检,见较多粗短的菌丝及成簇孢子.皮损组织病理检查,过碘酸雪夫(PAS)染色见角质层内较多菌丝和孢子.弹力纤维染色示弹力纤维减少,部分弹力纤维纤细、断裂.诊断:萎缩性花斑糠疹.治疗:口服伊曲康唑胶囊200mg/d共1周,外用2%舍他康唑乳膏4周,皮疹消退,真菌直接镜检复查阴性.

  8. Differences in F-Wave Characteristics between Spinobulbar Muscular Atrophy and Amyotrophic Lateral Sclerosis. (United States)

    Fang, Jia; Cui, Liying; Liu, Mingsheng; Guan, Yuzhou; Li, Xiaoguang; Li, Dawei; Cui, Bo; Shen, Dongchao; Ding, Qingyun


    There is limited data on the differences in F-wave characteristics between spinobulbar muscular atrophy (SBMA) and lower motor neuron dominant (LMND) amyotrophic lateral sclerosis (ALS). We compared the parameters of F-waves recorded bilaterally from the median, ulnar, tibial, and deep peroneal nerves in 32 SBMA patients, 37 patients with LMND ALS, and 30 normal controls. The maximum F-wave amplitudes, frequencies of giant F-waves, and frequencies of patients with giant F-waves in all nerves examined were significantly higher in the SBMA patients than in the ALS patients and the normal controls. The mean F-wave amplitude, maximum F-wave amplitude, frequency of giant F-waves, and frequency of patients with giant F-waves in the median and deep peroneal nerves were comparable between the ALS patients and normal controls. Giant F-waves were detected in multiple nerves and were often symmetrical in the SBMA patients compared with the ALS patients. The number of nerves with giant F-waves seems to be the most robust variable for differentiation of SBMA from ALS, with an area under the curve of 0.908 (95% CI: 0.835-0.982). A cut-off value of the number of nerves with giant F-waves (≥3) for diagnosing SBMA showed high sensitivity and specificity: 85% sensitivity and 81% specificity vs. ALS patients. No significant correlations were found between the pooled frequency of giant F-waves and disease duration in the SBMA (r = 0.162, P = 0.418) or ALS groups (r = 0.107, P = 0.529). Our findings suggested that F-waves might be used to discriminate SBMA from ALS, even at early stages of disease.

  9. Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. (United States)

    Atsuta, Naoki; Watanabe, Hirohisa; Ito, Mizuki; Banno, Haruhiko; Suzuki, Keisuke; Katsuno, Masahisa; Tanaka, Fumiaki; Tamakoshi, Akiko; Sobue, Gen


    Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motoneuron disease caused by a CAG-repeat expansion in the androgen receptor (AR) gene and for which no curative therapy exists. However, since recent research may provide opportunities for medical treatment, information concerning the natural history of SBMA would be beneficial in planning future clinical trials. We investigated the natural course of SBMA as assessed by nine activities of daily living (ADL) milestones in 223 Japanese SBMA patients (mean age at data collection = 55.2 years; range = 30-87 years) followed from 1 to 20 years. All the patients were diagnosed by genetic analysis. Hand tremor was an early event that was noticed at a median age of 33 years. Muscular weakness occurred predominantly in the lower limbs, and was noticed at a median age of 44 years, followed by the requirement of a handrail to ascend stairs at 49, dysarthria at 50, dysphagia at 54, use of a cane at 59 and a wheelchair at 61 years. Twenty-one of the patients developed pneumonia at a median age of 62 and 15 of them died at a median age of 65 years. The most common cause of death in these cases was pneumonia and respiratory failure. The ages at onset of each ADL milestone were strongly correlated with the length of CAG repeats in the AR gene. However CAG-repeat length did not correlate with the time intervals between each ADL milestone, suggesting that although the onset age of each ADL milestone depends on the CAG-repeat length in the AR gene, the rate of disease progression does not. The levels of serum testosterone, an important triggering factor for polyglutamine-mediated motoneuron degeneration, were maintained at relatively high levels even at advanced ages. These results provide beneficial information for future clinical therapeutic trials, although further detailed prospective studies are also needed.

  10. Differences in F-wave characteristics between Spinobulbar Muscular Atrophy and Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Jia eFang


    Full Text Available There is limited data on the differences in F-wave characteristics between spinobulbar muscular atrophy (SBMA and lower motor neuron dominant (LMND amyotrophic lateral sclerosis (ALS. We compared the parameters of F-waves recorded bilaterally from the median, ulnar, tibial, and deep peroneal nerves in 32 SBMA patients, 37 patients with LMND ALS, and 30 normal controls. The maximum F-wave amplitudes, frequencies of giant F-waves, and frequencies of patients with giant F-waves in all nerves examined were significantly higher in the SBMA patients than in the ALS patients and the normal controls. The mean F-wave amplitude, maximum F-wave amplitude, frequency of giant F-waves, and frequency of patients with giant F-waves in the median and deep peroneal nerves were comparable between the ALS patients and normal controls. Giant F-waves were detected in multiple nerves and were often symmetrical in the SBMA patients compared with the ALS patients. The number of nerves with giant F-waves seems to be the most robust variable for differentiation of SBMA from ALS, with an area under the curve of 0.908 (95% CI: 0.835–0.982. A cut-off value of the number of nerves with giant F-waves (≥ 3 for diagnosing SBMA showed high sensitivity and specificity: 85% sensitivity and 81% specificity vs. ALS patients. No significant correlations were found between the pooled frequency of giant F-waves and disease duration in the SBMA (r = 0.162, P = 0.418 or ALS groups (r = 0.107, P = 0.529. Our findings suggested that F-waves might be used to discriminate SBMA from ALS, even at early stages of disease.

  11. Compound heterozygous mutation in two unrelated cases of Chinese spinal muscular atrophy patients

    Institute of Scientific and Technical Information of China (English)

    QU Yu-jin; SONG Fang; YANG Yan-ling; JIN Yu-wei; BAI Jin-li


    Background Infantile proximal spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder. Approximately 90-95% cases of SMA result from homozygous deletion of survival motor neuron gene 1(SMN1) and 5% cases are caused by compound heterozygous mutation (a SMN1 deletion on one allele and a subtle mutation on the other allele).Methods In this research, two unrelated patients were clinically diagnosed according to the criteria of proximal SMA. Genetic diagnosis was performed to detect the homozygous deletion of exon 7 of SMN1 by PCR-restriction fragment length polymorphism (RFLP) and genomic sequencing. Multiplex ligation-dependent probe amplification (MLPA) analysis was carried out to measure copy numbers of SMN1, SMN2 and neuronal apoptosis inhibitor protein (NAIP) in the patients. Further sequencing of SMN1allele-specific PCR (AS-PCR) and SMN1 clones were also performed to analyze the point mutation of SMN1 gene. Additionally,the pedigree analysis of these two families was carried out to identify the transmission of the mutation.Results The inconsistent results using PCR-RFLP and genomic sequencing showed homozygous deletion of exon 7 of SMN1 and heterozygous deletion accompanied with a suspicious mutation in SMN1 gene, respectively. MLPA analysis of these two cases exhibited one SMN1 copy deletion. One identical c.863G>T (p. Arg288Met) mutation was found in two cases by sequencing the SMN1 clones, which confirmed that both cases were SMA compound heterozygotes. One case showed partial conversion to form hybrid SMN (SMN2 17/SMN1 E8) identified by clones sequencing and another case carrying 3 SMN2 implied complete conversion from SMN1 to SMN2.Conclusion p. Arg288Met is more a disease-causing mutation than a polymorphism variation, and children with this mutation may have more severe phenotypes.

  12. Multimodal Discrimination of Alzheimer's Disease Based on Regional Cortical Atrophy and Hypometabolism.

    Directory of Open Access Journals (Sweden)

    Hyuk Jin Yun

    Full Text Available Structural MR image (MRI and 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET have been widely employed in diagnosis of both Alzheimer's disease (AD and mild cognitive impairment (MCI pathology, which has led to the development of methods to distinguish AD and MCI from normal controls (NC. Synaptic dysfunction leads to a reduction in the rate of metabolism of glucose in the brain and is thought to represent AD progression. FDG-PET has the unique ability to estimate glucose metabolism, providing information on the distribution of hypometabolism. In addition, patients with AD exhibit significant neuronal loss in cerebral regions, and previous AD research has shown that structural MRI can be used to sensitively measure cortical atrophy. In this paper, we introduced a new method to discriminate AD from NC based on complementary information obtained by FDG and MRI. For accurate classification, surface-based features were employed and 12 predefined regions were selected from previous studies based on both MRI and FDG-PET. Partial least square linear discriminant analysis was employed for making diagnoses. We obtained 93.6% classification accuracy, 90.1% sensitivity, and 96.5% specificity in discriminating AD from NC. The classification scheme had an accuracy of 76.5% and sensitivity and specificity of 46.5% and 89.6%, respectively, for discriminating MCI from AD. Our method exhibited a superior classification performance compared with single modal approaches and yielded parallel accuracy to previous multimodal classification studies using MRI and FDG-PET.

  13. [Diffusion tensor imaging of the visual pathway in glaucomatous optic nerve atrophy]. (United States)

    Engelhorn, T; A Schmidt, M; Dörfler, A; Michelson, G


    In Germany more than one million inhabitants suffer from glaucoma, more than 100,000 are threatened with blindness because glaucoma is often diagnosed too late or not at all. Diagnosis and monitoring is usually carried out "only" by examination of the retina and not the whole visual pathway. However, the eye is just "the tip of the iceberg" of the actual visual pathway, which extends through the brain to the visual cortex. The interdisciplinary holistic assessment of the whole visual pathway in glaucoma is of crucial importance because glaucoma is a complex neurodegenerative disease. Subtypes, such as normal tension glaucoma (NTG), seem to originate from primary damage to the intracranial visual pathway with secondary retrograde retinal degeneration. Recent studies including glaucoma patients and healthy controls could show that diffusion tensor imaging with calculation of diffusion coefficients, i.e. fractional anisotropy (FA), mean and radial diffusivity (MD and RD) as markers of axonal integrity, provide the potential to assess the intracranial visual pathway with a high correlation to established ophthalmological examinations. In particular, calculation of FA maps of the visual pathway and accompanying voxel-based approaches, can be integrated into clinical routine. Thus, detection of glaucoma-related intracranial alterations, even in early stages of the disease, as well as differentiation of different glaucoma subtypes, is made possible. Furthermore, the diagnosis of normal tension glaucoma seems to be possible much earlier with these new imaging techniques compared to established ophthalmological work-up. Moreover, holistic imaging provides new insights into the pathophysiology of this form of glaucoma. This review article gives an overview of these novel magnetic resonance imaging techniques for assessment of the visual pathway in glaucomatous optic nerve atrophy and reveals the potential of an interdisciplinary approach.

  14. Multiple system atrophy with syndrome of inappropriate antidiuretic hormone secretion: clinical analysis on three cases

    Directory of Open Access Journals (Sweden)

    Man-qing XIE


    Full Text Available Background Multiple system atrophy (MSA is a neurodegenerative disorder affecting motor (either extrapyramidal or cerebellar and autonomic nervous systems. The main clinical manifestations of MSA are parkinsonism, cerebellar ataxia and autonomic dysfunction. It may also affect the hypothalamus and related fibers, resulting in syndrome of inappropriate antidiuretic hormone secretion (SIADH and hyponatremia. This study aims to identify the clinical characteristics of MSA with SIADH, so as to provide evidence for clinical diagnosis and treatment. Methods Clinical manifestations, laboratory examinations and imaging features, diagnosis and treatment of 3 MSA patients with SIADH in our hospital from 2011 to 2015 were retrospectively analyzed. Results Among 3 MSA patients, 2 cases were parkinsonism-predominant (MSA-P and the other one was cerebellar-predominant (MSA-C. All of them presented severe hyponatremia. The lowest serum sodium concentration was 123, 118 and 121 mmol/L, respectively. The level of urinary sodium concentration was 91, 114 and 129 mmol/L, respectively. One was diagnosed as definite SIADH, and the other 2 cases were possible SIADH. Two cases were complicated with infection (one Legionella pneumophila and one pulmonary infection, which was greatly improved after anti-infection treatment and sodium supplement. The other case died of refractory hyponatremia in the end. Conclusions MSA patients with autogenous or concurrent infection may be susceptible to SIADH, therefore water-sodium balance management is important for MSA patients. MSA with SIADH is rare, and refractory hyponatremia may indicate a poor prognosis. DOI: 10.3969/j.issn.1672-6731.2017.02.009

  15. Mapping the Progression of Atrophy in Early- and Late-Onset Alzheimer's Disease. (United States)

    Migliaccio, Raffaella; Agosta, Federica; Possin, Katherine L; Canu, Elisa; Filippi, Massimo; Rabinovici, Gil D; Rosen, Howard J; Miller, Bruce L; Gorno-Tempini, Maria Luisa


    The term early-onset Alzheimer's disease (EOAD) identifies patients who meet criteria for AD, but show onset of symptoms before the age of 65. We map progression of gray matter atrophy in EOAD patients compared to late-onset AD (LOAD). T1-weighted MRI scans were obtained at diagnosis and one-year follow-up from 15 EOAD, 10 LOAD, and 38 age-matched controls. Voxel-based and tensor-based morphometry were used, respectively, to assess the baseline and progression of atrophy. At baseline, EOAD patients already showed a widespread atrophy in temporal, parietal, occipital, and frontal cortices. After one year, EOAD had atrophy progression in medial temporal and medial parietal cortices. At baseline, LOAD patients showed atrophy in the medial temporal regions only, and, after one year, an extensive pattern of atrophy progression in the same neocortical cortices of EOAD. Although atrophy mainly involved different lateral neocortical or medial temporal hubs at baseline, it eventually progressed along the same brain default-network regions in both groups. The cortical region showing a significant progression in both groups was the medial precuneus/posterior cingulate.

  16. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Vis, J.B. de; Zwanenburg, J.J.; Kleij, L.A. van der; Spijkerman, J.M.; Hendrikse, J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Biessels, G.J. [University Medical Center Utrecht, Department of Neurology, Brain Center Rudolf Magnus, Utrecht (Netherlands); Petersen, E.T. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Hvidovre Hospital, Danish Research Centre for Magnetic Resonance, Hvidovre (Denmark)


    To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T{sub 2} of the CSF relates to brain atrophy. Twenty-eight subjects [mean age 64 (sd 2) years] were included; T{sub 1}-weighted and CSF MRI were performed. The first echo data of the CSF MRI sequence was used to obtain intracranial volume, CSF partial volume was measured voxel-wise to obtain CSF volume (V{sub CSF}) and the T{sub 2} of CSF (T{sub 2,CSF}) was calculated. The correlation between V{sub CSF} / T{sub 2,CSF} and brain atrophy scores [global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA)] was evaluated. Relative total, peripheral subarachnoidal, and ventricular V{sub CSF} increased significantly with increased scores on the GCA and MTA (R = 0.83, 0.78 and 0.78 and R = 0.72, 0.62 and 0.86). Total, peripheral subarachnoidal, and ventricular T{sub 2} of the CSF increased significantly with higher scores on the GCA and MTA (R = 0.72, 0.70 and 0.49 and R = 0.60, 0.57 and 0.41). A fast, fully automated CSF MRI volumetric sequence is an alternative for qualitative atrophy scales. The T{sub 2} of the CSF is related to brain atrophy and could thus be a marker of neurodegenerative disease. (orig.)

  17. Severe brain atrophy in the elderly as a risk factor for lower respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Okada R


    Full Text Available Rieko Okada,1 Takashi Okada,2 Akira Okada,2 Hideyuki Muramoto,3 Masahisa Katsuno,4 Gen Sobue,4 Nobuyuki Hamajima11Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 2Okada Medical Clinic, 3Muramoto Clinic, 4Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, JapanBackground: The purpose of this study is to determine whether elderly subjects with severe brain atrophy, which is associated with neurodegeneration and difficulty swallowing (dysphagia, are more susceptible to lower respiratory tract infections (LRTI, including pneumonia.Methods: The severity of brain atrophy was assessed by computed tomography in 51 nursing home residents aged 60–96 years. The incidence of LRTI, defined by body temperature ≥ 38.0°C, presence of two or more respiratory symptoms, and use of antibiotics, was determined over 4 years. The incidence of LRTI was compared according to the severity and type of brain atrophy.Results: The incidence rate ratio of LRTI was significantly higher (odds ratio 4.60, 95% confidence interval 1.18–17.93, fully adjusted P = 0.028 and the time to the first episode of LRTI was significantly shorter (log-rank test, P = 0.019 in subjects with severe brain atrophy in any lobe. Frontal and parietal lobe atrophy was associated with a significantly increased risk of LRTI, while temporal lobe atrophy, ventricular dilatation, and diffuse white matter lesions did not influence the risk of LRTI.Conclusion: Elderly subjects with severe brain atrophy are more susceptible to LRTI, possibly as a result of neurodegeneration causing dysphagia and silent aspiration. Assessing the severity of brain atrophy might be useful to identify subjects at increased risk of respiratory infections in a prospective manner.Keywords: brain atrophy, dysphagia, elderly, pneumonia, respiratory infection, white matter lesions

  18. The combined influence of stretch, mobility and electrical stimulation in the prevention of muscle fiber atrophy caused hypokinesia and hypodynamia (United States)

    Goldspink, G.; Goldspink, D.; Loughna, P.


    The morphological and biochemical changes which occur in the hind limb muscles of the rat in response to hypokinesia and hypodynamia were investigated. Hind limb cast fixation and suspension techniques were employed to study the musclar atrophy after five days of hypokinesia and hypodynamia induced by suspension, appreciable muscular atrophy was apparent, particularly in the anti-gravity muscles. The effect of passive stretching and electrical stimulation on muscle atrophy was studied. Changes in muscle protein mass were assessed with spectrophotometric and radioactive techniques. Passive stretch is shown to counteract muscle disuse atrophy. The change in the numbers of specific muscle fibers in atrophied muscles is discussed.

