Evoked potentials in multiple sclerosis.

PubMed

Kraft, George H

2013-11-01

Before the development of magnetic resonance imaging (MRI), evoked potentials (EPs)-visual evoked potentials, somatosensory evoked potentials, and brain stem auditory evoked responses-were commonly used to determine a second site of disease in patients being evaluated for possible multiple sclerosis (MS). The identification of an area of the central nervous system showing abnormal conduction was used to supplement the abnormal signs identified on the physical examination-thus identifying the "multiple" in MS. This article is a brief overview of additional ways in which central nervous system (CNS) physiology-as measured by EPs-can still contribute value in the management of MS in the era of MRIs. Copyright © 2013 Elsevier Inc. All rights reserved.

Movement Disorders and Other Motor Abnormalities in Adults With 22q11.2 Deletion Syndrome

PubMed Central

Boot, Erik; Butcher, Nancy J; van Amelsvoort, Thérèse AMJ; Lang, Anthony E; Marras, Connie; Pondal, Margarita; Andrade, Danielle M; Fung, Wai Lun Alan; Bassett, Anne S

2015-01-01

Movement abnormalities are frequently reported in children with 22q11.2 deletion syndrome (22q11.2DS), but knowledge in this area is scarce in the increasing adult population. We report on five individuals illustrative of movement disorders and other motor abnormalities in adults with 22q11.2DS. In addition to an increased susceptibility to neuropsychiatric disorders, seizures, and early-onset Parkinson disease, the underlying brain dysfunction associated with 22q11.2DS may give rise to an increased vulnerability to multiple movement abnormalities, including those influenced by medications. Movement abnormalities may also be secondary to treatable endocrine diseases and congenital musculoskeletal abnormalities. We propose that movement abnormalities may be common in adults with 22q11.2DS and discuss the implications and challenges important to clinical practice. PMID:25684639

Cytogenetic Studies of Rwandan Pediatric Patients Presenting with Global Developmental Delay, Intellectual Disability and/or Multiple Congenital Anomalies.

PubMed

Uwineza, Annette; Hitayezu, Janvier; Jamar, Mauricette; Caberg, Jean-Hubert; Murorunkwere, Seraphine; Janvier, Ndinkabandi; Bours, Vincent; Mutesa, Leon

2016-02-01

Global developmental delay (GDD) is defined as a significant delay in two or more developmental domains: gross or fine motor, speech/language, cognitive, social/personal and activities of daily living. Many of these children will go on to be diagnosed with intellectual disability (ID), which is most commonly defined as having an IQ <75 in addition to impairment in adaptive functioning. Cytogenetic studies have been performed in 664 Rwandan pediatric patients presenting GDD/ID and/or multiple congenital abnormalities (MCA). Karyotype analysis was performed in all patients and revealed 260 chromosomal abnormalities. The most frequent chromosomal abnormality was Down syndrome and then Edward syndrome and Patau syndrome. Other identified chromosomal abnormalities included 47,XX,+del(9)(q11), 46,XY,del(13)(q34) and 46,XX,der(22)t(10;22)(p10;p10)mat. In conclusion, our results highlight the high frequency of cytogenetically detectable abnormalities in this series, with implications for the burden on the healthcare. This study demonstrates the importance of cytogenetic analysis in patients with GDD/ID and MCA. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Impact of genetic abnormalities after allogeneic stem cell transplantation in multiple myeloma: a report of the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

Roos-Weil, Damien; Moreau, Philippe; Avet-Loiseau, Hervé; Golmard, Jean-Louis; Kuentz, Mathieu; Vigouroux, Stéphane; Socié, Gérard; Furst, Sabine; Soulier, Jean; Le Gouill, Steven; François, Sylvie; Thiebaut, Anne; Buzyn, Agnès; Maillard, Natacha; Yakoub-Agha, Ibrahim; Raus, Nicole; Fermand, Jean-Paul; Michallet, Mauricette; Blaise, Didier; Dhédin, Nathalie

2011-10-01

The impact of cytogenetic abnormalities in multiple myeloma after allogeneic stem cell transplantation has not been clearly defined. This study examines whether allogeneic stem cell transplantation could be of benefit for myeloma patients with high-risk cytogenetic abnormalities. This is a retrospective multicenter analysis of the registry of the Société Française de Greffe de Moelle et de Thérapie Cellulaire, including 143 myeloma patients transplanted between 1999 and 2008. The incidences of cytogenetic abnormalities were 59% for del(13q), 25% for t(4;14), 25% for del(17p) and 4% for t(14;16). When comparing the population carrying an abnormality to that without the same abnormality, no significant difference was found in progression-free survival, overall survival or progression rate. Patients were grouped according to the presence of any of the poor prognosis cytogenetic abnormalities t(4;14), del(17p) or t(14;16) (n=53) or their absence (n=32). No difference in outcomes was observed between these two groups: the 3-year progression-free survival, overall survival and progression rates were 30% versus 17% (P=0.9), 45% versus 39% (P=0.8) and 53% versus 75% (P=0.9), respectively. These data indicate that allogeneic stem cell transplantation could potentially be of benefit to high-risk myeloma patients.

Plasma Cell Neoplasms (Including Multiple Myeloma)—Patient Version

Cancer.gov

Plasma cell neoplasms occur when abnormal plasma cells form cancerous tumors. When there is only one tumor, the disease is called a plasmacytoma. When there are multiple tumors, it is called multiple myeloma. Start here to find information on plasma cell neoplasms treatment, research, and statistics.

Color blindness among multiple sclerosis patients in Isfahan.

PubMed

Shaygannejad, Vahid; Golabchi, Khodayar; Dehghani, Alireza; Ashtari, Fereshteh; Haghighi, Sepehr; Mirzendehdel, Mahsa; Ghasemi, Majid

2012-03-01

Multiple sclerosis (MS) is a disease of young and middle aged individuals with a demyelinative axonal damage nature in central nervous system that causes various signs and symptoms. As color vision needs normal function of optic nerve and macula, it is proposed that MS can alter it via influencing optic nerve. In this survey, we evaluated color vision abnormalities and its relationship with history of optic neuritis and abnormal visual evoked potentials (VEPs) among MS patients. The case group was included of clinically definitive MS patients and the same number of normal population was enrolled as the control group. Color vision of all the participants was evaluated by Ishihara test and then visual evoked potential (VEPs) and history of optic neuritis (ON) was assessed among them. Then, frequency of color blindness was compared between the case and the control group. Finally, color blinded patients were compared to those with the history of ON and abnormal VEPs. 63 MS patients and the same number of normal populations were enrolled in this study. 12 patients had color blindness based on the Ishihara test; only 3 of them were among the control group, which showed a significant different between the two groups (P = 0.013). There was a significant relationship between the color blindness and abnormal VEP (R = 0.53, P = 0.023) but not for the color blindness and ON (P = 0.67). This study demonstrates a significant correlation between color blindness and multiple sclerosis including ones with abnormal prolonged VEP latencies. Therefore, in individuals with acquired color vision impairment, an evaluation for potentially serious underlying diseases like MS is essential.

Eye and tentacle abnormalities in embryos of the atlantic oyster drill, Urosalpinx cinerea

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

Reinhart, K.; Myers, T.D.

1975-12-01

Multiple development of eyes and cephalic tentacles was observed in developing embryos of the Atlantic oyster drill, Urosalpinx cinerea. These abnormalities were found in 2.7 percent of embryos previously exposed to 0.01 ppM mercuric chloride and in 0.4 percent of control animals. Animals were noted with one to three tentacles and one to six eyes. The most prevalent combination of abnormalities observed was three eyes and two tentacles per animal.

The cam impinging femur has multiple morphologic abnormalities.

PubMed

Ellis, Andrew R; Noble, Philip C; Schroder, Steven J; Thompson, Matthew T; Stocks, Gregory W

2011-09-01

This study was performed to establish whether the "cam" impinging femur has a single deformity of the head-neck junction or multiple abnormalities. Average dimensions (anteversion angle, α angle of Notzli, β angle of Beaulé, normalized anterior head offset) were compared between normal and impinging femora. The results demonstrated that impinging femora had wider necks, larger heads, and decreased head-neck ratios. There was no difference in neck-shaft angle or anteversion angle. Forty-six percent of impinging femora had significant posterior head displacement (>2mm), which averaged 1.93 mm for the cam impinging group, and 0.78 mm for the normal group. In conclusion, surgical treatment limited to localized recontouring of the head-neck profile may fail to address significant components of the underlying abnormality. Copyright © 2011 Elsevier Inc. All rights reserved.

Hemophagocytic syndrome in a cat with multiple myeloma.

PubMed

Dunbar, Mark D; Lyles, Sarah

2013-03-01

An 11-year-old, castrated male, Domestic Medium Hair cat was presented to the University of Florida Small Animal Hospital with a 2-week history of upper respiratory infection and increased serum globulins, as reported by the referring veterinarian. Physical examination was unremarkable other than melanosis of the left iris, with no evidence of ocular, nasal, or respiratory disease. Laboratory abnormalities included moderate nonregenerative anemia, mild leukopenia, mild hyperfibrinogenemia, severe hyperglobulinemia, mild hypoalbuminemia, and hypocholesterolemia. Abdominal radiographs and ultrasonographic examination revealed mild splenomegaly with no other abnormalities. Thoracic radiographs revealed no abnormalities. Cytologic evaluation of fine-needle aspirates from the spleen, liver, and bone marrow revealed numerous plasma cells and many vacuolated macrophages exhibiting marked phagocytosis of mature erythrocytes and platelets, occasionally metarubricytes and leukocytes, and rarely plasma cells. The cytologic interpretation was multiple myeloma and associated hemophagocytic syndrome (HPS). Serum protein electrophoresis revealed a monoclonal gammopathy, providing further evidence for a multiple myeloma. To the authors' knowledge, this is the first report of HPS secondary to neoplasia in a cat. © 2012 American Society for Veterinary Clinical Pathology.

Two Cases of Generalized Seizures and the Velocardiofacial Syndrome - A Clinically Significant Association?

ERIC Educational Resources Information Center

El Tahir, M. O.; Kerr, M.; Jones, R. G.

2004-01-01

Velocardiofacial syndrome (VCFS) is caused by a micro deletion of chromosome 22q11 and associated with multiple system abnormalities. There is an increasing recognition of associations with psychiatric disorders. Neurological and brain abnormalities have been reported but to date no association with generalized epilepsy has been reported in…

Management of airway difficulties during induction of general anesthesia in an American miniature horse with dwarfism.

PubMed

Hatfield, Cindy L; Riley, Christopher B

2007-02-01

This report describes previously unreported upper airway abnormalities encountered in a 5-month-old American miniature horse colt presented for elective surgery. Caution should be exercised when administering general anesthesia or heavy sedation to individuals of this breed that present with multiple congenital abnormalities.

A General Approach to the Evaluation of Ventilation-Perfusion Ratios in Normal and Abnormal Lungs

ERIC Educational Resources Information Center

Wagner, Peter D.

1977-01-01

Outlines methods for manipulating multiple gas data so as to gain the greatest amount of insight into the properties of ventilation-perfusion distributions. Refers to data corresponding to normal and abnormal lungs. Uses a two-dimensional framework with the respiratory gases of oxygen and carbon dioxide. (CS)

Multiple granular cell tumors with metachronous occurrence in tongue and vulva. Clinicopathological and immunohistochemical study

PubMed Central

Vera-Sirera, Beatriz; Zabala, Pablo; Aviño-Mira, Carlos; Vera-Sempere, Francisco J.

2014-01-01

Granular cell tumor (GCT) usually occurs as a single tumor, although sometimes multiple lesions can occur. In present report we analyze the clinicopathological and immunohistochemical features of a multiple GCT involving the tongue of a 14-year-old girl, with no other abnormalities, with a metachronous occurrence of a second GCT in vulva, after a period of 10 years. Both tumors revealed S-100, vimentin and CD57 positivity. In addition, over expression of calretinin was observed in tumor cells located in the vicinity of pseudoepitheliomatous hyperplasia (PEH) of the tongue. Tumor vasculature situated close to the PEH showed marked CD105 reactivity, data not described so far, suggesting an interaction between PEH cells and underlying stroma, since GCT completely lacks CD105 vessels. Our study emphasizes that patients with GCT, especially young patients, should be followed long-term, looking for multiple tumors or other abnormalities suggestive of a systemic syndrome, given the associations described in multiple GCT. PMID:25949003

A neurophysiological study of facial numbness in multiple sclerosis: Integration with clinical data and imaging findings.

PubMed

Koutsis, Georgios; Kokotis, Panagiotis; Papagianni, Aikaterini E; Evangelopoulos, Maria-Eleftheria; Kilidireas, Constantinos; Karandreas, Nikolaos

2016-09-01

To integrate neurophysiological findings with clinical and imaging data in a consecutive series of multiple sclerosis (MS) patients developing facial numbness during the course of an MS attack. Nine consecutive patients with MS and recent-onset facial numbness were studied clinically, imaged with routine MRI, and assessed neurophysiologically with trigeminal somatosensory evoked potential (TSEP), blink reflex (BR), masseter reflex (MR), facial nerve conduction, facial muscle and masseter EMG studies. All patients had unilateral facial hypoesthesia on examination and lesions in the ipsilateral pontine tegmentum on MRI. All patients had abnormal TSEPs upon stimulation of the affected side, excepting one that was tested following remission of numbness. BR was the second most sensitive neurophysiological method with 6/9 examinations exhibiting an abnormal R1 component. The MR was abnormal in 3/6 patients, always on the affected side. Facial conduction and EMG studies were normal in all patients but one. Facial numbness was always related to abnormal TSEPs. A concomitant R1 abnormality on BR allowed localization of the responsible pontine lesion, which closely corresponded with MRI findings. We conclude that neurophysiological assessment of MS patients with facial numbness is a sensitive tool, which complements MRI, and can improve lesion localization. Copyright © 2016 Elsevier B.V. All rights reserved.

Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome.

PubMed

Vootla, Vamshidhar R; Daniel, Myrta

2015-01-01

Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome.

Identification of Balance Deficits in People with Parkinson Disease; is the Sensory Organization Test Enough?

PubMed

Gera, G; Freeman, D L; Blackinton, M T; Horak, F B; King, L

2016-02-01

Balance deficits in people with Parkinson's disease can affect any of the multiple systems encompassing balance control. Thus, identification of the specific deficit is crucial in customizing balance rehabilitation. The sensory organization test, a test of sensory integration for balance control, is sometimes used in isolation to identify balance deficits in people with Parkinson's disease. More recently, the Mini-Balance Evaluations Systems Test, a clinical scale that tests multiple domains of balance control, has begun to be used to assess balance in patients with Parkinson's disease. The purpose of our study was to compare the use of Sensory Organization Test and Mini-Balance Evaluations Systems Test in identifying balance deficits in people with Parkinson's disease. 45 participants (27M, 18F; 65.2 ± 8.2 years) with idiopathic Parkinson's disease participated in the cross-sectional study. Balance assessment was performed using the Sensory Organization Test and the Mini-Balance Evaluations Systems Test. People were classified into normal and abnormal balance based on the established cutoff scores (normal balance: Sensory Organization Test >69; Mini-Balance Evaluations Systems Test >73). More subjects were classified as having abnormal balance with the Mini-Balance Evaluations Systems Test (71% abnormal) than with the Sensory Organization Test (24% abnormal) in our cohort of people with Parkinson's disease. There were no subjects with a normal Mini-Balance Evaluations Systems Test score but abnormal Sensory Organization Test score. In contrast, there were 21 subjects who had an abnormal Mini-Balance Evaluations Systems Test score but normal Sensory Organization Test scores. Findings from this study suggest that investigation of sensory integration deficits, alone, may not be able to identify all types of balance deficits found in patients with Parkinson's disease. Thus, a comprehensive approach should be used to test of multiple balance systems to provide customized rehabilitation.

Color blindness among multiple sclerosis patients in Isfahan

PubMed Central

Shaygannejad, Vahid; Golabchi, Khodayar; Dehghani, Alireza; Ashtari, Fereshteh; Haghighi, Sepehr; Mirzendehdel, Mahsa; Ghasemi, Majid

2012-01-01

Background: Multiple sclerosis (MS) is a disease of young and middle aged individuals with a demyelinative axonal damage nature in central nervous system that causes various signs and symptoms. As color vision needs normal function of optic nerve and macula, it is proposed that MS can alter it via influencing optic nerve. In this survey, we evaluated color vision abnormalities and its relationship with history of optic neuritis and abnormal visual evoked potentials (VEPs) among MS patients. Materials and Methods: The case group was included of clinically definitive MS patients and the same number of normal population was enrolled as the control group. Color vision of all the participants was evaluated by Ishihara test and then visual evoked potential (VEPs) and history of optic neuritis (ON) was assessed among them. Then, frequency of color blindness was compared between the case and the control group. Finally, color blinded patients were compared to those with the history of ON and abnormal VEPs. Results: 63 MS patients and the same number of normal populations were enrolled in this study. 12 patients had color blindness based on the Ishihara test; only 3 of them were among the control group, which showed a significant different between the two groups (P = 0.013). There was a significant relationship between the color blindness and abnormal VEP (R = 0.53, P = 0.023) but not for the color blindness and ON (P = 0.67). Conclusions: This study demonstrates a significant correlation between color blindness and multiple sclerosis including ones with abnormal prolonged VEP latencies. Therefore, in individuals with acquired color vision impairment, an evaluation for potentially serious underlying diseases like MS is essential. PMID:23267377

Pregnancy interruption after second trimester diagnosis of fetal structural anomalies: the New Jersey Fetal Abnormalities Registry.

PubMed

Rauch, Eden R; Smulian, John C; DePrince, Kristin; Ananth, Cande V; Marcella, Stephen W

2005-10-01

The purpose of this study was to identify factors that predict a decision to interrupt a pregnancy in which there are fetal anomalies in the second trimester. The New Jersey Fetal Abnormalities Registry prospectively recruits and collects information on pregnancies (> or = 15 weeks of gestation) from New Jersey residents in whom a fetal structural anomaly has been suspected by maternal-fetal medicine specialists. Enrolled pregnancies that have major fetal structural abnormalities identified from 15 to 23 weeks of gestation were included. Outcomes were classified as either elective interruption or a natural pregnancy course, which might include a spontaneous fetal death or live birth. Predictors of elective interruption of pregnancy were examined with univariable and multivariable logistic regression analyses. Of the 97 cases, 33% of the women (n = 32) interrupted the pregnancy. Significant variables in the regression model that were associated with a decision to interrupt a pregnancy were earlier identification of fetal anomalies (19.0 +/- 2 weeks of gestation vs 20.5 +/- 2 weeks of gestation; P = .003), the presence of multiple anomalies (78% [25/32] vs 52% [33/63]; P = .01], and a presumption of lethality (56% [18/32] vs 14% [9/65]; P = .0001). These variables corresponded to an odds ratio for pregnancy interruption of 4.2 (95% CI, 1.0, 17.0) for multiple anomalies, 0.8 (95% CI, 0.7, 1.0) for each week of advancing gestational age, and 36.1 (95% CI, 2.9, 450.7) for presumed lethal abnormalities. Early diagnosis, the identification of multiple abnormalities, and an assessment of likely lethality of fetal anomalies are important factors for the optimization of parental autonomy in deciding pregnancy management.

Acquired dysfibrinogenemia secondary to multiple myeloma.

PubMed

Kotlín, Roman; Sobotková, Alzbeta; Riedel, Tomás; Salaj, Peter; Suttnar, Jirí; Reicheltová, Zuzana; Májek, Pavel; Khaznadar, Tarek; Dyr, Jan E

2008-01-01

Abnormal coagulation properties indicative of a dysfibrinogen were found in the plasma of a 72-year-old male with multiple myeloma (IgGkappa, stage IIIA). The patient had high paraprotein concentration (85.75 g/l) and prolonged thrombin time (76.8 s), activated partial thromboplastin time (39.5 s), prothrombin time (23.5 s) and reptilase time (72.0 s). The fibrinogen level was increased. The fibrin polymerization induced by both thrombin and reptilase was impaired. Scanning electron microscopy revealed abnormal clot morphology. After six months of treatment, the paraprotein level decreased (19.48 g/l) and coagulation normalized as well as fibrin polymerization and fibrin clot morphology. It was found that the paraprotein interacts with the gamma-chain of fibrinogen. Acquired dysfibrinogenemia associated with multiple myeloma was diagnosed in the 72-year-old patient.

Multiple myeloma associated with acquired cutis laxa.

PubMed

Cho, S Y; Maguire, R F

1980-08-01

Acquired cutis laxa is a rare disorder characterized by diffuse laxity of the skin and loss of connective tissue support with involvement of the lungs, gastrointestinal tract, pelvic organs, and aorta. The case report presented herein describes a forty-six year old woman with multiple myeloma and cutis laxa. Her history included several severe allergic reactions and the gradual development of lax skin, loss of connective tissue support throughout the body, and emphysema. At autopsy, multiple myeloma, diffuse laxity of the skin, and panacinar emphysema were found. The amount of elastic fiber in the skin, lungs, and aorta was decreased and showed abnormal fragmentation. Results of direct immunofluorescence study demonstrated IgG bound to dermal elastic fibers. Speculation regarding an immunologic etiology of the elastic tissue abnormality is presented herein.

Comparison of multifocal visual evoked potential, standard automated perimetry and optical coherence tomography in assessing visual pathway in multiple sclerosis patients

PubMed Central

Laron, Michal; Cheng, Han; Zhang, Bin; Schiffman, Jade S.; Tang, Rosa A.; Frishman, Laura J.

2010-01-01

Background Multifocal visual evoked potentials (mfVEP) measure local response amplitude and latency in the field of vision Objective To compare the sensitivity of mfVEP, Humphrey visual field (HVF) and optical coherence tomography (OCT) in detecting visual abnormality in multiple sclerosis (MS) patients. Methods MfVEP, HVF, and OCT (retinal nerve fiber layer [RNFL]) were performed in 47 MS-ON eyes (last optic neuritis (ON) attack ≥ 6 months prior) and 65 MS-no-ON eyes without ON history. Criteria to define an eye as abnormal were: mfVEP 1) amplitude/latency: either amplitude or latency probability plots meeting cluster criteria with 95% specificity 2) amplitude or latency alone (specificity: 97% and 98%, respectively); HVF and OCT, mean deviation and RNFL thickness meeting p < 0.05, respectively. Results MfVEP (amplitude/latency) identified more abnormality in MS-ON eyes (89%) than HVF (72%), OCT (62%), mfVEP amplitude (66%) or latency (67%) alone. 18% of MS-no-ON eyes were abnormal for both mfVEP (amplitude/latency) and HVF compared to 8% with OCT. Agreement between tests ranged from 60% to 79%. MfVEP (amplitude/latency) categorized an additional 15% of MS-ON eyes as abnormal compared to HVF and OCT combined. Conclusions MfVEP, which detects both demyelination (increased latency) and neural degeneration (reduced amplitude) revealed more abnormality than HVF or OCT in MS patients. PMID:20207786

Hemostatic Abnormalities in Multiple Myeloma Patients

PubMed Central

Gogia, Aarti; Sikka, Meera; Sharma, Satender; Rusia, Usha

2018-01-01

Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated factor VIII and plasma fibrinogen, one or more marker was present in 24 (82.7%). D-dimer was the most common prothrombotic marker, being elevated in 22 (75.9%) patients. One or more laboratory parameter of hemostasis was abnormal in all 29 (100%) patients. Though thrombotic complications are reported to be less frequent as compared to hemorrhagic manifestations, one or more marker of thrombosis was present in 24 (82.7%) patients. Conclusion: This study provided laboratory evidence of hemostatic dysfunction which may be associated with thrombotic or bleeding complications at diagnosis in all MM patients. Hence, screening for these abnormalities at the time of diagnosis should help improved prognosis in such cases. PMID:29373903

Neurofilament light polypeptide gene N98S mutation in mice leads to neurofilament network abnormalities and a Charcot-Marie-Tooth Type 2E phenotype.

PubMed

Adebola, Adijat A; Di Castri, Theo; He, Chui-Zhen; Salvatierra, Laura A; Zhao, Jian; Brown, Kristy; Lin, Chyuan-Sheng; Worman, Howard J; Liem, Ronald K H

2015-04-15

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited neurological disorder with a prevalence of 1 in 2500 people worldwide. Patients suffer from degeneration of the peripheral nerves that control sensory information of the foot/leg and hand/arm. Multiple mutations in the neurofilament light polypeptide gene, NEFL, cause CMT2E. Previous studies in transfected cells showed that expression of disease-associated neurofilament light chain variants results in abnormal intermediate filament networks associated with defects in axonal transport. We have now generated knock-in mice with two different point mutations in Nefl: P8R that has been reported in multiple families with variable age of onset and N98S that has been described as an early-onset, sporadic mutation in multiple individuals. Nefl(P8R/+) and Nefl(P8R/P8R) mice were indistinguishable from Nefl(+/+) in terms of behavioral phenotype. In contrast, Nefl(N98S/+) mice had a noticeable tremor, and most animals showed a hindlimb clasping phenotype. Immunohistochemical analysis revealed multiple inclusions in the cell bodies and proximal axons of spinal cord neurons, disorganized processes in the cerebellum and abnormal processes in the cerebral cortex and pons. Abnormal processes were observed as early as post-natal day 7. Electron microscopic analysis of sciatic nerves showed a reduction in the number of neurofilaments, an increase in the number of microtubules and a decrease in the axonal diameters. The Nefl(N98S/+) mice provide an excellent model to study the pathogenesis of CMT2E and should prove useful for testing potential therapies. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multiple Factors Are Involved in the Dysarthria Associated with Parkinson's Disease: A Review with Implications for Clinical Practice and Research

ERIC Educational Resources Information Center

Sapir, Shimon

2014-01-01

Purpose: Motor speech abnormalities are highly common and debilitating in individuals with idiopathic Parkinson's disease (IPD). These abnormalities, collectively termed hypokinetic dysarthria (HKD), have been traditionally attributed to hypokinesia and bradykinesia secondary to muscle rigidity and dopamine deficits. However, the role of…

Using impedance cardiography with postural change to stratify patients with hypertension.

PubMed

DeMarzo, Arthur P

2011-06-01

Early detection of cardiovascular disease in patients with hypertension could initiate appropriate treatment to control blood pressure and prevent the progression of cardiovascular disease. The goal of this study was to show how impedance cardiography waveform analysis with postural change can be used to detect subclinical cardiovascular disease in patients with high blood pressure. Patients with high blood pressure had impedance cardiography data obtained in two positions, standing upright and supine. In 50 adults, impedance cardiography indicated that all patients had abnormal data, with 44 (88%) having multiple abnormalities. Impedance cardiography showed 32 (64%) had ventricular dysfunction, 48 (96%) had vascular load abnormalities, 34 (68%) had hemodynamic abnormalities, 2 (4%) had hypovolemia, and 3 (6%) had hypervolemia. Hypertensive patients have diverse cardiovascular abnormalities that can be quantified by impedance cardiography. By stratifying patients with ventricular, vascular, and hemodynamic abnormalities, treatment could be customized based on the abnormal underlying mechanisms with the potential to rapidly control blood pressure, prevent progression of cardiovascular disease, and possibly reverse remodeling.

Magnetic resonance imaging (MRI) findings among children with fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS) and alcohol related neurodevelopmental disorders (ARND).

PubMed

Anna Dyląg, Katarzyna; Sikora-Sporek, Aleksanda; Bańdo, Bożena; Boroń-Zyss, Joanna; Drożdż, Dorota; Dumnicka, Paulina; Przybyszewska, Katarzyna; Sporek, Mateusz; Walocha, Jerzy W; Wojciechowski, Wadim; Urbanik, Andrzej

The aim of the study was to analyze the findings in MRI (magnetic resonance imaging) of the brain amongst children diagnosed with fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS) or alcohol related neurodevelopmental disorders (ARND). The issue has been studied in several researches previously but the experts agree that there is still few data on the MRI results in the group of younger children. MRI results of 121 patients with either FAS or pFAS or ARND diagnosed with Canadian criteria were analyzed regarding the presence of abnormalities. The group consisted of 71 patients diagnosed with FAS, 33 diagnosed with pFAS and 17 diagnosed with ARND. The mean age of the patients was 8.03 years (standard deviation 4.07). In the total group of FASD patients 61.98% of the patients’ MRI results were abnormal. The most common abnormality in MRI of the patients were demyelination plaques (incidence 23.1%) and corpus callosum narrowing (20.7%) as well as ventricular asymmetry (18.8%).The demyelination plaques and corpus callosum narrowing were more frequent among children ≤4 years old (41.7% vs 18.6%; p=0.016 and 50.0% vs.13.4%; p<0.001, respectively). Age ≤4 years predicted the presence of demyelination plaques and corpus callosum narrowing independently of FAS diagnosis. Among younger children, multiple central nervous system abnormalities were observed more often than in the older age group (54.2% vs. 14.4%; p<0.001). Odds ratio for multiple changes was 0.84 per one-year increase in age (95% CI 0.73-0.97), p=0.016. Furthermore, in the analysis according to the specific diagnosis, among the patients diagnosed with FAS, multiple anomalies were more common than in pFAS and ARND. Both age ≤4 years and FAS diagnosis were independent predictors for multiple anomalies in multiple logistic regression. In structural brain MRI of younger children, multiple anomalies were found more frequently than among older children. Demyelination plaques and corpus callosum narrowing were more common in younger FASD patients than in older ones.

Dysphagia and nutritional status in multiple sclerosis.

PubMed

Thomas, F J; Wiles, C M

1999-08-01

In this observational study of patients with multiple sclerosis (MS) admitted to a regional neurology centre we assessed the frequency of dysphagia (objectively defined), dysphagia related symptoms, bulbar signs and nutritional status. We studied 79 consecutive admissions with MS (24 at diagnostic admission and 55 more advanced cases admitted for treatment and/or rehabilitation): normative swallowing data were from 181 healthy controls. Swallowing symptoms and signs were semi-quantitatively measured and compared to healthy controls. Dysphagia was defined by a quantitative water test. Disability was determined by Kurtzke's Expanded Disability Status Scale and Barthel's index. Nutritional status was assessed by body mass index, estimated percentage body fat from skin fold thickness measurements at four sites, a global evaluation of nutrition, the presence of pressure sores and the pressure sore risk using the Waterlow score. Patients with MS were more likely to complain of abnormal swallowing, of coughing when eating, and of food 'going down the wrong way' than healthy controls (P < 0.005). These significantly associated symptoms had high specificity but relatively low sensitivity. 43% of patients had abnormal swallowing, almost half of whom did not complain of it: abnormal swallowing was associated with several factors including abnormal brainstem/cerebellar function, disability, vital capacity, and depression score. Those with abnormal swallowing had higher Waterlow scores (P < 0.001), but, overall, abnormal swallowing was not associated with a difference in nutritional indices or incidence of pressure sores. In summary, abnormal swallowing is common in MS although often not complained of. It is associated with disordered brainstem/cerebellar function, overall disability, depressed mood and low vital capacity. It was not associated with major nutritional failure or pressure sores in this study.

Multiple Immune-Inflammatory and Oxidative and Nitrosative Stress Pathways Explain the Frequent Presence of Depression in Multiple Sclerosis.

PubMed

Morris, Gerwyn; Reiche, Edna Maria Vissoci; Murru, Andrea; Carvalho, André F; Maes, Michael; Berk, Michael; Puri, Basant K

2018-01-02

Patients with a diagnosis of multiple sclerosis (MS) or major depressive disorder (MDD) share a wide array of biological abnormalities which are increasingly considered to play a contributory role in the pathogenesis and pathophysiology of both illnesses. Shared abnormalities include peripheral inflammation, neuroinflammation, chronic oxidative and nitrosative stress, mitochondrial dysfunction, gut dysbiosis, increased intestinal barrier permeability with bacterial translocation into the systemic circulation, neuroendocrine abnormalities and microglial pathology. Patients with MS and MDD also display a wide range of neuroimaging abnormalities and patients with MS who display symptoms of depression present with different neuroimaging profiles compared with MS patients who are depression-free. The precise details of such pathology are markedly different however. The recruitment of activated encephalitogenic Th17 T cells and subsequent bidirectional interaction leading to classically activated microglia is now considered to lie at the core of MS-specific pathology. The presence of activated microglia is common to both illnesses although the pattern of such action throughout the brain appears to be different. Upregulation of miRNAs also appears to be involved in microglial neurotoxicity and indeed T cell pathology in MS but does not appear to play a major role in MDD. It is suggested that the antidepressant lofepramine, and in particular its active metabolite desipramine, may be beneficial not only for depressive symptomatology but also for the neurological symptoms of MS. One clinical trial has been carried out thus far with, in particular, promising MRI findings.