  19. Parry-Romberg syndrome (progressive hemifacial atrophy) with spasmodic dysphonia--a rare association. (United States)

    Mugundhan, K; Selvakumar, C J; Gunasekaran, K; Thiruvarutchelvan, K; Sivakumar, S; Anguraj, M; Arun, S


    Parry-Romberg syndrome is a rare clinical entity characterised by progressive hemifacial atrophy with appearance of 'saber'. Various neurological and otorhinolaryngological disorders are associated with this syndrome. The association of Parry -Romberg syndrome with Spasmodic dysphonia has rarely been reported. A 37 year old female presented with progressive atrophy of tissues of left side of face for 10 years and change in voice for 1 year. On examination, wasting and atrophy of tissues including tongue was noted on left side of the face. ENT examination revealed adductor spasmodic dysphonia. We report the rare association of Parry -Romberg syndrome with spasmodic dysphonia.

  20. Combining the boundary shift integral and tensor-based morphometry for brain atrophy estimation (United States)

    Michalkiewicz, Mateusz; Pai, Akshay; Leung, Kelvin K.; Sommer, Stefan; Darkner, Sune; Sørensen, Lauge; Sporring, Jon; Nielsen, Mads


    Brain atrophy from structural magnetic resonance images (MRIs) is widely used as an imaging surrogate marker for Alzheimers disease. Their utility has been limited due to the large degree of variance and subsequently high sample size estimates. The only consistent and reasonably powerful atrophy estimation methods has been the boundary shift integral (BSI). In this paper, we first propose a tensor-based morphometry (TBM) method to measure voxel-wise atrophy that we combine with BSI. The combined model decreases the sample size estimates significantly when compared to BSI and TBM alone.

  1. Little effects of Insulin-like Growth Factor-I on testicular atrophy induced by hypoxia


    Casares Amelia; Diaz-Sanchez Matias; Puche Juan; Garcia-Fernandez Maria; Castilla-Cortázar Inma; Diez-Caballero Fernando; Aliaga-Montilla M Aurelia; Rodriguez-Borrajo Coronación; Gonzalez-Barón Salvador


    Abstract Background Insulin-like Growth Factor-I (IGF-I) supplementation restores testicular atrophy associated with advanced liver cirrhosis that is a condition of IGF-I deficiency. The aim of this work was to evaluate the effect of IGF-I in rats with ischemia-induced testicular atrophy (AT) without liver disease and consequently with normal serum level of IGF-I. Methods Testicular atrophy was induced by epinephrine (1, 2 mg/Kg intra-scrotal injection five times per week) during 11 weeks. Th...

  2. Clinical significance of corpus callosum atrophy in a mixed elderly population

    DEFF Research Database (Denmark)

    Ryberg, C; Rostrup, E; Stegmann, M B;


    Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly......) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified...

  3. Immunohistochemical staining of radixin and moesin in prostatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Becich Michael J


    Full Text Available Abstract Background Some members of the Protein 4.1 superfamily are believed to be involved in cell proliferation and growth, or in the regulation of these processes. While the expression levels of two members of this family, radixin and moesin, have been studied in many tumor types, to our knowledge they have not been investigated in prostate cancer. Methods Tissue microarrays were immunohistochemically stained for either radixin or moesin, with the staining intensities subsequently quantified and statistically analyzed using One-Way ANOVA or nonparametric equivalent with subsequent Student-Newman-Keuls tests for multiple comparisons. There were 11 cases of normal donor prostates (NDP, 14 cases of benign prostatic hyperplasia (BPH, 23 cases of high-grade prostatic intraepithelial neoplasia (HGPIN, 88 cases of prostatic adenocarcinoma (PCa, and 25 cases of normal tissue adjacent to adenocarcinoma (NAC analyzed in the microarrays. Results NDP, BPH, and HGPIN had higher absolute staining scores for radixin than PCa and NAC, but with a significant difference observed between only HGPIN and PCa (p = Conclusions To our knowledge, these studies represent the first reports on the expression profiles of radixin and moesin in prostatic adenocarcinoma. The current study has shown that there were statistically significant differences observed between HGPIN and PCa and HGPIN and NAC in terms of radixin expression. The differences in the moesin profiles by tissue type were not statistically significant. Additional larger studies with these markers may further elucidate their potential roles in prostatic neoplasia progression.

  4. Mechanism of benign biliary stricture: A morphological and immunohistochemical study

    Institute of Scientific and Technical Information of China (English)

    Zhi-Min Geng; Ying-Min Yao; Qing-Guang Liu; Xin-Jie Niu; Xiao-Gong Liu


    AIM: To explore the mechanism of benign biliary stricture.METHODS: A model of trauma of bile duct was established in 28 dogs. The anastomosed tissues were resected and examined by light and electron microscopes on day 3, in wk 1, 3 and mo 3, 6 after operation. CD68, TGF-β1 and α-SMA were examined by immunohistochemical staining, respectively.RESULTS: The mucosal epithelium of the bile duct was slowly recovered, chronic inflammation lasted for a long time,fibroblasts proliferated actively, extracellular matrix was over-deposited. Myofibroblasts functioned actively and lasted through the whole process. The expression of macrophages in lamina propria under mucosa, TGF-β1 in granulation tissue,fibroblasts and endothelial cells of blood vessels, α-SMA in myofiroblasts were rather strong from the 1st wk to the 6th mo after operation.CONCLUSION: The type of healing occurring in bile duct belongs to overhealing. Myofibroblasts are the main cause for scar contracture and stricture of bile duct. High expressions of CD68, TGF-β1 and α-SMA are closely related to the active proliferation of fibroblasts, extracellular matrix overdeposition and scar contracture of bile duct.

  5. Immunohistochemical investigation of wound healing in response to fractional photothermolysis (United States)

    Helbig, Doris; Bodendorf, Marc Oliver; Grunewald, Sonja; Kendler, Michael; Simon, Jan C.; Paasch, Uwe


    Despite growing clinical evidence of ablative fractional photothermolysis (AFP), little is known about the spatiotemporal molecular changes within the targeted compartments. Six subjects received three different single AFP treatments using a scanned 250 μm CO2-laser beam. Spatiotemporal changes of skin regeneration were estimated by immunohistochemical investigation (HSP70, HSP72, HSP47, TGFβ, procollagen III, CD3, CD20, and CD68) in skin samples 1 h, 3 days, and 14 days postintervention. The remodeling was uniformly started by regrowth of the epidermal compartment followed by partial to complete replacement of the microscopic ablation zones (MAZ) by newly synthesized condensed procollagen III. From day 3 to 14, the number of macrophages as well as giant cells surrounding the MAZ increased. TGFβ expression was highest 1 h to 3 days following AFP. HSP70 and HSP72 expressions were highest 3-14 days postintervention in the spinocellular layer leading to an upregulation of HSP47. AFP performed by a scanned CO2-laser results in an early epidermal remodeling, which is followed by a dermal remodeling leading to a replacement of the MAZ with newly synthesized (pro)-collagen. During this, an inflammatory infiltrate with CD3+ and CD20+ cells surrounds the MAZ. The count of macrophages and giant cells involved in the replacement of the necrotic zones seems to be crucial for wound healing.

  6. Immunohistochemical localization of sex hormone receptors in two Raillietina tapeworms. (United States)

    Chen, L; Sun, Y M; Mu, L; Zeng, Y; Li, H Y; Yang, T H


    Sex hormone receptors play critical roles in development and reproduction. However, it is not known whether they exist in Raillietina tapeworms, and if they do, whether they have a similar function to that in vertebrates. We examined the immunohistochemical distributions of androgen receptors (ARs), estrogen receptors (ERs), and progesterone receptors (PRs) in the tissues of two tapeworm species: Raillietina echinobothrida and Raillietina tetragona. Immunopositive ARs were found in the entire reproductive system of R. echinobothrida, including the testes, ovaries, and oocysts, and weakly immunopositive ERs and PRs were found in the testes, ovaries, and oocysts. Immunopositive ARs were also found throughout the entire reproductive system of R. tetragona, including the testes, ovaries, and oocysts, and weakly immunopositive ERs were in the testes and oocysts; the PRs were distributed in an immunonegative manner. The results show that androgens and their receptors play critical roles in reproductive system development in the two tapeworms. The immunoreactivity and tissue localizations of the sex hormone receptors suggest that, in both species, they have similar functions as in vertebrates, and modulate reproduction.

  7. [Immuno-histochemical study of medullary thyroid carcinoma]. (United States)

    Bessho, T


    Five peptide hormones including calcitonin (CT) and gastrin-releasing peptide (GRP), serotonin (5HT), CEA, nervous tissue specific proteins and monoclonal antibody Leu-7 were immuno-histochemically studied on 60 cases of medullary thyroid carcinoma (MTC). In addition, localization of varied products in the tumor cells and its relations with the clinical features in some cases were evaluated. MTC contains a variety of products in many cases, and CT and CEA were positive in all cases. In 50 of the 57 cases (87.7%), GRP was positive, which suggested that GRP could be a novel tumor marker for this tumor. Furthermore, in tumor cells and C-cell hyperplastic foci, identical cells were sometimes revealed to possess both CT and GRP. Existence of somatostatin (SS), substance-P (SP), beta-MSH, 5 HT, Leu-7 and NSE in the tumor cells were confirmed. NSE was positive in 32 of the 47 cases (61.8%) which could confirm that MTC possesses neuroendocrine nature. In two cases of autopsy in which the tumors were highly malignant in clinical course and undifferentiated in histology, most tumor cells showed poor stainability for peptide hormones, suggesting that specific qualities as neuroendocrine tumor had been lost. In familial cases, the tumor tended to contain multiple substances.

  8. Immunohistochemical study of subepidermal connective of molluscan integument

    Directory of Open Access Journals (Sweden)

    S Corbetta


    Full Text Available Sections of integument from gastropod, bivalve and cephalopod species were studied immunohistochemically to determine reactivity to antibody against the type I-like collagen from Sepia cartilage and antibodies against components of the extracellular matrix (ECM of vertebrate connective tissue: type I, III, IV, V, and VI collagens, laminin, nidogen and heparan sulphate. All samples exhibited similar reactivities to the antibodies, although differences in the intensity and localization of the immunostaining were found that were clearly correlated with between-species differences in integumental ultrastructure. These findings indicate that the composition of the integumental ECM is similar in the three classes of molluscs examined and that several types of collagen are present. However molluscan subepidermal connective tissue differs from the ECM of vertebrate dermis: molluscan integumental ECM contains collagens similar to type I, V and VI collagens but has no type III-similar collagen. Furthermore molecules similar to the type IV collagen, laminin, nidogen and heparan sulphate of vertebrates were present ubiquitously in molluscan basement membrane, confirming the statement that the structure and composition of basement membrane have remained constant throughout the evolution of all animal phyla.

  9. Immunohistochemical correlates of TP53 somatic mutations in cancer. (United States)

    Murnyák, Balázs; Hortobágyi, Tibor


    Despite controversy on the correlation between p53 accumulation and TP53 mutational status, immunohistochemical (IHC) detection of overexpressed protein has long been used as a surrogate method for mutation analysis. The aim of our study was to characterise the IHC expression features of TP53 somatic mutations and define their occurrence in human cancers. A large-scale database analysis was conducted in the IARC TP53 Database (R17); 7878 mutations with IHC features were retrieved representing 60 distinct tumour sites. The majority of the alterations were immunopositive (p TP53 mutations were divided into three IHC groups according to mutation frequency and IHC positivity. Each group had female dominance. Among the IHC groups, significant correlations were observed with age at diagnosis in breast, bladder, liver, haematopoietic system and head & neck cancers. An increased likelihood of false negative IHC associated with rare nonsense mutations was observed in certain tumour sites. Our study demonstrates that p53 immunopositivity largely correlates with TP53 mutational status but expression is absent in certain mutation types.Besides, describing the complex IHC expression of TP53 somatic mutations, our results reveal some caveats for the diagnostic practice.

  10. Sonic hedgehog in oral squamous cell carcinoma: An immunohistochemical study (United States)

    Srinath, Sahana; Iyengar, Asha R; Mysorekar, Vijaya


    Background: Recent studies have revealed the involvement of hedgehog (Hh) signaling component in proliferation and invasive behavior of many carcinomas. Aim: This study aims to identify the expression of sonic Hh (SHH) protein of SHH pathway in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) using SHH (H-160) (Santa Cruz, sc-9042) which could have therapeutic implication in future. Materials and Methods: A total of 250 cases comprising 50 normal oral mucosa, 50 cases of oral epithelial dysplasia, 50 well, 50 moderate and 50 poorly differentiated OSCCs were included in the study. Immunohistochemical evaluation of SHH protein expression was conducted using monoclonal antibody. Interpretation of the expression was done by immunoreactive score of Remmele and Stegner (IRS) scoring method. Statistical Analysis: Chi-Square test was used to analyze the results. Results: The study showed that SHH signaling molecules are highly expressed in OSCC, and their expression was mainly in the cytoplasm of epithelial cells. Conclusion: The SHH signaling component is associated with the pathological parameter in OSCC and oral epithelial dysplasia. PMID:27721600

  11. Immunohistochemical Analysis of P63 Expression in Odontogenic Lesions

    Directory of Open Access Journals (Sweden)

    Saede Atarbashi Moghadam


    Full Text Available P63 may have a role in tumorigenesis and cytodifferentiation of odontogenic lesions. We investigated the immunohistochemical expression of P63 in a total of 30 cases of odontogenic cysts and tumors. The percentage of positive cells was calculated in the lining of odontogenic cysts and islands of ameloblastoma. P63 expression was evident in all types of odontogenic lesions. P63 was expressed throughout the lining epithelium of odontogenic keratocyst except surface parakeratinized layer. In addition, calcifying odontogenic cyst showed P63 expression in all layers. In almost all radicular and dentigerous cysts, the basal and parabasal layers were immunoreactive. Peripheral cells of ameloblastoma expressed P63; however, stellate reticulum had weaker immunostaining. No significant difference in P63 expression was observed between studied lesions (. Expression of P63 in odontogenic lesions suggests that this protein is important in differentiation and proliferation of odontogenic epithelial cells. However, it seems that it could not be a useful marker to differentiate between aggressive and nonaggressive lesions. P63 also represents a progenitor or basal cell marker, and it is not expressed in mature differentiated cells.

  12. Hepatic metastasis of thymoma: case report and immunohistochemical study (United States)

    Speisky, Daniela; de Davila, María Teresa García; Vigovich, Felix; Mendez, Julian; Maurette, Rafael; Ejarque, Marcos García; Spina, Juan Carlos; Iotti, Alejandro; Dezanzo, Pablo


    Thymomas are rare tumours characterised by their slow growth and capacity to invade directly by contiguity. While distant dissemination is infrequent, all sub-types of thymoma have the capacity to metastasise to extrathoracic organs. We present here the case of a female patient with a liver mass discovered 13 years after the removal of a mediastinal thymoma and after ten years from thyroidectomy for papillary carcinoma. The histopathological study showed that the lesion contained an epithelial component, which was immunohistochemically positive for pankeratin. It was accompanied by numerous small lymphocytes testing positive for TdT, CD3, CD4, CD5, CD8, CD99, and CD43. The result was consistent with hepatic metastatic thymoma sub-type B1, according to the World Health Organisation classification (WHO). Our case highlights the importance of morphological and immunohistological examinations in the differential diagnosis of visceral masses in patients with a history of thymoma. Given the infrequency of its metastasis and the increased risk of developing other primary tumours that these patients have, these studies play a significant role. PMID:28101136

  13. Immunohistochemical distribution of myotonic dystrophy kinase (DNK) in muscle

    Energy Technology Data Exchange (ETDEWEB)

    Whiting, E.J.; Tamai, K. [Univ. of Ottawa (Canada); Waring, J.D. [Chilrdren`s Hospital of Eastern Ontario, Ottawa (Canada)] [and others


    Myotonic dystrophy (DM) is the most common form of inherited neuromuscular disease in adults and is characterized by progressive muscle wasting and myotonia. The mutation responsible for DM has been identified as the expansion of a polymorphic (CTG)n repeat in the 3{prime} untranslated region of a gene encoding a putative serine/threonine kinase (DMK). We have raised a polyclonal raised a polyclonal rabbit antisera against a fusion protein encoding exons 11-15 of DMK. The antisera detects both the full length and a truncated isoform (missing amino acids corresponding to exons 13-15) of the human DMK expressed in a recombinant baculovirus system. In addition, it recognizes a 69 kDA protein on Western blots of both human and mouse myoblasts. Use of this antiserum in immunohistochemical studies of human tissue demonstrates that DMK is expressed in the cytoplasm of both skeletal and smooth muscle and is expressed postsynaptically (as determined by codistribution with acetylcholinesterase and acetylcholine receptors) within the vicinity of neuromuscular junction of skeletal muscle. Further, no obvious differences in DMK localization were observed between muscle tissues from normal and DM-affected individuals.

  14. Histochemical and immunohistochemical analyses of primary carcinoma of the liver.

    Directory of Open Access Journals (Sweden)



    Full Text Available Hematoxylin and eosin (H-E stained liver sections of 47 autopsy cases of hepatic malignancies were examined. There were 43 cases of hepatocellular carcinoma (subtypes of 30 trabecular, 7 solid, 5 pseudoglandular, and one scirrhous carcinoma, 3 of cholangiocellular carcinoma and one of mixed carcinoma. After immunohistochemical staining, benign hepatocytes reacted positively with anti-epithelial membrane antigen (EMA. Hepatocellular carcinoma cells reacted more weakly than benign hepatocytes. It was noted that the microtubular structure, which could not be demonstrated even by alcian blue or cationic ferric hydroxide colloid stabilized with cacodylate (Fe-CaC, was clearly detected with anti-EMA. The EMA-positive microtubular structures may indicate terminal cholangiolar differentiation. Based on EMA, seven more cases formerly classified as hepatocellular carcinoma by H-E were reclassified as mixed carcinoma, totaling eight (17.0%. The histologic classification of "mixed carcinoma" has been 1.5 to 2.0% of primary liver cancers in Japan, but we suggest there may be more cases of "mixed carcinoma" identified in the future. In conclusion, we emphasize that EMA staining is useful for more accurate classification of hepatic tumors.

  15. Immunohistochemical detection of P53 and Mdm2 in vitiligo (United States)

    Bakry, Ola A.; Hammam, Mostafa A.; Wahed, Moshira M. Abdel


    Background: Vitiligo is a common depigmented skin disorder that is caused by selective destruction of melanocytes. It is generally accepted that the main function of melanin resides in the protection of skin cells against the deleterious effect of ultraviolet rays (UVRs). Association of vitiligo and skin cancer has been a subject of controversy. Occurrence of skin cancer in long-lasting vitiligo is rare despite multiple evidences of DNA damage in vitiliginous skin. Aim: To detect the expression of P53 and Mdm2 proteins in both depigmented and normally pigmented skin of vitiligo patients and to compare it to control subjects suffering from nonmelanoma skin cancer (NMSC). Materials and Methods: Thirty-four patients with vitiligo and 30 age and sex-matched patients with nodulo-ulcerative basal cell carcinoma (BCC) as a control group were selected. Both patients and control subjects had outdoor occupations. Skin biopsies were taken from each case and control subjects. Histopathological examination of Hematoxylin and eosin-stained sections was done. Expression of P53 and Mdm2 proteins were examined immunohistochemically. Results: Both P53 and Mdm2 were strongly expressed in depigmented as well as normally pigmented skin of vitiligo patients. This expression involved the epidermis, skin adnexa and blood vessels with significant differences between cases and controls. Conclusions: The overexpression of P53 and Mdm2 proteins in both normally pigmented and depigmented skin of patients with vitiligo could contribute to the decreased occurrence of actinic damage and NMSC in these patients. PMID:23189248

  16. Immunohistochemical analysis of NOTCH1 and JAGGED1 expression in multiple myeloma and monoclonal gammopathy of undetermined significance. (United States)

    Skrtić, Anita; Korać, Petra; Krišto, Delfa Radić; Ajduković Stojisavljević, Radmila; Ivanković, Davor; Dominis, Mara


    Notch signaling is implicated in the pathogenesis of multiple myeloma expressing high level of active Notch proteins NOTCH1 and JAGGED1 in tumor plasma cells. We investigated expression of NOTCH1 and JAGGED1 in bone marrow trephine biopsies of 80 newly diagnosed multiple myeloma and 20 monoclonal gammopathy of undetermined significance patients using immunohistochemical methods. The number of positive tumor cells was counted per 1000 tumor cells and the intensity of staining was assessed semi quantitatively. Multiple myelomas expressed NOTCH1 in 92.31% (72/78) and JAGGED1 in 92.21% (71/77) cases. NOTCH1 staining was strong in the majority of cases (59.7%), whereas JAGGED1 was predominately weak (67.6% of cases). In contrast, both markers were negative in all monoclonal gammopathy of undetermined significance cases. However, upon progression of disease from monoclonal gammopathy of undetermined significance to multiple myeloma (seen in 4 patients), analysis of the subsequent bone marrow biopsy showed weak expression of both markers in tumorous plasma cells. Immunohistochemistry results were compared with the pattern of bone marrow infiltration, plasma cell differentiation, and the presence of t(11;14)(q13,q32), t(14;16)(q32;q23),and t(4;14)(p16.3;q23) and overall survival in multiple myeloma patients. A significant correlation was found between strong NOTCH1 staining in multiple myeloma plasma cells and the diffuse type of bone marrow infiltration (P = .002) and an immature morphologic type of plasma cells (P = .043). After a median follow-up of 20.3 months, in multiple myeloma patients no difference in overall survival between NOTCH1 (P = .484) and JAGGED1 (P = .822) positive and negative cases were found. In conclusion, our results indicate importance of NOTCH1 and JAGGED1 expression in plasma cell neoplasia and a possible diagnostic value of their immunohistochemical evaluation of bone marrow infiltrates for multiple myeloma.

  17. Ophthalmic findings of newly diagnosed leprosy patients in Istanbul Leprosy Hospital, Turkey. (United States)

    Cakiner, T; Karaçorlu, M A


    The objective of this study was to detect ocular lesions of newly diagnosed leprosy cases admitted to Istanbul Leprosy Hospital. The patients were categorized according to sex, age, type of leprosy and duration of the disease. Their eyes were categorized as with or without ocular findings due to leprosy. The total number of patients was 21. The mean age was 22+/-4.6 years, the duration of the disease was 36.3+/-19.6 months. Madarosis was the most common finding in this group. It was found in 15 patients (71.4%, 95% confidence interval (CI) 47.8-88.7%). As a second common finding related to corneal alterations, 13 patients had nerve thickening (61.9%, 95% CI 38.4-81.8%). None of our patients had trichiasis, episcleritis, scleritis, cataract, iris atrophy, iris pearl, abnormal vitreous or retinal findings.

  18. Reliability of clinical ICD-10 schizophrenia diagnoses

    DEFF Research Database (Denmark)

    Jakobsen, Klaus D; Frederiksen, Julie N; Hansen, Thomas;


    value (87%) of ICD-10 schizophrenia and an overall good agreement between clinical and OPCRIT-derived diagnoses (kappa=0.60). An even higher positive predictive value was obtained when diagnoses were amalgamated into a diagnostic entity of schizophrenia-spectrum disorders (98%). Near perfect agreement...

  19. De dokter en de diagnose-verzamelaar

    NARCIS (Netherlands)

    Geersing, Geert-Jan


    In the course of the medical curriculum, medical students are trained to recognise diagnoses. They classify these in their minds, together with detailed information on laboratory and imaging tests, as collections of diagnoses. The downside of this could be overdiagnosis. This paper describes some of

  20. Analysis of the presence or absence of atrophy of the subgenual and subcallosal cingulate cortices using voxel-based morphometry on MRI is useful to select prescriptions for patients with depressive symptoms

    Directory of Open Access Journals (Sweden)

    Niida A


    Full Text Available Akira Niida,1 Richi Niida,2 Hiroshi Matsuda,3 Makoto Motomura,4 Akihiko Uechi5 1Department of Radiology, Nanbu Hospital, Itoman City, Okinawa, Japan; 2Department of Psychiatry, Nanto Clinic, Urasoe City, Okinawa, Japan; 3Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Kodaira City, Tokyo, Japan; 4Department of Human Sciences, University of the Ryukyus, Nakagami County, Okinawa, Japan; 5Cognitive Neuroscience Research Project, Kansai Gaidai University, Hirakata City, Osaka, Japan Objective: We objectively evaluated the presence or absence of atrophy of the subgenual anterior cingulate cortex (sgACC and the subcallosal anterior cingulate cortex (scACC, using new voxel-based morphometry (VBM software employing Statistical Parametric Mapping software v8 and diffeomorphic anatomic registration through an exponentiated lie algebra. We prepared a database covering young-mature adulthood and investigated the clinical usefulness of the evaluation. Subjects and methods: One hundred seven patients with major depressive disorder (MDD, 74 patients with bipolar disorder (BD, and 240 healthy control subjects underwent 1.5T magnetic resonance imaging scanning. Using new VBM software and databases covering young-mature adults and the elderly, target volumes of interest were set in the sgACC and scACC, four indicators (severity, extent, ratio, and whole-brain extent were determined, and the presence or absence of atrophy of the sgACC and scACC was evaluated on the basis of the indicators. In addition, the relationships between the presence or absence of atrophy of the sgACC and scACC and performance of diagnosing MDD and BD and therapeutic drugs were investigated. Results: It was clarified that the disease is likely to be MDD when atrophy is detected in the sgACC, and likely to be BD when no atrophy is detected in the sgACC but is detected in the scACC. Regarding the relationship with therapeutic drugs, it was clarified that, when

  1. Diffusion tensor imaging in the characterization of multiple system atrophy

    Directory of Open Access Journals (Sweden)

    Rulseh AM


    Full Text Available Aaron Michael Rulseh,1–3 Jiri Keller,1,4 Jan Rusz,5,6 Michael Syka,1 Hana Brozova,6 Robert Rusina,6,7 Petra Havrankova,6 Katerina Zarubova,8 Hana Malikova,1 Robert Jech,6 Josef Vymazal1 1Department of Radiology, Na Homolce Hospital, Prague, Czech Republic; 2Department of Radiology, 1st Faculty of Medicine, General University Hospital, Charles University in Prague, Prague, Czech Republic; 3National Institute of Mental Health, Klecany, Czech Republic; 43rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 5Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic; 6Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 7Thomayer Hospital, Prague, Czech Republic; 8Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic Purpose: Multiple system atrophy (MSA is a rare neurodegenerative disease that remains poorly understood, and the diagnosis of MSA continues to be challenging. We endeavored to improve the diagnostic process and understanding of in vivo characteristics of MSA by diffusion tensor imaging (DTI.Materials and methods: Twenty MSA subjects, ten parkinsonian dominant (MSA-P, ten cerebellar dominant (MSA-C, and 20 healthy volunteer subjects were recruited. Fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity maps were processed using tract-based spatial statistics. Diffusion data were additionally evaluated in the basal ganglia. A support vector machine was used to assess diagnostic utility, leave-one-out cross-validation in the evaluation of classification schemes, and receiver operating characteristic analyses to determine cutoff values.Results: We detected widespread changes in the brain white matter of MSA subjects; however, no group-wise differences were found between MSA-C and MSA

  2. The yearly rate of Relative Thalamic Atrophy (yrRTA: a simple 2D/3D method for estimating deep gray matter atrophy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Manuel eMenéndez-González


    Full Text Available Despite a strong correlation to outcome, the measurement of gray matter (GM atrophy is not being used in daily clinical practice as a prognostic factor and monitor the effect of treatments in Multiple Sclerosis (MS. This is mainly because the volumetric methods available to date are sophisticated and difficult to implement for routine use in most hospitals. In addition, the meaning of raw results from volumetric studies on regions of interest are not always easy to understand. Thus, there is a huge need of a methodology suitable to be applied in daily clinical practice in order to estimate GM atrophy in a convenient and comprehensive way. Given the thalamus is the brain structure found to be more consistently implied in MS both in terms of extent of atrophy and in terms of prognostic value, we propose a solution based in this structure. In particular, we propose to compare the extent of thalamus atrophy (TA with the extent of unspecific, global brain atrophy, represented by ventricular enlargement. We name this ratio the yearly rate of Relative Thalamic Atrophy (yrRTA. In this report we aim to describe the concept of yrRTA and the guidelines for computing it under 2D and 3D approaches and explain the rationale behind this method. We have also conducted a very short crossectional retrospective study to proof the concept of yrRTA. However, we do not seek to describe here the validity of this parameter since these researches are being conducted currently and results will be addressed in future publications.

  3. Assessment atrophy jawbone after tooth extraction in connection with dental implantation

    Directory of Open Access Journals (Sweden)

    Maksyutov A.E.


    Full Text Available This article provides a clinically grounded classification of degrees of atrophy of the bone the alveolar processes of jaws in accordance with specific strategies for dental implantation

  4. Robust Identification of Alzheimer's Disease subtypes based on cortical atrophy patterns. (United States)

    Park, Jong-Yun; Na, Han Kyu; Kim, Sungsoo; Kim, Hyunwook; Kim, Hee Jin; Seo, Sang Won; Na, Duk L; Han, Cheol E; Seong, Joon-Kyung


    Accumulating evidence suggests that Alzheimer's disease (AD) is heterogenous and can be classified into several subtypes. Here, we propose a robust subtyping method for AD based on cortical atrophy patterns and graph theory. We calculated similarities between subjects in their atrophy patterns throughout the whole brain, and clustered subjects with similar atrophy patterns using the Louvain method for modular organization extraction. We applied our method to AD patients recruited at Samsung Medical Center and externally validated our method by using the AD Neuroimaging Initiative (ADNI) dataset. Our method categorized very mild AD into three clinically distinct subtypes with high reproducibility (>90%); the parietal-predominant (P), medial temporal-predominant (MT), and diffuse (D) atrophy subtype. The P subtype showed the worst clinical presentation throughout the cognitive domains, while the MT and D subtypes exhibited relatively mild presentation. The MT subtype revealed more impaired language and executive function compared to the D subtype.

  5. Robust Identification of Alzheimer’s Disease subtypes based on cortical atrophy patterns (United States)

    Park, Jong-Yun; Na, Han Kyu; Kim, Sungsoo; Kim, Hyunwook; Kim, Hee Jin; Seo, Sang Won; Na, Duk L.; Han, Cheol E.; Seong, Joon-Kyung; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Liu, Enchi; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; DeCarli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven G.; Shen, Li; Kelley, Faber; Kim, Sungeun; Nho, Kwangsik; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Doody, Rachelle S.; Villanueva Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; de Toledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; D’Agostino II, Daniel; Kielb, Stephanie; Galvin, James E.; Pogorelec, Dana M.; Cerbone, Brittany; Michel, Christina A.; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Wong, Terence Z.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc Adams Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz Arrastia, Ramon; King, Richard; Weiner, Myron; Martin Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H. S.; Lu, Po H.; Bartzokis, George; Graff Radford, Neill R.; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Farlow, Martin R.; Marie Hake, Ann; Matthews, Brandy R.; Herring, Scott; Hunt, Cynthia; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging Yuek; Feldman, Howard; Mudge, Benita; Assaly, Michele; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Marsel Mesulam, Marek; Lipowski, Kristine; Kuo Wu, Chuang; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Lynn Johnson, Patricia; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Hudson, Leon; Fletcher, Evan; Carmichael, Owen; Olichney, John; Kittur, Smita; Borrie, Michael; Lee, T. Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Santulli, Robert B.; Kitzmiller, Tamar J.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabether; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Smith, Karen Elizabeth; Relkin, Norman; Chaing, Gloria; Raudin, Lisa; Smith, Amanda; Fargher, Kristin; Raj, Balebail Ashok


    Accumulating evidence suggests that Alzheimer’s disease (AD) is heterogenous and can be classified into several subtypes. Here, we propose a robust subtyping method for AD based on cortical atrophy patterns and graph theory. We calculated similarities between subjects in their atrophy patterns throughout the whole brain, and clustered subjects with similar atrophy patterns using the Louvain method for modular organization extraction. We applied our method to AD patients recruited at Samsung Medical Center and externally validated our method by using the AD Neuroimaging Initiative (ADNI) dataset. Our method categorized very mild AD into three clinically distinct subtypes with high reproducibility (>90%); the parietal-predominant (P), medial temporal-predominant (MT), and diffuse (D) atrophy subtype. The P subtype showed the worst clinical presentation throughout the cognitive domains, while the MT and D subtypes exhibited relatively mild presentation. The MT subtype revealed more impaired language and executive function compared to the D subtype. PMID:28276464

  6. Atrophying pityriasis versicolor: is this a new variant of pityriasis versicolor? (United States)

    Yang, Yun-Seok; Shin, Min-Kyung; Haw, Choong-Rim


    An atypical clinical form of pityriasis versicolor has been infrequently reported, in which cutaneous atrophy is associated with individual pityriasis versicolor lesions. The pathogenesis of this atrophy remains unclear, but is believed to be a delayed-type hypersensitivity reaction to antigens derived from the Malassezia species. A 60-year-old man presented with multiple, slightly scaly, and depressed maculopatches or plaques on the trunk and extremities. Our microscopic examination of the skin scrapings on a KOH preparation revealed numerous short hyphae and spores. The patient was treated daily with 200 mg of itraconazole in combination with topical antifungals, achieving clinical improvement and mycological recovery, which was confirmed upon follow-up 1 month later. This is the first case report of atrophying pityriasis versicolor in Korea. It needs to be differentiated from other atrophying disorders of the skin.

  7. Glutamate prevents intestinal atrophy via luminal nutrient sensing in a mouse model of total parenteral nutrition

    DEFF Research Database (Denmark)

    Xiao, Weidong; Feng, Yongjia; Holst, Jens Juul


    Small intestine luminal nutrient sensing may be crucial for modulating physiological functions. However, its mechanism of action is incompletely understood. We used a model of enteral nutrient deprivation, or total parenteral nutrition (TPN), resulting in intestinal mucosal atrophy and decreased...

  8. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders

    Directory of Open Access Journals (Sweden)

    Jia Fang


    Conclusions: The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

  9. Atrophy of sacrospinal muscle groups in patients with chronic, diffusely radiating lumbar back pain

    Energy Technology Data Exchange (ETDEWEB)

    Laasonen, E.M.


    After surgery necessitated by lumbar back pain syndromes, radiolucency verified by CT may appear in the sacrospinal muscle group on the operate side. This radiolucency represents muscular atrophy and is in its most severe form a result of the replacement of muscle tissue with adipose tissue. Such muscular atrophy appeared in the present series in 31 out of all 156 patients (19.9%) and in 29 out of 94 patients operated on because of radiating lumbar back pain (30.9%). The radiological appearance, extent, and HU values of this muscular atrophy are presented in detail. Only weak correlations with the multitude of clinical symptoms and signs were found in this retrospective study. The effects of irreversible muscular atrophy on the indications for surgery and physiotherapy are discussed.

  10. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy

    DEFF Research Database (Denmark)

    Suetta, Charlotte; Frandsen, Ulrik; Nielsen, Line;


    Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle...... atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2......-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1a and PGC-1ß (1-4 days) and a ~10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast...