Transnodal lymphangiography and post-CT for protein-losing enteropathy in Noonan syndrome.

PubMed

Matsumoto, Tomohiro; Kudo, Takahiro; Endo, Jun; Hashida, Kazunobu; Tachibana, Nao; Murakoshi, Takatsugu; Hasebe, Terumitsu

2015-01-01

Noonan syndrome, which is a multiple congenital disorder, may be associated with lymphatic abnormalities. Protein-losing enteropathy (PLE) developing in Noonan syndrome is rare. We performed transnodal lymphangiography by directly accessing bilateral inguinal nodes under ultrasound guidance in a 17-year-old female with PLE developing in Noonan syndrome to assess detailed anatomical findings regarding lymphatic vessels. There have been no reports on transnodal lymphangiography for Noonan syndrome. Post-lymphangiographic CT images revealed multiple lymphatic abnormalities and lipiodol extravasation into the duodenum and the proximal jejunum. Transnodal lymphangiography was easy and safe for PLE developing in Noonan syndrome, and post-lymphangiographic CT provided invaluable information.

Using impedance cardiography to detect subclinical cardiovascular disease in women with multiple risk factors: a pilot study.

PubMed

Demarzo, Arthur P

2009-01-01

Early detection of cardiovascular disease (CVD) could initiate appropriate treatment and prevent progression. This study used impedance cardiography (ICG) waveform analysis with postural change to detect functional CVD in women older than 40 years with no history of CVD and >or=2 of the following risk factors: cigarette smoking, poor diet, physical inactivity, central adiposity, family history of premature CVD, hypertension, and dyslipidemia. A study group of 32 women underwent ICG in standing and supine positions. An age-matched control group had 20 women with an active lifestyle, no risk factors, and no history of CVD. All women in the control group had normal ICG data. All women in the study group had some abnormal ICG data, with 28 (87.5%) having multiple ICG abnormalities. ICG data indicated that 13 (40.6%) had ventricular dysfunction, 14 (43.8%) had high vascular resistive load, and 30 (93.8%) had elevated vascular pulsatile load. The data suggest that subclinical CVD, detectable by ICG, is prevalent in women older than 40 years with multiple risk factors. Abnormal ICG results could expedite the initiation of customized treatment as part of a preventive approach to CVD. (c) 2009 Wiley Periodicals, Inc.

Pathogenic implications of iron accumulation in multiple sclerosis

PubMed Central

Williams, Rachel; Buchheit, Cassandra L.; Berman, Nancy E. J.; LeVine, Steven M.

2011-01-01

Iron, an essential element used for a multitude of biochemical reactions, abnormally accumulates in the central nervous system of patients with multiple sclerosis (MS). The mechanisms of abnormal iron deposition in MS are not fully understood, nor do we know whether these deposits have adverse consequences, i.e., contribute to pathogenesis. With some exceptions, excess levels of iron are represented concomitantly in multiple deep gray matter structures often with bilateral representation, while in white matter pathological iron deposits are usually located at sites of inflammation that are associated with veins. These distinct spatial patterns suggest disparate mechanisms of iron accumulation between these regions. Iron has been postulated to promote disease activity in MS by various means: 1) iron can amplify the activated state of microglia resulting in the increased production of proinflammatory mediators; 2) excess intracellular iron deposits could promote mitochondria dysfunction; and 3) improperly managed iron could catalyze the production of damaging reactive oxygen species. The pathological consequences of abnormal iron deposits may be dependent on the affected brain region and/or accumulation process. Here we review putative mechanisms of enhanced iron uptake in MS and address the likely roles of iron in the pathogenesis of this disease. PMID:22004421

Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome

PubMed Central

Vootla, Vamshidhar R.; Daniel, Myrta

2015-01-01

Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome. PMID:26351414

Manometric abnormalities of the oesophagus in patients with Parkinson's disease.

PubMed

Castell, J A; Johnston, B T; Colcher, A; Li, Q; Gideon, R M; Castell, D O

2001-08-01

Dysphagia in Parkinson's disease (PD) is known to correlate with abnormalities of oropharyngeal function. Oesophageal abnormalities have not been previously demonstrated to correlate with dysphagia. The aim of the study was to determine if motor dysfunction of the oesophageal body correlates with dysphagia or disease severity in PD. Twenty-two patients with PD were assessed for the severity of their dysphagia (scale of 1-7) and severity of PD (Hoehn and Yahr scale 1-4). All underwent oesophageal manometry. Dysphagia was present daily in 10 patients (45%). Parkinson's disease was graded as severe (Hoehn and Yahr > or =3) in eight (36%) patients. Oesophageal manometry was abnormal in 16 (73%) patients. Thirteen patients had either complete aperistalsis or multiple simultaneous contractions (diffuse oesophageal spasm). These findings were significantly more common in patients with daily dysphagia (90% vs. 33%; P < 0.005), and were not related to duration or severity of PD. We conclude that the presence of aperistalsis or multiple simultaneous contractions in the oesophagus does correlate with dysphagia and is independent of PD severity or duration. This may reflect selective involvement of either the dorsal motor nucleus of the vagus or the oesophageal myenteric plexus.

Congenital keratoglobus with multiple cardiac anomalies: a case presentation and literature review.

PubMed

Ozer, Pinar A; Yalniz-Akkaya, Zuleyha

2015-07-01

Keratoglobus is a rare condition of bilateral corneal ectasia, which results in high myopia, irregular astigmatism, scarring, and rarely spontaneous globe rupture. Globoid protrusion of a clear, diffusely thin cornea is the pathology. The congenital form has been associated with blue sclera in which there is a systemic connective tissue disorder with abnormal collagen synthesis like Ehlers-Danlos syndrome, Marfan syndrome, and osteogenesis imperfecta. Some concomitant abnormalities reported with kertoglobus include joint hypermobility, dental and skeletal abnormalities, osteal fragility, and deafness. Acquired forms have been reported to be associated with vernal keratoconjunctivitis and thyroid ophthalmopathy. We report the case of a 16-year-old boy with keratoglobus who presented with a history of photophobia and a low vision in both eyes since birth. He has been followed up by our pediatric cardiology department due to multiple cardiac anomalies. He had hypermobility of large joints, easy bruising, thin and hyperextensible skin with visible veins, which were also described in his elder brother. We aimed to discuss the etiology and the association of keratoglobus with some systemic abnormalities caused by collogen tissue disturbance, and make a brief review about the recent literature concerning the management of keratoglobus patients.

Nerve fibre layer analysis with GDx with a variable corneal compensator in patients with multiple sclerosis.

PubMed

Della Mea, Giovanni; Bacchetti, Sonia; Zeppieri, Marco; Brusini, Paolo; Cutuli, Daniela; Gigli, Gian Luigi

2007-01-01

To evaluate the ability of GDx with variable corneal compensator (VCC) compared to visual-evoked potentials (VEPs) and standard automated perimetry (SAP) in the detection of early optic nerve damage in patients with multiple sclerosis (MS). 46 eyes of 23 MS patients were included. Ten of them had a history of acute retrobulbar optic neuritis. A control group of 20 normal subjects was also included. All subjects underwent a complete ophthalmological examination and testing with SAP, GDx VCC and VEPs. 19 eyes (41.3%) were abnormal with GDx VCC compared to 38 eyes (82.6%) with SAP and 31 (64.4%) with VEPs. In the optic neuritis group, 9 eyes (69.2%) had optic nerve pallor; SAP was abnormal in 8 of these eyes (61.5%) while VEPs and GDx VCC were abnormal in 6 eyes (46.1%). 2/20 eyes (10.0%) in the control group gave a false-positive abnormal result with SAP. GDx VCC and VEP were normal for all the eyes in the control group. GDx VCC is less able to detect early defects in MS patients compared to the currently used standard techniques of SAP and VEPs. Copyright (c) 2007 S. Karger AG, Basel.

Effect of one anesthetic exposure on long-term behavioral changes in children.

PubMed

Chemaly, Maen; El-Rajab, Mariam A; Ziade, Fouad M; Naja, Zoher M

2014-11-01

To determine the association between one anesthetic exposure and behavioral outcome at age 10 to 12 years. Retrospective comparative study. University-affiliated pediatrics department. The medical records of children who underwent anesthesia between January 2004 and December 2005 at our institution were reviewed. The records of 292 children were included in the study group and 300 children in the control group. The study group involved children who had one anesthetic exposure before age of 4 years and the control group had children who were not exposed to anesthesia. The primary outcome was behavioral change as assessed by the Eyberg Child Behavior Inventory (ECBI) questionnaire. The rate of behavioral abnormalities before the age of 11 years was 28.4% in the study group (P<0.001) and 5.7% in the control group. The risk of developing behavioral abnormalities was prominent in children being exposed to surgery versus those exposed during a diagnostic procedure (32.4% vs 4.8%; P<0.0001). Eighty-three point nine percent of the children who were exposed to longer duration anesthesia (more than 3 hrs) had behavioral abnormalities (P<0.0001), while 48.8% of children who received anesthesia at younger ages (0 - 6 mos) had behavioral abnormalities (P<0.0001). Exposure to multiple anesthetic agents versus one anesthetic agent was a significant risk factor for development of behavioral abnormalities (P<0.0001). The incidence of behavioral abnormalities increased when anesthesia and surgery were accompanied by younger age, longer duration of surgery, and use of multiple anesthetic agents. Copyright © 2014 Elsevier Inc. All rights reserved.

Choline metabolism-based molecular diagnosis of cancer: an update

PubMed Central

Glunde, Kristine; Penet, Marie-France; Jiang, Lu; Jacobs, Michael A; Bhujwalla, Zaver M

2016-01-01

Abnormal choline metabolism continues to be identified in multiple cancers. Molecular causes of abnormal choline metabolism are changes in choline kinase-α, ethanolamine kinase-α, phosphatidylcholine-specific phospholipase C and -D and glycerophosphocholine phosphodiesterases, as well as several choline transporters. The net outcome of these enzymatic changes is an increase in phosphocholine and total choline (tCho) and, in some cancers, a relative decrease of glycerophosphocholine. The increased tCho signal detected by 1H magnetic resonance spectroscopy is being evaluated as a diagnostic marker in multiple cancers. Increased expression and activity of choline transporters and choline kinase-α have spurred the development of radiolabeled choline analogs as PET imaging tracers. Both tCho 1H magnetic resonance spectroscopy and choline PET are being investigated to detect response to treatment. Enzymes mediating the abnormal choline metabolism are being explored as targets for cancer therapy. This review highlights recent molecular, therapeutic and clinical advances in choline metabolism in cancer. PMID:25921026

Simpson-Golabi-Behmel syndrome types I and II.

PubMed

Tenorio, Jair; Arias, Pedro; Martínez-Glez, Víctor; Santos, Fernando; García-Miñaur, Sixto; Nevado, Julián; Lapunzina, Pablo

2014-09-20

Simpson-Golabi-Behmel syndrome (SGBS) is a rare overgrowth syndrome clinically characterized by multiple congenital abnormalities, pre/postnatal overgrowth, distinctive craniofacial features, macrocephaly, and organomegaly. Abnormalities of the skeletal system, heart, central nervous system, kidney, and gastrointestinal tract may also be observed. Intellectual disability, early motor milestones and speech delay are sometimes present; however, there are a considerable number of individuals with normal intelligence.

Pigmentary retinopathy associated with the mitochondrial DNA 3243 point mutation.

PubMed

Sue, C M; Mitchell, P; Crimmins, D S; Moshegov, C; Byrne, E; Morris, J G

1997-10-01

Fourteen patients from four unrelated families were studied to determine the prevalence of retinal pigmentary abnormalities associated with the MELAS A to G 3243 point mutation. Neurologic and ophthalmic examinations, retinal photography, pattern shift visual evoked potentials, and electroretinography were performed in all patients. Eight of the 14 patients had retinal pigmentary abnormalities characterized by symmetric areas of depigmentation involving predominantly the posterior pole and midperipheral retina. None of the patients had optic atrophy and only one patient with pigmentary retinal abnormalities had impaired visual acuity. None of the diabetic subjects (n = 6) had signs of diabetic retinopathy. Fluorescein angiography demonstrated mottled hyper- and hypofluorescent areas indicating multiple window defects in the retinal pigmentary epithelium. Visual evoked potentials showed delayed P100 responses in four of the eight patients with retinal pigmentary abnormalities. We conclude that there is a high prevalence of retinal pigmentary abnormalities in patients with MELAS A to G 3243 point mutation. These abnormalities are usually asymptomatic and best detected by retinal photography.

An implication of the short physical performance battery (SPPB) as a predictor of abnormal pulmonary function in aging people.

PubMed

Choi, Ho-Chun; Son, Ki Young; Cho, Belong; Park, Sang Min; Cho, Sung-Il

2012-01-01

If association between the decline in physical performance and the decline in pulmonary function is confirmed, the SPPB could be used as a predictor for pulmonary functional declines in aging people because of its convenient use. This study aimed to elucidate the association of the SPPB with the pulmonary function test (PFT) to determine the usefulness of the SPPB as a predictor of PFT decline. The SPPB and PFT were performed on random sample nested in the Korean Longitudinal Study of Aging (KLoSA) panel, a national representative sample of aging people in Korea. Comparisons of adjusted means of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory ratio (FER) defined as FEV1/FVC between normal and abnormal SPPB groups were performed using the t-test. The association between PFT and SPPB abnormality was examined using multiple logistic regression analysis. Additionally, the associations of gait speed and chair stand time with FEV1 and FVC were examined using multiple linear regression analysis. Five hundred and eighteen subjects were included in analysis. Approximately 43% (222/518) of the subjects were male and 65% (338/518) were 60 years or older. Adjusted means of FEV1 and FER were significantly or marginally lower when SPPB score was abnormal in both overall and non-smoking men (p=0.009 and 0.053 for overall, p<0.001 and p<0.080 for non-smokers), but FVC was lower only in non-smoking men (p=0.024). Abnormal SPPB score was significantly associated with abnormal PFT regardless of sex. (adjusted odds ratio=OR=3.76, 95%CI=1.96-7.22 for men, adjusted OR=2.11, 95%CI 1.28-3.47 for women). Gait speed was significantly or marginally associated with FEV1 and FVC in participants 60 years or older, regardless of sex. We conclude that abnormal SPPB score was associated with abnormal pulmonary function. Thus, the SPPB has the potential to be used as an early predictor of abnormal pulmonary function in clinical settings and epidemiological study. Copyright © 2011. Published by Elsevier Ireland Ltd.

Refeeding syndrome.

PubMed

Fernández López, M T; López Otero, M J; Alvarez Vázquez, P; Arias Delgado, J; Varela Correa, J J

2009-01-01

Refeeding syndrome is a complex syndrome that occurs as a result of reintroducing nutrition (oral, enteral or parenteral) to patients who are starved or malnourished. Patients can develop fluid-balance abnormalities, electrolyte disorders (hypophosphataemia, hypokalaemia and hypomagnesaemia), abnormal glucose metabolism and certain vitamin deficiencies. Refeeding syndrome encompasses abnormalities affecting multiple organ systems, including neurological, pulmonary, cardiac, neuromuscular and haematological functions. Pathogenic mechanisms involved in the refeeding syndrome and clinical manifestations have been reviewed. We provide suggestions for the prevention and treatment of refeeding syndrome. The most important steps are to identify patients at risk, reintroduce nutrition cautiously and correct electrolyte and vitamin deficiencies properly.

Current concepts of metabolic abnormalities in HIV patients: focus on lipodystrophy.

PubMed

Kolter, Donald P

2003-12-01

HIV infection is associated with a number of metabolic abnormalities, including lipodystrophy, a difficult-to-define disorder whose characteristics include hyperlipidemia, insulin resistance, and fat redistribution. Current data suggest that lipodystrophy is caused by multiple factors. Dual-nucleoside reverse transcriptase inhibitor therapy combined with protease inhibitor therapy has been shown to increase the risk of metabolic abnormalities, but susceptibility independent of drug effects has also been shown. While many of the treatments for the broad range of signs and symptoms of lipodystrophy bring about improvements in patient status, none have been demonstrated to bring about a return to baseline levels.

Distribution of maternal age and birth order groups in cases with unclassified multiple congenital abnormalities according to the number of component abnormalities: a national population-based case-control study.

PubMed

Csermely, Gyula; Czeizel, Andrew E; Veszprémi, Béla

2015-02-01

Multiple congenital abnormalities are caused by chromosomal aberrations, mutant major genes and teratogens. A minor proportion of these patients are identified as syndromes but the major part belonging to the group of unclassified multiple CAs (UMCAs). The main objective of this study was to evaluate the maternal age and birth order in pregnant women who had offspring affected with UMCA. The strong association between numerical chromosomal aberrations, e.g., Down syndrome and advanced maternal age is well-known and tested here. The Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980 to 1996, yielded a large population-based national data set with 22,843 malformed newborns or fetuses ("informative cases") included 1349 UMCA cases with their 2407 matched controls. Case-control comparison of maternal age and birth order was made for cases with UMCA, stratified by component numbers and their controls. In addition, 834 cases with Down syndrome were compared to 1432 matched controls. The well-known advanced maternal age with the higher risk for Down syndrome was confirmed. The findings of the study suggest that the young age of mothers associates with the higher risk of UMCA, in addition birth order 4 or more associates with the higher risk for UMCA with 2 and 3 component CAs. This study was the first to analyze the possible maternal and birth order effect for cases with UMCA, and the young age and higher birth order associated with a higher risk for UMCA. © 2014 Wiley Periodicals, Inc.

Migraine: Multiple Processes, Complex Pathophysiology

PubMed Central

Noseda, Rodrigo; Borsook, David

2015-01-01

Migraine is a common, multifactorial, disabling, recurrent, hereditary neurovascular headache disorder. It usually strikes sufferers a few times per year in childhood and then progresses to a few times per week in adulthood, particularly in females. Attacks often begin with warning signs (prodromes) and aura (transient focal neurological symptoms) whose origin is thought to involve the hypothalamus, brainstem, and cortex. Once the headache develops, it typically throbs, intensifies with an increase in intracranial pressure, and presents itself in association with nausea, vomiting, and abnormal sensitivity to light, noise, and smell. It can also be accompanied by abnormal skin sensitivity (allodynia) and muscle tenderness. Collectively, the symptoms that accompany migraine from the prodromal stage through the headache phase suggest that multiple neuronal systems function abnormally. As a consequence of the disease itself or its genetic underpinnings, the migraine brain is altered structurally and functionally. These molecular, anatomical, and functional abnormalities provide a neuronal substrate for an extreme sensitivity to fluctuations in homeostasis, a decreased ability to adapt, and the recurrence of headache. Advances in understanding the genetic predisposition to migraine, and the discovery of multiple susceptible gene variants (many of which encode proteins that participate in the regulation of glutamate neurotransmission and proper formation of synaptic plasticity) define the most compelling hypothesis for the generalized neuronal hyperexcitability and the anatomical alterations seen in the migraine brain. Regarding the headache pain itself, attempts to understand its unique qualities point to activation of the trigeminovascular pathway as a prerequisite for explaining why the pain is restricted to the head, often affecting the periorbital area and the eye, and intensifies when intracranial pressure increases. PMID:25926442

Array-CGH analysis in Rwandan patients presenting development delay/intellectual disability with multiple congenital anomalies.

PubMed

Uwineza, Annette; Caberg, Jean-Hubert; Hitayezu, Janvier; Hellin, Anne Cecile; Jamar, Mauricette; Dideberg, Vinciane; Rusingiza, Emmanuel K; Bours, Vincent; Mutesa, Leon

2014-07-12

Array-CGH is considered as the first-tier investigation used to identify copy number variations. Right now, there is no available data about the genetic etiology of patients with development delay/intellectual disability and congenital malformation in East Africa. Array comparative genomic hybridization was performed in 50 Rwandan patients with development delay/intellectual disability and multiple congenital abnormalities, using the Agilent's 180 K microarray platform. Fourteen patients (28%) had a global development delay whereas 36 (72%) patients presented intellectual disability. All patients presented multiple congenital abnormalities. Clinically significant copy number variations were found in 13 patients (26%). Size of CNVs ranged from 0,9 Mb to 34 Mb. Six patients had CNVs associated with known syndromes, whereas 7 patients presented rare genomic imbalances. This study showed that CNVs are present in African population and show the importance to implement genetic testing in East-African countries.

[Cornelia de Lange Syndrome and multiple hormonal deficiency, an unusual association. Clinical case].

PubMed

Mora-Bautista, Víctor M; Mendoza-Rojas, Víctor; Contreras-García, Gustavo A

2017-06-01

Cornelia de Lange syndrome is a genetic disease characterized by distinctive facial features, failure to thrive, microcephaly and several malformations associated. Its main endocrinological features are anomalies of the genitalia. We present a 13-year-old boy, who suffered from complicated aspiration pneumonia and showed Cornelia de Lange syndrome phenotype, with global developmental delay, suction-swallowing abnormalities, short stature and abnormal genitalia associated. His bone age was delayed, so he underwent full endocrinological panel. Central hypothyroidism, growth hormone deficiency and low luteinizing hormone-follicle-stimulating hormone levels were observed and multiple pituitary hormone deficiencies diagnosis was made. Basal cortisol, adrenocorticotropic hormone and prolactin levels were normal. He received thyroid hormonal substitution. Multiple pituitary hormone deficiencies are an unusual feature of De Lange syndrome. We suggest evaluating all different endocrine axes in these patients. Sociedad Argentina de Pediatría.

[Research on the incidence and prevalence of congenital abnormalities in Iaşi district and Iaşi city, from 2001 to 2008].

PubMed

Chiosac, Alina Andreea Andreescu; Manole, Alina; Gorduza, E V; Stamatin, Maria; Titianus, Monica; Ivan, A

2010-01-01

Congenital abnormalities (CA) are deviations from the normal embryonic development that appear antenatal and they are characterized by the alteration of the morphology and function of an organ, system of organs or even of the entire body. The study, on a period of eight years, included 1685 children with CA, from which 58% were males and 50% were from the country-side. It has been observed that 36% of the CA cases were premature births and 64% were normal term births. Also, 21% of the children with CA weighed less than 2700 grams at birth and 79% weighed more than 2700 grams at birth. The birth's APGAR score has been less than 7 in 30% of the cases and higher than 7 in 70% of the cases. 72% of the cases were natural births and 28% were caesarian births. 88% of the CA cases were singular congenital abnormalities and 12% were multiple congenital abnormalities. 24% of the CA were cardiac abnormalities and 21% were skeletal abnormalities. 3% of the subjects of the study have died, of which 69% died from cardiac abnormalities, 22% from hydrocephalus abnormalities, 7% from diaphragmatic hernia and 2% from renal congenital abnormalities.

Abnormal human chorionic gonadotropin (hCG) trends after transfer of multiple embryos resulting in viable singleton pregnancies.

PubMed

Brady, Paula C; Farland, Leslie V; Missmer, Stacey A; Racowsky, Catherine; Fox, Janis H

2018-03-01

The purpose of this study is to investigate whether abnormal hCG trends occur at a higher incidence among women conceiving singleton pregnancies following transfer of multiple (two or more) embryos (MET), as compared to those having a single embryo transfer (SET). Retrospective cohort study was performed of women who conceived singleton pregnancies following fresh or frozen autologous IVF/ICSI cycles with day 3 or day 5 embryo transfers between 2007 and 2014 at a single academic medical center. Cycles resulting in one gestational sac on ultrasound followed by singleton live birth beyond 24 weeks of gestation were included. Logistic regression models adjusted a priori for patient age at oocyte retrieval and day of embryo transfer were used to estimate the Odds Ratio of having an abnormal hCG rise (defined as a rise or < 66% in 2 days) following SET as compared to MET. Among patients receiving two or more embryos, 6.1% (n = 84) had abnormal hCG rises between the first and second measurements, compared to 2.7% (n = 17) of patients undergoing SET (OR 2.16, 95% CI 1.26-3.71). Among patients with initially abnormal hCG rises who had a third level checked (89%), three-quarters had normal hCG rises between the second and third measurements. Patients who deliver singletons following MET were more likely to have suboptimal initial hCG rises, potentially due to transient implantation of other non-viable embryo(s). While useful for counseling, these findings should not change standard management of abnormal hCG rises following IVF. The third hCG measurements may clarify pregnancy prognosis.

Structural abnormalities and altered regional brain activity in multiple sclerosis with simple spinal cord involvement.

PubMed

Yin, Ping; Liu, Yi; Xiong, Hua; Han, Yongliang; Sah, Shambhu Kumar; Zeng, Chun; Wang, Jingjie; Li, Yongmei

2018-02-01

To assess the changes of the structural and functional abnormalities in multiple sclerosis with simple spinal cord involvement (MS-SSCI) by using resting-state functional MRI (RS-fMRI), voxel based morphology (VBM) and diffusion tensor tractography. The amplitude of low-frequency fluctuation (ALFF) of 22 patients with MS-SSCI and 22 healthy controls (HCs) matched for age, gender and education were compared by using RS-fMRI. We also compared the volume, fractional anisotropy (FA) and apparent diffusion coefficient of the brain regions in baseline brain activity by using VBM and diffusion tensor imaging. The relationships between the expanded disability states scale (EDSS) scores, changed parameters of structure and function were further explored. (1) Compared with HCs, the ALFF of the bilateral hippocampus and right middle temporal gyrus in MS-SSCI decreased significantly. However, patients exhibited increased ALFF in the left middle frontal gyrus, left posterior cingulate gyrus and right middle occipital gyrus ( two-sample t-test, after AlphaSim correction, p < 0.01, voxel size > 40). The volume of right middle frontal gyrus reduced significantly (p < 0.01). The FA and ADC of right hippocampus, the FA of left hippocampus and right middle temporal gyrus were significantly different. (2) A significant correlation between EDSS scores and ALFF was noted only in the left posterior cingulate gyrus. Our results detected structural and functional abnormalities in MS-SSCI and functional parameters were associated with clinical abnormalities. Multimodal imaging plays an important role in detecting structural and functional abnormalities in MS-SSCI. Advances in knowledge: This is the first time to apply RS-fMRI, VBM and diffusion tensor tractography to study the structural and functional abnormalities in MS-SSCI, and to explore its correlation with EDSS score.

Fetal karyotyping for chromosome abnormalities after an unexplained elevated maternal serum alpha-fetoprotein screening.

PubMed

Feuchtbaum, L B; Cunningham, G; Waller, D K; Lustig, L S; Tompkinson, D G; Hook, E B

1995-08-01

To study the chromosome abnormality rate among women with elevated levels of maternal serum alpha-fetoprotein (MSAFP) and the types of chromosome abnormalities in this population, and to compare this rate with reports in the literature and the rate observed in the general population. We studied 8097 women who chose to undergo amniocentesis and fetal karyotyping after having an elevated MSAFP test of 2.5 multiples of the median (MOM) or higher. All abnormal karyotypes were reviewed and grouped according to whether the elevated MSAFP value could be explained by a ventral wall or neural tube defect. The overall chromosome abnormality rate was 13.83 per 1000 amniocenteses. The rate in the "unexplained" group was 10.92 per 1000 amniocenteses. Just over half (53%) of the abnormal karyotypes were autosomal anomalies, and 47% were sex chromosome abnormalities. The autosomal aneuploidies observed most frequently were triploidy and trisomy 13. The sex chromosome abnormalities observed most frequently were the XXY and XYY karyotypes. Women who have unexplained elevated MSAFP values of 2.5 MOM or greater have a twofold increase in the rate of chromosome abnormalities in their fetuses compared with the general population (P < or = .001). This rate is consistent with other studies that used a 2.5 MOM cutoff. Studies that used a 2.0 MOM cutoff have reported chromosome abnormality rates that do not vary from general population estimates.

A Multicenter Access and Distribution Protocol for Unlicensed Cryopreserved Cord Blood Units (CBUs)

ClinicalTrials.gov

2018-05-15

Hematologic Malignancies; Inherited Disorders of Metabolism; Inherited Abnormalities of Platelets; Histiocytic Disorders; Acute Myelogenous Leukemia (AML or ANLL); Acute Lymphoblastic Leukemia (ALL); Other Acute Leukemia; Chronic Myelogenous Leukemia (CML); Myelodysplastic (MDS) / Myeloproliferative (MPN) Diseases; Other Leukemia; Hodgkin Lymphoma; Non-hodgkin Lymphoma; Multiple Myeloma/ Plasma Cell Disorder (PCD); Inherited Abnormalities of Erythrocyte Differentiation or Function; Disorders of the Immune System; Automimmune Diseases; Severe Aplastic Anemia

Simultaneous regression of Philadelphia chromosome and multiple nonrecurrent clonal chromosomal abnormalities with imatinib mesylate in a patient autografted 22 years before for chronic myelogenous leukemia.

PubMed

Van Den Akker, J; Coppo, P; Portnoï, M F; Barbu, V; Bories, D; Gorin, N C

2007-09-01

A 31-year-old patient developed chronic myelogenous leukemia (CML) in November, 1983. In November 1984, following a diagnosis of acceleration, he received an autologous hemopoietic transplant after conditioning with cyclophosphamide and total body irradiation. The autologous marrow was purged with mafosfamide. Over 20 years, the patient remained in chronic phase of CML. Multiple nonrecurrent clonal chromosomal abnormalities appeared leading to a very complex karyotype, including among others involvement of chromosomes 1, 7, 9, 13, 19, and X. Fluorescent in situ hybridization showed that the two chromosomes 9 were involved. Acute myeloid crisis was diagnosed in February, 2004. Treatment with imatinib mesylate resulted within 6 months in a total disappearance of all chromosomal abnormalities with a complete cytogenetic and molecular response, which persists 3 years later. We question whether the ex vivo purging procedure with mafosfamide has favored the occurrence of these particular cytogenetic abnormalities (with no independent oncogenic potential) within the original leukemic stem cell pool. It remains unclear whether the autologous transplantation has indeed resulted into some prolongation of the duration of the chronic phase, which lasted for 20 years. At time of acute crisis, the dramatic response to imatinib mesylate leading to a complete cytogenetic and molecular response is noteworthy.

Abnormal dynamics of language in schizophrenia.

PubMed

Stephane, Massoud; Kuskowski, Michael; Gundel, Jeanette

2014-05-30

Language could be conceptualized as a dynamic system that includes multiple interactive levels (sub-lexical, lexical, sentence, and discourse) and components (phonology, semantics, and syntax). In schizophrenia, abnormalities are observed at all language elements (levels and components) but the dynamic between these elements remains unclear. We hypothesize that the dynamics between language elements in schizophrenia is abnormal and explore how this dynamic is altered. We, first, investigated language elements with comparable procedures in patients and healthy controls. Second, using measures of reaction time, we performed multiple linear regression analyses to evaluate the inter-relationships among language elements and the effect of group on these relationships. Patients significantly differed from controls with respect to sub-lexical/lexical, lexical/sentence, and sentence/discourse regression coefficients. The intercepts of the regression slopes increased in the same order above (from lower to higher levels) in patients but not in controls. Regression coefficients between syntax and both sentence level and discourse level semantics did not differentiate patients from controls. This study indicates that the dynamics between language elements is abnormal in schizophrenia. In patients, top-down flow of linguistic information might be reduced, and the relationship between phonology and semantics but not between syntax and semantics appears to be altered. Published by Elsevier Ireland Ltd.

Magnifying Endoscopic Features of Follicular Lymphoma Involving the Stomach: A Report of Two Cases

PubMed Central

Takata, Katsuyoshi; Kawano, Seiji; Fujii, Nobuharu; Kawahara, Yoshiro; Yoshino, Tadashi; Okada, Hiroyuki

2016-01-01

A 70-year-old woman presented with follicular lymphoma involving the stomach, duodenum, jejunum, bone, and lymph nodes. Esophagogastroduodenoscopy revealed multiple depressed lesions in the stomach. Examination with magnifying endoscopy showed branched abnormal vessels along with gastric pits, which were irregularly shaped but were preserved. The second case was a 45-year-old man diagnosed with stage II1 follicular lymphoma with duodenal, ileal, and colorectal involvement, as well as lymphadenopathy of the mesenteric lymph nodes. Esophagogastroduodenoscopy performed six years after the diagnosis revealed multiple erosions in the gastric body and angle. Magnifying endoscopic observation with narrow-band imaging showed that the gastric pits were only partially preserved and were destroyed in most of the stomach. Branched abnormal vessels were also seen. Pathological features were consistent with follicular lymphoma in both cases. The structural differences reported between the two cases appear to reflect distinct pathologies. Disappearance of gastric pits in the latter case seems to result from loss of epithelial cells, probably due to chronic inflammation. In both cases, branched abnormal vasculature was observed. These two cases suggest that magnified observations of abnormal branched microvasculature may facilitate endoscopic detection and recognition of the extent of gastric involvement in patients with follicular lymphoma. PMID:27747111

Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.