  11. Ultrawide-field fundus photography of the first reported case of gyrate atrophy from Australia. (United States)

    Moloney, Thomas P; O'Hagan, Stephen; Lee, Lawrence


    Gyrate atrophy of the choroid and retina is a rare chorioretinal dystrophy inherited in an autosomal recessive pattern. We describe the first documented case of gyrate atrophy from Australia in a 56-year-old woman with a history of previous diagnosis of retinitis pigmentosa and worsening night vision in her right eye over several years. She was myopic and bilaterally pseudophakic, and fundus examination revealed pale optic discs and extensive peripheral chorioretinal atrophy exposing bare sclera bilaterally with only small islands of normal-appearing retina at each posterior pole. Visual field testing showed grossly constricted fields, blood testing showed hyperornithinemia, and further questioning revealed consanguinity between the patient's parents. We then used the patient's typical retinal findings of gyrate atrophy to demonstrate the potential use of ultrawide-field fundus photography and angiography in diagnosis and monitoring response in future treatment.

  12. R1: Immunohistochemical study of mucins in human intestinal spirochetosis. (United States)

    Ogata, Sho; Shimizu, Ken; Tominaga, Susumu; Nakanishi, Kuniaki


    Most patients with human intestinal spirochetosis (HIS; a colorectal bacterial infection caused by Brachyspira species) seem asymptomatic, and its pathogenicity remains unclear. Recently, alterations in mucin expression were reported in animal Brachyspira infection. The present question was "Is mucin expression altered in HIS?". Using antibodies for MUCs 1, 2, 4, 5 AC, and 6, we immunohistochemically compared 215 specimens from 83 histology-confirmed HIS cases with 106 specimens from 26 non-HIS cases. Positive staining (which included even focal positive staining) was rated "high (+)" or "low (+)". Results were analysed for four categories of lesions, and associations between MUC expression and spirochetal presence were also analysed. In the "specimens without polyps or adenocarcinoma" category: high (+) MUC2-positivity was more frequent in HIS than in control. In the hyperplasia/serrated polyp category: in HIS (vs. control), the MUC5AC-positivity rate was lower, while high (+) MUC4-positivity was more frequent. In the conventional adenoma category: in HIS (vs. control), the MUC1-positivity rate was lower, while both high (+) MUC2-positivity and high (+) MUC5AC-positivity were less frequent. In the adenocarcinoma category: high (+) MUC2-positivity was more frequent in HIS than in control. Among the above mucins, only MUC1-positivity was significantly associated with an absence of the so-called fringe formation, an absence of spiral organisms within mucus, and an absence of strong immunopositive materials within the epithelial layer and within the subepithelial layer. The results suggest that Brachyspira infection or a related change in the microbiome may alter the large intestine mucin-expression profile in humans.

  13. Helicobacter pylori in Cholecystectomy Specimens-Morphological and Immunohistochemical Assessment (United States)

    Reddy, Venkatarami; Jena, Amitabh; Gavini, Siva; Thota, Asha; Nandyala, Rukamangadha; Chowhan, Amit Kumar


    Introduction Helicobacter pylori (H.pylori) is associated with gastritis, peptic ulcer, gastric carcinoma and gastric lymphoma. Current literature describes presence of H.pylori in various extra-gastric locations and its association with many diseases. Apart from the conventional location of gastric and duodenal mucosa, H.pylori have been isolated and cultured from gallbladder. Aim Analysis of cholecystectomy specimens to detect H.pylori by means of immunohistochemical staining. Materials and Methods There were a total of 118 cholecystectomy specimens received in the Department of Pathology in three months duration. We have performed immunostaining for H.pylori in 45 consecutive cases of cholecystectomy specimen. Clinical and other investigational information were retrieved from the medical records department. For each case, routine Haematoxylin and Eosin stain was studied. Immunohistochemistry (IHC) was done using purified polyclonal Helicobacter pylori antiserum. Results Majority of the patients had undergone laparoscopic cholecystectomy for the presenting complaint of right hypochondrial pain. Multiple pigmented stones were present in majority (27/45) of them. Immunostain for H.pylori was positive in ten cases. Six of these cases had pigmented gall stones, two had stones not specified and in two of the cases there were no stones. Conclusion Helicobacter pylori is present in gall bladder and is commonly seen in association with stones. A more detailed study of cholecystectomy cases (both neoplastic and non-neoplastic) with serological, culture and molecular data of H.pylori is desirable to study the pathogenesis of cholecystitis, its association with gall stones and other gall bladder disorders. PMID:27437221

  14. Denervation causes fiber atrophy and myosin heavy chain co-expression in senescent skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Sharon L Rowan

    Full Text Available Although denervation has long been implicated in aging muscle, the degree to which it is causes the fiber atrophy seen in aging muscle is unknown. To address this question, we quantified motoneuron soma counts in the lumbar spinal cord using choline acetyl transferase immunhistochemistry and quantified the size of denervated versus innervated muscle fibers in the gastrocnemius muscle using the in situ expression of the denervation-specific sodium channel, Nav₁.₅, in young adult (YA and senescent (SEN rats. To gain insights into the mechanisms driving myofiber atrophy, we also examined the myofiber expression of the two primary ubiquitin ligases necessary for muscle atrophy (MAFbx, MuRF1. MN soma number in lumbar spinal cord declined 27% between YA (638±34 MNs×mm⁻¹ and SEN (469±13 MNs×mm⁻¹. Nav₁.₅ positive fibers (1548±70 μm² were 35% smaller than Nav₁.₅ negative fibers (2367±78 μm²; P<0.05 in SEN muscle, whereas Nav₁.₅ negative fibers in SEN were only 7% smaller than fibers in YA (2553±33 μm²; P<0.05 where no Nav₁.₅ labeling was seen, suggesting denervation is the primary cause of aging myofiber atrophy. Nav₁.₅ positive fibers had higher levels of MAFbx and MuRF1 (P<0.05, consistent with involvement of the proteasome proteolytic pathway in the atrophy of denervated muscle fibers in aging muscle. In summary, our study provides the first quantitative assessment of the contribution of denervation to myofiber atrophy in aging muscle, suggesting it explains the majority of the atrophy we observed. This striking result suggests a renewed focus should be placed on denervation in seeking understanding of the causes of and treatments for aging muscle atrophy.

  15. Bilateral spontaneous dislocation of posterior chamber intraocular lens in a patient with gyrate atrophy

    Directory of Open Access Journals (Sweden)

    Michael Kinori


    Full Text Available We report a patient with gyrate atrophy, a rare metabolic disease, who had bilateral late spontaneous posterior dislocation of in-the-bag posterior chamber intraocular lens (PCIOL. He underwent pars plana vitrectomy, PCIOL retrieval and anterior chamber intraocular lens implantation in both eyes. This report may imply that patients with gyrate atrophy are at risk for spontaneous dislocation of intraocular lenses.

  16. In Vitro Modeling of Microgravity-Induced Muscle Atrophy and Spaceflight Radiation


    Harding, Charles; Takemoto, Jon; Vargis, Elizabeth


    Muscular atrophy, defined as the loss of muscle tissue, is a serious issue for immobilized patients on Earth and in human spaceflight, where microgravity prevents normal muscle loading. A major factor in muscular atrophy is oxidative stress, which is amplified not only by muscle disuse, but also by the increased levels of ionizing radiation in spaceflight. Additionally, elevated radiation exposure can damage DNA, increasing cancer risk. To model oxidative stress and DNA damage generated by...

  17. [Psychosocial intellectual development of children with infantile cystinosis and cerebral atrophy (author's transl)]. (United States)

    Ehrich, J H; Wolff, G; Stoeppler, L; Heyer, R; Offner, G; Brodehl, J


    The psychosocial and intellectual development of 4 boys with nephropathic cystinosis and brain atrophy documented by cranial computerized tomography was investigated by use of biographical data and psychological tests (HAWIK, Deutscher Rechtschreibtest). Inspite of the brain atrophy the patients showed low-normal intellectual capacities and mainly average school performance. There were no psychosocial abnormalities correlated to the primary metabolic disease. However, renal dwarfism led to mascotism requiring psychotherapy.

  18. The Finnish lapphund retinal atrophy locus maps to the centromeric region of CFA9


    Sargan David R; Wickström Kaisa; Aguirre-Hernández Jesús


    Abstract Background Dogs have the second largest number of genetic diseases, after humans. Among the diseases present in dogs, progressive retinal atrophy has been reported in more than a hundred breeds. In some of them, the mutation has been identified and genetic tests have allowed the identification of carriers, thus enabling a drastic reduction in the incidence of the disease. The Finnish lapphund is a dog breed presenting late-onset progressive retinal atrophy for which the disease locus...

  19. Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Elskamp, I.J. van den; Boden, B.; Barkhof, F. [VU University Medical Center, Department of Radiology, MS Center Amsterdam, Amsterdam (Netherlands); Dattola, V. [VU University Medical Center, Department of Radiology, MS Center Amsterdam, Amsterdam (Netherlands); University of Messina, Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, Messina (Italy); Knol, D.L. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Filippi, M. [Scientific Institute and University Ospedale San Raffaele, Neuroimaging Research Unit, Milan (Italy); Kappos, L. [University Hospital, University of Basel, Department of Neurology, Basel (Switzerland); Fazekas, F. [Medical University of Graz, Department of Neurology, Graz (Austria); Wagner, K. [Bayer-Schering Pharma, Berlin (Germany); Pohl, C. [Bayer-Schering Pharma, Berlin (Germany); University Hospital Bonn, Department of Neurology, Bonn (Germany); Sandbrink, R. [Bayer-Schering Pharma, Berlin (Germany); Heinrich-Heine-University Dusseldorf, Department of Neurology, Dusseldorf (Germany); Polman, C.H. [VU University Medical Center, Department of Neurology, MS Center Amsterdam, Amsterdam (Netherlands); Uitdehaag, B.M.J. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); VU University Medical Center, Department of Neurology, MS Center Amsterdam, Amsterdam (Netherlands)


    Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis (MS) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents. In this study, we evaluate the rate of cerebral atrophy in a 6-month period, investigate the predictive and explanatory value of other magnetic resonance imaging (MRI) measures in relation to cerebral atrophy, and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure. One hundred thirty-five relapsing-remitting multiple sclerosis patients underwent six monthly MRI scans from which the percentage brain volume change (PBVC) and the number and volume of gadolinium (Gd)-enhancing lesions, T2 lesions, and persistent black holes (PBH) were determined. By means of multiple linear regression analysis, the relationship between focal MRI variables and PBVC was assessed. Sample size calculations were performed for all patients and subgroups selected for enhancement or a high T2 lesion load at baseline. A significant atrophy occurred over 6 months (PBVC = -0.33%, SE = 0.061, p < 0.0001). The number of baseline T2 lesions (p = 0.024), the on-study Gd-enhancing lesion volume (p = 0.044), and the number of on-study PBHs (p = 0.003) were associated with an increased rate of atrophy. For a 50% decrease in rate of atrophy, the sample size calculations showed that approximately 283 patients per arm are required in an unselected sampled population and 185 patients per arm are required in a selected population. Within a 6-month period, significant atrophy can be detected and on-study associations of PBVC and PBHs emphasizes axonal loss to be a driving mechanism. Application as primary outcome measure in short-term clinical trials with feasible sample size requires a potent drug to obtain sufficient power. (orig.)

  20. Pronounced Impairment of Everyday Skills and Self-Care in Posterior Cortical Atrophy.


    Shakespeare, T. J.; Yong, K. X.; Foxe, D.; Hodges, J.; Crutch, S. J.


    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visual dysfunction and parietal, occipital, and occipitotemporal atrophy. The aim of this study was to compare the impact of PCA and typical Alzheimer's disease (tAD) on everyday functional abilities and neuropsychiatric status. The Cambridge Behavioural Inventory-Revised was given to carers of 32 PCA and 71 tAD patients. PCA patients showed significantly greater impairment in everyday skills and sel...

  1. Measurement of hippocampal atrophy using 4D graph-cut segmentation: application to ADNI. (United States)

    Wolz, Robin; Heckemann, Rolf A; Aljabar, Paul; Hajnal, Joseph V; Hammers, Alexander; Lötjönen, Jyrki; Rueckert, Daniel


    We propose a new method of measuring atrophy of brain structures by simultaneously segmenting longitudinal magnetic resonance (MR) images. In this approach a 4D graph is used to represent the longitudinal data: edges are weighted based on spatial and intensity priors and connect spatially and temporally neighboring voxels represented by vertices in the graph. Solving the min-cut/max-flow problem on this graph yields the segmentation for all timepoints in a single step. By segmenting all timepoints simultaneously, a consistent and atrophy-sensitive segmentation is obtained. The application to hippocampal atrophy measurement in 568 image pairs (Baseline and Month 12 follow-up) as well as 362 image triplets (Baseline, Month 12, and Month 24) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) confirms previous findings for atrophy in Alzheimer's disease (AD) and healthy aging. Highly significant correlations between hippocampal atrophy and clinical variables (Mini Mental State Examination, MMSE and Clinical Dementia Rating, CDR) were found and atrophy rates differ significantly according to subjects' ApoE genotype. Based on one year atrophy rates, a correct classification rate of 82% between AD and control subjects is achieved. Subjects that converted from Mild Cognitive Impairment (MCI) to AD after the period for which atrophy was measured (i.e., after the first 12 months) and subjects for whom conversion is yet to be identified were discriminated with a rate of 64%, a promising result with a view to clinical application. Power analysis shows that 67 and 206 subjects are needed for the AD and MCI groups respectively to detect a 25% change in volume loss with 80% power and 5% significance.

  2. IgM MGUS anti-MAG neuropathy with predominant muscle weakness and extensive muscle atrophy. (United States)

    Kawagashira, Yuichi; Kondo, Naohide; Atsuta, Naoki; Iijima, Masahiro; Koike, Haruki; Katsuno, Masahisa; Tanaka, Fumiaki; Kusunoki, Susumu; Sobue, Gen


    We report a patient with anti-myelin-associated glycoprotein (MAG) neuropathy, predominantly exhibiting severe motor symptoms, accompanied by extensive muscle atrophy mimicking Charcot-Marie-Tooth disease. Nerve conduction studies revealed mild retardation of motor conduction velocities and significant prolongation of distal latency. Sural nerve biopsy revealed widely spaced myelin and positive staining of myelinated fibers with an IgM antibody. Predominant motor symptoms with muscle atrophy can be one of the clinical manifestations of anti-MAG neuropathy.

  3. Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease. (United States)

    Ossenkoppele, Rik; Cohn-Sheehy, Brendan I; La Joie, Renaud; Vogel, Jacob W; Möller, Christiane; Lehmann, Manja; van Berckel, Bart N M; Seeley, William W; Pijnenburg, Yolande A; Gorno-Tempini, Maria L; Kramer, Joel H; Barkhof, Frederik; Rosen, Howard J; van der Flier, Wiesje M; Jagust, William J; Miller, Bruce L; Scheltens, Philip; Rabinovici, Gil D


    Alzheimer's disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel-based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, "visual variant," n=93), logopenic variant primary progressive aphasia (lvPPA, "language variant," n=74), and memory-predominant AD categorized as early age-of-onset (EOAD, 65 years, n=114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n=80). Even at the earliest clinical stage (CDR=0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant-specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome-specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex-hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome-specific vulnerable networks at the earliest clinical stages of AD.

  4. Differential effects of ischemic vascular disease and Alzheimer's disease on brain atrophy and cognition. (United States)

    Zheng, Ling; Vinters, Harry V; Mack, Wendy J; Weiner, Michael W; Chui, Helena C


    We previously reported that pathologic measures of arteriosclerosis (AS), cerebral infarction, and Alzheimer’s disease (AD) are independently correlated with cortical gray matter (CGM) atrophy measured by in vivo magnetic resonance imaging (MRI). Here, we use path analyses to model the associations between these three pathology measures and cognitive impairment, as mediated by CGM atrophy, after controlling for age and education. In this sample of 116 elderly persons followed longitudinally to autopsy (ischemic vascular disease (IVD) program project), differential patterns were observed between AS and atrophy/cognition versus AD and atrophy/cognition. The total effect of AD pathology on global cognition (β = -0.61, s.e. = 0.06) was four times stronger than that of AS (β = -0.15, s.e. = 0.08). The effect of AS on cognition appears to occur through cerebral infarction and CGM atrophy (β = -0.13, s.e. = 0.04). In contrast, the effects of AD pathology on global cognition (β = -0.50, s.e. = 0.07) occur through a direct pathway that is five times stronger than the indirect pathway acting through CGM atrophy (β = -0.09, s.e. = 0.03). The strength of this direct AD pathway was not significantly mitigated by adding hippocampal volume to the model. AD pathology affects cognition not only through brain atrophy, but also via an unmeasured pathway that could be related to synaptic dysfunction before the development of cortical atrophy.

  5. A genome-wide association study in multiple system atrophy (United States)

    Sailer, Anna; Nalls, Michael A.; Schulte, Claudia; Federoff, Monica; Price, T. Ryan; Lees, Andrew; Ross, Owen A.; Dickson, Dennis W.; Mok, Kin; Mencacci, Niccolo E.; Schottlaender, Lucia; Chelban, Viorica; Ling, Helen; O'Sullivan, Sean S.; Wood, Nicholas W.; Traynor, Bryan J.; Ferrucci, Luigi; Federoff, Howard J.; Mhyre, Timothy R.; Morris, Huw R.; Deuschl, Günther; Quinn, Niall; Widner, Hakan; Albanese, Alberto; Infante, Jon; Bhatia, Kailash P.; Poewe, Werner; Oertel, Wolfgang; Höglinger, Günter U.; Wüllner, Ullrich; Goldwurm, Stefano; Pellecchia, Maria Teresa; Ferreira, Joaquim; Tolosa, Eduardo; Bloem, Bastiaan R.; Rascol, Olivier; Meissner, Wassilios G.; Hardy, John A.; Revesz, Tamas; Holton, Janice L.; Gasser, Thomas; Wenning, Gregor K.; Singleton, Andrew B.


    Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). Methods: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. Results: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10−6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. Conclusions: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps. PMID:27629089

  6. Founder effect in spinal and bulbar muscular atrophy (SBMA). (United States)

    Tanaka, F; Doyu, M; Ito, Y; Matsumoto, M; Mitsuma, T; Abe, K; Aoki, M; Itoyama, Y; Fischbeck, K H; Sobue, G


    We analyzed the polymorphic (CAG)n and (GGC)n repeats of the androgen receptor gene in 113 unrelated X-linked spinal and bulbar muscular atrophy (SBMA) X chromosomes and 173 control X chromosomes in Japanese males. The control chromosomes had an average CAG repeat number of 21 +/- 3 with a range from 14-32 repeat units, and SBMA chromosomes had a range from 40-55 with a median of 47 +/- 3 copies. The control chromosomes had seven different alleles of the (GGC)n repeat with the range of 11 to 17; the most frequent size of (GGC)n was 16 (79%), while (GGC)17 was very rare (1%). However, in SBMA chromosomes only two alleles were seen; the most frequent size of (GGC)n was 16 (61%) followed by 17 (39%). (GGC)n size distribution was significantly different between SBMA and control chromosomes (P SBMA patients, which suggests that a founder effect makes a more significant contribution to generation of Japanese SBMA chromosomes than new mutations.

  7. Biomarkers in Rare Disorders: The Experience with Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Christina Brahe


    Full Text Available Spinal muscular atrophy (SMA is an autosomal recessive neuromuscular disorder caused by homozygous mutations of the SMN1 gene. Based on clinical severity, three forms of SMA are recognized (type I–III. All patients have at least one (usually 2–4 copies of a highly homologous gene (SMN2 which produces insufficient levels of functional SMN protein, due to alternative splicing of exon7. Recently, evidence has been provided that SMN2 expression can be enhanced by different strategies. The availability of potential candidates to treat SMA has raised a number of issues, including the availability of data on the natural history of the disease, the reliability and sensitivity of outcome measures, the duration of the studies, and the number and clinical homogeneity of participating patients. Equally critical is the availability of reliable biomarkers. So far, different tools have been proposed as biomarkers in SMA, classifiable into two groups: instrumental (the Compound Motor Action Potential, the Motor Unit Number Estimation, and the Dual-energy X-ray absorptiometry and molecular (SMN gene products dosage, either transcripts or protein. However, none of the biomarkers available so far can be considered the gold standard. Preclinical studies on SMA animal models and double-blind, placebo-controlled studies are crucial to evaluate the appropriateness of biomarkers, on the basis of correlations with clinical outcome.

  8. Transmission of multiple system atrophy prions to transgenic mice. (United States)

    Watts, Joel C; Giles, Kurt; Oehler, Abby; Middleton, Lefkos; Dexter, David T; Gentleman, Steve M; DeArmond, Stephen J; Prusiner, Stanley B


    Prions are proteins that adopt alternative conformations, which become self-propagating. Increasing evidence argues that prions feature in the synucleinopathies that include Parkinson's disease, Lewy body dementia, and multiple system atrophy (MSA). Although TgM83(+/+) mice homozygous for a mutant A53T α-synuclein transgene begin developing CNS dysfunction spontaneously at ∼10 mo of age, uninoculated TgM83(+/-) mice (hemizygous for the transgene) remain healthy. To determine whether MSA brains contain α-synuclein prions, we inoculated the TgM83(+/-) mice with brain homogenates from two pathologically confirmed MSA cases. Inoculated TgM83(+/-) mice developed progressive signs of neurologic disease with an incubation period of ∼100 d, whereas the same mice inoculated with brain homogenates from spontaneously ill TgM83(+/+) mice developed neurologic dysfunction in ∼210 d. Brains of MSA-inoculated mice exhibited prominent astrocytic gliosis and microglial activation as well as widespread deposits of phosphorylated α-synuclein that were proteinase K sensitive, detergent insoluble, and formic acid extractable. Our results provide compelling evidence that α-synuclein aggregates formed in the brains of MSA patients are transmissible and, as such, are prions. The MSA prion represents a unique human pathogen that is lethal upon transmission to Tg mice and as such, is reminiscent of the prion causing kuru, which was transmitted to chimpanzees nearly 5 decades ago.

  9. Retinal thinning correlates with clinical severity in multiple system atrophy. (United States)

    Ahn, Jeeyun; Lee, Jee-Young; Kim, Tae Wan


    To analyze retinal thickness changes in multiple system atrophy (MSA) and correlate changes with disease severity and subtypes of MSA. A total of 36 MSA (27 MSA-P and 9 MSA-C) patients and 71 healthy control subjects underwent general ophthalmologic examination and optical coherence tomography (OCT) scans. Peripapillary retinal nerve fiber layer (RNFL) thickness and perifoveal retinal thickness were analyzed separately. The generalized estimating equation model was used with age as a covariate to adjust for within-patient inter-eye correlations and the effect of age on retinal or RNFL thickness. Correlation analysis between RNFL, perifoveal thickness, and clinical parameters, the Unified MSA Rating Scale (UMSARS) and Global Disability Score (GDS), was also done. MSA patients showed significantly decreased peripapillary RNFL thickness in the inferior (P = 0.047) and inferotemporal (P = 0.017) sectors and significant perifoveal thinning in the superior outer sector (P = 0.042) compared to healthy controls. Both RNFL and perifoveal thinning were more marked and widespread in MSA-P than MSA-C patients. The UMSARS and GDS showed significant negative correlation with center and total macular perifoveal thickness and also the inferior and nasal outer sectors. Peripapillary RNFL and perifoveal retinal thinning were observed in MSA patients and retinal thinning correlated with the clinical severity of MSA. Structural changes in the retina may reflect the degree and pattern of neurodegeneration occurring in MSA.

  10. Clinical Characteristics of Cases with Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Mehmet Canpolat


    Full Text Available Introduction: The aim of this study is was to evaluate the clinical features of cases with diagnosis of spinal muscular atrophy (SMA. Materials and Methods: Thirty-eight pediatric patients were evaluated retrospectively. All patients were followed in the Pediatric Neurology Department of Erciyes University Faculty of Medicine. The diagnosis of patients had been confirmed by genetic analysis of homozygous deletions of survival motor neuron 1 gene. Detailed history, newborn symptoms, nutritional characteristics, initial complaints, physical examination, concomitant pathologies, genetic characteristics, and treatment modalities were investigated in all patients. Results: The study population consisted of 19 boys (50% and 19 girls (50%. The mean age of patients was 26.9±25.7 months (range: 3-96 months. The mean follow-up period was 12.2±13.3 months (range: 2-48 months. According to SMA classification, 22 patients (57.8% were type 1, 8 patients (21.1% were type 2, and 8 patients were (21.1% type 3. Neonatal respiratory distress, age at early diagnosis, nutritional problems, and recurrent lung diseases were detected as poor prognostic factors. Conclusions: SMA is a neuromuscular disease that requires multidisciplinary approach to medical care. There is a wide range of clinical severity. Identification of poor prognostic factors will help in terms of guiding close monitoring and timely treatments of children with SMA.

  11. Clinical features of adult spinal muscular atrophy:46 cases

    Institute of Scientific and Technical Information of China (English)

    Xiaojun He; Ping Zhang; Guanghui Chen


    BACKGROUND: Spinal muscular atrophy (SMA) is a kind of degenerative disease of nervous system. There are 4 types in clinic, especially types Ⅰ, Ⅱ and Ⅲ are common, and the researches on those 3 types are relative mature. Type Ⅳ is a kind of adult spinal muscular atrophy (ASMA), which has low incidence rate and is often misdiagnosed as amyotrophic lateral sclerosis, muscular dystrophy, cervical syndrome, or others.OBJECTIVE: To observe the clinical features of 46 ASMA patients and analyze the relationship between course and activity of daily living.DESIGN: Case analysis.SETTING: Departments of Neurology of the 81 Hospital of Chinese PLA, the Second Affiliated Hospital of Nanjing Medical College and General Hospital of Nanjing Military Area Command of Chinese PLA.PARTICIPANTS: A total of 46 ASMA patients were selected from the Departments of Neurology of the 81Hospital of Chinese PLA, the Second Affiliated Hospital of Nanjing Medical College and General Hospital of Nanjing Military Area Command of Chinese PLA between April 1998 and January 2002. All patients were consentient. Among 46 cases, there were 37 males and 9 females with the mean age of 42 years. The patients' courses in all ranged from 6 months to 23 years, concretely, courses of 37 cases were less than or equal to 5 years, and those of 9 cases were more than or equal to 6 years.METHODS : ① All the 46 ASMA patients were asked to check blood sedimentation, anti O, serum creatinine,creatine, blood creatine phosphokinase (CPK) and muscular biopsy as early as possible. ② X-ray was used to measure plain film of cervical vertebra borderline film of cranium and neck at proximal end of upper limb of 25 cases and plain film of abdominal vertebra at proximal end of lower limb of 17 cases.③ Cerebrospinal fluid of lumbar puncture was checked on 42 cases, for routine examination, biochemical examination, and immunoglobulin examination. Electromyogram (EMG) was also examined to 42 cases. ④ Barthel index

  12. Dental implants for severely atrophied jaws due to ectodermal dysplasia

    Directory of Open Access Journals (Sweden)

    Preetha Balaji


    Full Text Available The aim was to present the successful esthetical and functional rehabilitation of partial anodontia in a case of severe ectodermal dysplasia with complete atrophy of the jaws. A 17-year-old male with Class III malocclusion with partial anodontia sought dental implant treatment. His expectation was that of Class I occlusion. The challenge in the case was to match the expectation, reality, and the clinical possibilities. Ridge augmentation was performed with a combination of rib graft and recombinant human bone morphogenetic protein-2. Simultaneously, 6 implants (Nobel Biocare™ - Tapered Groovy were placed in maxillary arch and 10 in the mandible. Simultaneous placement ensured faster and better osseointegration though a mild compromise of the primary stability was observed initially. After adequate healing, Customized Zirconia Procera™ system was used to build the framework. Zirconia crown was cemented to the framework. Radiological and clinical evidence of osseointegration was observed in all 16 dental implants. Successful conversion of Class III to Class I occlusion was achieved with the combination of preprosthetic alveolar ridge augmentation, Procera™ Implant Bridge system. Abnormal angulations and or placement of dental implants would result in failure of the implant. Hence conversion of Class III to Class I occlusion needs complete and complex treatment planning so that the entire masticatory apparatus is sufficiently remodeled. Planning should consider the resultant vectors that would otherwise result in failure of framework or compromise the secondary stability of the dental implant during function. A successful case of rehabilitation of complex partial anodontia is presented.

  13. Urinary and erectile dysfunction in multiple system atrophy (MSA). (United States)

    Papatsoris, A G; Papapetropoulos, S; Singer, C; Deliveliotis, C


    Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined etiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar, and pyramidal signs. Despite the lack of effective therapies, some of the symptoms may be, at least temporarily, improved with adequate symptomatic therapies. Urinary and erectile dysfunction (ED) symptoms are prominent early features in male MSA patients. Lower urinary tract infections (UTIs) are a major cause of morbidity and mortality in this disorder. More than 50% of MSA patients suffer from recurrent lower UTIs and a significant number (approximately 25%) die of complications related to them. Urogenital symptoms in MSA are usually due to a complex mixture of central and peripheral nervous abnormalities, sometimes superimposed on previous local pathological conditions such as benign prostatic hyperplasia and perineal laxity. There have been instances were MSA-related urological symptoms were confused with symptoms of benign prostatic hyperplasia, leading to unnecessary urological surgery. In this review, we present the phenotypic range and therapeutic approaches for common storage and voiding urological symptoms and ED, in patients with MSA.

  14. Optimization of Spinal Muscular Atrophy subject's muscle activity during gait (United States)

    Umat, Gazlia; Rambely, Azmin Sham


    Spinal Muscular Atrophy (SMA) is a hereditary disease related muscle nerve disorder caused by degeneration of the anterior cells of the spinal cord. SMA is divided into four types according to the degree of seriousness. SMA patients show different gait with normal people. Therefore, this study focused on the effects of SMA patient muscle actions and the difference that exists between SMA subjects and normal subjects. Therefore, the electromyography (EMG) test will be used to track the behavior of muscle during walking and optimization methods are used to get the muscle stress that is capable of doing the work while walking. Involved objective function is non-linear function of the quadratic and cubic functions. The study concludes with a comparison of the objective function using the force that sought to use the moment of previous studies and the objective function using the data obtained from EMG. The results shows that the same muscles, peroneus longus and bisepsfemoris, were used during walking activity by SMA subjects and control subjects. Muscle stress force best solution achieved from part D in simulation carried out.

  15. False positives to confusable objects predict medial temporal lobe atrophy. (United States)

    Kivisaari, Sasa L; Monsch, Andreas U; Taylor, Kirsten I


    Animal models agree that the perirhinal cortex plays a critical role in object recognition memory, but qualitative aspects of this mnemonic function are still debated. A recent model claims that the perirhinal cortex is required to recognize the novelty of confusable distractor stimuli, and that damage here results in an increased propensity to judge confusable novel objects as familiar (i.e., false positives). We tested this model in healthy participants and patients with varying degrees of perirhinal cortex damage, i.e., amnestic mild cognitive impairment and very early Alzheimer's disease (AD), with a recognition memory task with confusable and less confusable realistic object pictures, and from whom we acquired high-resolution anatomic MRI scans. Logistic mixed-model behavioral analyses revealed that both patient groups committed more false positives with confusable than less confusable distractors, whereas healthy participants performed comparably in both conditions. A voxel-based morphometry analysis demonstrated that this effect was associated with atrophy of the anteromedial temporal lobe, including the perirhinal cortex. These findings suggest that also the human perirhinal cortex recognizes the novelty of confusable objects, consistent with its border position between the hierarchical visual object processing and medial temporal lobe memory systems, and explains why AD patients exhibit a heightened propensity to commit false positive responses with inherently confusable stimuli.

  16. Annular Lichenoid Dermatitis (of Youth) Immunohistochemical and Serological Evidence for Another Clinical Presentation of Borrelia Infection in Patients of Western Austria. (United States)

    Wilk, Michael; Zelger, Bettina G; Emberger, Michael; Zelger, Bernhard


    Annular lichenoid dermatitis of youth (ALDY) is a more recently described inflammatory disease of the skin of unknown etiology with clinical similarities to morphea. The authors clinically, histopathologically, and immunohistochemically investigated 14 biopsies from 12 patients in western Austria with this disease. There were 6 female and 6 male patients with solitary (n = 7) and multiple lesions (n = 5) affecting the trunk (n = 11), upper arm (n = 2), thigh (n = 1), and calf (n = 1). Clinically, early lesions were erythematous in nature leading to central paleness, scaling, wrinkling, dermal atrophy, slight pigmentation, and telangiectasia later on. Histopathologically, all specimens showed the typical features of ALDY with a superficial lichenoid process with sprinkling of lymphocytes along the basal cell layer and within the epidermis accompanied by mild fibrosis. Pigment incontinence, superficial fibrosis, and dilatation of superficial capillary vessels are prominent features in more advanced stages of disease. Immunohistologically, using a polyclonal antibody against Borrelia, 11/14 specimens revealed spirochetes, either vital (n = 4) or degenerated (n = 7), in close proximity to collagen bundles. Thirteen of 14 specimens in addition showed focal (n = 4) or clustered (n = 9) positivity for CD20 in the papillary dermis. Nine of 12 sera tested for Borrelia with an enzyme-linked immunosorbent assay were positive. Lichen sclerosus et atrophicus and morphea have previously been reported to be possibly related to Borrelia infection. We postulate that a similar relationship to Borrelia infection may be true for ALDY implying that ALDY may be an early superficial stage of morphea.

  17. Is Intracranial Atherosclerosis an Independent Risk Factor for Cerebral Atrophy? A Retrospective Evaluation

    Directory of Open Access Journals (Sweden)

    Zou Kelly H


    Full Text Available Abstract Background Our purpose was to study the association between the intracranial atherosclerosis as measured by cavernous carotid artery calcification (ICAC observed on head CT and atrophic changes of supra-tentorial brain demonstrated by MRI. Methods Institutional review board approval was obtained for this retrospective study incorporating 65 consecutive patients presenting acutely who had both head CT and MRI. Arterial calcifications of the intracranial cavernous carotids (ICAC were assigned a number (1 to 4 in the bone window images from CT scans. These 4 groups were then combined into high (grades 3 and 4 and low calcium (grades 1 and 2 subgroups. Brain MRI was independently evaluated to identify cortical and central atrophy. Demographics and cardiovascular risk factors were evaluated in subjects with high and low ICAC. Relationship between CT demonstrated ICAC and brain atrophy patterns were evaluated both without and with adjustment for cerebral ischemic scores and cardiovascular risk factors. Results Forty-six of the 65 (71% patients had high ICAC on head CT. Subjects with high ICAC were older, and had higher prevalence of hypertension, diabetes, coronary artery disease (CAD, atrial fibrillation and history of previous stroke (CVA compared to those with low ICAC. Age demonstrated strong correlation with both supratentorial atrophy patterns. There was no correlation between ICAC and cortical atrophy. There was correlation however between central atrophy and ICAC. This persisted even after adjustment for age. Conclusion Age is the most important determinant of atrophic cerebral changes. However, high ICAC demonstrated age independent association with central atrophy.

  18. Recommendations to quantify villous atrophy in video capsule endoscopy images of celiac disease patients (United States)

    Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H


    AIM To quantify the presence of villous atrophy in endoscopic images for improved automation. METHODS There are two main categories of quantitative descriptors helpful to detect villous atrophy: (1) Statistical and (2) Syntactic. Statistical descriptors measure the small intestinal substrate in endoscope-acquired images based on mathematical methods. Texture is the most commonly used statistical descriptor to quantify villous atrophy. Syntactic descriptors comprise a syntax, or set of rules, for analyzing and parsing the substrate into a set of objects with boundaries. The syntax is designed to identify and distinguish three-dimensional structures based on their shape. RESULTS The variance texture statistical descriptor is useful to describe the average variability in image gray level representing villous atrophy, but does not determine the range in variability and the spatial relationships between regions. Improved textural descriptors will incorporate these factors, so that areas with variability gradients and regions that are orientation dependent can be distinguished. The protrusion syntactic descriptor is useful to detect three-dimensional architectural components, but is limited to identifying objects of a certain shape. Improvement in this descriptor will require incorporating flexibility to the prototypical template, so that protrusions of any shape can be detected, measured, and distinguished. CONCLUSION Improved quantitative descriptors of villous atrophy are being developed, which will be useful in detecting subtle, varying patterns of villous atrophy in the small intestinal mucosa of suspected and known celiac disease patients. PMID:27803772

  19. l-Carnitine supplement reduces skeletal muscle atrophy induced by prolonged hindlimb suspension in rats. (United States)

    Jang, Jiwoong; Park, Jonghoon; Chang, Hyukki; Lim, Kiwon


    l-Carnitine was recently found to downregulate the ubiquitin proteasome pathway (UPP) and increase insulin-like growth factor 1 concentrations in animal models. However, the effect of l-carnitine administration on disuse muscle atrophy induced by hindlimb suspension has not yet been studied. Thus, we hypothesized that l-carnitine may have a protective effect on muscle atrophy induced by hindlimb suspension via the Akt1/mTOR and/or UPP. Male Wistar rats were assigned to 3 groups: hindlimb suspension group, hindlimb suspension with l-carnitine administration (1250 mg·kg(-1)·day(-1)) group, and pair-fed group adjusted hindlimb suspension. l-Carnitine administration for 2 weeks of hindlimb suspension alleviated the decrease in weight and fiber size in the soleus muscle. In addition, l-carnitine suppressed atrogin-1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. The present study shows that l-carnitine has a protective effect against soleus muscle atrophy caused by hindlimb suspension and decreased E3 ligase messenger RNA expression, suggesting the possibility that l-carnitine protects against muscle atrophy, at least in part, through the inhibition of the UPP. These observations suggest that l-carnitine could serve as an effective supplement in the decrease of muscle atrophy caused by weightlessness in the fields of clinical and rehabilitative research.

  20. Evolution of Cerebral Atrophy in a Patient with Super Refractory Status Epilepticus Treated with Barbiturate Coma (United States)

    George, Pravin; Nattanmai, Premkumar; Ahrens, Christine; Hantus, Stephen; Sarwal, Aarti


    Introduction. Status epilepticus is associated with neuronal breakdown. Radiological sequelae of status epilepticus include diffusion weighted abnormalities and T2/FLAIR cortical hyperintensities corresponding to the epileptogenic cortex. However, progressive generalized cerebral atrophy from status epilepticus is underrecognized and may be related to neuronal death. We present here a case of diffuse cerebral atrophy that developed during the course of super refractory status epilepticus management despite prolonged barbiturate coma. Methods. Case report and review of the literature. Case. A 19-year-old male with a prior history of epilepsy presented with focal clonic seizures. His seizures were refractory to multiple anticonvulsants and eventually required pentobarbital coma for 62 days and midazolam coma for 33 days. Serial brain magnetic resonance imaging (MRI) showed development of cerebral atrophy at 31 days after admission to our facility and progression of the atrophy at 136 days after admission. Conclusion. This case highlights the development and progression of generalized cerebral atrophy in super refractory status epilepticus. The cerebral atrophy was noticeable at 31 days after admission at our facility which emphasizes the urgency of definitive treatment in patients who present with super refractory status epilepticus. Further research into direct effects of therapeutic coma is warranted. PMID:28182114

  1. Evolution of Cerebral Atrophy in a Patient with Super Refractory Status Epilepticus Treated with Barbiturate Coma

    Directory of Open Access Journals (Sweden)

    Christopher R. Newey


    Full Text Available Introduction. Status epilepticus is associated with neuronal breakdown. Radiological sequelae of status epilepticus include diffusion weighted abnormalities and T2/FLAIR cortical hyperintensities corresponding to the epileptogenic cortex. However, progressive generalized cerebral atrophy from status epilepticus is underrecognized and may be related to neuronal death. We present here a case of diffuse cerebral atrophy that developed during the course of super refractory status epilepticus management despite prolonged barbiturate coma. Methods. Case report and review of the literature. Case. A 19-year-old male with a prior history of epilepsy presented with focal clonic seizures. His seizures were refractory to multiple anticonvulsants and eventually required pentobarbital coma for 62 days and midazolam coma for 33 days. Serial brain magnetic resonance imaging (MRI showed development of cerebral atrophy at 31 days after admission to our facility and progression of the atrophy at 136 days after admission. Conclusion. This case highlights the development and progression of generalized cerebral atrophy in super refractory status epilepticus. The cerebral atrophy was noticeable at 31 days after admission at our facility which emphasizes the urgency of definitive treatment in patients who present with super refractory status epilepticus. Further research into direct effects of therapeutic coma is warranted.


    Institute of Scientific and Technical Information of China (English)

    邢国刚; 樊小力; 吴苏娣; 宋新爱; 朱保恭; 唐斌


    Objective: To study the possible mechanism and prevention of disuse muscle atrophy. Methods: The shortened immobilization (plaster fixation) of rat' s soleus muscle (SOL) was used as the model of muscle and the lengthened immobilization of rat' s SOL muscle as "passive stretch" method. Types of skeletal muscle fibers were differentiated with m - ATPase staining technique. The changes of rat' s SOL muscle weight (wet weight) as well as the types and the mean cross - sectional area (CSA) of muscle fibers were examined respectively on day 2, 4,7, 14 and 21 under both shortened and lengthened immobilization and then the effect of passive stretch on soleus muscle atrophy in immobilized rats was observed. Results: When shortened immobilization was applied for 4 days, SOL muscle weight (wet weight) became lighter; the fiber crosssectional area (CSA) shrank and type Ⅰ muscle fibers started transforming into type Ⅱ, which all indicated immobilized muscles began to atrophy and as immobilization proceeded, muscle atrophy proceeded toward higher level. In contrast to that, when lengthened immobilization was applied, SOL muscle didn' t show any sign of atrophy until 7th day, and reached its highest level on day 14 and maintained that level even though immobilization continued. Conclusion: From the results, we conclude that passive stretch can either relieve or defer disuse muscle atrophy.


    Institute of Scientific and Technical Information of China (English)

    邢国刚; 樊小力; 吴苏娣; 宋新爱; 朱保恭; 唐斌


    Objective To study the possible mechanism and prevention of disused muscle atrophy. Methods The shortened immobilization (plaster fixation) of rat's soleus muscle(SOL) was used as the model of muscle "disuse" and the lengthened immobilization of rat's SOL muscle as "passive stretch" method. Types of skeletal muscle fibers were differentiated with m-ATPase staining technique. The changes of rat's SOL weight (wet weight) as well as the types and the mean cross sectional area (CSA) of muscle fibers were examined respectively on days 2,4,7,14 and 21 under both shortened and lengthened immobilization, and then the effect of passive stretch on soleus muscle atrophy in immobilized rats was observed. Results When shortened immobilization was applied for 4 days, SOL weight (wet weight ) became lighter, the fiber cross-sectional area (CSA) shrank, and type Ⅰ muscle fibers started to transform into type Ⅱ, which all indicated that immobilized muscles began to atrophy, and as immobilization proceeded, muscle atrophy proceeded toward higher level. In contrast to that, when lengthened immobilization was applied, SOL didn't show any signs of atrophy until day 7, the sign reached its highest level on day 14 and maintained that level even though immobilization continued. Conclusion From the results, we conclude that the passive stretch can either relieve or retard the disused muscle atrophy.

  4. Increased cortical atrophy in patients with Alzheimer's disease and type 2 diabetes mellitus (United States)

    Biessels, G J; De Leeuw, F‐E; Lindeboom, J; Barkhof, F; Scheltens, P


    Background The risk of Alzheimer's disease (AD) is increased in type 2 diabetes (DM2). This increased risk has been attributed to vascular comorbidity, but other mechanisms, such as accelerated ageing of the brain, have also been implicated. Objective To determine whether AD in patients with DM2 is associated with an increased occurrence of vascular lesions in the brain, by increased cerebral atrophy, or a combination of both. Methods In total, 29 patients with AD and DM2 and 58 patients with AD and without DM2 were included in the study. Clinical characteristics were recorded, and a neuropsychological examination and magnetic resonance imaging (MRI) scan were performed. MRI scans were rated for cortical and subcortical atrophy, medial temporal lobe atrophy, white matter lesions, and infarcts. Results The neuropsychological profiles of the two groups were identical. Patients with AD and DM2 had increased cortical atrophy on MRI (p<0.05) compared with the non‐DM2 group. In addition, infarcts were more common (odds ratio 2.4; 95% CI 0.8 to 7.8), but this effect did not account for the increased atrophy. The other MR measures did not differ between the groups. Conclusion The results suggest that non‐vascular mechanisms, leading to increased cortical atrophy, are also involved in the increased risk of AD in DM2. PMID:16484636

  5. Dehydroepiandrosterone intra vaginal administration for the management of postmenopausal vulvovaginal atrophy. (United States)

    Archer, David F


    The effects of intravaginal administration of dehydroepiandrosterone (DHEA) for the management of symptomatic vulvovaginal atrophy are reviewed. A literature search related to vulvovaginal atrophy, vaginal atrophy, atrophic vaginitis, estrogen, dehydroepiandrosterone, vulvar itching, burning, dryness, dyspareunia, and libido was performed. Relevant articles addressing the incidence, management, and outcome of DHEA therapy were identified and used for this Expert Opinion. DHEA compared to a placebo is an effective treatment improving symptoms of vaginal atrophy: dyspareunia, burning, itching, and dryness. Objective parameters of vaginal atrophy, specifically pH, vaginal maturation index (VMI), and investigator-evaluated changes in the vagina: moisture, epithelia integrity and color were improved compared to baseline and placebo. There were significant improvements in libido and dyspareunia with the intravaginal use of DHEA that contribute to improved quality of life for postmenopausal women. Dehydroepiandrosterone administered intravaginally on a daily basis is an effective treatment for symptoms, and signs of vulvovaginal atrophy along with libido in postmenopausal women. This article is part of a Special Issue entitled 'Essential role of DHEA'.

  6. Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies. (United States)

    Nedelska, Zuzana; Ferman, Tanis J; Boeve, Bradley F; Przybelski, Scott A; Lesnick, Timothy G; Murray, Melissa E; Gunter, Jeffrey L; Senjem, Matthew L; Vemuri, Prashanti; Smith, Glenn E; Geda, Yonas E; Graff-Radford, Jonathan; Knopman, David S; Petersen, Ronald C; Parisi, Joseph E; Dickson, Dennis W; Jack, Clifford R; Kantarci, Kejal


    Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and medial temporal lobe volumes compared with Alzheimer's disease dementia (AD) on magnetic resonance imaging. However, frequently coexistent AD-type pathology may influence the pattern of regional brain atrophy rates in DLB patients. We investigated the pattern and magnitude of the atrophy rates from 2 serial MRIs in autopsy-confirmed DLB patients (n = 20) and mixed DLB/AD patients (n = 22), compared with AD (n = 30) and elderly nondemented control subjects (n = 15), followed antemortem. DLB patients without significant AD-type pathology were characterized by lower global and regional rates of atrophy, similar to control subjects. The mixed DLB/AD patients displayed greater atrophy rates in the whole brain, temporoparietal cortices, hippocampus and amygdala, and ventricle expansion, similar to AD patients. In the DLB and DLB/AD patients, the atrophy rates correlated with Braak neurofibrillary tangle stage, cognitive decline, and progression of motor symptoms. Global and regional atrophy rates are associated with AD-type pathology in DLB, and these rates can be used as biomarkers of AD progression in patients with LB pathology.

  7. Atrophy of muscles surrounding the shoulder in hemiplegia. Analysis with MRI

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Fumio; Kobayashi, Tsunesaburo; Matsumoto, Shinichi [Fukushima Rosai Hospital, Iwaki (Japan)


    Decrease of range of motion and subluxation of shoulders are common secondary dysfunctions after the stroke. The purpose of this study is to evaluate the atrophy of muscles surrounding shoulders in hemiplegic patients and to delineate the correlations between those atrophies and shoulder functions. MRI studies were done on bilateral shoulders in 13 hemiplegic patients with shoulder pain. The cross sectional areas of muscles surrounding shoulder, i.e., subscapularis, supraspinatus, infraspinatus, teres minor and deltoid muscle were measured on those images obtained. The degree of atrophies were evaluated by dividing cross-sectional area of the muscle on affected shoulder by that of non-affected shoulder, that is muscle atrophy ratio [MAR], for each muscle in every case. Also, the range of movements [ROM], the degree of subluxation and muscle strength of shoulder flexion were evaluated. All muscle cross-sectional areas on the affected side were significantly smaller than those of muscles on the unaffected side (p<0.01). The means of MARs were 0.68, 0.69, 0.86, 0.72 and 0.69 for subscapularis, supraspinatus, infraspinatus, teres minor and deltoid muscle. The pattern of muscle atrophies, however, varies from case to case. Both correlations of ROM versus supraspinatus MAR and degree of shoulder subluxation versus deltoid MAR were statistically significant (p<0.05). These results indicate the contribution of muscle atrophy to the shoulder dysfunction in hemiplegic patients. (author).

  8. Calcified Neurocysticercosis Associates with Hippocampal Atrophy: A Population-Based Study (United States)

    Del Brutto, Oscar H.; Salgado, Perla; Lama, Julio; Del Brutto, Victor J.; Campos, Xavier; Zambrano, Mauricio; García, Héctor H.


    Calcified neurocysticercosis has been associated with hippocampal atrophy in patients with refractory epilepsy, but the relevance of this association in the population at large is unknown. We assessed calcified cysticerci and its association with hippocampal atrophy in elderly persons living in Atahualpa, an Ecuadorian village endemic for neurocysticercosis. All Atahualpa residents ≥ 60 years of age were invited to undergo computed tomography/magnetic resonance imaging for neurocysticercosis detection. Twenty-eight (11%) out of 248 enrolled persons had calcified cysticerci (case-patients) and were matched 1:1 by age, sex, and years of education to individuals without neurocysticercosis on computed tomography/magnetic resonance imaging (controls). Four case-patients and none of the controls had epilepsy (P = 0.134). Cognitive performance was similar across both groups. The Scheltens' medial temporal atrophy scale was used for hippocampal rating in case-patients and matched controls without neurocysticercosis. Mean score in the Scheltens' scale was higher in case-patients than in controls (P < 0.001). Atrophic hippocampi were noticed in 19 case-patients and five controls (P = 0.003). Atrophy was bilateral in 11 case-patients and unilateral in eight. All case-patients with unilateral hippocampal atrophy had at least one ipsilateral calcification. This study shows an association between calcified cysticerci and hippocampal atrophy and raises the possibility of an inflammation-mediated hippocampal damage as the responsible mechanism for these findings. PMID:25349375

  9. Brain atrophy rates in first degree relatives at risk for Alzheimer's. (United States)

    Lampert, Erika J; Roy Choudhury, Kingshuk; Hostage, Christopher A; Rathakrishnan, Bharath; Weiner, Michael; Petrella, Jeffrey R; Doraiswamy, P Murali


    A positive family history (FH) raises the risk for late-onset Alzheimer's disease though, other than the known risk conferred by apolipoprotein ε4 (ApoE4), much of the genetic variance remains unexplained. We examined the effect of family history on longitudinal regional brain atrophy rates in 184 subjects (42% FH+, mean age 79.9) with mild cognitive impairment (MCI) enrolled in a national biomarker study. An automated image analysis method was applied to T1-weighted MR images to measure atrophy rates for 20 cortical and subcortical regions. Mixed-effects linear regression models incorporating repeated-measures to control for within-subject variation over multiple time points tested the effect of FH over a follow-up of up to 48 months. Most of the 20 regions showed significant atrophy over time. Adjusting for age and gender, subjects with a positive FH had greater atrophy of the amygdala (p atrophy rates was numerically greater in ε3 homozygotes than in E4 carriers, but this difference was not significant. FH+ subjects had numerically greater 4-year cognitive decline and conversion rates than FH- subjects but the difference was not statistically significant after adjusting for ApoE and other variables. We conclude that a positive family history of AD may influence cortical and temporal lobe atrophy in subjects with mild cognitive impairment, but it does not have a significant additional effect beyond the known effect of the E4 genotype.

  10. Calcified neurocysticercosis associates with hippocampal atrophy: a population-based study. (United States)

    Del Brutto, Oscar H; Salgado, Perla; Lama, Julio; Del Brutto, Victor J; Campos, Xavier; Zambrano, Mauricio; García, Héctor H


    Calcified neurocysticercosis has been associated with hippocampal atrophy in patients with refractory epilepsy, but the relevance of this association in the population at large is unknown. We assessed calcified cysticerci and its association with hippocampal atrophy in elderly persons living in Atahualpa, an Ecuadorian village endemic for neurocysticercosis. All Atahualpa residents ≥ 60 years of age were invited to undergo computed tomography/magnetic resonance imaging for neurocysticercosis detection. Twenty-eight (11%) out of 248 enrolled persons had calcified cysticerci (case-patients) and were matched 1:1 by age, sex, and years of education to individuals without neurocysticercosis on computed tomography/magnetic resonance imaging (controls). Four case-patients and none of the controls had epilepsy (P = 0.134). Cognitive performance was similar across both groups. The Scheltens' medial temporal atrophy scale was used for hippocampal rating in case-patients and matched controls without neurocysticercosis. Mean score in the Scheltens' scale was higher in case-patients than in controls (P < 0.001). Atrophic hippocampi were noticed in 19 case-patients and five controls (P = 0.003). Atrophy was bilateral in 11 case-patients and unilateral in eight. All case-patients with unilateral hippocampal atrophy had at least one ipsilateral calcification. This study shows an association between calcified cysticerci and hippocampal atrophy and raises the possibility of an inflammation-mediated hippocampal damage as the responsible mechanism for these findings.