PubMed

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

PubMed Central

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS. PMID:23691320

Neurological abnormalities associated with CDMA exposure.

PubMed

Hocking, B; Westerman, R

2001-09-01

Dysaesthesiae of the scalp and neurological abnormality after mobile phone use have been reported previously, but the roles of the phone per se or the radiations in causing these findings have been questioned. We report finding a neurological abnormality in a patient after accidental exposure of the left side of the face to mobile phone radiation [code division multiple access (CDMA)] from a down-powered mobile phone base station antenna. He had headaches, unilateral left blurred vision and pupil constriction, unilateral altered sensation on the forehead, and abnormalities of current perception thresholds on testing the left trigeminal ophthalmic nerve. His nerve function recovered during 6 months follow-up. His exposure was 0.015-0.06 mW/cm(2) over 1-2 h. The implications regarding health effects of radiofrequency radiation are discussed.

Association of human papillomavirus infection and abnormal anal cytology among HIV-infected MSM in Beijing, China.

PubMed

Yang, Yu; Li, Xiangwei; Zhang, Zhihui; Qian, Han-Zhu; Ruan, Yuhua; Zhou, Feng; Gao, Cong; Li, Mufei; Jin, Qi; Gao, Lei

2012-01-01

In the recent years, dramatic increases in HIV transmission among men who have sex with men (MSM) have been observed in China. Human papillomavirus (HPV) infection related anal cancer is more common among HIV-infected MSM as compared to the general population. However, HPV infection and anal cytology has been rarely studied in HIV-infected MSM in China. HIV-infected MSM in Beijing, China were invited to participate in this study between January and April 2011. Anal swabs were collected for examining cytology and HPV genotypes. Ninety-five eligible participants with complete questionnaire and laboratory data were included in the analyses. Thirty six of them (37.9%) showed abnormal anal cytology as follows: atypical squamous cells of undetermined significance (ASC-US) in 19 (20.0%), atypical squamous cells but cannot exclude HSIL (ASC-H) in 1 (1.1%), low-grade squamous intraepithelial lesion (LSIL) in 15 (15.8%), and high-grade squamous intraepithelial lesion (HSIL) in 1 (1.1%). HPV6 (20.0%), HPV16 (10.9%), HPV56 (10.9%), HPV52 (9.1%) and HPV39 (9.1%) were observed most frequently among those with normal anal cytology, while different distribution was found in the ones with abnormal anal cytology as HPV6 (19.4%), HPV16 (19.4%), HPV45 (16.7%), HPV52 (16.7%) and HPV18 (11.1%). In addition, HPV16, HPV45, HPV52 and HPV18 were the most frequent high-risk types in patients with abnormal anal cytology. HPV multiplicity was found to be significantly related to the prevalence of abnormal anal cytology (p for trend = 0.04). High prevalence of HPV infection and abnormal anal cytology was observed among HIV-infected MSM in China. Infection of multiple HPV types or high-risk types was found to be associated with an increased risk of abnormal anal cytology.

Association of Human Papillomavirus Infection and Abnormal Anal Cytology among HIV-Infected MSM in Beijing, China

PubMed Central

Zhang, Zhihui; Qian, Han-Zhu; Ruan, Yuhua; Zhou, Feng; Gao, Cong; Li, Mufei; Jin, Qi; Gao, Lei

2012-01-01

Background In the recent years, dramatic increases in HIV transmission among men who have sex with men (MSM) have been observed in China. Human papillomavirus (HPV) infection related anal cancer is more common among HIV-infected MSM as compared to the general population. However, HPV infection and anal cytology has been rarely studied in HIV-infected MSM in China. Methods HIV-infected MSM in Beijing, China were invited to participate in this study between January and April 2011. Anal swabs were collected for examining cytology and HPV genotypes. Results Ninety-five eligible participants with complete questionnaire and laboratory data were included in the analyses. Thirty six of them (37.9%) showed abnormal anal cytology as follows: atypical squamous cells of undetermined significance (ASC-US) in 19 (20.0%), atypical squamous cells but cannot exclude HSIL (ASC-H) in 1 (1.1%), low-grade squamous intraepithelial lesion (LSIL) in 15 (15.8%), and high-grade squamous intraepithelial lesion (HSIL) in 1 (1.1%). HPV6 (20.0%), HPV16 (10.9%), HPV56 (10.9%), HPV52 (9.1%) and HPV39 (9.1%) were observed most frequently among those with normal anal cytology, while different distribution was found in the ones with abnormal anal cytology as HPV6 (19.4%), HPV16 (19.4%), HPV45 (16.7%), HPV52 (16.7%) and HPV18 (11.1%). In addition, HPV16, HPV45, HPV52 and HPV18 were the most frequent high-risk types in patients with abnormal anal cytology. HPV multiplicity was found to be significantly related to the prevalence of abnormal anal cytology (p for trend = 0.04). Conclusions High prevalence of HPV infection and abnormal anal cytology was observed among HIV-infected MSM in China. Infection of multiple HPV types or high-risk types was found to be associated with an increased risk of abnormal anal cytology. PMID:22558293

Control of Visually Guided Saccades in Multiple Sclerosis: Disruption to Higher-Order Processes

ERIC Educational Resources Information Center

Fielding, Joanne; Kilpatrick, Trevor; Millist, Lynette; White, Owen

2009-01-01

Ocular motor abnormalities are a common feature of multiple sclerosis (MS), with more salient deficits reflecting tissue damage within brainstem and cerebellar circuits. However, MS may also result in disruption to higher level or cognitive control processes governing eye movement, including attentional processes that enhance the neural processing…

Acute monocytic leukemia and multiple abnormalities in a child with duplication of 1q detected by GTG-banding and SKY.

PubMed

Scrideli, Carlos A; Baruffi, Marcelo R; Squire, Jeremy A; Ramos, Ester S; Karaskova, Jana; Heck, Benjamin; Tone, Luiz G

2005-12-01

Patients with 1q duplication have demonstrated a wide range of multiple congenital abnormalities. Alterations involving this chromosomal region have being described in hematopoietic malignancies and a series of candidate genes that may be associated with neoplasias have been mapped in this region. We describe a case of partial trisomy 1q "syndrome" and acute monocytic leukemia. Cytogenetic study of the bone marrow cells by GTG-banding and spectral karyotyping (SKY) showed dup(1)(q23q44) in all cells analyzed. The dismorphological features with the dup(1q) suggest a constitutional chromosome alteration and the first, in our knowledge, association of a trisomy 1q "syndrome" with AML.

Diffusion tensor imaging of the optic tracts in multiple sclerosis: association with retinal thinning and visual disability.

PubMed

Dasenbrock, Hormuzdiyar H; Smith, Seth A; Ozturk, Arzu; Farrell, Sheena K; Calabresi, Peter A; Reich, Daniel S

2011-04-01

Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (P=.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=.51, P=.003) and total-macular-volume reduction (r=.59, P=.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. Copyright © 2010 by the American Society of Neuroimaging.

Diffusion Tensor Imaging of the Optic Tracts in Multiple Sclerosis: Association with Retinal Thinning and Visual Disability

PubMed Central

Dasenbrock, Hormuzdiyar H.; Smith, Seth A.; Ozturk, Arzu; Farrell, Sheena K.; Calabresi, Peter A.; Reich, Daniel S.

2009-01-01

Background and purpose Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Methods Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. Results After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (p=0.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=0.51, p=0.003) and total-macular-volume reduction (r=0.59, p=0.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Conclusions Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. PMID:20331501

Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2)

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

Greenberg, F.; Lewis, R.A.; Potocki, L.

1996-03-29

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly, mental retardation (MCA/MR) syndrome associated with deletion of chromosome 17 band p11.2. As part of a multi-disciplinary clinical, cytogenetic, and molecular approach to SMS, detailed clinical studies including radiographic neurologic, developmental, ophthalmologic, otolaryngologic, and audiologic evaluations were performed on 27 SMS patients. Significant findings include otolaryngologic abnormalities in 94%, eye abnormalities in 85%, sleep abnormalities (especially reduced REM sleep) in 75%, hearing impairment in 68% (approximately 65% conductive and 35% sensorineural), scoliosis in 65% brain abnormalities (predominantly ventriculomegaly) in 52%, cardiac abnormalities in at least 37%, renal anomalies (especially duplication of themore » collecting system) in 35%, low thyroxine levels in 29%, low immunoglobulin levels in 23%, and forearm abnormalities in 16%. The measured IQ ranged between 20-78, most patients falling in the moderate range of mental retardation at 40-54, although several patients scored in the mild or borderline range. The frequency of these many abnormalities in SMS suggests that patients should be evaluated thoroughly for associated complications both at the time of diagnosis and at least annually thereafter. 42 refs., 2 figs., 3 tabs.« less

Relationship of neuromotor disturbances to psychosis symptoms in first-episode neuroleptic-naive schizophrenia patients.

PubMed

Cortese, Leonardo; Caligiuri, Michael P; Malla, Ashok K; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

2005-06-01

From the very inception of the modern diagnostic scheme for psychotic disorders, abnormalities in motor function have been observed in these conditions. Despite convergence from multiple areas of research supporting the notion that multiple frontal-subcortical circuits regulate motor and limbic behavior, the precise relationship between motor abnormalities and psychopathology has not been elucidated. The goals of this study were to examine the prevalence of extrapyramidal signs (EPS) in first-episode schizophrenia patients and their relationships to three psychopathological dimensions (positive psychosis syndrome, negative syndrome, and disorganization). We assessed EPS using traditional observer-based as well as quantitative instrumental measures in 39 neuroleptic-naive first-episode schizophrenia subjects. Subjects were followed for 6 months after initiating antipsychotic treatment to examine the stability of motor-limbic relationships. Four main findings emerged from this study. First, depending on the measure used the prevalence of dyskinesia prior to treatment ranged from 13% to 20%. The prevalence of parkinsonism ranged from 18% to 28%. Second, severity of dyskinesia was associated with the positive psychotic syndrome; whereas parkinsonism was associated with the positive psychosis, negative syndrome and disorganization. Third, psychopathology improved significantly across all symptom dimensions following antipsychotic treatment, while EPS remained stable. This suggests that some motor abnormalities in schizophrenia may reflect trait characteristics. Fourth, abnormalities on the pre-treatment instrumental measure of parkinsonism predicted greater improvement on positive psychosis symptoms following treatment (p=0.008). Our findings support the notion that neuromotor disturbances may be a core feature of schizophrenia in a substantial proportion of patients and implicate multiple fronto-striatal circuits regulating limbic and neuromotor behavior in schizophrenia.

Surgical correction of urethral dilatation in an intersex goat.

PubMed

Karras, S; Modransky, P; Welker, B

1992-11-15

Multiple congenital urethral abnormalities were successfully corrected in a polled goat kid. Anatomic genito-urinary abnormalities identified were paired testes with associated epididymis, ductus deferens, and active endometrial tissue. Blood karyotyping revealed the female state--XX sex chromosomes. This case exemplifies the complex interactions in addition to Y dominant Mendelian genetics that determine reproductive tract development in goats. The resultant intersex state is clinically recognized with greater frequency in polled progeny.

Congenital cutis laxa with ligamentous laxity and delayed development, Dandy-Walker malformation and minor heart and osseous defects.

PubMed

Biver, A; De Rijcke, S; Toppet, V; Ledoux-Corbusier, M; Van Maldergem, L

1994-06-01

We present a female infant exhibiting congenital cutis laxa with retardation of growth and motor development, ligamentous laxity and congenital dislocation of the hips. This connective tissue disorder was associated with Dandy-Walker malformation, atrial and ventricular defect and minor bone abnormalities including multiple wormian bones, abnormal tubulation of long bones and absent twelfth pair of ribs. This association is believed to be unique.

Extraction of fault component from abnormal sound in diesel engines using acoustic signals

NASA Astrophysics Data System (ADS)

Dayong, Ning; Changle, Sun; Yongjun, Gong; Zengmeng, Zhang; Jiaoyi, Hou

2016-06-01

In this paper a method for extracting fault components from abnormal acoustic signals and automatically diagnosing diesel engine faults is presented. The method named dislocation superimposed method (DSM) is based on the improved random decrement technique (IRDT), differential function (DF) and correlation analysis (CA). The aim of DSM is to linearly superpose multiple segments of abnormal acoustic signals because of the waveform similarity of faulty components. The method uses sample points at the beginning of time when abnormal sound appears as the starting position for each segment. In this study, the abnormal sound belonged to shocking faulty type; thus, the starting position searching method based on gradient variance was adopted. The coefficient of similar degree between two same sized signals is presented. By comparing with a similar degree, the extracted fault component could be judged automatically. The results show that this method is capable of accurately extracting the fault component from abnormal acoustic signals induced by faulty shocking type and the extracted component can be used to identify the fault type.

Stress Cardiac MRI in Women With Myocardial Infarction and Nonobstructive Coronary Artery Disease.

PubMed

Mauricio, Rina; Srichai, Monvadi B; Axel, Leon; Hochman, Judith S; Reynolds, Harmony R

2016-10-01

In a prospective study, cardiac MRI (CMR) and intravascular ultrasound were performed in women with myocardial infarction (MI) and nonobstructive coronary artery disease (MINOCA). Forty participants underwent adenosine-stress CMR (sCMR). Abnormal perfusion may co-localize with ischemic late gadolinium enhancement (LGE) and T2-weighted signal hyperintensity (T2+), suggesting microvascular dysfunction contributed to MI. Qualitative perfusion analysis was performed by 2 independent readers. Abnormal myocardial perfusion reserve index (MPRI) was defined as global average ≤1.84. Abnormal rest perfusion was present in 10 patients (25%) and stress perfusion abnormalities in 25 (63%). Abnormal stress perfusion was not associated with LGE but tended to occur with T2+. Among patients with abnormal perfusion and LGE, the LGE pattern was ischemic in half. The locations of abnormal perfusion and LGE matched in 75%, T2+ in 100%. Abnormal stress perfusion was not associated with plaque disruption and matched in location in 63%. MPRI was abnormal in 10 patients (25%) and was not associated with LGE, T2+ or plaque disruption. Abnormal perfusion on sCMR is common among women with MINOCA. Abnormal perfusion usually co-localized with LGE and/or T2+ when present. Variability in LGE pattern leads to uncertainty about whether the finding of abnormal perfusion was cause or consequence of the tissue state leading to LGE. Low MPRI, possibly indicating diffuse microvascular disease, was observed with and without LGE and T2+. Multiple mechanisms may lead to abnormal perfusion on sCMR. Microvascular dysfunction may contribute to the pathogenesis of and coexist with other causes of MINOCA. © 2016 Wiley Periodicals, Inc.

An evaluation of data for 10 children born to mothers who attempted suicide by taking large doses of alprazolam during pregnancy.

PubMed

Gidai, J; Acs, N; Bánhidy, F; Czeizel, A E

2008-01-01

FDA has identified alprazolam, a new type of benzodiazepine, as pregnancy category D. The objective of this study was to evaluate the effects on fetal development of very large doses of alprazolam that were used for suicide attempts during pregnancy. Pregnant women were identified among the patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest, who were admitted as self-poisoned subjects from a total population of the three million people of Budapest and its surrounding region. Rates of congenital abnormalities, intrauterine fetal development, and cognitive-behavioral status were compared between children born to mothers who attempted suicide during pregnancy using alprazolam alone or in combination with other drugs and in their sib controls. Between 1984 and 1993, 559 pregnant women attempted suicide during pregnancy with drugs: 30 of these women self-poisoned with alprazolam, 10 delivered live-born infants who were examined. Doses of alprazolam used were between 7.5 and 100 mg, with a mean of 30 mg. Six of the 10 exposed children were born to mothers who attempted suicide between the 6th and 12th postconceptional weeks. Of the 10 exposed children, two had congenital abnormalities. One had a multiple congenital abnormality that included atypical gastroschisis and minor anomalies; an association of this defect and the 30 mg alprazolam used for self-poisoning in the 14th postconceptional week cannot be excluded. Another exposed child had mild pectus excavatum, but the times of the suicide attempt and the critical period for producing this defect did not overlap. Of 12 sibs, one had a multiple congenital abnormality. Thus, the rate of congenital abnormalities did not significantly differ between exposed children and their sibs. Mean birth weight was higher for babies born to mothers who attempted suicide by alprazolam during pregnancy than in their sib controls. Cognitive status and behavioral scale of the exposed children did not indicate fetotoxic effects, including neurotoxic effects, of large doses of alprazolam. The large doses of alprazolam used for self-poisoning during pregnancy did not result in a significantly higher rate of congenital abnormalities; however, there were only 10 self-poisoned pregnant women, and an association of one multiple congenital abnormality with a large dose of alprazolam cannot be excluded. The findings in this study did not identify fetotoxicity, including neurotoxicity, of very large doses of alprazolam. Our study shows that the self-poisoning model is feasible and provides beneficial information for use in estimating human teratogenic and fetotoxic risks of drugs.

A multiple translocation event in a patient with hexadactyly, facial dysmorphism, mental retardation and behaviour disorder characterised comprehensively by molecular cytogenetics. Case report and review of the literature.

PubMed

Seidel, Jörg; Heller, Anita; Senger, Gabriele; Starke, Heike; Chudoba, Ilse; Kelbova, Christina; Tönnies, Holger; Neitzel, Heidemarie; Haase, Claudia; Beensen, Volkmar; Zintl, Felix; Claussen, Uwe; Liehr, Thomas

2003-09-01

We report a 13-year-old female patient with multiple congenital abnormalities (microcephaly, facial dysmorphism, anteverted dysplastic ears and postaxial hexadactyly), mental retardation, and adipose-gigantism. Ultrasonography revealed no signs of a heart defect or renal abnormalities. She showed no speech development and suffered from a behavioural disorder. CNS abnormalities were excluded by cerebral MRI. Initial cytogenetic studies by Giemsa banding revealed an aberrant karyotype involving three chromosomes, t(2;4;11). By high resolution banding and multicolour fluoresence in-situ hybridisation (M-FISH, MCB), chromosome 1 was also found to be involved in the complex chromosomal aberrations, confirming the karyotype 46,XX,t(2;11;4).ish t(1;4;2;11)(q43;q21.1;p12-p13.1;p14.1). To the best of our knowledge no patient has been previously described with such a complex translocation involving 4 chromosomes. This case demonstrates that conventional chromosome banding techniques such as Giemsa banding are not always sufficient to characterise complex chromosomal abnormalities. Only by the additional utilisation of molecular cytogenetic techniques could the complexity of the present chromosomal rearrangements and the origin of the involved chromosomal material be detected. Further molecular genetic studies will be performed to clarify the chromosomal breakpoints potentially responsible for the observed clinical symptoms. This report demonstrates that multicolour-fluorescence in-situ hybridisation studies should be performed in patients with congenital abnormalities and suspected aberrant karyotypes in addition to conventional Giemsa banding.

Neuroimaging studies of social cognition in schizophrenia.

PubMed

Fujiwara, Hironobu; Yassin, Walid; Murai, Toshiya

2015-05-01

Impaired social cognition is considered a core contributor to unfavorable psychosocial functioning in schizophrenia. Rather than being a unitary process, social cognition is a collection of multifaceted processes that recruit multiple brain structures, thus structural and functional neuroimaging techniques are ideal methodologies for revealing the underlying pathophysiology of impaired social cognition. Many neuroimaging studies have suggested that in addition to white-matter deficits, schizophrenia is associated with decreased gray-matter volume in multiple brain areas, especially fronto-temporal and limbic regions. However, few schizophrenia studies have examined associations between brain abnormalities and social cognitive disabilities. During the last decade, we have investigated structural brain abnormalities in schizophrenia using high-resolution magnetic resonance imaging, and our findings have been confirmed by us and others. By assessing different types of social cognitive abilities, structural abnormalities in multiple brain regions have been found to be associated with disabilities in social cognition, such as recognition of facial emotion, theory of mind, and empathy. These structural deficits have also been associated with alexithymia and quality of life in ways that are closely related to the social cognitive disabilities found in schizophrenia. Here, we overview a series of neuroimaging studies from our laboratory that exemplify current research into this topic, and discuss how it can be further tackled using recent advances in neuroimaging technology. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Sensitivity of visual evoked potentials and spectral domain optical coherence tomography in early relapsing remitting multiple sclerosis.

PubMed

Behbehani, Raed; Ahmed, Samar; Al-Hashel, Jasem; Rousseff, Rossen T; Alroughani, Raed

2017-02-01

Visual evoked potentials and spectral-domain optical coherence tomography are common ancillary studies that assess the visual pathways from a functional and structural aspect, respectively. To compare prevalence of abnormalities of Visual evoked potentials (VEP) and spectral-domain optical coherence tomography (SDOCT) in patients with relapsing remitting multiple sclerosis (RRMS). A cross-sectional study of 100 eyes with disease duration of less than 5 years since the diagnosis. Correlation between retinal nerve fiber layer and ganglion-cell/inner plexiform layer with pattern-reversal visual evoked potentials amplitude and latency and contrast sensitivity was performed. The prevalence of abnormalities in pattern-reversal visual VEP was 56% while that of SOCT was 48% in all eyes. There was significant negative correlations between the average RNFL (r=-0.34, p=0.001) and GCIPL (r=-0.39, p<0.001) with VEP latency. In eyes with prior optic neuritis, a significant negative correlation was seen between average RNFL (r=-0.33, p=0.037) and GCIPL (r=-0.40, p=0.010) with VEP latency. We have found higher prevalence of VEP abnormalities than SCOCT in early relapsing-remitting multiple sclerosis. This suggests that VEP has a higher sensitivity for detecting lesions of the visual pathway in patients with early RRMS. Copyright © 2016 Elsevier B.V. All rights reserved.

Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6.

PubMed

Larson, Austin A; Balasubramaniam, Shanti; Christodoulou, John; Burrage, Lindsay C; Marom, Ronit; Graham, Brett H; Diaz, George A; Glamuzina, Emma; Hauser, Natalie; Heese, Bryce; Horvath, Gabriella; Mattman, Andre; van Karnebeek, Clara; Lane Rutledge, S; Williamson, Amy; Estrella, Lissette; Van Hove, Johan K L; Weisfeld-Adams, James D

2018-01-04

Elevations of specific acylcarnitines in blood reflect carboxylase deficiencies, and have utility in newborn screening for life-threatening organic acidemias and other inherited metabolic diseases. In this report, we describe a newly-identified association of biochemical features of multiple carboxylase deficiency in individuals harboring mitochondrial DNA (mtDNA) mutations in MT-ATP6 and in whom organic acidemias and multiple carboxylase deficiencies were excluded. Using retrospective chart review, we identified eleven individuals with abnormally elevated propionylcarnitine (C3) or hydroxyisovalerylcarnitine (C5OH) with mutations in MT-ATP6, most commonly m.8993T>G in high heteroplasmy or homoplasmy. Most patients were ascertained on newborn screening; most had normal enzymatic or molecular genetic testing to exclude biotinidase and holocarboxylase synthetase deficiencies. MT-ATP6 is associated with some cases of Leigh disease; clinical outcomes in our cohort ranged from death from neurodegenerative disease in early childhood to clinically and developmentally normal after several years of follow-up. These cases expand the biochemical phenotype associated with MT-ATP6 mutations, especially m.8993T>G, to include acylcarnitine abnormalities mimicking carboxylase deficiency states. Clinicians should be aware of this association and its implications for newborn screening, and consider mtDNA sequencing in patients exhibiting similar acylcarnitine abnormalities that are biotin-unresponsive and in whom other enzymatic deficiencies have been excluded. Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)—Patient Version

Cancer.gov

Plasma cell neoplasms occur when abnormal plasma cells or myeloma cells form tumors in the bones or soft tissues of the body. Multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are different types of plasma cell neoplasms. Find out about risk factors, symptoms, diagnostic tests, prognosis, and treatment for these diseases.

Assisting people with multiple disabilities actively correct abnormal standing posture with a Nintendo Wii balance board through controlling environmental stimulation.

PubMed

Shih, Ching-Hsiang; Shih, Ching-Tien; Chu, Chiung-Ling

2010-01-01

The latest researches adopted software technology turning the Nintendo Wii Balance Board into a high performance change of standing posture (CSP) detector, and assessed whether two persons with multiple disabilities would be able to control environmental stimulation using body swing (changing standing posture). This study extends Wii Balance Board functionality for standing posture correction (i.e., actively adjust abnormal standing posture) to assessed whether two persons with multiple disabilities would be able to actively correct their standing posture by controlling their favorite stimulation on/off using a Wii Balance Board with a newly developed standing posture correcting program (SPCP). The study was performed according to an ABAB design, in which A represented baseline and B represented intervention phases. Data showed that both participants significantly increased time duration of maintaining correct standing posture (TDMCSP) to activate the control system to produce environmental stimulation during the intervention phases. Practical and developmental implications of the findings were discussed.

The diagnostic value of earlier and later components of Vestibular Evoked Myogenic Potentials (VEMP) in multiple sclerosis.

PubMed

Eleftheriadou, A; Deftereos, S N; Zarikas, V; Panagopoulos, G; Sfetsos, S; Karageorgiou, C L; Ferekidou, E; Kandiloros, D; Korres, S

2009-01-01

To evaluate the ability of VEMP to disclose spatial dissemination of Multiple Sclerosis. Forty-six MS patients with auditory and/or vestibular symptoms were studied. Patients were divided in two groups. Group 1 included 24 patients with brainstem MRI findings, and Group 2 included 22 patients without MRI findings. VEMP and BAEP have been recorded and assessed. Abnormal p13n23 wave was observed in 50%, while unilateral absence or bilateral delay of the n34p44 in 43% of the patients. The overall diagnostic value considering abnormal cases suggested by both first and second VEMP waves was increased to 71%. Statistically significant differences revealed between patients and controls for p13 latency (p=0.018). The p13n23 was abnormal in 7 patients, although MRI scanning did not reveal brainstem lesions. In 9 out of 18 MS patients suffering from unilateral hearing loss, n34p44 was present in the unaffected ears and absent in the affected side, although p13n23 was normal. Abnormal VEMP imply the presence of lesions undetected by MRI neuroimaging, which verifies the diagnostic value of the method. Unilateral absence of n34p44 complex was related with sensorineural hearing loss, supporting the hypothesis that n34p44 is of cochlear origin.

Positive identification by a skull with multiple epigenetic traits and abnormal structure of the neurocranium, viscerocranium, and the skeleton.

PubMed

Kuharić, Josip; Kovacic, Natasa; Marusic, Petar; Marusic, Ana; Petrovecki, Vedrana

2011-05-01

Wormian bones are small ossicles appearing within the cranial sutures in more than 40% of skulls, most commonly at the lambdoid suture and pterion. During the skeletal analysis of an unidentified male war victim, we observed multiple wormian bones and a patent metopic suture. Additionally, the right elbow was deformed, probably as a consequence of an old trauma. The skull was analyzed by cranial measurements and computerized tomography, revealing the presence of cranial deformities including hyperbrachicrania, localized reduction in hemispheral widths, increased cranial capacity, and sclerosis of the viscerocranium. Besides unique anatomical features and their anthropological value, such skeletal abnormalities also have a forensic value as the evidence to support the final identification of the victim. © 2011 American Academy of Forensic Sciences.

tRNA and Its Activation Targets as Biomarkers and Regulators of Breast Cancer

DTIC Science & Technology

2013-09-01

linked tRNA misregulation to cancer. We have previously reported that tRNA levels are significantly elevated in breast cancer and multiple myeloma ...significantly elevated in breast cancer and multiple myeloma cells. To further investigate the cellular and physiological effects of tRNA overexpression, we...tRNA levels are elevated in breast cancer and multiple myeloma cell lines (Pavon-Eternod et al. 2009; Zhou et al. 2009). Though abnormal RNA polymerase

Going on with false beliefs: What if satisfaction of search was really suppression of recognition?

NASA Astrophysics Data System (ADS)

Mello-Thoms, Claudia; Trieu, Phuong Dung; Brennan, Patrick C.

2014-03-01

Satisfaction of search (SOS) is a well known phenomenon in radiology, in which the detection of one abnormality facilitates the neglect of other abnormalities. Over the years SOS has been thoroughly studied primarily in chest and in trauma, and it has been found to be an elusive effect, appearing in some settings but not in others. Unfortunately, very little is known about SOS in mammography. In this study we will explore SOS in breast cancer detection by considering a case set of digital mammograms as interpreted by breast radiologists. However, the primary goal of the study will be to challenge the core of the paradigm; for decades, many have associated SOS with incomplete search, but as Kundel has put eloquently when addressing the SPIE Medical Imaging in 2004 [1], "observers do not stop viewing when one abnormality has been found on an image with multiple abnormalities". What else could cause SOS then? According to our previous work, the first "perceived" abnormality reported by a radiologist has an influential role in the report of any other "perceived" abnormalities on the case, which supports the idea that perhaps SOS is caused a perceptual suppression of the recognition of different abnormalities. In other words, once the radiologist has made a first report (regardless of whether that first report is a TP or FP), detection and hence reporting of other abnormalities present in the case are greatly dependent on whether these associated abnormalities "fit the profile" of what has been already found.

Introduction to the special section: Myelin and oligodendrocyte abnormalities in schizophrenia.

PubMed

Haroutunian, Vahram; Davis, Kenneth L

2007-08-01

A central tenet of modern views of the neurobiology of schizophrenia is that the symptoms of schizophrenia arise from a failure of adequate communication between different brain regions and disruption of the circuitry that underlies behaviour and perception. Historically this disconnectivity syndrome has been approached from a neurotransmitter-based perspective. However, efficient communication between brain circuits is also contingent on saltatory signal propagation and salubrious myelination of axons. The papers in this Special Section examine the neuroanatomical and molecular biological evidence for abnormal myelination and oligodendroglial function in schizophrenia through studies of post-mortem brain tissue and animal model systems. The picture that emerges from the studies described suggests that although schizophrenia is not characterized by gross abnormalities of white matter such as those evident in multiple sclerosis, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths.

Assisting People with Multiple Disabilities Actively Correct Abnormal Standing Posture with a Nintendo Wii Balance Board through Controlling Environmental Stimulation

ERIC Educational Resources Information Center

Shih, Ching-Hsiang; Shih, Ching-Tien; Chu, Chiung-Ling

2010-01-01

The latest researches adopted software technology turning the Nintendo Wii Balance Board into a high performance change of standing posture (CSP) detector, and assessed whether two persons with multiple disabilities would be able to control environmental stimulation using body swing (changing standing posture). This study extends Wii Balance Board…

Microprocessor Based Real-Time Monitoring of Multiple ECG Signals

PubMed Central

Nasipuri, M.; Basu, D.K.; Dattagupta, R.; Kundu, M.; Banerjee, S.

1987-01-01

A microprocessor based system capable of realtime monitoring of multiple ECG signals has been described. The system consists of a number of microprocessors connected in a hierarchical fashion and capable of working concurrently on ECG data collected from different channels. The system can monitor different arrhythmic abnormalities for at least 36 patients even for a heart rate of 500 beats/min.

Non-mosaic tetrasomy 9p in a liveborn infant with multiple congenital anomalies: Case report and comparison with trisomy 9p

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

Leichtman, L.G.; Zackowski, J.L.; Storto, P.D.

1996-06-14

Tetrasomy of the short(p) arm of chromosome 9 has been reported in few cases. Most of these children present with microbrachycephaly, wide forehead, hypertelorism, lowset, malformed ears, beaked noses, and micrognathia. Additional anomalies include short neck, congenital heart disease, genital abnormalities, multiple limb defects, hypotonia, and early death.

PET/MRI of metabolic activity in osteoarthritis: A feasibility study.