  11. The gross motor function measure is a valid and sensitive outcome measure for spinal muscular atrophy. (United States)

    Nelson, Leslie; Owens, Hollis; Hynan, Linda S; Iannaccone, Susan T


    Spinal muscular atrophy is a genetic disease of the anterior horn cell with high morbidity rate in childhood. Certain drugs may be of benefit and are in or under consideration for Phase II trials. Outcome measures that are age appropriate and representative of disease activity remain under study. Several have not yet been validated for spinal muscular atrophy. The Gross Motor Function Measure is a measure of motor function. We showed previously that the Gross Motor Function Measure is a reliable outcome measure to assess motor function in children with spinal muscular atrophy. By collating our data from 40 spinal muscular atrophy patients, ages 5 through 17 years, we now show the validity of the Gross Motor Function Measure when compared to Quantitative Muscle Testing and ambulatory status in children with spinal muscular atrophy. The median for Gross Motor Function Measure total scores for walkers was 237 (range: 197-261) and for non-walkers, 64 (range: 4-177; PGross Motor Function Measure is valid and sensitive as an outcome measure for clinical trials in pediatric spinal muscular atrophy.

  12. Muscle fatigue, nNOS and muscle fiber atrophy in limb girdle muscular dystrophy. (United States)

    Angelini, Corrado; Tasca, Elisabetta; Nascimbeni, Anna Chiara; Fanin, Marina


    Muscle fatigability and atrophy are frequent clinical signs in limb girdle muscular dystrophy (LGMD), but their pathogenetic mechanisms are still poorly understood. We review a series of different factors that may be connected in causing fatigue and atrophy, particularly considering the role of neuronal nitric oxide synthase (nNOS) and additional factors such as gender in different forms of LGMD (both recessive and dominant) underlying different pathogenetic mechanisms. In sarcoglycanopathies, the sarcolemmal nNOS reactivity varied from absent to reduced, depending on the residual level of sarcoglycan complex: in cases with complete sarcoglycan complex deficiency (mostly in beta-sarcoglycanopathy), the sarcolemmal nNOS reaction was absent and it was always associated with early severe clinical phenotype and cardiomyopathy. Calpainopathy, dysferlinopathy, and caveolinopathy present gradual onset of fatigability and had normal sarcolemmal nNOS reactivity. Notably, as compared with caveolinopathy and sarcoglycanopathies, calpainopathy and dysferlinopathy showed a higher degree of muscle fiber atrophy. Males with calpainopathy and dysferlinopathy showed significantly higher fiber atrophy than control males, whereas female patients have similar values than female controls, suggesting a gender difference in muscle fiber atrophy with a relative protection in females. In female patients, the smaller initial muscle fiber size associated to endocrine factors and less physical effort might attenuate gender-specific muscle loss and atrophy.

  13. Topical Mineralocorticoid Receptor Blockade Limits Glucocorticoid-Induced Epidermal Atrophy in Human Skin. (United States)

    Maubec, Eve; Laouénan, Cédric; Deschamps, Lydia; Nguyen, Van Tuan; Scheer-Senyarich, Isabelle; Wackenheim-Jacobs, Anne-Catherine; Steff, Maud; Duhamel, Stéphanie; Tubiana, Sarah; Brahimi, Nesrine; Leclerc-Mercier, Stéphanie; Crickx, Béatrice; Perret, Claudine; Aractingi, Selim; Escoubet, Brigitte; Duval, Xavier; Arnaud, Philippe; Jaisser, Frederic; Mentré, France; Farman, Nicolette


    A major deleterious side effect of glucocorticoids is skin atrophy. Glucocorticoids activate the glucocorticoid and the mineralocorticoid (MR) receptor, both present in the epidermis. We hypothesized that glucocorticoid-induced epidermal atrophy may be related to inappropriate occupancy of MR by glucocorticoids. We evaluated whether epidermal atrophy induced by the topical glucocorticoid clobetasol could be limited by coadministration of MR antagonist. In cultured human skin explants, the epidermal atrophy induced by clobetasol was significantly limited by MR antagonism (canrenoate and eplerenone). Blockade of the epithelial sodium channel ENaC by phenamil was also efficient, identifying a role of MR-ENaC cascade in keratinocytes, acting through restoration of clobetasol-induced impairment of keratinocyte proliferation. In the SPIREPI randomized double-blind controlled trial, gels containing clobetasol, the MR antagonist spironolactone, both agents, or placebo were applied on four zones of the forearms of 23 healthy volunteers for 28 days. Primary outcome was histological thickness of the epidermis with clobetasol alone or clobetasol+spironolactone. Spironolactone alone did not affect the epidermal thickness but coapplication of clobetasol and spironolactone significantly limited clobetasol-induced atrophy and was well tolerated. Altogether, these findings identify MR as a factor regulating epidermal homeostasis and suggest that topical MR blockade could limit glucocorticoid-induced epidermal atrophy.

  14. Regional gray matter atrophy and neuropsychologcal problems in relapsing-remitting multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    Aiyu Lin; Fuyong Chen; Fang Liu; Zhiwen Li; Ying Liu; Shifang Lin; Xiaoyi Wang; Jiting Zhu


    In multiple sclerosis, gray matter atrophy is extensive, and cognitive deficits and mood disorders are frequently encountered. It has been conjectured that focal atrophy is associated with emotional de-cline. However, conventional MRI has revealed that the pathological characteristics cannot ful y account for the mood disorders. Moreover, there is no correlation between cognitive disorders and MRI results in clinical y isolated syndromes or in cases of definite multiple sclerosis. In this case-control study, voxel-based morphometric analysis was performed on 11 subjects with relapsing-remitting multiple sclerosis, and the results show that these patients exhibit gray matter atrophy. Moreover, the gray matter atrophy in the superior and middle gyri of the right frontal lobe in patients with multiple sclerosis was correlated with scores from the Hamilton Anxiety Rating Scale. The scores obtained with the Repeatable Battery for the Assessment of Neuropsychological Status were associated with gray matter atrophy in the middle gyrus of the left frontal lobe, the superior and middle gyrus of the right frontal lobe, the middle gyrus of the left cingulate, the superior and middle gyri of the left frontal lobe, and the triangular area of the left frontal lobe. However, there was no statistical significance. These findings suggest that the cingulate and frontal cortices of the nant hemisphere are the most severely atrophic regions of the brain, and this atrophy is correlated with cognitive decline and emotional abnormalities.

  15. Age- and gender-related changes in contractile properties of non-atrophied EDL muscle.

    Directory of Open Access Journals (Sweden)

    Stephen Chan

    Full Text Available BACKGROUND: In humans, ageing causes skeletal muscles to become atrophied, weak, and easily fatigued. In rodent studies, ageing has been associated with significant muscle atrophy and changes in the contractile properties of the muscles. However, it is not entirely clear whether these changes in contractile properties can occur before there is significant atrophy, and whether males and females are affected differently. METHODS AND RESULTS: We investigated various contractile properties of whole isolated fast-twitch EDL muscles from adult (2-6 months-old and aged (12-22 months-old male and female mice. Atrophy was not present in the aged mice. Compared with adult mice, EDL muscles of aged mice had significantly lower specific force, longer tetanus relaxation times, and lower fatiguability. In the properties of absolute force and muscle relaxation times, females were affected by ageing to a greater extent than males. Additionally, EDL muscles from a separate group of male mice were subjected to eccentric contractions of 15% strain, and larger force deficits were found in aged than in adult mice. CONCLUSION: Our findings provide further insight into the muscle atrophy, weakness and fatiguability experienced by the elderly. We have shown that even in the absence of muscle atrophy, there are definite alterations in the physiological properties of whole fast-twitch muscle from ageing mice, and for some of these properties the alterations are more pronounced in female mice than in male mice.

  16. Age- and Gender-Related Changes in Contractile Properties of Non-Atrophied EDL Muscle (United States)

    Chan, Stephen; Head, Stewart I.


    Background In humans, ageing causes skeletal muscles to become atrophied, weak, and easily fatigued. In rodent studies, ageing has been associated with significant muscle atrophy and changes in the contractile properties of the muscles. However, it is not entirely clear whether these changes in contractile properties can occur before there is significant atrophy, and whether males and females are affected differently. Methods and Results We investigated various contractile properties of whole isolated fast-twitch EDL muscles from adult (2–6 months-old) and aged (12–22 months-old) male and female mice. Atrophy was not present in the aged mice. Compared with adult mice, EDL muscles of aged mice had significantly lower specific force, longer tetanus relaxation times, and lower fatiguability. In the properties of absolute force and muscle relaxation times, females were affected by ageing to a greater extent than males. Additionally, EDL muscles from a separate group of male mice were subjected to eccentric contractions of 15% strain, and larger force deficits were found in aged than in adult mice. Conclusion Our findings provide further insight into the muscle atrophy, weakness and fatiguability experienced by the elderly. We have shown that even in the absence of muscle atrophy, there are definite alterations in the physiological properties of whole fast-twitch muscle from ageing mice, and for some of these properties the alterations are more pronounced in female mice than in male mice. PMID:20808812

  17. Immunohistochemical patterns of follicular dendritic cell meshwork and Ki-67 in small B-cell lymphomas

    Institute of Scientific and Technical Information of China (English)



    Objective To identify the immunohistochemical patterns of follicular dendritic cell(FDC)meshwork and Ki-67labeling index in small B-cell lymphomas(SBLs) and their significance in differential diagnosis.Methods

  18. Estrogen and progesterone receptors in endometrial carcinoma: comparison of immunohistochemical and biochemical analysis

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Lyndrup, J;


    In 159 endometrial carcinomas, estrogen (ER) and progesterone receptors (PR) were determined biochemically by dextran-coated charcoal (DCC) assay and immunohistochemically (ICA) on frozen sections. ICA receptor content was estimated by a total histologic score (HSCORE), including all tissue...

  19. Early onset cerebellar ataxia with retained tendon reflexes (EOCA and olivopontocerebellar atrophy (OPCA : a computed tomographic study.

    Directory of Open Access Journals (Sweden)

    Pal P


    Full Text Available Computed tomographic (CT studies in olivopontocerebellar atrophies (OPCA and ′early onset cerebellar ataxia with retained tendon reflexes (EOCA′ are few and vary widely in methodology and criteria for cerebellar and brainstem atrophy. In this prospective study, CT scan observations on 26 patients (EOCA-11, OPCA-15 were compared with 31 controls using qualitative and quantitative assessment of cisterns, ventricles and atrophy of brain. Vermian and/or cerebellar hemispheric (predominantly anterior atrophy was present in 80.8% and both were equally common. Cerebral cortical atrophy (26.9% and leukoariosis (15.4% were less frequently seen. Statistically significant atrophy of pons, brachium pontis, cerebellum and midbrain was noted in patient group. No significant differences were observed between EOCA and OPCA groups. Evidence of atrophy did not correlate with either the duration of illness or the severity of cerebellar ataxia in both the groups. The severity of brainstem atrophy in 14 patients with and 12 patients without abnormal brainstem auditory evoked response did not differ significantly. This study highlights the methodology of CT evaluation for brainstem and cerebellar atrophy, draws attention to cerebral atrophy and emphasizes the lack of significant differences in CT morphology between OPCA and EOCA patients.

  20. The sessile drop method for immunohistochemical processing of unmounted sections of nervous tissue. (United States)

    Nadelhaft, I


    A novel method for the immunohistochemical processing of free-floating tissue sections is described. Sections are immersed within drops of solution arranged on a hydrophobic surface. The procedure consists of sequentially suctioning away one fluid drop and replacing it by another, while the section remains in place. The technique permits easy testing of different antiserum dilutions, comparisons among different immunohistochemical protocols, and comparison of different antisera on serial tissue sections. Comparison is made to processing mounted sections.

  1. How Are Overweight and Obesity Diagnosed? (United States)

    ... body mass index (BMI) and possibly a high waist circumference, and tests to rule out other medical conditions. ... diagnosed as obese if you have a large waist circumference that suggests increased amounts of fat in your ...

  2. How Are Pelvic Floor Disorders Diagnosed? (United States)

    ... Information Clinical Trials Resources and Publications How are pelvic floor disorders diagnosed? Skip sharing on social media links ... fee ). This test is used to evaluate the pelvic floor and rectum while the patient is having a ...

  3. How Is Sickle Cell Disease Diagnosed? (United States)

    ... page from the NHLBI on Twitter. How Is Sickle Cell Disease Diagnosed? Screening Tests People who do not ... Content: NEXT >> Featured Video Living With and Managing Sickle Cell Disease (Nicholas) 09/02/2011 In this video— ...

  4. Diagnosing Diabetes and Learning about Prediabetes (United States)

    ... Size: A A A Listen En Español Diagnosing Diabetes and Learning About Prediabetes There are several ways ... mg/dl – 199 mg/dl Preventing Type 2 Diabetes You will not develop type 2 diabetes automatically ...

  5. Diagnosing Asthma in Very Young Children (United States)

    ... Listen Español Text Size Email Print Share Diagnosing Asthma in Babies & Toddlers Page Content Article Body One ... family with recurrent bronchitis or sinus problems. When Asthma is Not the Cause Your pediatrician will listen ...

  6. How Are Obesity and Overweight Diagnosed? (United States)

    ... Clinical Trials Resources and Publications How are obesity & overweight diagnosed? Skip sharing on social media links Share ... common way to determine if a person is overweight or obese is to calculate body mass index ( ...

  7. Challenges in diagnosing tuberculosis in children

    DEFF Research Database (Denmark)

    Rahman, Nadia; Pedersen, Karin Kæreby; Nielsen, Vibeke Rosenfeldt


    Clinical investigations of childhood tuberculosis (TB) are challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. We investigated the challenges in diagnosing TB in children in a low-incidence country.......Clinical investigations of childhood tuberculosis (TB) are challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. We investigated the challenges in diagnosing TB in children in a low-incidence country....

  8. Investigating Immunohistochemical Expression of cyclooxygenase-2 in oral lichen planus

    Directory of Open Access Journals (Sweden)

    Maryam Seyedmajidi


    Full Text Available Background and goal: (cox2 Cyclooxygenase -2 as an enzyme is not present in normal tissues and in fact is a type of inductive enzyme during pathological phenomena such as inflammation and cancer are significantly increased. Increased expression of cox-2 in gastric carcinoma, pancreatic, lung and oral squamous cell carcinoma has been shown and seems to be one of the performance mechanisms of the inhibition of apoptosis in tumor cells. Regarding the role of cox-2 in apoptosis mechanisms and the creation of dysplastic changes and malignant, the study aimed to evaluate the immunohistochemical expression of cox-2 in oral lichen planus and were compared with normal mucosa and gingivitis. Methods: The study was performed on 30 paraffin blocks related to patients referred to oral and maxillofacial pathology department in Dental School of Babol with confirmed diagnosis of oral lichen planus was done. The same number of samples of normal mucosa and samples of gingivitis were studied. Slices prepared from the above blocks bycoloring immunostaining cox-2 were stained and after reviewing the slides obtained, data using statistical software spss20 and x2 tests, Mann-Whitney and parametric tests such as T test was analyzed and P ˂0.05 was considered significant Results: In this study, significantly percentage of stained cells and staining intensity of cells in the basal layer of lichen planus was higher than normal mucosa (p <0.001. In parabasal layer the results were similar (p <0.001. This results in comparison to lichen planus and gingivitis in basal layer (p <0.001 and parabasal was seen (p <10.0. On the other hand, significantly the percentage of stained cells and staining intensity of cells in the basal layer of gingivitis was more than normal mucosa (p <0.001. In above comparison, similar result in the parabasal layer was seen (p <0.001. The percentage of stained cells and staining intensity of cells in lymphocytic infiltration was significantly higher

  9. Intranasal location and immunohistochemical characterization of the equine olfactory epithelium

    Directory of Open Access Journals (Sweden)

    Alexandra Kupke


    Full Text Available The olfactory epithelium (OE is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system (CNS. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g. Borna disease virus (BoDV, equine herpesvirus 1 (EHV-1, hendra virus, influenza virus, rabies virus, vesicular stomatitis virus (VSV can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g. horses would help to underscore transferability of rodent models. Analysis of the complete noses of 5 adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a. Immunohistochemically, olfactory marker protein (OMP and doublecortin (DCX expression was found in more cells of OE type a, whereas expression of proliferating cell nuclear antigen (PCNA and tropomyosin receptor kinase A (TrkA was present in more cells of type b. Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b. Protein expression profile was comparable to canine and rodent OE but equine type a and b were

  10. Intranasal Location and Immunohistochemical Characterization of the Equine Olfactory Epithelium (United States)

    Kupke, Alexandra; Wenisch, Sabine; Failing, Klaus; Herden, Christiane


    The olfactory epithelium (OE) is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g., Borna disease virus, equine herpesvirus 1 (EHV-1), hendra virus, influenza virus, rabies virus, vesicular stomatitis virus can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines, or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g., horses would help to underscore transferability of rodent models. Analysis of the complete noses of five adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a. Immunohistochemically, olfactory marker protein and doublecortin (DCX) expression was found in more cells of OE type a, whereas expression of proliferating cell nuclear antigen and tropomyosin receptor kinase A was present in more cells of type b. Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b. Protein expression profile was comparable to canine and rodent OE but equine types a and b were located differently within the nose and