PubMed

Kogan, Feliks; Fan, Audrey P; McWalter, Emily J; Oei, Edwin H G; Quon, Andrew; Gold, Garry E

2017-06-01

To evaluate positron emission tomography / magnetic resonance imaging (PET/MRI) knee imaging to detect and characterize osseous metabolic abnormalities and correlate PET radiotracer uptake with osseous abnormalities and cartilage degeneration observed on MRI. Both knees of 22 subjects with knee pain or injury were scanned at one timepoint, without gadolinium, on a hybrid 3.0T PET-MRI system following injection of 18 F-fluoride or 18 F-fluorodeoxyglucose (FDG). A musculoskeletal radiologist identified volumes of interest (VOIs) around bone abnormalities on MR images and scored bone marrow lesions (BMLs) and osteophytes using a MOAKS scoring system. Cartilage appearance adjacent to bone abnormalities was graded with MRI-modified Outerbridge classifications. On PET standardized uptake values (SUV) maps, VOIs with SUV greater than 5 times the SUV in normal-appearing bone were identified as high-uptake VOI (VOI High ). Differences in 18 F-fluoride uptake between bone abnormalities, BML, and osteophyte grades and adjacent cartilage grades on MRI were identified using Mann-Whitney U-tests. SUV max in all subchondral bone lesions (BML, osteophytes, sclerosis) was significantly higher than that of normal-appearing bone on MRI (P < 0.001 for all). Of the 172 high-uptake regions on 18 F-fluoride PET, 63 (37%) corresponded to normal-appearing subchondral bone on MRI. Furthermore, many small grade 1 osteophytes (40 of 82 [49%]), often described as the earliest signs of osteoarthritis (OA), did not show high uptake. Lastly, PET SUV max in subchondral bone adjacent to grade 0 cartilage was significantly lower compared to that of grades 1-2 (P < 0.05) and grades 3-4 cartilage (P < 0.001). PET/MRI can simultaneously assess multiple early metabolic and morphologic markers of knee OA across multiple tissues in the joint. Our findings suggest that PET/MR may detect metabolic abnormalities in subchondral bone, which appear normal on MRI. 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;45:1736-1745. © 2016 International Society for Magnetic Resonance in Medicine.

Duplication 12q24----qter in an infant with Dandy-Walker syndrome.

PubMed

MacDonald, E A; Holden, J J

1985-04-01

A boy with the Dandy-Walker syndrome associated with multiple congenital abnormalities is described. Chromosomal analyses revealed an abnormal chromosome 21, inherited from his father who had a balanced translocation involving chromosomes 12 and 21: rcp(12;21)(q24.1;q22.1). The clinical features of this patient are compared with published descriptions for duplication 12q24----qter and a review of the literature pertaining to chromosomal anomalies found in other patients with the Dandy-Walker syndrome is presented.

TREATMENT OF METABOLIC ALTERATIONS IN POLYCYSTIC OVARY SYNDROME.

PubMed

Păvăleanu, Ioana; Gafiţanu, D; Popovici, Diana; Duceac, Letiţia Doina; Păvăleanu, Maricica

2016-01-01

Polycystic ovary syndrome is a common endocrinopathy characterized by oligo ovulation or anovulation, signs of androgen excess and multiple small ovarian cysts. It includes various metabolic abnormalities: insulin resistance, hyperinsulinemia, impaired glucose tolerance, visceral obesity, inflammation and endothelial dysfunction, hypertension and dyslipidemia. All these metabolic abnormalities have long-term implications. Treatment should be individualized and must not address a single sign or symptom. Studies are still needed to determine the benefits and the associated risks of the medication now available to practitioners.

Genetic aberrations in multiple myeloma characterized by cIg-FISH: a Brazilian context

PubMed Central

Segges, P.; Braggio, E.; Minnicelli, C.; Hassan, R.; Zalcberg, I.R.; Maiolino, A.

2016-01-01

Genetic abnormalities are critical prognostic factors for patients diagnosed with multiple myeloma (MM). This retrospective, multicenter study aimed to contribute with the genetic and clinical characterization of MM patients in a country with continental dimensions such as Brazil. Genetic abnormalities were assessed by cIg-fluorescent in situ hybridization (cIg-FISH) in a series of 152 MM patients (median age 55 years, 58.5% men). Overall, genetic abnormalities were detected in 52.7% (80/152) of patients. A 14q32 rearrangement was detected in 33.5% (n=51), including t(11;14), t(4;14) and t(14;16) in 18.4, 14.1, and 1% of cases, respectively. del(13q) was identified in 42.7% (n=65) of patients, of whom 49.2% (32/65) presented a concomitant 14q32 rearrangement. del(17p) had a frequency of 5.2% (n=8). del(13q) was associated with high plasma cell burden (≥50%, P=0.02), and del(17p) with advanced ISS stages (P=0.05) and extramedullary disease (P=0.03). t(4;14) was associated with advanced Durie-Salmon stages (P=0.008), renal insufficiency (P=0.01) and was more common in patients over 60 years old. This study reports similar frequencies of genetic abnormalities to most series worldwide, whereas the t(14;16) and del(17p), two high risk factors for newly diagnosed patients, exhibited lower frequencies. Our results expand the knowledge on the molecular features of MM in Brazil, a country where innovative therapies that could overcome a poor prognosis for some genetic abnormalities are not always available. PMID:27074166

Genetic aberrations in multiple myeloma characterized by cIg-FISH: a Brazilian context.

PubMed

Segges, P; Braggio, E; Minnicelli, C; Hassan, R; Zalcberg, I R; Maiolino, A

2016-01-01

Genetic abnormalities are critical prognostic factors for patients diagnosed with multiple myeloma (MM). This retrospective, multicenter study aimed to contribute with the genetic and clinical characterization of MM patients in a country with continental dimensions such as Brazil. Genetic abnormalities were assessed by cIg-fluorescent in situ hybridization (cIg-FISH) in a series of 152 MM patients (median age 55 years, 58.5% men). Overall, genetic abnormalities were detected in 52.7% (80/152) of patients. A 14q32 rearrangement was detected in 33.5% (n=51), including t(11;14), t(4;14) and t(14;16) in 18.4, 14.1, and 1% of cases, respectively. del(13q) was identified in 42.7% (n=65) of patients, of whom 49.2% (32/65) presented a concomitant 14q32 rearrangement. del(17p) had a frequency of 5.2% (n=8). del(13q) was associated with high plasma cell burden (≥50%, P=0.02), and del(17p) with advanced ISS stages (P=0.05) and extramedullary disease (P=0.03). t(4;14) was associated with advanced Durie-Salmon stages (P=0.008), renal insufficiency (P=0.01) and was more common in patients over 60 years old. This study reports similar frequencies of genetic abnormalities to most series worldwide, whereas the t(14;16) and del(17p), two high risk factors for newly diagnosed patients, exhibited lower frequencies. Our results expand the knowledge on the molecular features of MM in Brazil, a country where innovative therapies that could overcome a poor prognosis for some genetic abnormalities are not always available.

The role of ICP monitoring in patients with persistent cerebrospinal fluid leak following spinal surgery: a case series.

PubMed

Craven, Claudia; Toma, Ahmed K; Khan, Akbar A; Watkins, Laurence D

2016-09-01

Cerebrospinal fluid (CSF) leak following spinal surgery is a relatively common surgical complication. A disturbance in the underlying CSF dynamics could be the causative factor in a small group of patients with refractory CSF leaks that require multiple surgical repairs and prolonged hospital admission. A retrospective case series of patients with persistent post spinal surgery CSF leak referred to the hydrocephalus service for continuous intracranial pressure (ICP) monitoring. Patients' notes were reviewed for medical history, ICP data, radiological data, and subsequent management and outcome. Five patients (two males/three females, mean age, 35.4 years) were referred for ICP monitoring over a 12-month period. These patients had prolonged CSF leak despite multiple repair attempts 252 ± 454 days (mean ± SD). On ICP monitoring, all five patients had abnormal results, with the mean ICP 8.95 ± 4.41 mmHg. Four had abnormal pulse amplitudes, mean 6.15 mmHg ± 1.22 mmHg. All five patients underwent an intervention. Three patients underwent insertion of ventriculoperitoneal (VP) shunts. One patient had venous sinus stent insertion and one patient underwent medical management with acetazolamide. All five of the patients' CSF leak resolved post intervention. The mean time to resolution of CSF leak post intervention was 10.8  ± 12.9 days. Abnormal cerebrospinal fluid dynamics could be the underlying factor in patients with a persistent and treatment-refractory CSF leak post spinal surgery. Treatments aimed at lowering ICP may be beneficial in this group of patients. Whether abnormal pressure and dynamics represent a pre-existing abnormality or is induced by spinal surgery should be a subject of further study.

Deficits in Neurite Density Underlie White Matter Structure Abnormalities in First-Episode Psychosis.

PubMed

Rae, Charlotte L; Davies, Geoff; Garfinkel, Sarah N; Gabel, Matt C; Dowell, Nicholas G; Cercignani, Mara; Seth, Anil K; Greenwood, Kathryn E; Medford, Nick; Critchley, Hugo D

2017-11-15

Structural abnormalities across multiple white matter tracts are recognized in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterize microstructural white matter abnormalities for a deeper understanding of the developmental etiology of psychosis. Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using neurite orientation dispersion and density imaging, a multishell diffusion-weighted magnetic resonance imaging technique that distinguishes white matter fiber arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and control subjects and tested associations with age, symptom severity, and medication. Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fiber bundle arrangement (orientation dispersion index). There was no direct relationship with active symptoms. FA decreased and orientation dispersion index increased with age in patients, but not control subjects, suggesting accelerated effects of white matter geometry change. Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of neurite orientation dispersion and density imaging in psychosis, we found that processes compromising axonal fiber number, density, and myelination, rather than processes leading to spatial disruption of fiber organization, are implicated in the etiology of psychosis. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to psychosis. Copyright © 2017 Society of Biological Psychiatry. All rights reserved.

Multiple Myeloma

MedlinePlus

... a type of white blood cell called a plasma cell. Plasma cells help you fight infections by making antibodies ... Doctors know that myeloma begins with one abnormal plasma cell in your bone marrow — the soft, blood- ...

Reproducibility patterns of multiple rapid swallows during high resolution esophageal manometry provide insights into esophageal pathophysiology.

PubMed

Price, L H; Li, Y; Patel, A; Gyawali, C Prakash

2014-05-01

Multiple rapid swallows (MRS) during esophageal high resolution manometry (HRM) assess esophageal neuromuscular integrity by evaluating postdeglutitive inhibition and rebound contraction, but most reports performed only a single MRS sequence. We assessed patterns of MRS reproducibility during clinical HRM in comparison to a normal cohort. Consecutive clinical HRM studies were included if two separate MRS sequences (four to six rapid swallows ≤4 s apart) were successfully performed. Chicago Classification diagnoses were identified; contraction wave abnormalities were additionally recorded. MRS-induced inhibition (contraction ≤3 cm during inhibition phase) and rebound contraction was assessed, and findings compared to 18 controls (28.0 ± 0.7 year, 50.0% female). Reproducibility consisted of similar inhibition and contraction responses with both sequences; discordance was segregated into inhibition and contraction phases. Multiple rapid swallows were successfully performed in 89.3% patients and all controls; 225 subjects (56.2 ± 0.9 year, 62.7% female) met study inclusion criteria. Multiple rapid swallows were reproducible in 76.9% patients and 94.4% controls (inhibition phase: 88.0% vs 94.4%, contraction phase 86.7% vs 100%, respectively, p = ns). A gradient of reproducibility was noted, highest in well-developed motor disorders (achalasia spectrum, hypermotility disorders, and aperistalsis, 91.7-100%, p = ns compared to controls); and lower in lesser motor disorders (contraction wave abnormalities, esophageal body hypomotility) or normal studies (62.2-70.8%, p < 0.0001 compared to well-developed motor disorders). Inhibition phase was most discordant in contraction wave abnormalities, while contraction phase was most discordant when studies were designated normal. Multiple rapid swallows are highly reproducible, especially in well-developed motor disorders, and complement the standard wet swallow manometry protocol. © 2014 John Wiley & Sons Ltd.

Gorlin syndrome and bilateral ovarian fibroma

PubMed Central

Pirschner, Fernanda; Bastos, Pollyana Marçal; Contarato, George Luiz; Bimbato, Anna Carolina Bon Lima; Filho, Antônio Chambô

2012-01-01

INTRODUCTION Gorlin syndrome (GS), also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare hereditary, autosomal dominant disease that affects various systems. Its prevalence is estimated at 1/57,000 to 1/256,000 of the population. It is characterized by basal cell carcinomas, multiple odontogenic keratocysts, skeletal abnormalities and ovarian fibroma, among other disorders. PRESENTATION OF CASE To report the case of a young patient with Gorlin syndrome and bilateral ovarian fibroma. DISCUSSION A 20-year old patient with Gorlin syndrome presented with facial asymmetry, broad nasal root, dental abnormalities, micrognathism, convergent strabismus, multiple pigmented lesions on the trunk and face, pectus excavatum, kyphoscoliosis and a palpable mass in the abdomen occupying the entire pelvic region. CONCLUSION Gorlin–Goltz syndrome is a hereditary pathology that includes numerous clinical manifestations. Diagnosis is clinical and genetic confirmation is unnecessary. PMID:22771908

Levamisole-Adulterated Cocaine-Induced Skin Lesions: A Case Report and Literature Review.

PubMed

Khanapara, Dipen B; Panwala, Amruta; Dedania, Bhavtosh; Naut, Edgar R

2017-02-01

Levamisole is used as an agent to increase the total weight of street cocaine. We report the case of a 28-year-old female who presented with multiple painful, ulcerating lesions. She tested positive for cocaine and levamisole. Her skin lesions improved with abstinence from cocaine. Patients with levamisole-induced toxicity most often present with skin manifestations or joint pain. Leukopenia, neutropenia, and agranulocytosis are common lab abnormalities seen in these patients. Complete resolution of the skin lesions are observed approximatelythree weeks after abstinence. Patients known to use street drugs, who present with unexplained skin rash, neutropenia, and multiple immunological abnormalities, should be tested for both cocaine and levamisole. Urine toxicology screen is positive for cocaine approximately 72 hours after ingestion. Levamisole requires specialized testing that is not readily available commercially andis positive forless than 48 hours after exposure.

Chromosomal Abnormalities Are Major Prognostic Factors in Elderly Patients With Multiple Myeloma: The Intergroupe Francophone du Myélome Experience

PubMed Central

Avet-Loiseau, Hervé; Hulin, Cyrille; Campion, Loic; Rodon, Philippe; Marit, Gerald; Attal, Michel; Royer, Bruno; Dib, Mamoun; Voillat, Laurent; Bouscary, Didier; Caillot, Denis; Wetterwald, Marc; Pegourie, Brigitte; Lepeu, Gerard; Corront, Bernadette; Karlin, Lionel; Stoppa, Anne-Marie; Fuzibet, Jean-Gabriel; Delbrel, Xavier; Guilhot, Francois; Kolb, Brigitte; Decaux, Olivier; Lamy, Thierry; Garderet, Laurent; Allangba, Olivier; Lifermann, Francois; Anglaret, Bruno; Moreau, Philippe; Harousseau, Jean-Luc; Facon, Thierry

2013-01-01

Purpose Chromosomal abnormalities, especially t(4;14) and del(17p), are major prognostic factors in patients with multiple myeloma (MM). However, this has been especially demonstrated in patients age < 66 years treated with intensive approaches. The goal of this study was to address this issue in elderly patients treated with conventional-dose chemotherapy. Patients and Methods To answer this important question, we retrospectively analyzed a series of 1,890 patients (median age, 72 years; range, 66 to 94 years), including 1,095 with updated data on treatment modalities and survival. Results This large study first showed that the incidence of t(4;14) was not uniform over age, with a marked decrease in the oldest patients. Second, it showed that both t(4;14) and del(17p) retained their prognostic value in elderly patients treated with melphalan and prednisone–based chemotherapy. Conclusion t(4;14) and del(17p) are major prognostic factors in elderly patients with MM, both for progression-free and overall survival, indicating that these two abnormalities should be investigated at diagnosis of MM, regardless of age. PMID:23796999

A newborn with trisomy 13 who had tetralogy of Fallot and metopic synostosis: Case report.

PubMed

Karabel, M; Yolbaş, I; Kelekçi, S; Sen, V; Haspolat, Yk; Timuroğlu, L

2013-07-01

Trisomy 13 (Patau syndrome) was first described by Patau et al in 1960. It is characterized by serious head, facial, and extremity anomalies, congenital heart defects, and mental abnormalities. The incidence rate of Trisomy 13 is 1/10.000 live births. Accompanying symptoms and findings vary in rate and severity among the cases. Tetralogy of Fallot and metopic synostosis are very rare abnormalities in patients with Trisomy 13. In this study, we aimed to present a newborn girl with trisomy 13 who had multiple congenital malformations accompanied by tetralogy of Fallot and metopic synostosis. Description of the case: The patient was delivered at 40 weeks of gestation, and admitted to the neonatal intensive care unit due to respiratory distress and physical abnormalities. The newborn examination revealed multiple dysmorphic features. She had boot-shaped appearance on the chest radiograph. Chromosome analysis demonstrated mosaic trisomy 13. Patients with trisomy 13 may have different type of gene variations and malformations; however, the most common type of gene variation is classic trisomy 47, XX +13, and the most common malformations are facial anomalies and congenital heart defects. In addition, tetralogy of Fallot and metopic synostosis may accompany trisomy 13.

Morphological abnormalities of embryonic cranial nerves after in utero exposure to valproic acid: implications for the pathogenesis of autism with multiple developmental anomalies.

PubMed

Tashiro, Yasura; Oyabu, Akiko; Imura, Yoshio; Uchida, Atsuko; Narita, Naoko; Narita, Masaaki

2011-06-01

Autism is often associated with multiple developmental anomalies including asymmetric facial palsy. In order to establish the etiology of autism with facial palsy, research into developmental abnormalities of the peripheral facial nerves is necessary. In the present study, to investigate the development of peripheral cranial nerves for use in an animal model of autism, rat embryos were treated with valproic acid (VPA) in utero and their cranial nerves were visualized by immunostaining. Treatment with VPA after embryonic day 9 had a significant effect on the peripheral fibers of several cranial nerves. Following VPA treatment, immunoreactivity within the trigeminal, facial, glossopharyngeal and vagus nerves was significantly reduced. Additionally, abnormal axonal pathways were observed in the peripheral facial nerves. Thus, the morphology of several cranial nerves, including the facial nerve, can be affected by prenatal VPA exposure as early as E13. Our findings indicate that disruption of early facial nerve development is involved in the etiology of asymmetric facial palsy, and may suggest a link to the etiology of autism. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Variation in the levels of pregnancy-specific beta-1-glycoprotein in maternal serum from chromosomally abnormal pregnancies.

PubMed

Graham, G W; Crossley, J A; Aitken, D A; Connor, J M

1992-06-01

Human pregnancy-specific beta-1-glycoprotein (SP1) was assayed retrospectively in stored maternal serum (MS) samples from 82 chromosomally abnormal pregnancies and 377 matched controls. The median MSSP1 concentration in 48 Down's syndrome pregnancies was significantly elevated at 1.17 multiples of the control median (MOM), and significantly reduced (0.5 MOM) in a group of eight cases of unbalanced translocations. There was no significant difference in median SP1 concentrations in cases of trisomy 18, trisomy 13, balanced translocations, or sex chromosome abnormalities. A comparison with human chorionic gonadotrophin results in the same series of samples indicates that SP1 is a less sensitive predictor of Down's syndrome pregnancies.

High resolution manometry findings in patients with esophageal epiphrenic diverticula.

PubMed

Vicentine, Fernando P P; Herbella, Fernando A M; Silva, Luciana C; Patti, Marco G

2011-12-01

The pathophysiology of esophageal epiphrenic diverticula is still uncertain even though a concomitant motility disorder is found in the majority of patients in different series. High resolution manometry may allow detection of motor abnormalities in a higher number of patients with esophageal epiphrenic diverticula compared with conventional manometry. This study aims to evaluate the high resolution manometry findings in patients with esophageal epiphrenic diverticula. Nine individuals (mean age 63 ± 10 years, 4 females) with esophageal epiphrenic diverticula underwent high resolution manometry. A single diverticulum was observed in eight patients and multiple diverticula in one. Visual analysis of conventional tracings and color pressure plots for identification of segmental abnormalities was performed by two researchers experienced in high resolution manometry. Upper esophageal sphincter was normal in all patients. Esophageal body was abnormal in eight patients; lower esophageal sphincter was abnormal in seven patients. Named esophageal motility disorders were found in seven patients: achalasia in six, diffuse esophageal spasm in one. In one patient, a segmental hypercontractile zone was noticed with pressure of 196 mm Hg. High resolution manometry demonstrated motor abnormalities in all patients with esophageal epiphrenic diverticula.

[Impact analysis of shuxuetong injection on abnormal changes of ALT based on generalized boosted models propensity score weighting].

PubMed

Yang, Wei; Yi, Dan-Hui; Xie, Yan-Ming; Yang, Wei; Dai, Yi; Zhi, Ying-Jie; Zhuang, Yan; Yang, Hu

2013-09-01

To estimate treatment effects of Shuxuetong injection on abnormal changes on ALT index, that is, to explore whether the Shuxuetong injection harms liver function in clinical settings and to provide clinical guidance for its safe application. Clinical information of traditional Chinese medicine (TCM) injections is gathered from hospital information system (HIS) of eighteen general hospitals. This is a retrospective cohort study, using abnormal changes in ALT index as an outcome. A large number of confounding biases are taken into account through the generalized boosted models (GBM) and multiple logistic regression model (MLRM) to estimate the treatment effects of Shuxuetong injections on abnormal changes in ALT index and to explore possible influencing factors. The advantages and process of application of GBM has been demonstrated with examples which eliminate the biases from most confounding variables between groups. This serves to modify the estimation of treatment effects of Shuxuetong injection on ALT index making the results more reliable. Based on large scale clinical observational data from HIS database, significant effects of Shuxuetong injection on abnormal changes in ALT have not been found.

Factitious Graves' Disease Due to Biotin Immunoassay Interference-A Case and Review of the Literature.

PubMed

Elston, Marianne S; Sehgal, Shekhar; Du Toit, Stephen; Yarndley, Tania; Conaglen, John V

2016-09-01

Biotin (vitamin B7) is an essential co-factor for four carboxylases involved in fatty acid metabolism, leucine degradation, and gluconeogenesis. The recommended daily intake (RDI) of biotin is approximately 30 μg per day. Low-moderate dose biotin is a common component of multivitamin preparations, and high-dose biotin (10 000 times RDI) has been reported to improve clinical outcomes and quality of life in patients with progressive multiple sclerosis. Biotin is also a component of immunoassays, and supplementation may cause interference in both thyroid and non-thyroid immunoassays. To assess whether biotin ingestion caused abnormal thyroid function tests (TFTs) in a patient through assay interference. We report a patient with biotin-associated abnormal TFTs and a systematic review of the literature. A tertiary endocrine service in Hamilton, New Zealand. The patient had markedly abnormal TFTs that did not match the clinical context. After biotin cessation, TFTs normalized far more rapidly than possible given the half-life of T4, consistent with assay interference by biotin. Multiple other analytes also tested abnormal in the presence of biotin. Biotin ingested in moderate to high doses can cause immunoassay interference. Depending on the assay format, biotin interference can result in either falsely high or low values. Interference is not limited to thyroid tests and has the potential to affect a wide range of analytes. It is important for clinicians to be aware of this interaction to prevent misdiagnosis and inappropriate treatment.

Distinctive Menkes disease variant with occipital horns: Delineation of natural history and clinical phenotype

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

Proud, V.K.; Mussell, H.G.; Percy, A.K.

1996-10-02

To delineate further the clinical spectrum of Menkes disease, an X-linked recessive disorder of copper transport, we studied 4 related males, ranging in age from 4-38 years, with a unique phenotype that combines manifestations of classical and mild Menkes disease and occipital horn syndrome (OHS). The propositus, an 18-year-old man, was evaluated following an intracerebral hemorrhage at age 15 years and was noted to have marked hypotonia, motor delay with mental retardation, bladder diverticula, failure to thrive, and diarrhea from infancy; seizures from age 3 years; and abnormal hair (pili torti) and face, cutis laxa, and multiple joint dislocations. Radiographicmore » abnormalities included occipital exostoses, tortuous cerebral blood vessels with multiple branch occlusions, and hammer-shaped clavicles. Biochemical studies demonstrated reduced copper and ceruloplasmin levels in serum, and abnormal plasma catecholamine ratios. We reported previously the molecular defect in this family, a splice-site mutation that predicts formation of approximately 20% of the normal Menkes gene product. Here, we detail the clinical course and physical features and radiographic findings in these 4 individuals, and compare their phenotype with classical and mild Menkes and OHS. Unusual Menkes disease variants such as this may escape recognition due to anomalies that appear inconsistent with the diagnosis, particularly prolonged survival and later onset of seizures. Males with mental retardation and connective tissue abnormalities should be evaluated for biochemical evidence of defective copper transport. 28 refs., 8 figs.« less

Abnormal center-periphery gradient in spatial attention in simultanagnosia.

PubMed

Balslev, Daniela; Odoj, Bartholomaeus; Rennig, Johannes; Karnath, Hans-Otto

2014-12-01

Patients suffering from simultanagnosia cannot perceive more than one object at a time. The underlying mechanism is incompletely understood. One hypothesis is that simultanagnosia reflects "tunnel vision," a constricted attention window around gaze, which precludes the grouping of individual objects. Although this idea has a long history in neuropsychology, the question whether the patients indeed have an abnormal attention gradient around the gaze has so far not been addressed. Here we tested this hypothesis in two simultanagnosia patients with bilateral parieto-occipital lesions and two control groups, with and without brain damage. We assessed the participants' ability to discriminate letters presented briefly at fixation with and without a peripheral distractor or in the visual periphery, with or without a foveal distractor. A constricted span of attention around gaze would predict an increased susceptibility to foveated versus peripheral distractors. Contrary to this prediction and unlike both control groups, the patients' ability to discriminate the target decreased more in the presence of peripheral compared with foveated distractors. Thus, the attentional spotlight in simultanagnosia does not fall on foveated objects as previously assumed, but rather abnormally highlights the periphery. Furthermore, we found the same center-periphery gradient in the patients' ability to recognize multiple objects. They detected multiple, but not single objects more accurately in the periphery than at fixation. These results suggest that an abnormal allocation of attention around the gaze can disrupt the grouping of individual objects into an integrated visual scene.

Long-term Renal Function in Living Kidney Donors Who Had Histological Abnormalities at Donation.

PubMed

Fahmy, Lara M; Massie, Allan B; Muzaale, Abimereki D; Bagnasco, Serena M; Orandi, Babak J; Alejo, Jennifer L; Boyarsky, Brian J; Anjum, Saad K; Montgomery, Robert A; Dagher, Nabil N; Segev, Dorry L

2016-06-01

Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5-8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73 m decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (P < 0.01). In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, whereas no other subclinical histological abnormalities provided additional information.

Long-Term Renal Function in Living Kidney Donors who had Histological Abnormalities at Donation

PubMed Central

Fahmy, Lara M.; Massie, Allan B.; Muzaale, Abimereki D.; Bagnasco, Serena M.; Orandi, Babak J.; Alejo, Jennifer L.; Boyarsky, Brian J.; Anjum, Saad K.; Montgomery, Robert A.; Dagher, Nabil N.; Segev, Dorry L.

2016-01-01

Background Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. Methods We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Results Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5–8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73m2 decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (p<0.01). Conclusions In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, while no other subclinical histological abnormalities provided additional information. PMID:27152920

Variable Association between Components of the Metabolic Syndrome and Electrocardiographic Abnormalities in Korean Adults

PubMed Central

Kim, Chul-Hee; Ko, Kwan-Ho; Park, Seong-Wook; Park, Joong-Yeol; Lee, Ki-Up

2010-01-01

Background/Aims Resting electrocardiogram (ECG) abnormalities have been strongly associated with cardiovascular disease mortality. Little is known, however, about the association between individual components of metabolic syndrome and ECG abnormalities, especially in Asian populations. Methods We examined clinical and laboratory data from 31,399 subjects (age 20 to 89 years) who underwent medical check-ups. ECG abnormalities were divided into minor and major abnormalities based on Novacode criteria. Ischemic ECG findings were separately identified and analyzed. Results The overall prevalence rates of ECG abnormalities were significantly higher in subjects with than in those without metabolic syndrome (p < 0.01). Ischemic ECG was strongly associated with metabolic syndrome in all age groups of both sexes, except for younger women. In multiple logistic regression analysis, metabolic syndrome was independently associated with ischemic ECG (odds ratio, 2.30 [2.04 to 2.62]; p < 0.01), after adjusting for sex, age, smoking, and family history of cardiovascular disease. Of the metabolic syndrome components, hyperglycemia in younger subjects and hypertension in elderly subjects were major factors for ischemic ECG changes, whereas hypertriglyceridemia was not an independent risk factor in any age group. The association between ischemic ECG findings and central obesity was weaker in women than in men. Conclusions Metabolic syndrome was strongly associated with ECG abnormalities, especially ischemic ECG findings, in Koreans. The association between each component of metabolic syndrome and ECG abnormalities varied according to age and sex. PMID:20526391

Retinal architecture and mfERG: Optic nerve head component response characteristics in MS.

PubMed

Schnurman, Zane S; Frohman, Teresa C; Beh, Shin C; Conger, Darrel; Conger, Amy; Saidha, Shiv; Galetta, Steven; Calabresi, Peter A; Green, Ari J; Balcer, Laura J; Frohman, Elliot M

2014-05-27

To describe a novel neurophysiologic signature of the retinal ganglion cell and to elucidate its relationship to abnormalities in validated structural and functional measures of the visual system. We used multifocal electroretinogram-generated optic nerve head component (ONHC) responses from normal subjects (n = 18), patients with multiple sclerosis (MS) (n = 18), and those with glaucoma (n = 3). We then characterized the relationship between ONHC response abnormalities and performance on low-contrast visual acuity, multifocal visual-evoked potential-induced cortical responses, and average and quadrant retinal nerve fiber layer (RNFL) thicknesses, as measured by spectral-domain optical coherence tomography. Compared with the eyes of normal subjects, the eyes of patients with MS exhibited an increased number of abnormal or absent ONHC responses (p < 0.0001). For every 7-letter reduction in low-contrast letter acuity, there were corresponding 4.6 abnormal ONHC responses at 2.5% contrast (p < 0.0001) and 6.6 abnormalities at the 1.25% contrast level (p < 0.0001). Regarding average RNFL thickness, for each 10-μm thickness reduction, we correspondingly observed 6.8 abnormal ONHC responses (p = 0.0002). The most robust association was between RNFL thinning in the temporal quadrant and ONHC response abnormalities (p < 0.0001). Further characterization of ONHC abnormalities (those that are reversible and irreversible) may contribute to the development of novel neurotherapeutic strategies aimed at achieving neuroprotective, and perhaps even neurorestorative, effects in disorders that target the CNS in general, and MS in particular. © 2014 American Academy of Neurology.

Use Massive Parallel Sequencing and Exome Capture Technology to Sequence the Exome of Fanconi Anemia Children and Their Patents

ClinicalTrials.gov

2013-11-21

Fanconi Anemia; Autosomal or Sex Linked Recessive Genetic Disease; Bone Marrow Hematopoiesis Failure, Multiple Congenital Abnormalities, and Susceptibility to Neoplastic Diseases.; Hematopoiesis Maintainance.

Smoldering Multiple Myeloma

PubMed Central

Gao, Minjie; Yang, Guang; Kong, Yuanyuan; Wu, Xiaosong; Shi, Jumei

2015-01-01

Smoldering multiple myeloma (SMM) is an asymptomatic precursor stage of multiple myeloma (MM) characterized by clonal bone marrow plasma cells (BMPC) ≥ 10% and/or M protein level ≥ 30 g/L in the absence of end organ damage. It represents an intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and symptomatic MM. The risk of progression to symptomatic MM is not uniform, and several parameters have been reported to predict the risk of progression. These include the level of M protein and the percentage of BMPC, the proportion of immunophenotypically aberrant plasma cells, and the presence of immunoparesis, free light-chain (FLC) ratio, peripheral blood plasma cells (PBPC), pattern of serum M protein evolution, abnormal magnetic resonance imaging (MRI), cytogenetic abnormalities, IgA isotype, and Bence Jones proteinuria. So far treatment is still not recommended for SMM, because several trials suggested that patients with SMM do not benefit from early treatment. However, the Mateos et al. trial showed a survival benefit after early treatment with lenalidomide plus dexamethasone in patients with high-risk SMM. This trial has prompted a reevaluation of early treatment in an asymptomatic patient population. PMID:26000300

The first Korean patient with Potocki-Shaffer syndrome: a rare cause of multiple exostoses.

PubMed

Sohn, Young Bae; Yim, Shin-Young; Cho, Eun-Hae; Kim, Ok-Hwa

2015-02-01

Potocki-Shaffer syndrome (PSS, OMIM #601224) is a rare contiguous gene deletion syndrome caused by haploinsufficiency of genes located on the 11p11.2p12. Affected individuals have a number of characteristic features including multiple exostoses, biparietal foramina, abnormalities of genitourinary system, hypotonia, developmental delay, and intellectual disability. We report here on the first Korean case of an 8-yr-old boy with PSS diagnosed by high resolution microarray. Initial evaluation was done at age 6 months because of a history of developmental delay, hypotonia, and dysmorphic face. Coronal craniosynostosis and enlarged parietal foramina were found on skull radiographs. At age 6 yr, he had severe global developmental delay. Multiple exostoses of long bones were detected during a radiological check-up. Based on the clinical and radiological features, PSS was highly suspected. Subsequently, chromosomal microarray analysis identified an 8.6 Mb deletion at 11p11.2 [arr 11p12p11.2 (Chr11:39,204,770-47,791,278)×1]. The patient continued rehabilitation therapy for profound developmental delay. The progression of multiple exostosis has being monitored. This case confirms and extends data on the genetic basis of PSS. In clinical and radiologic aspect, a patient with multiple exostoses accompanying with syndromic features, including craniofacial abnormalities and mental retardation, the diagnosis of PSS should be considered.

Factors associated with abnormal eating attitudes among Greek adolescents.

PubMed

Bilali, Aggeliki; Galanis, Petros; Velonakis, Emmanuel; Katostaras, Theofanis

2010-01-01

To estimate the prevalence of abnormal eating attitudes among Greek adolescents and identify possible risk factors associated with these attitudes. Cross-sectional, school-based study. Six randomly selected schools in Patras, southern Greece. The study population consisted of 540 Greek students aged 13-18 years, and the response rate was 97%. The dependent variable was scores on the Eating Attitudes Test-26, with scores > or = 20 indicating abnormal eating attitudes. Bivariate analysis included independent Student t test, chi-square test, and Fisher's exact test. Multivariate logistic regression analysis was applied for the identification of the predictive factors, which were associated independently with abnormal eating attitudes. A 2-sided P value of less than .05 was considered statistically significant. The prevalence of abnormal eating attitudes was 16.7%. Multivariate logistic regression analysis demonstrated that females, urban residents, and those with a body mass index outside normal range, a perception of being overweight, body dissatisfaction, and a family member on a diet were independently related to abnormal eating attitudes. The results indicate that a proportion of Greek adolescents report abnormal eating attitudes and suggest that multiple factors contribute to the development of these attitudes. These findings are useful for further research into this topic and would be valuable in designing preventive interventions. Copyright 2010 Society for Nutrition Education. Published by Elsevier Inc. All rights reserved.

Abnormal anal cytology risk in women with known genital squamous intraepithelial lesion.

PubMed

do Socorro Nobre, Maria; Jacyntho, Claudia Marcia; Eleutério, José; Giraldo, Paulo César; Gonçalves, Ana Katherine

2016-01-01

The purpose of this study was to assess the risk of abnormal anal cytology in women with known genital squamous intraepithelial lesion. This study evaluated 200 women with and without genital squamous intraepithelial lesion who were recruited for anal Pap smears. Women who had abnormal results on equally or over atypical squamous cells of undetermined significance were classified as having abnormal anal cytology. A multiple logistic regression analysis (stepwise) was performed to identify the risk for developing abnormal anal cytology. Data were analyzed using the SPSS 20.0 program. The average age was 41.09 (±12.64). Of the total participants, 75.5% did not practice anal sex, 91% did not have HPV-infected partners, 92% did not have any anal pathology, and 68.5% did not have anal bleeding. More than half (57.5%) had genital SIL and a significant number developed abnormal anal cytology: 13% in the total sample and 17.4% in women with genital SIL. A significant association was observed between genital squamous intraepithelial lesion and anal squamous intraepithelial lesion (PR=2.46; p=0.03). In the logistic regression model, women having genital intraepithelial lesion were more likely to have abnormal anal Pap smear (aPR=2.81; p=0.02). This report shows that women with genital squamous intraepithelial lesion must be more closely screened for anal cancer. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

The association between reduced knee joint proprioception and medial meniscal abnormalities using MRI in knee osteoarthritis: results from the Amsterdam osteoarthritis cohort.

PubMed

van der Esch, M; Knoop, J; Hunter, D J; Klein, J-P; van der Leeden, M; Knol, D L; Reiding, D; Voorneman, R E; Gerritsen, M; Roorda, L D; Lems, W F; Dekker, J

2013-05-01

Osteoarthritis (OA) of the knee is characterized by pain and activity limitations. In knee OA, proprioceptive accuracy is reduced and might be associated with pain and activity limitations. Although causes of reduced proprioceptive accuracy are divergent, medial meniscal abnormalities, which are highly prevalent in knee OA, have been suggested to play an important role. No study has focussed on the association between proprioceptive accuracy and meniscal abnormalities in knee OA. To explore the association between reduced proprioceptive accuracy and medial meniscal abnormalities in a clinical sample of knee OA subjects. Cross-sectional study in 105 subjects with knee OA. Knee proprioceptive accuracy was assessed by determining the joint motion detection threshold in the knee extension direction. The knee was imaged with a 3.0 T magnetic resonance (MR) scanner. Number of regions with medial meniscal abnormalities and the extent of abnormality in the anterior and posterior horn and body were scored according to the Boston-Leeds Osteoarthritis Knee Score (BLOKS) method. Multiple regression analyzes were used to examine whether reduced proprioceptive accuracy was associated with medial meniscal abnormalities in knee OA subjects. Mean proprioceptive accuracy was 2.9° ± 1.9°. Magnetic resonance imaging (MRI)-detected medial meniscal abnormalities were found in the anterior horn (78%), body (80%) and posterior horn (90%). Reduced proprioceptive accuracy was associated with both the number of regions with meniscal abnormalities (P < 0.01) and the extent of abnormality (P = 0.02). These associations were not confounded by muscle strength, joint laxity, pain, age, gender, body mass index (BMI) and duration of knee complaints. This is the first study showing that reduced proprioceptive accuracy is associated with medial meniscal abnormalities in knee OA. The study highlights the importance of meniscal abnormalities in understanding reduced proprioceptive accuracy in persons with knee OA. Copyright © 2013 Osteoarthritis Research Society International. All rights reserved.

Focal neurological deficits

MedlinePlus

... include: Abnormal blood vessels (vascular malformation) Brain tumor Cerebral palsy Degenerative nerve illness (such as multiple sclerosis) Disorders of a single nerve or nerve group (for example, carpal tunnel syndrome ) Infection of the brain (such as meningitis or encephalitis) Injury Stroke Home ...

Gorlin syndrome and bilateral ovarian fibroma.

PubMed

Pirschner, Fernanda; Bastos, Pollyana Marçal; Contarato, George Luiz; Bimbato, Anna Carolina Bon Lima; Filho, Antônio Chambô

2012-01-01

Gorlin syndrome (GS), also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare hereditary, autosomal dominant disease that affects various systems. Its prevalence is estimated at 1/57,000 to 1/256,000 of the population. It is characterized by basal cell carcinomas, multiple odontogenic keratocysts, skeletal abnormalities and ovarian fibroma, among other disorders. To report the case of a young patient with Gorlin syndrome and bilateral ovarian fibroma. A 20-year old patient with Gorlin syndrome presented with facial asymmetry, broad nasal root, dental abnormalities, micrognathism, convergent strabismus, multiple pigmented lesions on the trunk and face, pectus excavatum, kyphoscoliosis and a palpable mass in the abdomen occupying the entire pelvic region. Gorlin-Goltz syndrome is a hereditary pathology that includes numerous clinical manifestations. Diagnosis is clinical and genetic confirmation is unnecessary. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

The Spine in Patients With Osteogenesis Imperfecta.

PubMed

Wallace, Maegen J; Kruse, Richard W; Shah, Suken A

2017-02-01

Osteogenesis imperfecta is a genetic disorder of type I collagen. Although multiple genotypes and phenotypes are associated with osteogenesis imperfecta, approximately 90% of the mutations are in the COL1A1 and COL1A2 genes. Osteogenesis imperfecta is characterized by bone fragility. Patients typically have multiple fractures or limb deformity; however, the spine can also be affected. Spinal manifestations include scoliosis, kyphosis, craniocervical junction abnormalities, and lumbosacral pathology. The incidence of lumbosacral spondylolysis and spondylolisthesis is higher in patients with osteogenesis imperfecta than in the general population. Use of diphosphonates has been found to decrease the rate of progression of scoliosis in patients with osteogenesis imperfecta. A lateral cervical radiograph is recommended in patients with this condition before age 6 years for surveillance of craniocervical junction abnormalities, such as basilar impression. Intraoperative and anesthetic considerations in patients with osteogenesis imperfecta include challenges related to fracture risk, airway management, pulmonary function, and blood loss.

Chronic cerebro-spinal venous insufficiency (CCSVI) and multiple sclerosis.

PubMed

Ghezzi, A; Comi, G; Federico, A

2011-02-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS caused by the interplay of genetic and environmental factors. In the last years, it has been suggested that an abnormal venous drainage due to stenosis or malformation of the internal jugular and/or azygous veins may play a major pathogenetic role in MS. This abnormality called chronic cerebro-spinal venous insufficiency (CCSVI) could result in increased permeability of blood brain barrier, local iron deposition and secondary multifocal inflammation. In the present paper, literature data in favour and against this hypothesis are reported. A great variability of CCSVI has been found in both MS patients (ranging from 0 to 100%) and in control subjects (from 0 to 23%). This large variability is explained by methodological aspects, problems in assessing CCSVI, and differences among clinical series. It is urgent to perform appropriate epidemiological studies to define the possible relationship between CCSVI and MS.

Venous obstruction in permanent pacemaker patients: an isotopic study

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

Pauletti, M.; Di Ricco, G.; Solfanelli, S.

1981-01-01

Isotope venography was used to study the venous circulation proximal to the superior vena cava in two groups of pacemaker patients, one with a single endocavitary electrode and the other with multiple pacing catheters. A control group of patients without pacemakers was also studied. Numerous abnormalities were found, especially in the group with multiple electrodes. These findings suggest that venous obstruction is a common complication of endocardial pacing.

Multiple congenital defects associated with trisomy for long arm of No. 4.

PubMed

Issa, M; Potter, A M; Blank, C E

1976-08-01

The clinical and cytogenetic findings of a male infant with multiple congenital anomalies and trisomy for the distal third of the long arm of No. 4 are described. The abnormal chromosome was inherited from the mother who had a balanced translocation, t(4;9)(q31;q34). Trisomy for the long arm of No. 4 has previously been described in only 3 patients.

Degenerative joint disease: multiple joint involvement in young and mature dogs.

PubMed

Olsewski, J M; Lust, G; Rendano, V T; Summers, B A

1983-07-01

Radiologic, pathologic, and ancillary methods were used to determine the occurrence of degenerative joint disease involving multiple joints of immature and adult dogs. Animals were selected for the development of hip joint dysplasia and chronic degenerative joint disease. Of disease-prone dogs, 82% (45 of 55 dogs) had radiologic changes, indicative of hip dysplasia, by 1 year of age. At necropsy, more abnormal joints were identified than by radiographic examination. Among 92 dogs between 3 to 11 months of age that had joint abnormalities, 71% had hip joint involvement; 38%, shoulder joint involvement; 22%, stifle joint involvement; and 40% had multiple joint involvement. Polyarthritis was asymptomatic and unexpected. Radiographic examination of older dogs also revealed evidence of degenerative joint disease in many joints. Multiple joint involvement was substantiated at necropsy of young and mature dogs. A similar pattern of polyarticular osteoarthritis was revealed in a survey (computer search) of necropsy reports from medical case records of 100 adult and elderly dogs. Usually, the joint disease was an incidental observation, unrelated to the clinical disease or to the cause of death. The frequent occurrence of degenerative changes in several joints of dogs aged 6 months to 17 years indicated that osteoarthritis may be progressive in these joints and raises the possibility that systemic factors are involved in the disease process.

Visceral larva migrans presenting as multiple intracranial and intraspinal abscesses.

PubMed

Moiyadi, Alefia; Mahadevan, Anita; Anandh, Balasubramaniam; Shivashankar, Ravi Shankar; Chickabasavaiah, Yasha Thagadur; Shankar, Susarla Krishna

2007-08-01

Involvement of nervous system by toxocariasis is rare and can produce a spectrum of pathology that includes eosinophillic meningoencephalitis, meningomyelitis, space occupying lesions, vasculitis causing seizures or behavioral abnormalities posing diagnostic dilemmas. We describe a 38-year-old man who presented with multiple intracranial and intramedullary abscesses caused by visceral larva migrans. Neurohelminthiasis as a cause of multiple abscesses, though rare, should be entertained as a differential diagnosis particularly in tropical South-east Asian countries where helminthiasis is still an epidemiological concern prevalent in the pediatric age group.

Trichilemmal cyst nevus: a new complex organoid epidermal nevus.

PubMed

Tantcheva-Poor, Iliana; Reinhold, Katja; Krieg, Thomas; Happle, Rudolf

2007-11-01

A 31-year-old woman had an organoid nevus characterized by multiple trichilemmal cysts arranged in a bandlike pattern. The involved streaks followed Blaschko's lines and were covered, in addition, by multiple filiform hyperkeratoses and comedo-like plugs. Some histopathologic features of this complex nevus were reminiscent of those of well-established organoid nevi such as nevus comedonicus, porokeratotic eccrine nevus, or hair follicle nevus, but the presence of multiple large trichilemmal cysts was a conspicuously distinctive abnormality. Consequently, we propose for this new organoid nevus the names "trichilemmal cyst nevus" or "nevus trichilemmocysticus."

[Thrombotic microangiopathy].

PubMed

Beutel, G; Kielstein, J T; Ganser, A

2013-09-01

Thrombotic microangiopathy should be suspected every time the combination of microangiopathic hemolytic anemia without a coexisting cause, thrombocytopenia as well as renal and/or neurologic abnormalities occurs. The general term thrombotic microangiopathy includes different subtypes of the disease leading to abnormalities in multiple organ systems by endothelial injury and formation of platelet-rich thrombi in small vessels. The main types include thrombotic thrombocytopenic purpura in case of dominant neurologic abnormalities and the hemolytic uremic syndrome in case of acute kidney injury, respectively. Although these syndromes differ in their etiologies, clinical features, response to treatment, and prognosis, an early initiation of a direct therapeutic intervention frequently determines the clinical course of the patient. Irrespectively of the underlying etiology, plasma exchange is an essential component of acute therapeutic intervention while ongoing diagnostics are used to identify the definite treatment.

Effects of resocialization on post-weaning social isolation-induced abnormal aggression and social deficits in rats.

PubMed

Tulogdi, Aron; Tóth, Máté; Barsvári, Beáta; Biró, László; Mikics, Eva; Haller, József

2014-01-01

As previously shown, rats isolated from weaning develop abnormal social and aggressive behavior characterized by biting attacks targeting vulnerable body parts of opponents, reduced attack signaling, and increased defensive behavior despite increased attack counts. Here we studied whether this form of violent aggression could be reversed by resocialization in adulthood. During the first weak of resocialization, isolation-reared rats showed multiple social deficits including increased defensiveness and decreased huddling during sleep. Deficits were markedly attenuated in the second and third weeks. Despite improved social functioning in groups, isolated rats readily showed abnormal features of aggression in a resident-intruder test performed after the 3-week-long resocialization. Thus, post-weaning social isolation-induced deficits in prosocial behavior were eliminated by resocialization during adulthood, but abnormal aggression was resilient to this treatment. Findings are compared to those obtained in humans who suffered early social maltreatment, and who also show social deficits and dysfunctional aggression in adulthood. © 2013 Wiley Periodicals, Inc.

Probability of Regenerating a Normal Limb After Bite Injury in the Mexican Axolotl (Ambystoma mexicanum).

PubMed

Thompson, Sierra; Muzinic, Laura; Muzinic, Christopher; Niemiller, Matthew L; Voss, S Randal

2014-06-01

Multiple factors are thought to cause limb abnormalities in amphibian populations by altering processes of limb development and regeneration. We examined adult and juvenile axolotls ( Ambystoma mexicanum ) in the Ambystoma Genetic Stock Center (AGSC) for limb and digit abnormalities to investigate the probability of normal regeneration after bite injury. We observed that 80% of larval salamanders show evidence of bite injury at the time of transition from group housing to solitary housing. Among 717 adult axolotls that were surveyed, which included solitary-housed males and group-housed females, approximately half presented abnormalities, including examples of extra or missing digits and limbs, fused digits, and digits growing from atypical anatomical positions. Bite injury likely explains these limb defects, and not abnormal development, because limbs with normal anatomy regenerated after performing rostral amputations. We infer that only 43% of AGSC larvae will present four anatomically normal looking adult limbs after incurring a bite injury. Our results show regeneration of normal limb anatomy to be less than perfect after bite injury.

Pleural abnormalities and exposure to elongate mineral particles in Minnesota iron ore (taconite) workers.

PubMed

Perlman, David; Mandel, Jeffrey H; Odo, Nnaemeka; Ryan, Andy; Lambert, Christine; MacLehose, Richard F; Ramachandran, Gurumurthy; Alexander, Bruce H

2018-05-01

Iron ore (taconite) mining and processing are an important industry in northern Minnesota and western Michigan. Concerns around exposures have centered largely on exposure to non-asbestiform amphibole elongate mineral particles (EMPs) found in the eastern portion of the Minnesota iron range. A cross sectional survey was undertaken of current and former taconite workers and spouses along with a detailed exposure assessment. Participants provided an occupational history and had a chest radiograph performed. A total of 1188 workers participated. Potential exposures to non-amphibole EMPs were evident across multiple jobs in all active mines. Pleural abnormalities were found in 16.8% of workers. There was an association of pleural abnormalities with cumulative EMP exposure that was not specific to the eastern portion of the range. There was evidence of a mild to moderate increase in pleural abnormalities in this population of miners, associated with geographically non-specific cumulative EMP exposure. © 2018 Wiley Periodicals, Inc.

XYY chromosome abnormality in sexual homicide perpetrators.

PubMed

Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas

2006-03-05

In a retrospective investigation of the court reports about sexual homicide perpetrators chromosome analysis had been carried out in 13 of 166 (7.8%) men. Three men (1.8%) with XYY chromosome abnormality were found. This rate is much higher than that found in unselected samples of prisoners (0.7-0.9%) or in the general population (0.01%). The three men had shown prepubescent abnormalities, school problems, and had suffered from physical abuse. The chromosome analysis in all cases had been carried out in connection with the forensic psychiatric court report due to the sexual homicide. However, two men had earlier psychiatric referrals. All were diagnosed as sexual sadistic, showed a psychopathic syndrome or psychopathy according to the Psychopathy Checklist-Revised [Hare RD, 1991, The Hare Psychopathy Checklist-Revised, Toronto, Ontario, Canada: Multi-Health Systems]. Two were multiple murderers. Especially forensic psychiatrists should be vigilant of the possibility of XYY chromosome abnormalities in sexual offenders. (c) 2006 Wiley-Liss, Inc.

Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study.

PubMed

Moodley, Jennifer R; Constant, Deborah; Hoffman, Margaret; Salimo, Anna; Allan, Bruce; Rybicki, Ed; Hitzeroth, Inga; Williamson, Anna-Lise

2009-08-07

Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy. A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 - 57.7) for those that were HC2 positive and had a viral load of 181.1 RLU. Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer.

Connectivity-based parcellation of the thalamus in multiple sclerosis and its implications for cognitive impairment: A multicenter study.

PubMed

Bisecco, Alvino; Rocca, Maria A; Pagani, Elisabetta; Mancini, Laura; Enzinger, Christian; Gallo, Antonio; Vrenken, Hugo; Stromillo, Maria Laura; Copetti, Massimiliano; Thomas, David L; Fazekas, Franz; Tedeschi, Gioacchino; Barkhof, Frederik; Stefano, Nicola De; Filippi, Massimo

2015-07-01

In this multicenter study, we performed a tractography-based parcellation of the thalamus and its white matter connections to investigate the relationship between thalamic connectivity abnormalities and cognitive impairment in multiple sclerosis (MS). Dual-echo, morphological and diffusion tensor (DT) magnetic resonance imaging (MRI) scans were collected from 52 relapsing-remitting MS patients and 57 healthy controls from six European centers. Patients underwent an extensive neuropsychological assessment. Thalamic connectivity defined regions (CDRs) were segmented based on their cortical connectivity using diffusion tractography-based parcellation. Between-group differences of CDRs and cortico-thalamic tracts DT MRI indices were assessed. A vertex analysis of thalamic shape was also performed. A random forest analysis was run to identify the best imaging predictor of global cognitive impairment and deficits of specific cognitive domains. Twenty-two (43%) MS patients were cognitively impaired (CI). Compared to cognitively preserved, CI MS patients had increased fractional anisotropy of frontal, motor, postcentral and occipital connected CDRs (0.002

Epilepsy in the setting of full trisomy 18: A multicenter study on 18 affected children with and without structural brain abnormalities.

PubMed

Matricardi, Sara; Spalice, Alberto; Salpietro, Vincenzo; Di Rosa, Gabriella; Balistreri, Maria Cristina; Grosso, Salvatore; Parisi, Pasquale; Elia, Maurizio; Striano, Pasquale; Accorsi, Patrizia; Cusmai, Raffaella; Specchio, Nicola; Coppola, Giangennaro; Savasta, Salvatore; Carotenuto, Marco; Tozzi, Elisabetta; Ferrara, Pietro; Ruggieri, Martino; Verrotti, Alberto

2016-09-01

This paper reports on the clinical aspects, electroencephalographic (EEG) features, and neuroimaging findings in children with full trisomy 18 and associated epilepsy, and compares the evolution and outcome of their neurological phenotype. We retrospectively studied 18 patients (10 males and 8 females; aged 14 months to 9 years) with full trisomy 18 and epilepsy. All patients underwent comprehensive assessment including neuroimaging studies of the brain. We divided patients into two groups according to neuroimaging findings: (Group 1) 10 patients harboring structural brain malformations, and (Group 2) 8 patients with normal brain images. Group 1 had a significantly earlier age at seizure onset (2 months) compared to Group 2 (21 months). The seizure semiology was more severe in Group 1, who presented multiple seizure types, need for polytherapy (80% of patients), multifocal EEG abnormalities and poorer outcome (drug resistant epilepsy in 90% of patients) than Group 2 who presented a single seizure type, generalized or focal, and non-specific EEG pattern; these patients were successfully treated with monotherapy with good outcome. Imaging revealed a wide and complex spectrum of structural brain abnormalities including anomalies of the commissures, cerebellar malformations, cortical abnormalities, and various degrees of cortical atrophy. Epilepsy in full trisomy 18 may develop during the first months of life and can be associated with structural brain malformations. Patients with brain malformations can show multiple seizure types and can frequently be resistant to therapy with antiepileptic drugs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Biomechanical factors and physical examination findings in osteoarthritis of the knee: associations with tissue abnormalities assessed by conventional radiography and high-resolution 3.0 Tesla magnetic resonance imaging.

PubMed

Knoop, Jesper; Dekker, Joost; Klein, Jan-Paul; van der Leeden, Marike; van der Esch, Martin; Reiding, Dick; Voorneman, Ramon E; Gerritsen, Martijn; Roorda, Leo D; Steultjens, Martijn P M; Lems, Willem F

2012-10-05

We aimed to explore the associations between knee osteoarthritis (OA)-related tissue abnormalities assessed by conventional radiography (CR) and by high-resolution 3.0 Tesla magnetic resonance imaging (MRI), as well as biomechanical factors and findings from physical examination in patients with knee OA. This was an explorative cross-sectional study of 105 patients with knee OA. Index knees were imaged using CR and MRI. Multiple features from CR and MRI (cartilage, osteophytes, bone marrow lesions, effusion and synovitis) were related to biomechanical factors (quadriceps and hamstrings muscle strength, proprioceptive accuracy and varus-valgus laxity) and physical examination findings (bony tenderness, crepitus, bony enlargement and palpable warmth), using multivariable regression analyses. Quadriceps weakness was associated with cartilage integrity, effusion, synovitis (all detected by MRI) and CR-detected joint space narrowing. Knee joint laxity was associated with MRI-detected cartilage integrity, CR-detected joint space narrowing and osteophyte formation. Multiple tissue abnormalities including cartilage integrity, osteophytes and effusion, but only those detected by MRI, were found to be associated with physical examination findings such as crepitus. We observed clinically relevant findings, including a significant association between quadriceps weakness and both effusion and synovitis, detected by MRI. Inflammation was detected in over one-third of the participants, emphasizing the inflammatory component of OA and a possible important role for anti-inflammatory therapies in knee OA. In general, OA-related tissue abnormalities of the knee, even those detected by MRI, were found to be discordant with biomechanical and physical examination features.

An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis.

PubMed

Brown, J William L; Pardini, Matteo; Brownlee, Wallace J; Fernando, Kryshani; Samson, Rebecca S; Prados Carrasco, Ferran; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

2017-02-01

In established multiple sclerosis, tissue abnormality-as assessed using magnetization transfer ratio-increases close to the lateral ventricles. We aimed to determine whether or not (i) these changes are present from the earliest clinical stages of multiple sclerosis; (ii) they occur independent of white matter lesions; and (iii) they are associated with subsequent conversion to clinically definite multiple sclerosis and disability. Seventy-one subjects had MRI scanning a median of 4.6 months after a clinically isolated optic neuritis (49 females, mean age 33.5 years) and were followed up clinically 2 and 5 years later. Thirty-seven healthy controls (25 females, mean age 34.4 years) were also scanned. In normal-appearing white matter, magnetization transfer ratio gradients were measured 1-5 mm and 6-10 mm from the lateral ventricles. In control subjects, magnetization transfer ratio was highest adjacent to the ventricles and decreased with distance from them; in optic neuritis, normal-appearing white matter magnetization transfer ratio was lowest adjacent to the ventricles, increased over the first 5 mm, and then paralleled control values. The magnetization transfer ratio gradient over 1-5 mm differed significantly between the optic neuritis and control groups [+0.059 percentage units/mm (pu/mm) versus -0.033 pu/mm, P = 0.010], and was significantly steeper in those developing clinically definite multiple sclerosis within 2 years compared to those who did not (0.132 pu/mm versus 0.016 pu/mm, P = 0.020). In multivariate binary logistic regression the magnetization transfer ratio gradient was independently associated with the development of clinically definite multiple sclerosis within 2 years (magnetization transfer ratio gradient odds ratio 61.708, P = 0.023; presence of T 2 lesions odds ratio 8.500, P = 0.071). At 5 years, lesional measures overtook magnetization transfer ratio gradients as significant predictors of conversion to multiple sclerosis. The magnetization transfer ratio gradient was not significantly affected by the presence of brain lesions [T 2 lesions (P = 0.918), periventricular T 2 lesions (P = 0.580) or gadolinium-enhancing T 1 lesions (P = 0.724)]. The magnetization transfer ratio gradient also correlated with Expanded Disability Status Scale score 5 years later (Spearman r = 0.313, P = 0.027). An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis, is clinically relevant, and may arise from one or more mechanisms that are at least partly independent of lesion formation. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Association of abnormal plasma bilirubin with aggressive HCC phenotype

PubMed Central

Carr, Brian I.; Guerra, Vito; Giannini, Edoardo G.; Farinati, Fabio; Ciccarese, Francesca; Rapaccini, Gian Ludovico; Marco, Maria Di; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

2014-01-01

Background Cirrhosis-related abnormal liver function is associated with predisposition to HCC, features in several HCC classification systems and is an HCC prognostic factor. Aims To examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. Methods A 2,416 patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely blood AFP levels, tumor size, presence of PVT and tumor multifocality. Results In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even for small tumor size patients. A multiple logistic regression model for PVT or tumor multifocality showed increased OddsRatios for elevated levels of GGTP, bilirubin and AFP and for larger tumor sizes. Conclusions HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had increased incidence of PVT and tumor multifocality and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

Sensorineural Deafness, Distinctive Facial Features and Abnormal Cranial Bones

PubMed Central

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R.; Matsushita, Mark; Raskind, Wendy H.

2008-01-01

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. PMID:18553554

Analysis of Knee Joint Line Obliquity after High Tibial Osteotomy.

PubMed

Oh, Kwang-Jun; Ko, Young Bong; Bae, Ji Hoon; Yoon, Suk Tae; Kim, Jae Gyoon

2016-11-01

The aim of this study was to evaluate which lower extremity alignment (knee and ankle joint) parameters affect knee joint line obliquity (KJLO) in the coronal plane after open wedge high tibial osteotomy (OWHTO). Overall, 69 knees of patients that underwent OWHTO were evaluated using radiographs obtained preoperatively and from 6 weeks to 3 months postoperatively. We measured multiple parameters of knee and ankle joint alignment (hip-knee-ankle angle [HKA], joint line height [JLH], posterior tibial slope [PS], femoral condyle-tibial plateau angle [FCTP], medial proximal tibial angle [MPTA], mechanical lateral distal femoral angle [mLDFA], KJLO, talar tilt angle [TTA], ankle joint obliquity [AJO], and the lateral distal tibial ground surface angle [LDTGA]; preoperative [-pre], postoperative [-post], and the difference between -pre and -post values [-Δ]). We categorized patients into two groups according to the KJLO-post value (the normal group [within ± 4 degrees, 56 knees] and the abnormal group [greater than ± 4 degrees, 13 knees]), and compared their -pre parameters. Multiple logistic regression analysis was used to examine the contribution of the -pre parameters to abnormal KJLO-post. The mean HKA-Δ (-9.4 ± 4.7 degrees) was larger than the mean KJLO-Δ (-2.1 ± 3.2 degrees). The knee joint alignment parameters (the HKA-pre, FCTP-pre) differed significantly between the two groups ( p  < 0.05). In addition, the HKA-pre (odds ratio [OR] = 1.27, p  = 0.006) and FCTP-pre (OR = 2.13, p  = 0.006) were significant predictors of abnormal KJLO-post. However, -pre ankle joint parameters (TTA, AJO, and LDTGA) did not differ significantly between the two groups and were not significantly associated with the abnormal KJLO-post. The -pre knee joint alignment and knee joint convergence angle evaluated by HKA-pre and FCTP-pre angle, respectively, were significant predictors of abnormal KJLO after OWHTO. However, -pre ankle joint parameters were not significantly associated with abnormal KJLO after OWHTO. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pdgfrα functions in endothelial-derived cells to regulate neural crest cells and the development of the great arteries.

PubMed

Aghajanian, Haig; Cho, Young Kuk; Rizer, Nicholas W; Wang, Qiaohong; Li, Li; Degenhardt, Karl; Jain, Rajan

2017-09-01

Originating as a single vessel emerging from the embryonic heart, the truncus arteriosus must septate and remodel into the aorta and pulmonary artery to support postnatal life. Defective remodeling or septation leads to abnormalities collectively known as conotruncal defects, which are associated with significant mortality and morbidity. Multiple populations of cells must interact to coordinate outflow tract remodeling, and the cardiac neural crest has emerged as particularly important during this process. Abnormalities in the cardiac neural crest have been implicated in the pathogenesis of multiple conotruncal defects, including persistent truncus arteriosus, double outlet right ventricle and tetralogy of Fallot. However, the role of the neural crest in the pathogenesis of another conotruncal abnormality, transposition of the great arteries, is less well understood. In this report, we demonstrate an unexpected role of Pdgfra in endothelial cells and their derivatives during outflow tract development. Loss of Pdgfra in endothelium and endothelial-derived cells results in double outlet right ventricle and transposition of the great arteries. Our data suggest that loss of Pdgfra in endothelial-derived mesenchyme in the outflow tract endocardial cushions leads to a secondary defect in neural crest migration during development. © 2017. Published by The Company of Biologists Ltd.