  11. Immunohistochemical study on gastrointestinal endocrine cells of four reptiles

    Institute of Scientific and Technical Information of China (English)

    Xu-Gen Huang; Xiao-Bing Wu


    AIM: To darify the types, regional distributions and distribution densities as well as morphological features of gastrointestinal (GI) endocrine cells in various parts of the gastrointestinal track (GIT) of four reptiles, Gekko japonicus, Eumeces chinensis, Sphenomorphus indicus and Eumeces elegans.METHODS: Paraffin-embedded sections (5 μm) of seven parts (cardia, fundus, pylorus, duodenum, jejunum, ileum,rectum) of GIT dissected from the four reptiles were prepared. GI endocrine cells were revealed by using immunohistochemical techniques of streptavidin-peroxidase (S-P) method. Seven types of antisera against 5-hydroxytryptamine (5-HT), somatostatin (SS), gastrin (GAS),glucagon (GLU), substance P (SP), insulin and pancreatic polypeptide were identified and then GI endocrine cells were photomicrographed and counted.RESULTS: The GI endocrine system of four reptiles was a complex structure containing many endocrine cell types similar in morphology to those found in higher vertebrates.Five types of GI endocrine cells, namely 5-HT, SS, GAS,SP and GLU immunoreactive (IR) cells were identified in the GIT of G. japonicus, E. chinensis and S. indicus, while in the GIT of E. elegans only the former three types of endocrine cells were observed. No PP- and INS- IR cells were found in all four reptiles. 5-HT-IR cells, which were most commonly found in the pylorus or duodenum, distributed throughout the whole GIT of four reptiles. However, their distribution patterns varied from each other. SS-IR cells,which were mainly found in the stomach especially in the pylorus and/or fundus, were demonstrated in the whole GIT of E. chinensis, only showed restricted distribution in the other three species. GAS-IR cells, with a much restricted distribution, were mainly demonstrated in the pylorus and/or the proximal small intestine of four reptiles. GLU-IR cells exhibited a limited and species-dependent variant distribution in the GIT of four reptiles. SP-IR cells were found throughout the

  12. Feline cutaneous nerve sheath tumours: histological features and immunohistochemical evaluations. (United States)

    Mandara, M T; Fabriani, E; Pavone, S; Pumarola, M


    Feline cutaneous nerve sheath tumours (CNSTs) are uncommonly reported in the skin, since they are underestimated relative to the more common spindle cell tumours of soft tissue. In this study, 26 nerve sheath tumours selected from 337 skin neoplasms of cats were examined. Histologically, they were classified into malignant (MPNSTs) and benign tumours (BPNSTs) based on degree of cellular atypia and polymorphism as well as mitotic rate and diffuse necrosis. CPNSTs were tipically characterised by Antoni A pattern, in some cases associated with Antoni B pattern. In the malignant peripheral nerve sheath tumours (MPNSTs) the polymorphism was marked, while it was mild to moderate in the benign forms (BPNSTs). In the MPNSTs the mitotic activity was generally higher than in the BPNSTs. In five cases, including three MPNSTs and two BPNSTs, there were multinucleated giant cells. Necrotic foci occurred in a BPNST and in two MPNSTs, while osseous/chondroid metaplasia was found in two cases. Immunohistochemically, all the tumours showed a marked diffuse vimentin expression. S-100 protein was expressed in 17 cases, including 81.8% of BPNSTs and 57.14% of MPNSTs. Twenty-five tumours expressed NSE and twenty-four cases showed immunoreaction for laminin. Thirteen tumours were positive for GFAP, while five tumours were positive for SMA. PGP 9.5 expression was detected in all cases, except for two MPNSTs. NGFR was expressed in eleven cases, including four MPNSTs and seven BPNSTs. Ki67 was expressed in twenty tumours without any relationship with morphologic malignancy of the neoplasm. In this case series we confirmed neoplastic spindloid cells with wavy cytoplasm arranged in compact areas, with occasional nuclear palisading or whirls, and interchanged with loosely arranged areas, as the morphological features supporting a diagnosis of CPNST. A constant concurrent expression of vimentin, NSE, and laminin might confirm the diagnosis of PNST in the absence of clear S-100 protein

  13. αA crystallin may protect against geographic atrophy-meta-analysis of cataract vs. cataract surgery for geographic atrophy and experimental studies.

    Directory of Open Access Journals (Sweden)

    Peng Zhou

    Full Text Available BACKGROUND: Cataract and geographic atrophy (GA, also called advanced "dry" age-related macular degeneration are the two major causes of visual impairment in the developed world. The association between cataract surgery and the development of GA was controversial in previous studies. METHODS/PRINCIPAL FINDINGS: We performed a meta-analysis by pooling the current evidence in literature and found that cataract is associated with an increased risk of geographic atrophy with a summary odds ratio (OR of 3.75 (95% CI: 95% CI: 1.84-7.62. However, cataract surgery is not associated with the risk of geographic atrophy (polled OR=3.23, 95% CI: 0.63-16.47. Further experiments were performed to analyze how the αA-crystallin, the major component of the lens, influences the development of GA in a mouse model. We found that theαA-crystallin mRNA and protein expression increased after oxidative stress induced by NaIO(3 in immunohistochemistry of retinal section and western blot of posterior eyecups. Both functional and histopathological evidence confirmed that GA is more severe in αA-crystallin knockout mice compared to wild-type mice. CONCLUSIONS: Therefore, αA-crystallin may protect against geographic atrophy. This study provides a better understanding of the relationship between cataract, cataract surgery, and GA.

  14. Variants associated with Gaucher disease in multiple system atrophy (United States)

    Mitsui, Jun; Matsukawa, Takashi; Sasaki, Hidenao; Yabe, Ichiro; Matsushima, Masaaki; Dürr, Alexandra; Brice, Alexis; Takashima, Hiroshi; Kikuchi, Akio; Aoki, Masashi; Ishiura, Hiroyuki; Yasuda, Tsutomu; Date, Hidetoshi; Ahsan, Budrul; Iwata, Atsushi; Goto, Jun; Ichikawa, Yaeko; Nakahara, Yasuo; Momose, Yoshio; Takahashi, Yuji; Hara, Kenju; Kakita, Akiyoshi; Yamada, Mitsunori; Takahashi, Hitoshi; Onodera, Osamu; Nishizawa, Masatoyo; Watanabe, Hirohisa; Ito, Mizuki; Sobue, Gen; Ishikawa, Kinya; Mizusawa, Hidehiro; Kanai, Kazuaki; Hattori, Takamichi; Kuwabara, Satoshi; Arai, Kimihito; Koyano, Shigeru; Kuroiwa, Yoshiyuki; Hasegawa, Kazuko; Yuasa, Tatsuhiko; Yasui, Kenichi; Nakashima, Kenji; Ito, Hijiri; Izumi, Yuishin; Kaji, Ryuji; Kato, Takeo; Kusunoki, Susumu; Osaki, Yasushi; Horiuchi, Masahiro; Kondo, Tomoyoshi; Murayama, Shigeo; Hattori, Nobutaka; Yamamoto, Mitsutoshi; Murata, Miho; Satake, Wataru; Toda, Tatsushi; Filla, Alessandro; Klockgether, Thomas; Wüllner, Ullrich; Nicholson, Garth; Gilman, Sid; Tanner, Caroline M; Kukull, Walter A; Stern, Mathew B; Lee, Virginia M-Y; Trojanowski, John Q; Masliah, Eliezer; Low, Phillip A; Sandroni, Paola; Ozelius, Laurie J; Foroud, Tatiana; Tsuji, Shoji


    Objective Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case–control series. Methods We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. Results In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel–Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14–5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15–5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10−3). Interpretation The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA. PMID:25909086

  15. Ossifying fibromyxoid tumor of the breast mimicking fibroadenoma: a case report and differential diagnoses. (United States)

    Asirvatham, Jaya Ruth; Shah, Anand; Carreon, Chrystalle Katte; Bhuiya, Tawfiqul A; Kahn, Leonard B; Kostroff, Karen; Morgenstern, Nora J


    An 80-year-old woman presented with a palpable mass in the right breast. Mammographic findings were consistent with calcified fibroadenoma. An ultrasound was performed that showed a solid nodule with peripheral calcification. A core biopsy was obtained that revealed a spindle cell proliferation with a shell of mature bone. The histologic features, in combination with immunohistochemical studies, were those of an ossifying fibromyxoid tumor. Complete excision of the specimen further confirmed the diagnosis. To the best of our knowledge, this is the first reported case of ossifying fibromyxoid tumor occurring in the breast. We review the current literature on ossifying fibromyxoid tumor and discuss the differential diagnoses when confronted with bland spindle cells on a core biopsy of the breast.

  16. Fronto-striatal atrophy in behavioural variant frontotemporal dementia & Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Maxime eBertoux


    Full Text Available Behavioural variant frontotemporal dementia (bvFTD has only recently been associated with significant striatal atrophy, whereas the striatum appears to be relatively preserved in Alzheimer’s disease (AD. Considering the critical role the striatum has in cognition and behaviour, striatal degeneration, together with frontal atrophy, could be responsible of some characteristic symptoms in bvFTD and emerges therefore as promising novel diagnostic biomarker to distinguish bvFTD and AD. Previous studies have, however, only taken either cortical or striatal atrophy into account when comparing the two diseases. In this study, we establish for the first time a profile of fronto-striatal atrophy in 23 bvFTD and 29 AD patients at presentation, based on the structural connectivity of striatal and cortical regions. Patients are compared to 50 healthy controls by using a novel probabilistic connectivity atlas, which defines striatal regions by their cortical white matter connectivity, allowing us to explore the degeneration of the frontal and striatal regions that are functionally linked. Comparisons with controls revealed that bvFTD showed substantial fronto-striatal atrophy affecting the ventral as well as anterior and posterior dorso-lateral prefrontal cortices and the related striatal subregions. By contrast, AD showed few fronto-striatal atrophy, despite having significant posterior dorso-lateral prefrontal degeneration. Direct comparison between bvFTD and AD revealed significantly more atrophy in the ventral striatal-ventromedial prefrontal cortex regions in bvFTD. Consequently, deficits in ventral fronto-striatal regions emerge as promising novel and efficient diagnosis biomarker for bvFTD. Future investigations into the contributions of these fronto-striatal loops on bvFTD symptomology are needed to develop simple diagnostic and disease tracking algorithms.

  17. Grey matter atrophy of basal forebrain and hippocampus in mild cognitive impairment. (United States)

    Zhang, Haobo; Trollor, Julian N; Wen, Wei; Zhu, Wanlin; Crawford, John D; Kochan, Nicole A; Slavin, Melissa J; Brodaty, Henry; Reppermund, Simone; Kang, Kristan; Mather, Karen A; Sachdev, Perminder S


    The basal forebrain area (BFA) is closely connected to the hippocampus by virtue of cholinergic neuronal projections. Structural neuroimaging studies have shown reduced volumes of both structures in Alzheimer's disease and its prodromal stage mild cognitive impairment (MCI), but generally not in the same investigation. By combining voxel based morphometry and region of interest methods, we measured the grey matter (GM) volumes of the two brain regions with the goal of elucidating their contributions to MCI and its two subtypes (amnestic MCI and non-amnestic MCI) in an elderly epidemiological sample. The results replicated previous findings that the atrophies of both brain regions were associated with an increased likelihood of MCI and its two subtypes. However, in a regression model for the prediction of MCI with GM volumes for both regions used as predictors, only hippocampal atrophy remained significant. Two possible interpretations for this pattern of results were discussed. One is that the observed correlation between BFA atrophy and MCI is spurious and due to the hippocampal atrophy correlated with both. Alternatively, our observation is consistent with the possibility that BFA atrophy has a causal effect on MCI, which is mediated via its influence on hippocampal atrophy. Furthermore, we found that the left hippocampal atrophy had a stronger effect than the right hippocampus and bilateral BFA in the prediction of amnestic MCI occurrence when the four unilateral areas were entered into one regression model. In addition, a slight but statistically significant difference was found in the left hippocampal volume between APOE ε4 allele carriers and non-carriers, consistent with prior studies.

  18. Relation of cerebral small-vessel disease and brain atrophy to mild Parkinsonism in the elderly. (United States)

    Reitz, Christiane; Trenkwalder, Claudia; Kretzschmar, Konrad; Roesler, Andreas; V Eckardstein, Arnold; Berger, Klaus


    The association between cerebral small-vessel disease, brain atrophy, and the risk and severity of mild parkinsonian signs (MPS) remains unclear. The objective of this study is to examine the effect of lacunar brain infarcts, cerebral white matter lesions (WMLs), and cortical atrophy on the risk and severity of MPS. This study is a cross-sectional community-based cohort study comprising 268 subjects, 65 to 83 years of age, residing in the Augsburg region of southern Germany, and without contraindications for magnetic resonance imaging (MRI) of the brain. Main outcome measures. Subcortical and periventricular WMLs, lacunar brain infarcts, and cortical atrophy determined using a standardized MRI protocol developed for the Rotterdam Scan Study and an established rating scale. MPS, assessed in a standardized neurological examination and based on the Unified Parkinson's Disease Rating Scale motor scale. Lacunar brain infarcts and large subcortical white matter lesions were associated with an elevated risk of resting tremor. More severe cortical atrophy was related to an increased risk of rigidity and bradykinesia. In a linear regression analysis relating each individual MRI measurement with the severity of MPS, the number of lacunar brain infarcts and the degree of brain atrophy were correlated with the severity of resting tremor, whereas the size of subcortical and periventricular WMLs was correlated with the severity of rigidity. A higher degree of brain atrophy was associated with increased severity of either cardinal sign. In our study, presence and volume of lacunar brain infarcts, cerebral WMLs, and cortical atrophy were associated with the risk as well as severity of MPS. Determining the presence of these brain changes using brain imaging might contribute to identify persons at risk for MPS.

  19. Blockage of the Ryanodine Receptor via Azumolene Does Not Prevent Mechanical Ventilation-Induced Diaphragm Atrophy.

    Directory of Open Access Journals (Sweden)

    Erin E Talbert

    Full Text Available Mechanical ventilation (MV is a life-saving intervention for patients in respiratory failure. However, prolonged MV causes the rapid development of diaphragm muscle atrophy, and diaphragmatic weakness may contribute to difficult weaning from MV. Therefore, developing a therapeutic countermeasure to protect against MV-induced diaphragmatic atrophy is important. MV-induced diaphragm atrophy is due, at least in part, to increased production of reactive oxygen species (ROS from diaphragm mitochondria and the activation of key muscle proteases (i.e., calpain and caspase-3. In this regard, leakage of calcium through the ryanodine receptor (RyR1 in diaphragm muscle fibers during MV could result in increased mitochondrial ROS emission, protease activation, and diaphragm atrophy. Therefore, these experiments tested the hypothesis that a pharmacological blockade of the RyR1 in diaphragm fibers with azumolene (AZ would prevent MV-induced increases in mitochondrial ROS production, protease activation, and diaphragmatic atrophy. Adult female Sprague-Dawley rats underwent 12 hours of full-support MV while receiving either AZ or vehicle. At the end of the experiment, mitochondrial ROS emission, protease activation, and fiber cross-sectional area were determined in diaphragm muscle fibers. Decreases in muscle force production following MV indicate that the diaphragm took up a sufficient quantity of AZ to block calcium release through the RyR1. However, our findings reveal that AZ treatment did not prevent the MV-induced increase in mitochondrial ROS emission or protease activation in the diaphragm. Importantly, AZ treatment did not prevent MV-induced diaphragm fiber atrophy. Thus, pharmacological inhibition of the RyR1 in diaphragm muscle fibers is not sufficient to prevent MV-induced diaphragm atrophy.

  20. Blockage of the Ryanodine Receptor via Azumolene Does Not Prevent Mechanical Ventilation-Induced Diaphragm Atrophy. (United States)

    Talbert, Erin E; Smuder, Ashley J; Kwon, Oh Sung; Sollanek, Kurt J; Wiggs, Michael P; Powers, Scott K


    Mechanical ventilation (MV) is a life-saving intervention for patients in respiratory failure. However, prolonged MV causes the rapid development of diaphragm muscle atrophy, and diaphragmatic weakness may contribute to difficult weaning from MV. Therefore, developing a therapeutic countermeasure to protect against MV-induced diaphragmatic atrophy is important. MV-induced diaphragm atrophy is due, at least in part, to increased production of reactive oxygen species (ROS) from diaphragm mitochondria and the activation of key muscle proteases (i.e., calpain and caspase-3). In this regard, leakage of calcium through the ryanodine receptor (RyR1) in diaphragm muscle fibers during MV could result in increased mitochondrial ROS emission, protease activation, and diaphragm atrophy. Therefore, these experiments tested the hypothesis that a pharmacological blockade of the RyR1 in diaphragm fibers with azumolene (AZ) would prevent MV-induced increases in mitochondrial ROS production, protease activation, and diaphragmatic atrophy. Adult female Sprague-Dawley rats underwent 12 hours of full-support MV while receiving either AZ or vehicle. At the end of the experiment, mitochondrial ROS emission, protease activation, and fiber cross-sectional area were determined in diaphragm muscle fibers. Decreases in muscle force production following MV indicate that the diaphragm took up a sufficient quantity of AZ to block calcium release through the RyR1. However, our findings reveal that AZ treatment did not prevent the MV-induced increase in mitochondrial ROS emission or protease activation in the diaphragm. Importantly, AZ treatment did not prevent MV-induced diaphragm fiber atrophy. Thus, pharmacological inhibition of the RyR1 in diaphragm muscle fibers is not sufficient to prevent MV-induced diaphragm atrophy.