A newborn with trisomy 13 who had tetralogy of Fallot and metopic synostosis: Case report

PubMed Central

Karabel, M; Yolbaş, I; Kelekçi, S; Şen, V; Haspolat, YK; Timuroğlu, L

2013-01-01

Background and Aim: Trisomy 13 (Patau syndrome) was first described by Patau et al in 1960. It is characterized by serious head, facial, and extremity anomalies, congenital heart defects, and mental abnormalities. The incidence rate of Trisomy 13 is 1/10.000 live births. Accompanying symptoms and findings vary in rate and severity among the cases. Tetralogy of Fallot and metopic synostosis are very rare abnormalities in patients with Trisomy 13. In this study, we aimed to present a newborn girl with trisomy 13 who had multiple congenital malformations accompanied by tetralogy of Fallot and metopic synostosis. Description of the case: The patient was delivered at 40 weeks of gestation, and admitted to the neonatal intensive care unit due to respiratory distress and physical abnormalities. The newborn examination revealed multiple dysmorphic features. She had boot-shaped appearance on the chest radiograph. Chromosome analysis demonstrated mosaic trisomy 13. Conclusion: Patients with trisomy 13 may have different type of gene variations and malformations; however, the most common type of gene variation is classic trisomy 47, XX +13, and the most common malformations are facial anomalies and congenital heart defects. In addition, tetralogy of Fallot and metopic synostosis may accompany trisomy 13. PMID:24470740

Preoperative Status and Risk of Complications in Patients with Hip Fracture

PubMed Central

McLaughlin, Mary Ann; Orosz, Gretchen M; Magaziner, Jay; Hannan, Edward L; McGinn, Thomas; Morrison, R Sean; Hochman, Tsivia; Koval, Kenneth; Gilbert, Marvin; Siu, Albert L

2006-01-01

BACKGROUND Limited information is available on preoperative status and risks for complications for older patients having surgery for hip fracture. Our objective was to identify potentially modifiable clinical findings that should be considered in decisions about the timing of surgery. METHODS We conducted a prospective cohort study with data obtained from medical records and through structured interviews with patients. A total of 571 adults with hip fracture who were admitted to 4 metropolitan hospitals were included. RESULTS Multiple logistic regression was used to identify risk factors (including 11 categories of physical and laboratory findings, classified as mild and severe abnormalities) for in-hospital complications. The presence of more than 1 (odds ratiol [OR] 9.7, 95% confidence interval [CI] 2.8 to 33.0) major abnormality before surgery or the presence of major abnormalities on admission that were not corrected prior to surgery (OR 2.8, 95% CI 1.2 to 6.4) was independently associated with the development of postoperative complications. We also found that minor abnormalities, while warranting correction, did not increase risk (OR 0.70, 95% CI 0.28 to 1.73). CONCLUSIONS In this study of older adults undergoing urgent surgery, potentially reversible abnormalities in laboratory and physical examination occurred frequently and significantly increased the risk of postoperative complications. Major clinical abnormalities should be corrected prior to surgery, but patients with minor abnormalities may proceed to surgery with attention to these medical problems perioperatively. PMID:16390507

[Association of folate metabolism genes MTRR and MTHFR with complex congenital abnormalities among Chinese population in Shanxi Province, China].

PubMed

Zhang, Qin; Bai, Bao-Ling; Liu, Xiao-Zhen; Miao, Chun-Yue; Li, Hui-Li

2014-08-01

To explore the association of polymorphisms in folate metabolism genes, methionine synthase reductase (MTRR) gene and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with complex congenital abnormalities and to further investigate its association with complex congenital abnormalities derived from three germ layers. A total of 250 cases of birth defects (with complex congenital abnormalities including congenital heart disease, neural tube defects, and craniofacial anomalies) in Shanxi Province, China were included in the study. MTRR single nucleotide polymorphism (SNP) (rs1801394) and MTHFR SNP (rs1801133) were genotyped by the SNaPshot method, and the genotyping results were compared with those of controls (n=420). SNPs rs1801394 and rs1801133 were associated with multiple birth defects. For the recessive model, individuals with GG genotype at rs1801394 and CC genotype at rs1801133 had a relatively low risk of developing birth defects, so the two genotypes were protective factors against birth defects. The homozygous recessive genotype at rs1801133, which served as a protective factor, was associated with ectoderm- or endoderm-derived complex congenital abnormalities, while the homozygous recessive genotype at rs1801394, which served as a protective factor, was associated with ectoderm-, mesoderm- or endoderm-derived complex congenital abnormalities. Among the Chinese population in Shanxi Province, the SNPs in folate metabolism genes (MTRR and MTHFR) are associated with complex congenital abnormalities and related to ectoderm, mesoderm or endoderm development.

Hypercoagulable states in patients with multiple myeloma can affect the thalidomide-associated venous thromboembolism.

PubMed

Talamo, Giampaolo P; Ibrahim, Sulfi; Claxton, David; Tricot, Guido J; Fink, Louis M; Zangari, Maurizio

2009-07-01

The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple myeloma patients treated with thalidomide at baseline for hypercoagulability. With a median follow-up of 11 months, 10 of 49 multiple myeloma patients developed a thrombotic episode. Laboratory assays revealed an underlying abnormality in nine of the 10 patients; hypercoagulable screenings were normal in 36 of the 39 patients who did not develop venous thromboembolism (P < 0.0001). Our retrospective study results suggest that the multiple myeloma patients with thromboembolic complications during treatment with thalidomide have a frequent concomitant underlying thrombophilic state.

Spectrum of PORCN mutations in Focal Dermal Hypoplasia

USDA-ARS?s Scientific Manuscript database

Focal Dermal Hypoplasia (FDH), also known as Goltz syndrome (OMIM 305600), is a genetic disorder that affects multiple organ systems early in development. Features of FDH include skin abnormalities, (hypoplasia, atrophy, linear pigmentation, and herniation of fat through dermal defects); papillomas...

Chinese children with autism: A multiple chemical elements profile in erythrocytes.

PubMed

Wu, Jing; Liu, Duo-Jian; Shou, Xiao-Jing; Zhang, Ji-Shui; Meng, Fan-Chao; Liu, Ya-Qiong; Han, Song-Ping; Zhang, Rong; Jia, Jin-Zhu; Wang, Jing-Yu; Han, Ji-Sheng

2018-06-01

Several lines of evidence suggested that abnormal levels of certain chemical elements may contribute to the development of autism spectrum disorders (ASD). The present work aimed to investigate the multiple chemical elements profile in the erythrocytes of autistic versus typically developing children (TDC) of China. Analyses were carried out to explore the possible association between levels of elements and the risk as well as the severity of ASD. Erythrocyte levels of 11 elements (32%) among 34 detected elements in autistic group were significantly different from those in the TDC group. To our knowledge, this is the first study which compared the levels of rare earth elements in erythrocytes between children with or without ASD. Five elements including Pb, Na, Ca, Sb, and La are associated with the Childhood Autism Rating Scale (CARS) total score. Also, a series of tendencies were found in this research which was believed to affect auditory response, taste, smell, and touch, as well as fear or nervousness. It can be concluded that Chinese autistic children suffer from multi-chemical element imbalances which involves a complex combination of genetic and environmental factors. The results showed a significant correlation between abnormal levels of several chemical elements and the severity of the autistic syndrome. It is suggested that abnormal levels of some chemical elements may contribute to the development of autism spectrum disorders (ASD). In this work, the impact of element imbalances on the risk and severity of ASD was investigated, focusing on the analysis of abnormal levels of the multi-chemical elements profile in erythrocytes compared with typically developing children. Furthermore, the results showed a significant correlation between abnormal levels of several chemical elements and the severity of the autistic syndrome. Autism Res 2018, 11: 834-845. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Impact of initial FDG-PET/CT and serum-free light chain on transformation of conventionally defined solitary plasmacytoma to multiple myeloma.

PubMed

Fouquet, Guillemette; Guidez, Stéphanie; Herbaux, Charles; Van de Wyngaert, Zoé; Bonnet, Sarah; Beauvais, David; Demarquette, Hélène; Adib, Salim; Hivert, Bénédicte; Wemeau, Mathieu; Berthon, Céline; Terriou, Louis; Coiteux, Valérie; Macro, Margaret; Decaux, Olivier; Facon, Thierry; Huglo, Damien; Leleu, Xavier

2014-06-15

Solitary plasmacytoma (SP) is a localized proliferation of monoclonal plasma cells in either bone or soft tissue, without evidence of multiple myeloma (MM), and whose prognosis is marked by a high risk of transformation to MM. We studied the impact of FDG-PET/CT (2[18F]fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography) on the risk of transformation of SP to overt MM among other markers in a series of 43 patients diagnosed with SP. Median age was 57.5 years; 48% of patients had an abnormal involved serum-free light chain (sFLC) value, and 64% had an abnormal sFLC ratio at diagnosis. Thirty-three percent had two or more hypermetabolic lesions on initial PET/CT, and 20% had two or more focal lesions on initial MRI. With a median follow-up of 50 months, 14 patients transformed to MM with a median time (TTMM) of 71 months. The risk factors that significantly shortened TTMM at diagnosis were two or more hypermetabolic lesions on PET/CT, abnormal sFLC ratio and involved sFLC, and to a lesser extent at completion of treatment, absence of normalized involved sFLC and PET/CT or MRI. In a multivariate analysis, abnormal initial involved sFLC [OR = 10; 95% confidence interval (CI), 1-87; P = 0.008] and PET/CT (OR = 5; 95% CI, 0-9; P = 0.032) independently shortened TTMM. An abnormal involved sFLC value and the presence of at least two hypermetabolic lesions on PET/CT at diagnosis of SP were the two predictors of early evolution to myeloma in our series. This data analysis will need confirmation in a larger study, and the study of these two risk factors may lead to a different management of patients with SP in the future. . ©2014 American Association for Cancer Research.

Guidelines to identify abnormalities after childhood urinary tract infections: a prospective audit.

PubMed

Coulthard, Malcolm G; Lambert, Heather J; Vernon, Susan J; Hunter, Elizabeth W; Keir, Michael J

2014-05-01

To compare the childhood urinary tract infection (UTI) guidelines from the Royal College of Physicians (RCP) in 1991 and from National Institute of Health and Care Excellence (NICE) (CG54) in 2007 by measuring their efficiency at detecting urinary tract abnormalities. Children with UTIs within the Newcastle Primary Care Trust (population 70,800 children) were referred and imaged according to the RCP guidelines during 2008, and these were compared to the activity that would have been undertaken if we had implemented the CG54 guidelines, including following them through 2011 to identify those with recurrent UTIs. The numbers of children imaged, the imaging burden and efficiency, and urinary tract abnormalities detected by each guideline. Fewer children would have been imaged by CG54 than RCP (150 vs 427), but its sensitivity was lower, at 44% for detecting scarring, 10% for identifying vesicoureteric reflux and 40% for other abnormalities. Overall, it would have only detected one-quarter of the abnormal cases (8 vs 32) and would have missed five of nine children with scarring, including three with multiple lesions and one with renal impairment. Imposing an age restriction of <8 years to the RCP guidelines would reduce its screening rate by 20% and still detect 90% of the abnormalities. The CG54 guidelines do not alter the imaging efficiency compared to the RCP guidelines, but they are considerably less sensitive.

Developmental antecedents of abnormal eating attitudes and behaviors in adolescence.

PubMed

Le Grange, Daniel; O'Connor, Meredith; Hughes, Elizabeth K; Macdonald, Jacqui; Little, Keriann; Olsson, Craig A

2014-11-01

This study capitalizes on developmental data from an Australian population-based birth cohort to identify developmental markers of abnormal eating attitudes and behaviors in adolescence. The aims were twofold: (1) to develop a comprehensive path model identifying infant and childhood developmental correlates of Abnormal Eating Attitudes and Behaviors in adolescence, and (2) to explore potential gender differences. Data were drawn from a 30-year longitudinal study that has followed the health and development of a population based cohort across 15 waves of data collection from infancy since 1983: The Australian Temperament Project. Participants in this analysis were the 1,300 youth who completed the 11th survey at 15-16 years (1998) and who completed the eating disorder inventory at this time point. Developmental correlates of Abnormal Eating Attitudes and Behaviors in mid-adolescence were temperamental persistence, early gestational age, persistent high weight, teen depression, stronger peer relationships, maternal dieting behavior, and pubertal timing. Overall, these factors accounted for 28% of the variance in Abnormal Eating Attitudes and Behaviors at 15-16 years of age. Depressive symptoms, maternal dieting behavior, and early puberty were more important factors for girls. Late puberty was a more important factor for boys. Findings address an important gap in our understanding of the etiology of Abnormal Eating Attitudes and Behaviors in adolescence and suggest multiple targets for preventive intervention. © 2014 Wiley Periodicals, Inc.

The causes of hypopituitarism in the absence of abnormal pituitary imaging.

PubMed

Wilson, V; Mallipedhi, A; Stephens, J W; Redfern, R M; Price, D E

2014-01-01

Hypopituitarism in the absence of a history of pituitary pathology or abnormal pituitary imaging is rare. To identify the cause of hypopituitarism in individuals in whom pituitary imaging was normal. Retrospective analysis of electronic patient record. A review of the pituitary function in the 506 patients on the Morriston Hospital pituitary database revealed 230 had some degree of hypopituitarism and of these, 21 (9%) had normal pituitary imaging. Of this group, six patients had a past medical history of subarachnoid haemorrhage, head injury or meningitis, and mainly suffered from a deficiency of antidiuretic hormone. One patient had a stroke resulting in multiple anterior hormone deficiencies and six individuals had idiopathic cranial diabetes insipidus (DI). Subsequent investigations of the remaining eight patients with normal pituitary imaging revealed that two had neurosarcoidosis both of whom had panhypopituitarism. Four patients had haemochromatosis which resulted in gonadotropin deficiency in two, DI in one and panhypopituitarism in the other. There were two individuals with confirmed hypopituitarism and multiple hormone deficiencies in which no cause could be identified. These results show that hypopituitarism in the absence of pituitary pathology or an identifiable cause is rare. In patients with multiple anterior pituitary hormone deficiencies haemochromatosis and sarcoidosis should be considered.

Optical coherence tomography angiography retinal vascular network assessment in multiple sclerosis.

PubMed

Lanzillo, Roberta; Cennamo, Gilda; Criscuolo, Chiara; Carotenuto, Antonio; Velotti, Nunzio; Sparnelli, Federica; Cianflone, Alessandra; Moccia, Marcello; Brescia Morra, Vincenzo

2017-09-01

Optical coherence tomography (OCT) angiography is a new method to assess the density of the vascular networks. Vascular abnormalities are considered involved in multiple sclerosis (MS) pathology. To assess the presence of vascular abnormalities in MS and to evaluate their correlation to disease features. A total of 50 MS patients with and without history of optic neuritis (ON) and 46 healthy subjects were included. All underwent spectral domain (SD)-OCT and OCT angiography. Clinical history, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Score (MSSS) and disease duration were collected. Angio-OCT showed a vessel density reduction in eyes of MS patients when compared to controls. A statistically significant reduction in all SD-OCT and OCT angiography parameters was noticed both in eyes with and without ON when compared with control eyes. We found an inverse correlation between SD-OCT parameters and MSSS ( p = 0.003) and between vessel density parameters and EDSS ( p = 0.007). We report a vessel density reduction in retina of MS patients. We highlight the clinical correlation between vessel density and EDSS, suggesting that angio-OCT could be a good marker of disease and of disability in MS.

Intracardiac echocardiographic guidance for hemodynamic assessment in a patient with congenital abnormalities and a prosthetic aortic valve.

PubMed

Papafaklis, M I; Ligthart, J M R; Vaina, S; Witsenburg, M; Bogers, A J J C; Serruys, P W

2005-01-01

In this case report, we present the use of intracardiac echocardiography (ICE) for guiding the cardiac catheterization and subsequent hemodynamic investigation in an unusual patient case with multiple congenital abnormalities (bicuspid aortic valve, left cervical aortic arch, two aortic coarctations) and two aortic valve replacement operations in the past. The ICE catheter (AcuNav) permitted us to accurately and safely puncture the interatrial septum and place the Swan-Ganz catheter in the left ventricle; additionally, visualization of the aortic coarctation in the ascending aorta was also achieved.

Prenatal diagnosis of left isomerism with normal heart: a case report

PubMed Central

De Paola, Nico; Ermito, Santina; Nahom, Antonella; Dinatale, Angela; Pappalardo, Elisa Maria; Carrara, Sabina; Cavaliere, Alessandro; Brizzi, Cristiana

2009-01-01

Objective: Left isomerism, also called polysplenia, is a laterality disturbance associated with with paired leftsidedness viscera and multiple small spleens. Left isomerism, heart congenital abnormalities and gastrointestinal malformation are strongly associated. Methods: We present a case of prenatal diagnosis of left isomerism in a fetus with a structurally normal heart. Conclusion: Left isomerism syndrone may coesist with a structurally normal heart. If prenatal left isomerism is suspected, even in presence of a normal heart, is mandatory to esclude sign of gastrointestinal abnormalities, as late poly hy dramnios, and cardiac rhytm disturbance during the pregnancy and neonatal age. PMID:22439041

A "reverse" Maffucci's syndrome: case report and short review of the literature.

PubMed

Matzaroglou, Charalampos; Megas, Panagiotis; Panagiotopoulos, Elias; Notopoulos, Athanasios; Saridis, Alkis; Sourgiadaki, Efrosini; Koumoundourou, Dimitra; Dimakopoulos, Panagiotis

2005-01-01

Maffucci's syndrome is a congenital, non-hereditary mesodermal dysplasia associated with multiple enchondromas and after some years accompanied by hemangiomas. We describe a rare case of "reverse" Maffucci's syndrome in a 42-year-old woman who has suffered from multiple hemangiomas for the last 24 years. The last two years she complained for heel pain. Bone scintigraphic examination showed abnormal findings in the left calcaneal bone. The scintigraphy, radiology and histology findings revealed multiple enchondromas, so the diagnosis was changed into Maffucci's syndrome. After one year, the left calcaneal bone showed sarcomatous transformation.

Predictors of Outcome following Acquired Brain Injury in Children

ERIC Educational Resources Information Center

Johnson, Abigail R.; DeMatt, Ellen; Salorio, Cynthia F.

2009-01-01

Acquired brain injury (ABI) in children and adolescents can result from multiple causes, including trauma, central nervous system infections, noninfectious disorders (epilepsy, hypoxia/ischemia, genetic/metabolic disorders), tumors, and vascular abnormalities. Prediction of outcomes is important, to target interventions, allocate resources,…

Spool-shaped proximal pedal phalanges.

PubMed

Sutro, C J; Sutro, W H

1986-01-01

We have observed that "spool-shaped" proximal pedal phalanges sometimes are found in single or multiple toes, often affecting both feet. These changes may be present in normal as well as abnormal feet. The etiology is unknown. Such changes do not occur in the hands.

In Vivo Imaging of Cortical Inflammation and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI

DTIC Science & Technology

2015-09-01

abnormalities in MS associated with changes in cortical myelin and/or iron concentration. The purpose of this project is to evaluate inflammation and...al., 2011). We demonstrated that surface-based mapping of quanti - tative T2* as a function of cortical depth (laminar analysis) from ultra-high...cortical grey matter (NACGM), to better understand their role in determining laminar quanti - tative T2* changes in multiple sclerosis. Materials and

Enchondromatosis with features of dysspondyloenchondromatosis and Maffucci syndrome.

PubMed

Haga, N; Nakamura, K; Taniguchi, K; Nakamura, S

1998-01-01

We report a girl with multiple enchondromatosis, unequal leg length, short stature, congenital scoliosis, lymphangioma, and cutaneous hemangiomata. The skeletal findings were consistent with the clinical and radiological features of dysspondyloenchondromatosis except that short stature was not apparent in the neonatal period. Dysspondyloenchondromatosis is a rare disorder, one of the several types of multiple enchondromatosis with spinal abnormalities. In previous reports of this condition the association of vascular lesions usually found in Maffucci syndrome has not been described.

New MR imaging assessment tool to define brain abnormalities in very preterm infants at term.

PubMed

Kidokoro, H; Neil, J J; Inder, T E

2013-01-01

WM injury is the dominant form of injury in preterm infants. However, other cerebral structures, including the deep gray matter and the cerebellum, can also be affected by injury and/or impaired growth. Current MR imaging injury assessment scales are subjective and are challenging to apply. Thus, we developed a new assessment tool and applied it to MR imaging studies obtained from very preterm infants at term age. MR imaging scans from 97 very preterm infants (< 30 weeks' gestation) and 22 healthy term-born infants were evaluated retrospectively. The severity of brain injury (defined by signal abnormalities) and impaired brain growth (defined with biometrics) was scored in the WM, cortical gray matter, deep gray matter, and cerebellum. Perinatal variables for clinical risks were collected. In very preterm infants, brain injury was observed in the WM (n=23), deep GM (n=5), and cerebellum (n=23). Combining measures of injury and impaired growth showed moderate to severe abnormalities most commonly in the WM (n=38) and cerebellum (n=32) but still notable in the cortical gray matter (n=16) and deep gray matter (n=11). WM signal abnormalities were associated with a reduced deep gray matter area but not with cerebellar abnormality. Intraventricular and/or parenchymal hemorrhage was associated with cerebellar signal abnormality and volume reduction. Multiple clinical risk factors, including prolonged intubation, prolonged parenteral nutrition, postnatal corticosteroid use, and postnatal sepsis, were associated with increased global abnormality on MR imaging. Very preterm infants demonstrate a high prevalence of injury and growth impairment in both the WM and gray matter. This MR imaging scoring system provides a more comprehensive and objective classification of the nature and extent of abnormalities than existing measures.

Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11

PubMed Central

Renvoisé, Benoît; Chang, Jaerak; Singh, Rajat; Yonekawa, Sayuri; FitzGibbon, Edmond J; Mankodi, Ami; Vanderver, Adeline; Schindler, Alice B; Toro, Camilo; Gahl, William A; Mahuran, Don J; Blackstone, Craig; Pierson, Tyler Mark

2014-01-01

Objective Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism. Methods We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes. Results Fibroblasts prepared from patients with SPG15 have selective enlargement of LAMP1-positive structures, and they consistently exhibited abnormal lysosomal storage by electron microscopy. A similar enlargement of LAMP1-positive structures was also observed in cells from multiple SPG11 patients, though prominent abnormal lysosomal storage was not evident. The stabilities of the SPG15 protein spastizin/ZFYVE26 and the SPG11 protein spatacsin were interdependent. Interpretation Emerging studies implicating these two proteins in interactions with the late endosomal/lysosomal adaptor protein complex AP-5 are consistent with shared abnormalities in lysosomes, supporting a converging mechanism for these two disorders. Recent work with Zfyve26−/− mice revealed a similar phenotype to human SPG15, and cells in these mice had endolysosomal abnormalities. SPG15 and SPG11 are particularly notable among HSPs because they can also present with juvenile parkinsonism, and this lysosomal trafficking or storage defect may be relevant for other forms of parkinsonism associated with lysosomal dysfunction. PMID:24999486

Prospective Evaluation of Transcatheter Arterial Chemoembolization (TACE) with Multiple Anti-Cancer Drugs (Epirubicin, Cisplatin, Mitomycin C, 5-Fluorouracil) Compared with TACE with Epirubicin for Treatment of Hepatocellular Carcinoma

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

Sahara, Shinya; Kawai, Nobuyuki; Sato, Morio, E-mail: morisato@mail.wakayama-med.ac.jp

Purpose: To compare the efficacy of transcatheter arterial chemoembolization (TACE) using multiple anticancer drugs (epirubicin, cisplatin, mitomycin C, and 5-furuorouracil: Multi group) with TACE using epirubicin (EP group) for hepatocellular carcinoma (HCC). Materials and Methods: The study design was a single-center, prospective, randomized controlled trial. Patients with unrespectable HCC confined to the liver, unsuitable for radiofrequency ablation, were assigned to the Multi group or the EP group. We assessed radiographic response as the primary endpoint; secondary endpoints were progression-free survival (PFS), safety, and hepatic branch artery abnormality (Grade I, no damage or mild vessel wall irregularity; Grade II, overt stenosis;more » Grade III, occlusion; Grades II and III indicated significant hepatic artery damage). A total of 51 patients were enrolled: 24 in the Multi group vs. 27 in the EP group. Results: No significant difference in HCC patient background was found between the groups. Radiographic response, PFS, and 1- and 2-year overall survival of the Multi vs. EP group were 54% vs. 48%, 6.1 months vs. 8.7 months, and 95% and 65% vs. 85% and 76%, respectively, with no significant difference. Significantly greater Grade 3 transaminase elevation was found in the Multi group (p = 0.023). Hepatic artery abnormality was observed in 34% of the Multi group and in 17.1% of the EP group (p = 0.019). Conclusion: TACE with multiple anti-cancer drugs was tolerable but appeared not to contribute to an increase in radiographic response or PFS, and caused significantly more hepatic arterial abnormalities compared with TACE with epirubicin alone.« less

Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals

PubMed Central

Canto, Marcia Irene; Hruban, Ralph H.; Fishman, Elliot K.; Kamel, Ihab R.; Schulick, Richard; Zhang, Zhe; Topazian, Mark; Takahashi, Naoki; Fletcher, Joel; Petersen, Gloria; Klein, Alison P.; Axilbund, Jennifer; Griffin, Constance; Syngal, Sapna; Saltzman, John R.; Mortele, Koenraad J.; Lee, Jeffrey; Tamm, Eric; Vikram, Raghunandan; Bhosale, Priya; Margolis, Daniel; Farrell, James; Goggins, Michael

2012-01-01

BACKGROUND & AIMS The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, non-invasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRI). METHODS We screened 225 asymptomatic adult HRI at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS Ninety-two of 216 HRI (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n=5) by any of the imaging modalities. Fifty-one of the 84 HRI with a cyst (60.7%) had multiple lesions, typically small (mean 0.55 cm, range 2–39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects <50 years old, 34% of subjects 50–59 years old, and 53% of subjects 60–69 years old (P<.0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRI, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRI (82 intraductal papillary mucinous neoplasms [IPMN] and 3 pancreatic endocrine tumors). Three of 5 HRI who underwent pancreatic resection had high-grade dysplasia in <3 cm IPMNs and in multiple intraepithelial neoplasias. CONCLUSIONS Screening of asymptomatic HRI frequently detects small pancreatic cysts, including curable, non-invasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT. PMID:22245846

Parametric modelling of cardiac system multiple measurement signals: an open-source computer framework for performance evaluation of ECG, PCG and ABP event detectors.

PubMed

Homaeinezhad, M R; Sabetian, P; Feizollahi, A; Ghaffari, A; Rahmani, R

2012-02-01

The major focus of this study is to present a performance accuracy assessment framework based on mathematical modelling of cardiac system multiple measurement signals. Three mathematical algebraic subroutines with simple structural functions for synthetic generation of the synchronously triggered electrocardiogram (ECG), phonocardiogram (PCG) and arterial blood pressure (ABP) signals are described. In the case of ECG signals, normal and abnormal PQRST cycles in complicated conditions such as fascicular ventricular tachycardia, rate dependent conduction block and acute Q-wave infarctions of inferior and anterolateral walls can be simulated. Also, continuous ABP waveform with corresponding individual events such as systolic, diastolic and dicrotic pressures with normal or abnormal morphologies can be generated by another part of the model. In addition, the mathematical synthetic PCG framework is able to generate the S4-S1-S2-S3 cycles in normal and in cardiac disorder conditions such as stenosis, insufficiency, regurgitation and gallop. In the PCG model, the amplitude and frequency content (5-700 Hz) of each sound and variation patterns can be specified. The three proposed models were implemented to generate artificial signals with varies abnormality types and signal-to-noise ratios (SNR), for quantitative detection-delineation performance assessment of several ECG, PCG and ABP individual event detectors designed based on the Hilbert transform, discrete wavelet transform, geometric features such as area curve length (ACLM), the multiple higher order moments (MHOM) metric, and the principal components analysed geometric index (PCAGI). For each method the detection-delineation operating characteristics were obtained automatically in terms of sensitivity, positive predictivity and delineation (segmentation) error rms and checked by the cardiologist. The Matlab m-file script of the synthetic ECG, ABP and PCG signal generators are available in the Appendix.

Probability of regenerating a normal limb after bite injury in the Mexican axolotl (Ambystoma mexicanum)

PubMed Central

Thompson, Sierra; Muzinic, Laura; Muzinic, Christopher; Niemiller, Matthew L.

2014-01-01

Abstract Multiple factors are thought to cause limb abnormalities in amphibian populations by altering processes of limb development and regeneration. We examined adult and juvenile axolotls (Ambystoma mexicanum) in the Ambystoma Genetic Stock Center (AGSC) for limb and digit abnormalities to investigate the probability of normal regeneration after bite injury. We observed that 80% of larval salamanders show evidence of bite injury at the time of transition from group housing to solitary housing. Among 717 adult axolotls that were surveyed, which included solitary‐housed males and group‐housed females, approximately half presented abnormalities, including examples of extra or missing digits and limbs, fused digits, and digits growing from atypical anatomical positions. Bite injury probably explains these limb defects, and not abnormal development, because limbs with normal anatomy regenerated after performing rostral amputations. We infer that only 43% of AGSC larvae will present four anatomically normal looking adult limbs after incurring a bite injury. Our results show regeneration of normal limb anatomy to be less than perfect after bite injury. PMID:25745564

Multimodal image analysis of clinical influences on preterm brain development

PubMed Central

Ball, Gareth; Aljabar, Paul; Nongena, Phumza; Kennea, Nigel; Gonzalez‐Cinca, Nuria; Falconer, Shona; Chew, Andrew T.M.; Harper, Nicholas; Wurie, Julia; Rutherford, Mary A.; Edwards, A. David

2017-01-01

Objective Premature birth is associated with numerous complex abnormalities of white and gray matter and a high incidence of long‐term neurocognitive impairment. An integrated understanding of these abnormalities and their association with clinical events is lacking. The aim of this study was to identify specific patterns of abnormal cerebral development and their antenatal and postnatal antecedents. Methods In a prospective cohort of 449 infants (226 male), we performed a multivariate and data‐driven analysis combining multiple imaging modalities. Using canonical correlation analysis, we sought separable multimodal imaging markers associated with specific clinical and environmental factors and correlated to neurodevelopmental outcome at 2 years. Results We found five independent patterns of neuroanatomical variation that related to clinical factors including age, prematurity, sex, intrauterine complications, and postnatal adversity. We also confirmed the association between imaging markers of neuroanatomical abnormality and poor cognitive and motor outcomes at 2 years. Interpretation This data‐driven approach defined novel and clinically relevant imaging markers of cerebral maldevelopment, which offer new insights into the nature of preterm brain injury. Ann Neurol 2017;82:233–246 PMID:28719076

Maternal characteristics and birth outcomes of pregnant women who had offspring with congenital ear abnormalities - a population-based case-control study.

PubMed

Paput, László; Bánhidy, Ferenc; Czeizel, Andrew E

2011-09-01

To describe the maternal characteristics and birth outcomes of newborn infants affected with isolated ear congenital abnormalities (IECA), mainly isolated anotia/microtia and unclassified multiple congenital abnormalities (CAs) including anotia/microtia (UMAM). Cases with IECA and UMAM were compared with their matched controls and all controls without any defect and malformed controls affected with other defects in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities. The mothers of 354 cases with IECA did not show significant difference in age, but their mean birth order was higher while their socio-economic status based on the maternal employment status was lower compared to the figures of their matched controls. There was a male excess among cases with microtia and mainly with UMAM. The evaluation of birth outcomes of newborns affected with IECA indicated intrauterine fetal growth retardation. Newborn infants with isolated microtia had intrauterine growth retardation and the association of this developmental defect localized for a small region of head with the general fetal development raises interesting theoretical question.

[Genetic diagnostics of pathogenic splicing abnormalities in the clinical laboratory--pitfalls and screening approaches].

PubMed

Niimi, Hideki; Ogawa, Tomomi; Note, Rhougou; Hayashi, Shirou; Ueno, Tomohiro; Harada, Kenu; Uji, Yoshinori; Kitajima, Isao

2010-12-01

In recent years, genetic diagnostics of pathogenic splicing abnormalities are increasingly recognized as critically important in the clinical genetic diagnostics. It is reported that approximately 10% of pathogenic mutations causing human inherited diseases are splicing mutations. Nonetheless, it is still difficult to identify splicing abnormalities in routine genetic diagnostic settings. Here, we studied two different kinds of cases with splicing abnormalities. The first case is a protein S deficiency. Nucleotide analyses revealed that the proband had a previously reported G to C substitution in the invariant AG dinucleotide at the splicing acceptor site of intronl/exon2, which produces multiple splicing abnormalities resulting in protein S deficiency. The second case is an antithrombin (AT) deficiency. This proband had a previously reported G to A substitution, at nucleotide position 9788 in intron 4, 14 bp in front of exon 5, which created a de novo exon 5 splice site and resulted in AT deficiency. From a practical standpoint, we discussed the pitfalls, attentions, and screening approaches in genetic diagnostics of pathogenic splicing abnormalities. Due to the difficulty with full-length sequence analysis of introns, and the lack of RNA samples, splicing mutations may escape identification. Although current genetic testing remains to be improved, to screen for splicing abnormalities more efficiently, it is significant to use an appropriate combination of various approaches such as DNA and/or RNA samples, splicing mutation databases, bioinformatic tools to detect splice sites and cis-regulatory elements, and in vitro and/or in vivo experimentally methods as needed.

Identification of aberrant gene expression associated with aberrant promoter methylation in primordial germ cells between E13 and E16 rat F3 generation vinclozolin lineage.

PubMed

Taguchi, Y-h

2015-01-01

Transgenerational epigenetics (TGE) are currently considered important in disease, but the mechanisms involved are not yet fully understood. TGE abnormalities expected to cause disease are likely to be initiated during development and to be mediated by aberrant gene expression associated with aberrant promoter methylation that is heritable between generations. However, because methylation is removed and then re-established during development, it is not easy to identify promoter methylation abnormalities by comparing normal lineages with those expected to exhibit TGE abnormalities. This study applied the recently proposed principal component analysis (PCA)-based unsupervised feature extraction to previously reported and publically available gene expression/promoter methylation profiles of rat primordial germ cells, between E13 and E16 of the F3 generation vinclozolin lineage that are expected to exhibit TGE abnormalities, to identify multiple genes that exhibited aberrant gene expression/promoter methylation during development. The biological feasibility of the identified genes were tested via enrichment analyses of various biological concepts including pathway analysis, gene ontology terms and protein-protein interactions. All validations suggested superiority of the proposed method over three conventional and popular supervised methods that employed t test, limma and significance analysis of microarrays, respectively. The identified genes were globally related to tumors, the prostate, kidney, testis and the immune system and were previously reported to be related to various diseases caused by TGE. Among the genes reported by PCA-based unsupervised feature extraction, we propose that chemokine signaling pathways and leucine rich repeat proteins are key factors that initiate transgenerational epigenetic-mediated diseases, because multiple genes included in these two categories were identified in this study.

Identification of aberrant gene expression associated with aberrant promoter methylation in primordial germ cells between E13 and E16 rat F3 generation vinclozolin lineage

PubMed Central

2015-01-01

Background Transgenerational epigenetics (TGE) are currently considered important in disease, but the mechanisms involved are not yet fully understood. TGE abnormalities expected to cause disease are likely to be initiated during development and to be mediated by aberrant gene expression associated with aberrant promoter methylation that is heritable between generations. However, because methylation is removed and then re-established during development, it is not easy to identify promoter methylation abnormalities by comparing normal lineages with those expected to exhibit TGE abnormalities. Methods This study applied the recently proposed principal component analysis (PCA)-based unsupervised feature extraction to previously reported and publically available gene expression/promoter methylation profiles of rat primordial germ cells, between E13 and E16 of the F3 generation vinclozolin lineage that are expected to exhibit TGE abnormalities, to identify multiple genes that exhibited aberrant gene expression/promoter methylation during development. Results The biological feasibility of the identified genes were tested via enrichment analyses of various biological concepts including pathway analysis, gene ontology terms and protein-protein interactions. All validations suggested superiority of the proposed method over three conventional and popular supervised methods that employed t test, limma and significance analysis of microarrays, respectively. The identified genes were globally related to tumors, the prostate, kidney, testis and the immune system and were previously reported to be related to various diseases caused by TGE. Conclusions Among the genes reported by PCA-based unsupervised feature extraction, we propose that chemokine signaling pathways and leucine rich repeat proteins are key factors that initiate transgenerational epigenetic-mediated diseases, because multiple genes included in these two categories were identified in this study. PMID:26677731

Probabilistic images (PBIS): A concise image representation technique for multiple parameters

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

Wu, L.C.; Yeh, S.H.; Chen, Z.

1984-01-01

Based on m parametric images (PIs) derived from a dynamic series (DS), each pixel of DS is regarded as an m-dimensional vector. Given one set of normal samples (pixels) N and another of abnormal samples A, probability density functions (pdfs) of both sets are estimated. Any unknown sample is classified into N or A by calculating the probability of its being in the abnormal set using the Bayes' theorem. Instead of estimating the multivariate pdfs, a distance ratio transformation is introduced to map the m-dimensional sample space to one dimensional Euclidean space. Consequently, the image that localizes the regional abnormalitiesmore » is characterized by the probability of being abnormal. This leads to the new representation scheme of PBIs. Tc-99m HIDA study for detecting intrahepatic lithiasis (IL) was chosen as an example of constructing PBI from 3 parameters derived from DS and such a PBI was compared with those 3 PIs, namely, retention ratio image (RRI), peak time image (TNMAX) and excretion mean transit time image (EMTT). 32 normal subjects and 20 patients with proved IL were collected and analyzed. The resultant sensitivity and specificity of PBI were 97% and 98% respectively. They were superior to those of any of the 3 PIs: RRI (94/97), TMAX (86/88) and EMTT (94/97). Furthermore, the contrast of PBI was much better than that of any other image. This new image formation technique, based on multiple parameters, shows the functional abnormalities in a structural way. Its good contrast makes the interpretation easy. This technique is powerful compared to the existing parametric image method.« less

Abnormal frontal theta oscillations underlie the cognitive flexibility deficits in children with high-functioning autism spectrum disorders.

PubMed

Yeung, Michael K; Han, Yvonne M Y; Sze, Sophia L; Chan, Agnes S

2016-03-01

Deficits in cognitive flexibility have been suggested to underlie the repetitive and stereotyped behavior in individuals with autism spectrum disorders (ASD). Because cognitive flexibility is primarily mediated by the frontal lobe, where structural and functional abnormalities have been extensively found in these individuals, it is conceivable that their deficits in cognitive flexibility are related to abnormal activations of the frontal lobe. The present study investigates cognitive flexibility and its underlying neurophysiological activities as indicated by theta oscillations in children with ASD. Twenty-five children with high-functioning ASD and 25 IQ- and age-matched typically developing (TD) children were subjected to neuropsychological assessments on cognitive flexibility and electroencephalography recordings. The children with ASD performed significantly worse than the TD children across the tasks of cognitive flexibility, including the modified Wisconsin Card Sorting Test (WCST). These children also demonstrated a reduced increase of the theta power localized in multiple brain regions, including various sectors of the frontal lobe at the late stage (i.e., 600 ms-900 ms poststimulus interval) but not the early stage (i.e., 250 ms-550 ms poststimulus interval) of the performance of the modified WCST. The suppressed late frontal theta activities were further shown to be significantly correlated with a poorer performance on the cognitive flexibility measures. Our findings suggest that abnormal activations of multiple cortical regions, especially the frontal lobe, form the neural basis of the cognitive flexibility deficits in children with ASD. In addition, we found an EEG marker of cognitive flexibility which could be used to monitor treatment outcomes objectively. (c) 2016 APA, all rights reserved).

Tetra-phocomelia: the seal limb deformity - a case report.

PubMed

Samal, Sunil Kumar; Rathod, Setu; Ghose, Seetesh

2015-02-01

We report a case of term live baby with tetra-phocomelia born to a 35-year-old G3P2L2A0 with history of consanguineous marriage. She was an unbooked case from a tribal community with no previous antenatal visits. At 39 wk of gestation, she was admitted to our hospital with complaint of pain abdomen and on examination was found to be in second stage of labour. She delivered vaginally a term live 2.5 kg female baby with multiple anomalies. There was no history of drug intake, radiation exposure, maternal diabetes or family history of congenital anomalies to support the occurrence of tetra-phocomelia in this baby. The neonate also had multiple facial abnormalities like hypertelorism, microretrognathia and partial cleft palate. Further investigations revealed no abnormalities of internal organs. At present the baby is being followed up at our paediatric department. The case is reported owing to its rarity and term live birth.

Gastroscopic screening in 80 patients with pernicious anaemia.

PubMed Central

Stockbrügger, R W; Menon, G G; Beilby, J O; Mason, R R; Cotton, P B

1983-01-01

We have studied 80 patients with pernicious anaemia. Upper gastrointestinal endoscopy (with biopsy and cytology) showed no lesion other than atrophic gastritis in 34 patients. Thirty three patients, however, had varying degrees of gastric mucosal dysplasia, which was detected more frequently by histology than by cytology. The endoscopic appearance of the mucosa was abnormal in four of the six patients with moderate dysplasia, and in all three patients with severe dysplasia. One patient was found to have a small carcinoma in the gastric antrum, and underwent total gastrectomy; 18 patients had polyps (often multiple); four of these were treated by endoscopic polypectomy. One of the patients with polyps had multiple carcinoid tumours, and an asymptomatic parathyroid adenoma. Seventeen of the patients also underwent barium meal examination; abnormalities were revealed in only three of the seven patients with lesions visible at endoscopy. Our results justify further endoscopic studies in patients with pernicious anaemia, and sequential examinations to establish the natural history of gastric dysplasia. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6642278

Double trisomy 48,XXX,+18 with multiple dysmorphic features.

PubMed

Jiang, Zi-Yan; Wu, Xiao-Hui; Zou, Chao-Chun

2015-02-01

Chromosomal abnormality is a common cause of congenital anomalies, psychiatric disorders, and mental retardation. However, the double trisomy 48,XXX,+18 is a rare chromosome abnormality. Case report and literature review. A 7-hour-old girl presented to our unit because of poor response after birth. She presented with multiple dysmorphic features, including small for gestational age infant, flat nasal bridge, widely-spaced eyes, the left thumb deformities, flat facial profile, raised sternum, ventricular septal defect, the third lateral brain ventricle enlargement, and small liver. This case expands the spectrum of malformations reported in association with the double trisomy 48,XXX,+18. The literature on 16 fetuses or infants with the 48,XXX,+18 were also reviewed. These data suggested that in patients with clinical features similar to trisomy 18, especially with anomalies of the ears and/or reproductive malformations, double trisomy (48,XXX,+18) should be considered and karyotyping should be performed although it is a rare disease.

Paradoxically aggressive multiple sclerosis in the face of natalizumab therapy.

PubMed

Berger, J R

2008-06-01

In the pivotal trials of natalizumab in the treatment of relapsing-remitting multiple sclerosis (AFFIRM and SENTINEL), a dramatic reduction in relapse rate, new or enlarging T2-hyperintense lesions, and mean number of gadolinium-enhancing lesions was observed. While both relapses and new MRI lesions were observed in these trials, there has been no comment on the presence of aggressive disease in the face of natalizumab treatment. I report a 31-year-old woman with relapsing remitting MS of 12 years duration who developed aggressive demyelinating disease four months after the initiation of natalizumab. The clinical worsening was accompanied by a significant increase in new large T2-hyperintense signal abnormalities and in both solid and C-shaped contrast-enhancing lesions. Neither the clinical severity nor the striking MRI abnormalities had been noted earlier in her disease course. Neutralizing antibodies to natalizumab were not detected. She subsequently responded to combination therapy of pulsed methylprednisolone and daily glatiramer acetate.

Gait characteristics of individuals with multiple sclerosis before and after a 6-month aerobic training program.

PubMed

Rodgers, M M; Mulcare, J A; King, D L; Mathews, T; Gupta, S C; Glaser, R M

1999-07-01

Individuals who have multiple sclerosis (MS) typically experience problems with physical activities such as walking, resulting from the combined effects of skeletal muscle weakness, sensory disturbances, spasticity, gait ataxia, and reduction in aerobic capacity. The aim of this study was to determine whether a 6-mo exercise program designed for aerobic conditioning might also affect gait abnormalities in individuals with MS. Subjects included 18 individuals with MS who presented a range of disability. Passive range of motion (PROM) in the lower limbs was measured and gait analyzed before and after exercise conditioning. Three-dimensional kinematics, ground reaction forces (GRF), and electromyographic information were acquired as subjects walked at self-selected velocities. Hip PROM increased following conditioning. Mean walking velocity, cadence, and posterior shear GRF (push-off force) decreased. During walking, maximum ankle dorsiflexion decreased and ankle plantarflexion increased. Total knee flexion/extension range during the walking cycle decreased slightly as did maximum hip extension. Results suggest this 6-mo training program had minimal effect on gait abnormalities.

Tetra-Phocomelia: The Seal Limb Deformity - A Case Report

PubMed Central

Rathod, Setu; Ghose, Seetesh

2015-01-01

We report a case of term live baby with tetra-phocomelia born to a 35-year-old G3P2L2A0 with history of consanguineous marriage. She was an unbooked case from a tribal community with no previous antenatal visits. At 39 wk of gestation, she was admitted to our hospital with complaint of pain abdomen and on examination was found to be in second stage of labour. She delivered vaginally a term live 2.5 kg female baby with multiple anomalies. There was no history of drug intake, radiation exposure, maternal diabetes or family history of congenital anomalies to support the occurrence of tetra-phocomelia in this baby. The neonate also had multiple facial abnormalities like hypertelorism, microretrognathia and partial cleft palate. Further investigations revealed no abnormalities of internal organs. At present the baby is being followed up at our paediatric department. The case is reported owing to its rarity and term live birth. PMID:25859493

Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

PubMed Central

Wilson, Robert; Geyer, Stefan H.; Reissig, Lukas; Rose, Julia; Szumska, Dorota; Hardman, Emily; Prin, Fabrice; McGuire, Christina; Ramirez-Solis, Ramiro; White, Jacqui; Galli, Antonella; Tudor, Catherine; Tuck, Elizabeth; Mazzeo, Cecilia Icoresi; Smith, James C.; Robertson, Elizabeth; Adams, David J.; Mohun, Timothy; Weninger, Wolfgang J.

2017-01-01

Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates. PMID:27996060

Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome?

PubMed

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R; Matsushita, Mark; Raskind, Wendy H

2008-07-15

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair, and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. 2008 Wiley-Liss, Inc.

Avoiding Complications with MPFL Reconstruction.

PubMed

Smith, Marvin K; Werner, Brian C; Diduch, David R

2018-05-12

To discuss the potentially significant complications associated with medial patellofemoral ligament (MPFL) reconstruction. Additionally, to review the most current and relevant literature with an emphasis on avoiding these potential complications. Multiple cadaveric studies have characterized the anatomy of the MPFL and the related morphologic abnormalities that contribute to recurrent lateral patellar instability. Such abnormalities include patella alta, excessive tibial tubercle to trochlear grove (TT-TG) distance, trochlear dysplasia, and malalignment. Recent studies have evaluated the clinical outcomes associated with the treatment of concomitant pathology in combination with MPFL reconstruction, which is critical in avoiding recurrent instability and complications. Although there remains a lack of consensus regarding various critical aspects of MPFL reconstruction, certain concepts remain imperative. Our preferred methods and rationales for surgical techniques are described. These include appropriate work up, a combination of procedures to address abnormal morphology, anatomical femoral insertion, safe and secure patellar fixation, appropriate graft length fixation, and thoughtful knee flexion during fixation.

[Dandy-Walker complex: a clinicopathologic study of 9 cases].

PubMed

Zhang, Xiao-bo; Gu, Yi-qun; Sun, Xiao-fei; Wang, Ying-nan; Wang, Ai-chun

2013-12-01

To investigate the etiology, pathogenesis, clinicopathologic characteristics, clinical prognosis and treatment of Dandy-Walker syndrome. Nine cases of Dandy-Walker syndrome were included in the study. The autopsy findings and clinical history were evaluated along with review of the literature. The causes, pathogenetic mechanism, pathologic features and prognosis of Dandy-Walker syndrome were analyzed. Among 9 Dandy-Walker syndrome cases, six patients presented with variants of Dandy-Walker complex and 3 cases had classic Dandy-Walker malformation. In addition, 4 patients presented with combined lateral ventricle expansion and multiple malformations were seen in 7 cases. Combined umbilical cord abnormality was noted in 4 patients with variant of Dandy-Walker complex and combined placental abnormality was seen in one classic Dandy-Walker syndrome. Dandy-Walker syndrome is a rare disease. In addition to complex pathogenesis with possible genetic and environmental antigenic etiologies, placental and umbilical cord abnormality may be also related to its development.

Co-localisation of abnormal brain structure and function in specific language impairment

PubMed Central

Badcock, Nicholas A.; Bishop, Dorothy V.M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

2012-01-01

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. PMID:22137677

A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue.

PubMed

Elsayed, Maha; Magistretti, Pierre J

2015-01-01

Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment.

The Real Culprit in Systemic Lupus Erythematosus: Abnormal Epigenetic Regulation

PubMed Central

Wu, Haijing; Zhao, Ming; Chang, Christopher; Lu, Qianjin

2015-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and the presence of anti-nuclear antibodies. The pathogenesis of SLE has been intensively studied but remains far from clear. B and T lymphocyte abnormalities, dysregulation of apoptosis, defects in the clearance of apoptotic materials, and various genetic and epigenetic factors are attributed to the development of SLE. The latest research findings point to the association between abnormal epigenetic regulation and SLE, which has attracted considerable interest worldwide. It is the purpose of this review to present and discuss the relationship between aberrant epigenetic regulation and SLE, including DNA methylation, histone modifications and microRNAs in patients with SLE, the possible mechanisms of immune dysfunction caused by epigenetic changes, and to better understand the roles of aberrant epigenetic regulation in the initiation and development of SLE and to provide an insight into the related therapeutic options in SLE. PMID:25988383

Brain anomalies in velo-cardio-facial syndrome

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

Mitnick, R.J.; Bello, J.A.; Shprintzen, R.J.

Magnetic resonance imaging of the brain in 11 consecutively referred patients with velo-cardio-facial syndrome (VCF) showed anomalies in nine cases including small vermis, cysts adjacent to the frontal horns, and small posterior fossa. Focal signal hyperintensities in the white matter on long TR images were also noted. The nine patients showed a variety of behavioral abnormalities including mild development delay, learning disabilities, and characteristic personality traits typical of this common multiple anomaly syndrome which has been related to a microdeletion at 22q11. Analysis of the behavorial findings showed no specific pattern related to the brain anomalies, and the patients withmore » VCF who did not have detectable brain lesions also had behavioral abnormalities consistent with VCF. The significance of the lesions is not yet known, but the high prevalence of anomalies in this sample suggests that structural brain abnormalities are probably common in VCF. 25 refs.« less

A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue

PubMed Central

Elsayed, Maha; Magistretti, Pierre J.

2015-01-01

Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment. PMID:26733803

Tumor or abnormality identification from magnetic resonance images using statistical region fusion based segmentation.

PubMed

Subudhi, Badri Narayan; Thangaraj, Veerakumar; Sankaralingam, Esakkirajan; Ghosh, Ashish

2016-11-01

In this article, a statistical fusion based segmentation technique is proposed to identify different abnormality in magnetic resonance images (MRI). The proposed scheme follows seed selection, region growing-merging and fusion of multiple image segments. In this process initially, an image is divided into a number of blocks and for each block we compute the phase component of the Fourier transform. The phase component of each block reflects the gray level variation among the block but contains a large correlation among them. Hence a singular value decomposition (SVD) technique is adhered to generate a singular value of each block. Then a thresholding procedure is applied on these singular values to identify edgy and smooth regions and some seed points are selected for segmentation. By considering each seed point we perform a binary segmentation of the complete MRI and hence with all seed points we get an equal number of binary images. A parcel based statistical fusion process is used to fuse all the binary images into multiple segments. Effectiveness of the proposed scheme is tested on identifying different abnormalities: prostatic carcinoma detection, tuberculous granulomas identification and intracranial neoplasm or brain tumor detection. The proposed technique is established by comparing its results against seven state-of-the-art techniques with six performance evaluation measures. Copyright © 2016 Elsevier Inc. All rights reserved.

Abnormal metabolic brain networks in Parkinson's disease from blackboard to bedside.

PubMed

Tang, Chris C; Eidelberg, David

2010-01-01

Metabolic imaging in the rest state has provided valuable information concerning the abnormalities of regional brain function that underlie idiopathic Parkinson's disease (PD). Moreover, network modeling procedures, such as spatial covariance analysis, have further allowed for the quantification of these changes at the systems level. In recent years, we have utilized this strategy to identify and validate three discrete metabolic networks in PD associated with the motor and cognitive manifestations of the disease. In this chapter, we will review and compare the specific functional topographies underlying parkinsonian akinesia/rigidity, tremor, and cognitive disturbance. While network activity progressed over time, the rate of change for each pattern was distinctive and paralleled the development of the corresponding clinical symptoms in early-stage patients. This approach is already showing great promise in identifying individuals with prodromal manifestations of PD and in assessing the rate of progression before clinical onset. Network modulation was found to correlate with the clinical effects of dopaminergic treatment and surgical interventions, such as subthalamic nucleus (STN) deep brain stimulation (DBS) and gene therapy. Abnormal metabolic networks have also been identified for atypical parkinsonian syndromes, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Using multiple disease-related networks for PD, MSA, and PSP, we have developed a novel, fully automated algorithm for accurate classification at the single-patient level, even at early disease stages. Copyright © 2010 Elsevier B.V. All rights reserved.

Ultrasound predictors of mortality in monochorionic twins with selective intrauterine growth restriction.

PubMed

Ishii, K; Murakoshi, T; Hayashi, S; Saito, M; Sago, H; Takahashi, Y; Sumie, M; Nakata, M; Matsushita, M; Shinno, T; Naruse, H; Torii, Y

2011-01-01

The aim of this study was to evaluate the use of ultrasound assessment to predict risk of mortality in expectantly managed monochorionic twin fetuses with selective intrauterine growth restriction (sIUGR). This was a retrospective study of 101 monochorionic twin pregnancies diagnosed with sIUGR before 26 weeks of gestation. All patients were under expectant management during the observation period. At the initial evaluation, the presence or absence of each of the following abnormalities was documented: oligohydramnios; stuck twin phenomenon; severe IUGR < 3(rd) centile of estimated fetal weight; abnormal Doppler in the umbilical artery; and polyhydramnios in the larger twin. The relationships between these ultrasound findings and mortality of sIUGR fetuses were evaluated using multiple logistic regression analysis. Of 101 sIUGR twins, 22 (21.8%) fetuses suffered intrauterine demise and nine (8.9%) suffered neonatal death; 70 (69.3%) survived the neonatal period. Multiple logistic regression analysis revealed that the stuck twin phenomenon (odds ratio (OR): 14.5; 95% CI: 2.2-93.2; P = 0.006) and constantly absent diastolic flow in the umbilical artery (OR: 29.4; 95% CI: 3.3-264.0; P = 0.003) were significant risk factors for mortality. Not only abnormal Doppler flow in the umbilical artery but also severe oligohydramnios should be recognized as important indicators for mortality in monochorionic twins with sIUGR.

Relationships (II) of International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases with ventilatory functions indices for parenchymal abnormalities.

PubMed

Tamura, Taro; Suganuma, Narufumi; Hering, Kurt G; Vehmas, Tapio; Itoh, Harumi; Akira, Masanori; Takashima, Yoshihiro; Hirano, Harukazu; Kusaka, Yukinori

2015-01-01

The International Classification of High-Resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) is used to screen and diagnose respiratory illnesses. Using univariate and multivariate analysis, we investigated the relationship between subject characteristics and parenchymal abnormalities according to ICOERD, and the results of ventilatory function tests (VFT). Thirty-five patients with and 27 controls without mineral-dust exposure underwent VFT and HRCT. We recorded all subjects' occupational history for mineral dust exposure and smoking history. Experts independently assessed HRCT using the ICOERD parenchymal abnormalities (Items) grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). High-resolution computed tomography showed that 11 patients had RO; 15 patients, IR; and 19 patients, EM. According to the multiple regression model, age and height had significant associations with many indices ventilatory functions such as vital capacity, forced vital capacity, and forced expiratory volume in 1 s (FEV1). The EM summed grades on the upper, middle, and lower zones of the right and left lungs also had significant associations with FEV1 and the maximum mid-expiratory flow rate. The results suggest the ICOERD notation is adequate based on the good and significant multiple regression modeling of ventilatory function with the EM summed grades.

The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis.

PubMed

Morris, Gerwyn; Stubbs, Brendon; Köhler, Cristiano A; Walder, Ken; Slyepchenko, Anastasiya; Berk, Michael; Carvalho, André F

2018-04-04

Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways. In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop. This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

A novel NF1 mutation in a Chinese patient with giant café-au-lait macule in neurofibromatosis type 1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

PubMed

Tong, H-X; Li, M; Zhang, Y; Zhu, J; Lu, W-Q

2012-08-29

Neurofibromatosis type 1 (NF1; OMIM#162200) is a common neurocutaneous disorder that is characterized by multiple café-au-lait, skinfold freckling, Lisch nodules, and neurofibromas. Mutations in the NF1 gene, which encodes the neurofibromin protein, have been identified as the pathogenic gene of NF1. In this study, we present a clinical and molecular study of a Chinese patient with giant café-au-lait in NF1. The patient showed >6 café-au-lait spots on the body, axillary freckling, and multiple subcutaneous neurofibromas. He also had a malignant peripheral nerve sheath tumor and bone abnormalities. The germline mutational analysis of the NF1 gene revealed a novel missense mutation in exon 13. It is a novel heterozygous nucleotide G>A transition at position 2241 of the NF1 gene. We found no mutation in malignant peripheral nerve sheath tumor DNA from this patient. This expands the database for NF1 gene mutations in NF1. Its absence in the normal chromosomes suggests that it is responsible for the NF1 phenotype. To our knowledge, this is the first case of giant café-au-lait macule in NF1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

Region-specific deletions of RIM1 reproduce a subset of global RIM1α−/− phenotypes

PubMed Central

Haws, M E; Kaeser, P S; Jarvis, D L; Südhof, T C; Powell, C M

2012-01-01

The presynaptic protein RIM1α mediates multiple forms of presynaptic plasticity at both excitatory and inhibitory synapses. Previous studies of mice lacking RIM1α (RIM1α−/− throughout the brain showed that deletion of RIM1α results in multiple behavioral abnormalities. In an effort to begin to delineate the brain regions in which RIM1 deletion mediates these abnormal behaviors, we used conditional (floxed) RIM1 knockout mice (fRIM1). By crossing these fRIM1 mice to previously characterized transgenic cre lines, we aimed to delete RIM1 selectively in the dentate gyrus (DG), using a specific preproopiomelanocortin promoter driving cre recombinase (POMC-cre) line , and in pyramidal neurons of the CA3 region of hippocampus, using the kainate receptor subunit 1 promoter driving cre recombinase (KA-cre). Neither of these cre driver lines was uniquely selective to the targeted regions. In spite of this, we were able to reproduce a subset of the global RIM1α−/− behavioral abnormalities, thereby narrowing the brain regions in which loss of RIM1 is sufficient to produce these behavioral differences. Most interestingly, hypersensitivity to the pyschotomimetic MK-801 was shown in mice lacking RIM1 selectively in the DG, arcuate nucleus of the hypothalamus and select cerebellar neurons, implicating novel brain regions and neuronal subtypes in this behavior. PMID:22103334

Gorlin-Goltz syndrome: A series of three cases.

PubMed

Patankar, Amod P; Kshirsagar, Rajesh A; Dugal, Arun; Mishra, Akshay; Ram, Hari

2014-01-01

The Gorlin-Goltz syndrome (GGS) is also known as nevoid basal cell carcinoma syndrome. It is characterized by multiple keratocystic odontogenic tumors (KCOTs) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. The syndrome may be diagnosed early by a dentist during the routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article reports the series of 3 cases, emphasizing its clinical and radiographic manifestations of GGS.

Gorlin-Goltz syndrome: A series of three cases

PubMed Central

Patankar, Amod P.; Kshirsagar, Rajesh A.; Dugal, Arun; Mishra, Akshay; Ram, Hari

2014-01-01

The Gorlin-Goltz syndrome (GGS) is also known as nevoid basal cell carcinoma syndrome. It is characterized by multiple keratocystic odontogenic tumors (KCOTs) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. The syndrome may be diagnosed early by a dentist during the routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article reports the series of 3 cases, emphasizing its clinical and radiographic manifestations of GGS. PMID:25937738

VITAL SIGNS AND FIRST OCCURRENCES IN NORMAL AND ABNORMAL NEWBORN ASIAN ELEPHANT ( ELEPHAS MAXIMUS) CALVES.

PubMed

Wiedner, Ellen; Kiso, Wendy K; Aria, Janice; Isaza, Ramiro; Lindsay, William; Jacobson, Gary; Jacobson, Kathy; Schmitt, Dennis

2017-12-01

Sixteen years of medical records documenting 19 births within a herd of Asian elephants ( Elephas maximus) at a private facility in the southeastern United States were reviewed. Of the 19 calves, 11 were normal at birth, requiring no additional veterinary care, and eight were abnormal, requiring veterinary care immediately or within the first week of birth. Descriptive statistics were used to evaluate morphometrics, vital signs, and behavioral milestones in newborn calves both normal and abnormal. Blood work and urinalysis results from all calves were compared to values for adult elephants. Medical management of abnormal calves is described. All calves had faster heart rates and respiratory rates than did adult elephants, but rectal temperatures were the same. Calves were precocious with regard to sitting and standing but could be very slow to nurse. The most-common medical conditions of newborn calves were umbilical abnormalities and problems associated with nursing. Two calves required cardiopulmonary resuscitation after birth but made full recoveries. Some conditions were not apparent at birth but were recognized a few hours or days later. Following veterinary intervention, six of the eight calves made full recoveries, suggesting that early identification and treatment of problems can greatly decrease mortality. This is the first report of multiple veterinary and behavioral parameters in normal and abnormal neonatal Asian elephants from a facility with a calf survival rate above 90%. This information may be helpful to other elephant-holding facilities in providing care to their newborn elephant calves.

Refeeding syndrome or refeeding hypophosphatemia: a systematic review of cases.

PubMed

Skipper, Annalynn

2012-02-01

Nutrition support clinicians refer to the abnormalities in laboratory data and changes in clinical signs and symptoms that follow refeeding of starved or malnourished patients as refeeding syndrome. Theoretical descriptions of refeeding syndrome include a complex and extensive list of changes, such as hypophosphatemia, hypomagnesemia, hypokalemia, hyponatremia, hypocalcemia, hyperglycemia, and vitamin deficiency--all of which are accompanied by clinical signs and symptoms. In practice, clinicians see asymptomatic refeeding hypophosphatemia more often than a full-blown syndrome with multiple laboratory and clinical abnormalities. Confusion results because there is no widely accepted or uniformly applied set of defining characteristics for diagnosing refeeding syndrome. To gain insight into the clinical characteristics of refeeding syndrome described in the literature, a systematic review of reported cases and case series was conducted. Since 2000, 20 authors described 27 cases that contained sufficient data for review. Hypophosphatemia occurred in 26 patients (96%). While 19 patients (71%) experienced at least 1 other laboratory abnormality, only 14 (51%) exhibited a consistent pattern of abnormally low phosphorus and magnesium levels. Seven patients had hypocalcemia (26%), and hyponatremia was reported in 3 patients (11%). There were no reports of hyperglycemia. Mean data reported in case series containing data from 63 patients showed that hypophosphatemia was a consistent finding but that other abnormalities were not consistently identified. Findings suggest that refeeding hypophosphatemia is not accompanied by a consistent pattern of biochemical or clinical abnormalities among case reports or case series of patients reported to have refeeding syndrome.

Guidelines to identify abnormalities after childhood urinary tract infections: a prospective audit

PubMed Central

Coulthard, Malcolm G; Lambert, Heather J; Vernon, Susan J; Hunter, Elizabeth W; Keir, Michael J

2014-01-01

Objective To compare the childhood urinary tract infection (UTI) guidelines from the Royal College of Physicians (RCP) in 1991 and from National Institute of Health and Care Excellence (NICE) (CG54) in 2007 by measuring their efficiency at detecting urinary tract abnormalities. Design Children with UTIs within the Newcastle Primary Care Trust (population 70 800 children) were referred and imaged according to the RCP guidelines during 2008, and these were compared to the activity that would have been undertaken if we had implemented the CG54 guidelines, including following them through 2011 to identify those with recurrent UTIs. Main outcome measures The numbers of children imaged, the imaging burden and efficiency, and urinary tract abnormalities detected by each guideline. Results Fewer children would have been imaged by CG54 than RCP (150 vs 427), but its sensitivity was lower, at 44% for detecting scarring, 10% for identifying vesicoureteric reflux and 40% for other abnormalities. Overall, it would have only detected one-quarter of the abnormal cases (8 vs 32) and would have missed five of nine children with scarring, including three with multiple lesions and one with renal impairment. Imposing an age restriction of <8 years to the RCP guidelines would reduce its screening rate by 20% and still detect 90% of the abnormalities. Interpretation The CG54 guidelines do not alter the imaging efficiency compared to the RCP guidelines, but they are considerably less sensitive. PMID:24436366

Hair Follicle Miniaturization in a Woolly Hair Nevus: A Novel "Root" Perspective for a Mosaic Hair Disorder.

PubMed

Veraitch, Ophelia; Perez, Alfonso; Hoque, Shamali R; Vizcay-Barrena, Gema; Fleck, Roland A; Fenton, David A; Stefanato, Catherine M

2016-03-01

Woolly hair nevus is a mosaic disorder characterized by unruly, tightly curled hair in a circumscribed area of the scalp. This condition may be associated with epidermal nevi. We describe an 11-year-old boy who initially presented with multiple patches of woolly hair and with epidermal nevi on his left cheek and back. He had no nail, teeth, eye, or cardiac abnormalities. Analysis of plucked hairs from patches of woolly hair showed twisting of the hair shaft and an abnormal hair cuticle. Histopathology of a woolly hair patch showed diffuse hair follicle miniaturization with increased vellus hairs.

Clinical and laboratory aspects of Legionnaire's disease.

PubMed

Strampfer, M J; Cunha, B A

1987-12-01

Legionnaires' disease is an illness with protean manifestations that are due to infection with Legionella pneumophila. It occurs both in epidemic and sporadic form and usually presents as an atypical pneumonia. Relative bradycardia, abnormal liver function test results, and a patient presenting with an atypical pneumonia should alert the clinician to the possibility of Legionella. The presence of systemic involvement, specifically neurological, gastrointestinal, and renal abnormalities, should further suggest the diagnosis. Patients may demonstrate multiple extrapulmonary manifestations of legionnaires' disease, sometimes without pneumonia. Several methods are available to aid the clinician in making the diagnosis of legionnaires' disease, and the use of all tests will increase the overall sensitivity.

High Frequency of Neuroimaging Abnormalities Among Pediatric Patients With Sepsis Who Undergo Neuroimaging.

PubMed

Sandquist, Mary K; Clee, Mark S; Patel, Smruti K; Howard, Kelli A; Yunger, Toni; Nagaraj, Usha D; Jones, Blaise V; Fei, Lin; Vadivelu, Sudhakar; Wong, Hector R

2017-07-01

This study was intended to describe and correlate the neuroimaging findings in pediatric patients after sepsis. Retrospective chart review. Single tertiary care PICU. Patients admitted to Cincinnati Children's Hospital Medical Center with a discharge diagnosis of sepsis or septic shock between 2004 and 2013 were crossmatched with patients who underwent neuroimaging during the same time period. All neuroimaging studies that occurred during or subsequent to a septic event were reviewed, and all new imaging findings were recorded and classified. As many patients experienced multiple septic events and/or had multiple neuroimaging studies after sepsis, our statistical analysis utilized the most recent or "final" imaging study available for each patient so that only brain imaging findings that persisted were included. A total of 389 children with sepsis and 1,705 concurrent or subsequent neuroimaging studies were included in the study. Median age at first septic event was 3.4 years (interquartile range, 0.7-11.5). Median time from first sepsis event to final neuroimaging was 157 days (interquartile range, 10-1,054). The most common indications for final imaging were follow-up (21%), altered mental status (18%), and fever/concern for infection (15%). Sixty-three percentage (n = 243) of final imaging studies demonstrated abnormal findings, the most common of which were volume loss (39%) and MRI signal and/or CT attenuation abnormalities (21%). On multivariable logistic regression, highest Pediatric Risk of Mortality score and presence of oncologic diagnosis/organ transplantation were independently associated with any abnormal final neuroimaging study findings (odds ratio, 1.032; p = 0.048 and odds ratio, 1.632; p = 0.041), although early timing of neuroimaging demonstrated a negative association (odds ratio, 0.606; p = 0.039). The most common abnormal finding of volume loss was independently associated with highest Pediatric Risk of Mortality score (odds ratio, 1.037; p = 0.016) and oncologic diagnosis/organ transplantation (odds ratio, 2.207; p = 0.001) and was negatively associated with early timing of neuroimaging (odds ratio, 0.575; p = 0.037). The majority of pediatric patients with sepsis and concurrent or subsequent neuroimaging have abnormal neuroimaging findings. The implications of this high incidence for long-term neurologic outcomes and follow-up require further exploration.

Congenital malformations among newborns admitted in the neonatal unit of a tertiary hospital in Enugu, South-East Nigeria - a retrospective study

PubMed Central

2012-01-01

Background Congenital abnormalities are not uncommon among newborns and contribute to neonatal and infant morbidity and mortality. The prevalence and pattern of presentation vary from place to place. Many a time the exact etiology is unknown but genetic and environmental factors tend to be implicated. Methods The objective of this study was to determine the prevalence of congenital malformations among newborns admitted in a tertiary hospital in Enugu, the nature of these abnormalities and the outcome/prognosis. For purposes of this study, congenital abnormalities are defined as obvious abnormality of structure or form which is present at birth or noticed within a few days after birth. A cross-sectional retrospective study in which a review of the records of all babies admitted in the Newborn Special Care Unit (NBSCU) of the University of Nigeria Teaching Hospital (UNTH), Ituku/Ozalla, Enugu over a four year period (January 2007-April 2011) was undertaken. All babies admitted in the unit with the diagnosis of congenital abnormality were included in the study. Information extracted from the records included characteristics of the baby, maternal characteristics, nature/type of abnormalities and outcome. Data obtained was analyzed using SPSS 13. Rates and proportions were calculated with 95% confidence interval. The proportions were compared using students T-test. Level of significance was set at P < 0.05 Results Seventeen (17) out of a total of six hundred and seven newborn babies admitted in the newborn unit of UNTH over the study period (Jan 2007-March 2011) were found to have congenital abnormalities of various types, giving a prevalence of 2.8%. Common abnormalities seen in these babies were mainly surgical birth defects and included cleft lip/cleft palate, neural tube defects (occurring either singly or in combination with other abnormalities), limb abnormalities (often in combination with neural tube defects of various types), omphalocoele, umbilical herniae, ano-rectal malformations and dysmorphism associated with multiple congenital abnormalities. Conclusions The results of this study show that 2.8% of babies admitted to a Newborn Special Care Unit in a teaching hospital in Enugu had congenital abnormalities and that the commonest forms seen were mainly surgical birth defects and includes cleft lip/cleft palate and neural tube defects. PMID:22472067

Primary intestinal lymphangiectasia: Multiple detector computed tomography findings after direct lymphangiography.

PubMed

Sun, Xiaoli; Shen, Wenbin; Chen, Xiaobai; Wen, Tingguo; Duan, Yongli; Wang, Rengui

2017-10-01

To analyse the findings of multiple detector computed tomography (MDCT) after direct lymphangiography in primary intestinal lymphangiectasia (PIL). Fifty-five patients with PIL were retrospectively reviewed. All patients underwent MDCT after direct lymphangiography. The pathologies of 16 patients were confirmed by surgery and the remaining 39 patients were confirmed by gastroendoscopy and/or capsule endoscopy. After direct lymphangiography, MDCT found intra- and extraintestinal as well as lymphatic vessel abnormalities. Among the intra- and extraintestinal disorders, 49 patients had varying degrees of intestinal dilatation, 46 had small bowel wall thickening, 9 had pleural and pericardial effusions, 21 had ascites, 41 had mesenteric oedema, 20 had mesenteric nodules and 9 had abdominal lymphatic cysts. Features of lymphatic vessel abnormalities included intestinal trunk reflux (43.6%, n = 24), lumbar trunk reflux (89.1%, n = 49), pleural and pulmonary lymph reflux (14.5%, n = 8), pericardial and mediastinal lymph reflux (16.4%, n = 9), mediastinal and pulmonary lymph reflux (18.2%, n = 10), and thoracic duct outlet obstruction (90.9%, n = 50). Multiple detector computed tomography after direct lymphangiography provides a safe and accurate examination method and is an excellent tool for the diagnosis of PIL. © 2017 The Royal Australian and New Zealand College of Radiologists.

Core neuropathological abnormalities in progranulin-deficient mice are penetrant on multiple genetic backgrounds.

PubMed

Petkau, T L; Hill, A; Leavitt, B R

2016-02-19

Loss-of-function mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal lobar degeneration (FTLD). A high degree of heterogeneity in the age-of-onset, duration of disease, and clinical presentation of FTLD, even among families carrying the same GRN mutation, suggests that additional modifying genes may be important to pathogenesis. Progranulin-knockout mice display subtle behavioral abnormalities and progressive neuropathological changes, as well as altered dendritic morphology and synaptic deficits in the hippocampus. In this study we evaluated multiple neuropathological endpoints in aged progranulin knockout mice and their wild-type littermates on two different genetic backgrounds: C57Bl/6 and 129/SvImJ. We find that in most brain regions, both strains are susceptible to progranulin-mediated neuropathological phenotypes, including astrogliosis, microgliosis, and highly accelerated deposition of the aging pigment lipofuscin. Neuroinflammation due to progranulin deficiency is exaggerated in the B6 strain and present, but less pronounced, in the 129 strain. Differences between the strains in hippocampal neuron counts and neuronal morphology suggest a complex role for progranulin in the hippocampus. We conclude that core progranulin-mediated neurodegenerative phenotypes are penetrant on multiple inbred mouse strains, but that genetic background modulates progranulin's role in neuroinflammation and hippocampal biology. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

A SIMPLE POLYMERASE CHAIN REACTION-SEQUENCING ANALYSIS CAPABLE OF IDENTIFYING MULTIPLE MEDICALLY RELEVANT FILAMENTOUS FUNGAL SPECIES

EPA Science Inventory

Due to the accumulating evidence that suggests that numerous unhealthy conditions in the indoor environment are the result of abnormal growth of the filamentous fungi (mold) in and on building surfaces, it is necessary to accurately determine the organisms responsible for these m...

Smith-Lemli-Opitz syndrome: review and report of two affected siblings.

PubMed

Johnson, V P

1975-01-01

This paper reports two siblings with the Smith-Lemli-Opitz syndrome and reviews the literature on the subject. SLOS is a syndrome of multiple congenital anomalies with mental and growth retardation, unusual facies, genito-urinary and hand and foot abnormalities inherited as an autosomal recessive trait.

Environmentally toxicant exposures induced intragenerational transmission of liver abnormalities in mice

PubMed Central

Al-Griw, Mohamed A.; Treesh, Soad A.; Alghazeer, Rabia O.; Regeai, Sassia O.

2017-01-01

Environmental toxicants such as chemicals, heavy metals, and pesticides have been shown to promote transgenerational inheritance of abnormal phenotypes and/or diseases to multiple subsequent generations following parental and/or ancestral exposures. This study was designed to examine the potential transgenerational action of the environmental toxicant trichloroethane (TCE) on transmission of liver abnormality, and to elucidate the molecular etiology of hepatocyte cell damage. A total of thirty two healthy immature female albino mice were randomly divided into three equal groups as follows: a sham group, which did not receive any treatment; a vehicle group, which received corn oil alone, and TCE treated group (3 weeks, 100 μg/kg i.p., every 4th day). The F0 and F1 generation control and TCE populations were sacrificed at the age of four months, and various abnormalities histpathologically investigated. Cell death and oxidative stress indices were also measured. The present study provides experimental evidence for the inheritance of environmentally induced liver abnormalities in mice. The results of this study show that exposure to the TCE promoted adult onset liver abnormalities in F0 female mice as well as unexposed F1 generation offspring. It is the first study to report a transgenerational liver abnormalities in the F1 generation mice through maternal line prior to gestation. This finding was based on careful evaluation of liver histopathological abnormalities, apoptosis of hepatocytes, and measurements of oxidative stress biomarkers (lipid peroxidation, protein carbonylation, and nitric oxide) in control and TCE populations. There was an increase in liver histopathological abnormalities, cell death, and oxidative lipid damage in F0 and F1 hepatic tissues of TCE treated group. In conclusion, this study showed that the biological and health impacts of environmental toxicant TCE do not end in maternal adults, but are passed on to offspring generations. Hence, linking observed liver abnormality in the offspring to environmental exposure of their parental line. This study also illustrated that oxidative stress and apoptosis appear to be a molecular component of the hepatocyte cell injury. PMID:28884077

Abnormal notochord branching is associated with foregut malformations in the adriamycin treated mouse model.

PubMed

Hajduk, Piotr; Sato, Hideaki; Puri, Prem; Murphy, Paula

2011-01-01

Oesophageal atresia (OA) and tracheooesophageal fistula (TOF) are relatively common human congenital malformations of the foregut where the oesophagus does not connect with the stomach and there is an abnormal connection between the stomach and the respiratory tract. They require immediate corrective surgery and have an impact on the future health of the individual. These abnormalities are mimicked by exposure of rat and mouse embryos in utero to the drug adriamycin. The causes of OA/TOF during human development are not known, however a number of mouse mutants where different signalling pathways are directly affected, show similar abnormalities, implicating multiple and complex signalling mechanisms. The similarities in developmental outcome seen in human infants and in the adriamycin treated mouse model underline the potential of this model to unravel the early embryological events and further our understanding of the processes disturbed, leading to such abnormalities. Here we report a systematic study of the foregut and adjacent tissues in embryos treated with adriamycin at E7 and E8 and analysed between E9 and E12, comparing morphology in 3D in 149 specimens. We describe a spectrum of 8 defects, the most common of which is ventral displacement and branching of the notochord (in 94% of embryos at E10) and a close spatial correspondence between the site of notochord branching and defects of the foregut. In addition gene expression analysis shows altered dorso-ventral foregut patterning in the vicinity of notochord branches. This study shows a number of features of the adriamycin mouse model not previously reported, implicates the notochord as a primary site of disturbance in such abnormalities and underlines the importance of the model to further address the mechanistic basis of foregut congenital abnormalities.

Abnormal Notochord Branching Is Associated with Foregut Malformations in the Adriamycin Treated Mouse Model

PubMed Central

Hajduk, Piotr; Sato, Hideaki; Puri, Prem; Murphy, Paula

2011-01-01

Oesophageal atresia (OA) and tracheooesophageal fistula (TOF) are relatively common human congenital malformations of the foregut where the oesophagus does not connect with the stomach and there is an abnormal connection between the stomach and the respiratory tract. They require immediate corrective surgery and have an impact on the future health of the individual. These abnormalities are mimicked by exposure of rat and mouse embryos in utero to the drug adriamycin. The causes of OA/TOF during human development are not known, however a number of mouse mutants where different signalling pathways are directly affected, show similar abnormalities, implicating multiple and complex signalling mechanisms. The similarities in developmental outcome seen in human infants and in the adriamycin treated mouse model underline the potential of this model to unravel the early embryological events and further our understanding of the processes disturbed, leading to such abnormalities. Here we report a systematic study of the foregut and adjacent tissues in embryos treated with adriamycin at E7 and E8 and analysed between E9 and E12, comparing morphology in 3D in 149 specimens. We describe a spectrum of 8 defects, the most common of which is ventral displacement and branching of the notochord (in 94% of embryos at E10) and a close spatial correspondence between the site of notochord branching and defects of the foregut. In addition gene expression analysis shows altered dorso-ventral foregut patterning in the vicinity of notochord branches. This study shows a number of features of the adriamycin mouse model not previously reported, implicates the notochord as a primary site of disturbance in such abnormalities and underlines the importance of the model to further address the mechanistic basis of foregut congenital abnormalities. PMID:22132119

Cerebellar Influence on Motor Cortex Plasticity: Behavioral Implications for Parkinson’s Disease

PubMed Central

Kishore, Asha; Meunier, Sabine; Popa, Traian

2014-01-01

Normal motor behavior involves the creation of appropriate activity patterns across motor networks, enabling firing synchrony, synaptic integration, and normal functioning of these networks. Strong topography-specific connections among the basal ganglia, cerebellum, and their projections to overlapping areas in the motor cortices suggest that these networks could influence each other’s plastic responses and functions. The defective striatal signaling in Parkinson’s disease (PD) could therefore lead to abnormal oscillatory activity and aberrant plasticity at multiple levels within the interlinked motor networks. Normal striatal dopaminergic signaling and cerebellar sensory processing functions influence the scaling and topographic specificity of M1 plasticity. Both these functions are abnormal in PD and appear to contribute to the abnormal M1 plasticity. Defective motor map plasticity and topographic specificity within M1 could lead to incorrect muscle synergies, which could manifest as abnormal or undesired movements, and as abnormal motor learning in PD. We propose that the loss of M1 plasticity in PD reflects a loss of co-ordination among the basal ganglia, cerebellar, and cortical inputs which translates to an abnormal plasticity of motor maps within M1 and eventually to some of the motor signs of PD. The initial benefits of dopamine replacement therapy on M1 plasticity and motor signs are lost during the progressive course of disease. Levodopa-induced dyskinesias in patients with advanced PD is linked to a loss of M1 sensorimotor plasticity and the attenuation of dyskinesias by cerebellar inhibitory stimulation is associated with restoration of M1 plasticity. Complimentary interventions should target reestablishing physiological communication between the striatal and cerebellar circuits, and within striato-cerebellar loop. This may facilitate correct motor synergies and reduce abnormal movements in PD. PMID:24834063

Development of mediastinal lymphoma after radiotherapy for concurrent medulloblastoma and PNET in a patient with Gorlin syndrome.

PubMed

Jiang, Tao; Wang, Junmei; Wang, Ying; Li, Chunde

2016-08-12

Very young children with Gorlin syndrome are at risk for developing medulloblastoma. Patients with Gorlin syndrome may have multiple system abnormalities, including basal cell carcinomas, jaw cysts, desmoplastic medulloblastoma, palmar/plantar pits, rib abnormalities, and intracranial falx calcification. The early diagnosis of Gorlin syndrome in desmoplastic medulloblastoma patients is very important because these patients should receive chemotherapy as a first-line treatment and should avoid radiotherapy as much as possible. In the present study, a 5-year-old male patient had a concurrent cerebellar desmoplastic medulloblastoma and temporal primitive neuroectodermal tumor. Examinations of this patient revealed multiple café-au-lait spots, a jaw cyst, and a bifid rib. A molecular classification analysis revealed that the patient's cerebellar tumor was of the sonic hedgehog subtype. Twenty-seven months after tumor resection and cerebrospinal irradiation were performed, mediastinal lymphoma was found in the patient. The patient ultimately died of lymphoma. To the best of our knowledge, this is the first report of a concurrent medulloblastoma and primitive neuroectodermal tumor and the fourth report of multiple café-au-lait spots in a patient with Gorlin syndrome. This report is also the first account of the development of mediastinal lymphoma after spinal irradiation in a patient with Gorlin syndrome. Chemotherapy should be the first-line treatment for medulloblastoma patients with Gorlin syndrome. Young patients with medulloblastoma of the desmoplastic subtype and multiple café-au-lait spots should be thoroughly examined for Gorlin syndrome.

Reproductive disturbances in multiple neuroendocrine tumor syndromes.

PubMed

Lytras, Aristides; Tolis, George

2009-12-01

In the context of multiple neuroendocrine tumor syndromes, reproductive abnormalities may occur via a number of different mechanisms, such as hyperprolactinemia, increased GH/IGF-1 levels, hypogonadotropic hypogonadism, hypercortisolism, hyperandrogenism, hyperthyroidism, gonadotropin hypersecretion, as well as, tumorigenesis or functional disturbances in gonads or other reproductive organs. Precocious puberty and/or male feminization is a feature of McCune-Albright syndrome (MAS), neurofibromatosis type 1 (NF1), Carney complex (CNC), and Peutz-Jeghers syndrome (PJS), while sperm maturation and ovulation defects have been described in MAS and CNC. Although tumorigenesis of reproductive organs due to a multiple neuroendocrine tumor syndrome is very rare, certain lesions are characteristic and very unusual in the general population. Awareness leading to their recognition is important especially when other endocrine abnormalities coexist, as occasionally they may even be the first manifestation of a syndrome. Lesions such as certain types of ovarian cysts (MAS, CNC), pseudogynecomastia due to neurofibromas of the nipple-areola area (NF1), breast disease (CNC and Cowden disease (CD)), cysts and 'hypernephroid' tumors of the epididymis or bilateral papillary cystadenomas (mesosalpinx cysts) and endometrioid cystadenomas of the broad ligament (von Hippel-Lindau disease), testicular Sertoli calcifying tumors (CNC, PJS) monolateral or bilateral macroochidism and microlithiasis (MAS) may offer diagnostic clues. In addition, multiple neuroendocrine tumor syndromes may be complicated by reproductive malignancies including ovarian cancer in CNC, breast and endometrial cancer in CD, breast malignancies in NF1, and malignant sex-cord stromal tumors in PJS.

Maxillary Swelling as the First Evidence of Multiple Myeloma

PubMed Central

Kasamatsu, Atsushi; Kimura, Yasushi; Tsujimura, Hideki; Kanazawa, Harusachi; Koide, Nao; Miyamoto, Isao; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

2015-01-01

Multiple myeloma is a malignant neoplasm of plasma cells characterized by proliferation of a single clone of abnormal immunoglobulin-secreting plasma cells. Since the amount of hemopoietic bone marrow is decreased in the maxilla, oral manifestations of multiple myeloma are less common in the maxilla than in the mandible. We report the case of 33-year-old Japanese man who presented with a mass in the right maxillary alveolar region. Computed tomography and magnetic resonance images showed a soft tissue mass in the right maxilla eroding the anterior and lateral walls of the maxillary sinus and extending into the buccal space. The biopsy results, imaging, and laboratory investigations led to the diagnosis of multiple myeloma. This case report suggests that oral surgeons and dentists should properly address oral manifestations as first indications of multiple myeloma. PMID:26640721

HPV genotypes and associated cervical cytological abnormalities in women from the Pearl River Delta region of Guangdong province, China: a cross-sectional study

PubMed Central

2014-01-01

Background It is important to understand the specific HPV genotype distribution in screen-detected lesions. HPV Genotype is helpful for separating HPV-positive women at greater risk of cancer from those who can regress spontaneously and for preventing cervical cancer at early stage. The aim of this study was to investigate the high-risk HPV genotype distribution among cervical cytology abnormality in Pearl River Delta Region, Southern China Methods 5585 HPV-infected women were screened from 77069 women in Pearl River Delta Region. Information was obtained from 3226 screened subjects through questionnaires and personal interviews. Exfoliated cervical cells were collected by doctors for HPV test with MassARRAY (Sequenom, Sandiego, CA) technique based on the matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF) mass spectrometry (MS). The ThinPrep cytology test was performed to screen for cervical cancer. Unconditional logistic was used to determine the most common HPV carcinogenic types. Results Of the 3226 HPV-positive samples tested, 1744 (54.1%) with normal cervical cytology, 1482 (45.9%) with abnormal cytology. The five most common HPV types in this study were HPV16 (20.2%), HPV52 (17.1%), HPV58 (13.2%), HPV18 (9.5%), HPV6 (7.6%). Overall, HPV16 (OR = 10.5, 95% CI: 3.7 ~ 29.6), HPV33 (OR = 9.1, 95% CI: 2.8 ~ 29.2), HPV58 (OR = 6.3, 95% CI: 2.1 ~ 18.6), HPV31 (OR = 4.5, 95% CI: 1.3 ~ 15.5), multiple genotype infection (OR = 3.0, 95% CI: 1.7 ~ 14.7), especially HPV16 and HPV33, increased the risk of cytology abnormalities. Conclusions HPV16, HPV31, HPV33, HPV58, and multiple HPV genotype infection increased the risk of cytology abnormalities in Pearl River Delta Region and might be useful for the screening, preventing, treating, and monitoring of pre-cancer lesions in southern China. PMID:25016305

Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice

NASA Technical Reports Server (NTRS)

Levasseur, Regis; Barrios, Roberto; Elefteriou, Florent; Glass, Donald A 2nd; Lieberman, Michael W.; Karsenty, Gerard

2003-01-01

Gamma-glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase responsible for the degradation of glutathione in the gamma-glutamyl cycle. This cycle is implicated in the metabolism of cysteine, and absence of GGT causes a severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice have multiple metabolic abnormalities and are dwarf. We show here that this latter phenotype is due to a decreased of the growth plate cartilage total height resulting from a proliferative defect of chondrocytes. In addition, analysis of vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia. Histomorphometric studies showed that this low bone mass phenotype results from an increased osteoclast number and activity as well as from a marked decrease in osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor chondrocytes express GGT, suggesting that the observed defects are secondary to other abnormalities. N-acetylcysteine supplementation has been shown to reverse the metabolic abnormalities of the GGT-/- mice and in particular to restore the level of IGF-1 and sex steroids in these mice. Consistent with these previous observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic function. In contrast, resorbtion parameters are only partially normalized in GGT-/- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast biology at least partly independently of these hormones. These results establish the importance of cysteine metabolism for the regulation of bone remodeling and longitudinal growth.

Submicroscopic deletion involving the fibroblast growth factor receptor 1 gene in a patient with combined pituitary hormone deficiency.

PubMed

Fukami, Maki; Iso, Manami; Sato, Naoko; Igarashi, Maki; Seo, Misuzu; Kazukawa, Itsuro; Kinoshita, Eiichi; Dateki, Sumito; Ogata, Tsutomu

2013-01-01

Combined pituitary hormone deficiency (CPHD), isolated hypogonadotropic hypogonadism (IHH), Kallmann syndrome (KS), and septo-optic dysplasia (SOD) are genetically related conditions caused by abnormal development of the anterior midline in the forebrain. Although mutations in the fibroblast growth factor receptor 1 (FGFR1) gene have been implicated in the development of IHH, KS, and SOD, the relevance of FGFR1 abnormalities to CPHD remains to be elucidated. Here, we report a Japanese female patient with CPHD and FGFR1 haploinsufficiency. The patient was identified through copy-number analyses and direct sequencing of FGFR1 performed for 69 patients with CPHD. The patient presented with a combined deficiency of GH, LH and FSH, and multiple neurological abnormalities. In addition, normal TSH values along with a low free T4 level indicated the presence of central hypothyroidism. Molecular analyses identified a heterozygous ~ 8.5 Mb deletion involving 56 genes and pseudogenes. None of these genes except FGFR1 have been associated with brain development. No FGFR1 abnormalities were identified in the remaining 68 patients, although two patients carried nucleotide substitutions (p.V102I and p.S107L) that were assessed as benign polymorphism by in vitro functional assays. These results indicate a possible role of FGFR1 in anterior pituitary function and the rarity of FGFR1 abnormalities in patients with CPHD.

Live-cell imaging of nuclear-chromosomal dynamics in bovine in vitro fertilised embryos.

PubMed

Yao, Tatsuma; Suzuki, Rie; Furuta, Natsuki; Suzuki, Yuka; Kabe, Kyoko; Tokoro, Mikiko; Sugawara, Atsushi; Yajima, Akira; Nagasawa, Tomohiro; Matoba, Satoko; Yamagata, Kazuo; Sugimura, Satoshi

2018-05-10

Nuclear/chromosomal integrity is an important prerequisite for the assessment of embryo quality in artificial reproductive technology. However, lipid-rich dark cytoplasm in bovine embryos prevents its observation by visible light microscopy. We performed live-cell imaging using confocal laser microscopy that allowed long-term imaging of nuclear/chromosomal dynamics in bovine in vitro fertilised (IVF) embryos. We analysed the relationship between nuclear/chromosomal aberrations and in vitro embryonic development and morphological blastocyst quality. Three-dimensional live-cell imaging of 369 embryos injected with mRNA encoding histone H2B-mCherry and enhanced green fluorescent protein (EGFP)-α-tubulin was performed from single-cell to blastocyst stage for eight days; 17.9% reached the blastocyst stage. Abnormalities in the number of pronuclei (PN), chromosomal segregation, cytokinesis, and blastomere number at first cleavage were observed at frequencies of 48.0%, 30.6%, 8.1%, and 22.2%, respectively, and 13.0%, 6.2%, 3.3%, and 13.4%, respectively, for abnormal embryos developed into blastocysts. A multivariate analysis showed that abnormal chromosome segregation (ACS) and multiple PN correlated with delayed timing and abnormal blastomere number at first cleavage, respectively. In morphologically transferrable blastocysts, 30-40% of embryos underwent ACS and had abnormal PN. Live-cell imaging may be useful for analysing the association between nuclear/chromosomal dynamics and embryonic development in bovine embryos.

Pagetoid reticulosis (Woringer-Kolopp disease). An ultrastructural and immunocytological study.

PubMed

Takahashi, H; Takahashi, K; Tanno, K; Iijima, S

1982-05-01

Histopathological, immunocytological and ultrastructural observations are reported in the first case of pagetoid reticulosis (Woringer-Kolopp disease) in Japan. The patient was a 61-year-old woman with multiple skin lesions running a chronic and apparently benign clinical course. Histology of the skin biopsies revealed typical pagetoid appearance of the epidermis due to intraepidermal infiltration of abnormal cells. Ultrastructural investigation showed that the intraepidermal abnormal cells were classified into mycosis fungoides cells, Sézary cells, lymphoblast-like cells, and large blastoid cells and that the mycosis fungoides cells were a major cell population. Intermediate or transitional cells were found between these cells and large blastoid cells were mostly situated in the basal cell layer. By the rosetting assays of the free cell suspensions prepared from the epidermis of the biopsied skin lesions, 93% of the suspended cells were positive for spontaneous rosette formation with sheep erythrocytes. The immunoperoxidase technique demonstrated no cytoplasmic immunoglobulins in almost all the intraepidermal abnormal cells. These results indicate that the intraepidermal abnormal cells are T-lymphocytes. Thus, it is concluded that the present case is a cutaneous T-cell lymphoma of low-grade malignancy showing a prominent epidermotropism. This case is the first description of the disease in Japan.

The genetic basis of developmental abnormalities in interpopulation hybrids of the moss Ceratodon purpureus.

PubMed

McDaniel, Stuart F; Willis, John H; Shaw, A Jonathan

2008-07-01

Divergent populations are intrinsically reproductively isolated when hybrids between them either fail to develop properly or do not produce viable offspring. Intrinsic isolation may result from Dobzhansky-Muller (DM) incompatibilities, in which deleterious interactions among genes or gene products lead to developmental problems or underdominant chromosome structure differences between the parents. These mechanisms can be tested by studying marker segregation patterns in a hybrid mapping population. Here we examine the genetic basis of abnormal development in hybrids between two geographically distant populations of the moss Ceratodon purpureus. Approximately half of the hybrid progeny exhibited a severely reduced growth rate in early gametophyte development. We identified four unlinked quantitative trait loci (QTL) that interacted asymmetrically to cause the abnormal development phenotype. This pattern is consistent with DM interactions. We also found an excess of recombination between three marker pairs in the abnormally developing progeny, relative to that estimated in the normal progeny. This suggests that structural differences in these regions contribute to hybrid breakdown. Two QTL coincided with inferred structural differences, consistent with recent theory suggesting that rearrangements may harbor population divergence alleles. These observations suggest that multiple complex genetic factors contribute to divergence among populations of C. purpureus.

Potential diagnostic consequences of applying non-invasive prenatal testing: population-based study from a country with existing first-trimester screening.

PubMed

Petersen, O B; Vogel, I; Ekelund, C; Hyett, J; Tabor, A

2014-03-01

Targeted non-invasive prenatal testing (NIPT) tests for trisomies 21, 18 and 13 and sex chromosome aneuploidies and could be an alternative to traditional karyotyping. The aim of this study was to determine the risk of missing other abnormal karyotypes of probable phenotypic significance by NIPT. This was a retrospective population-based analysis of all singleton pregnancies booked for combined first-trimester screening (cFTS) in Denmark over a 4-year period. Data concerning maternal demographics, cFTS and prenatal or postnatal karyotypes were collected from the Danish Fetal Medicine database. Karyotypes were classified according to whether the chromosomal anomaly would have been detected by NIPT and whether it was likely to affect phenotype. cFTS was completed in 193638 pregnancies. 10205 (5.3%) had cytogenetic or molecular analysis performed. Of these, 1122 (11.0%) had an abnormal karyotype, of which 262 (23.4%) would have been missed by NIPT, but would probably have been clinically significant. The prevalence of such 'atypical abnormal karyotypes' was increased in women above 45 years of age, in pregnancies with increased nuchal translucency (NT) thickness (≥ 3.5 mm), with abnormal levels of free β-human chorionic gonadotropin (<0.2 or ≥ 5.0 multiples of the median (MoM)) or pregnancy-associated plasma protein-A<0.2 MoM. One or more of these factors was present in 3% of women, and the prevalence of atypical abnormal karyotypes in this high-risk cohort was 1.6%. A significant proportion of karyotypic abnormalities will be missed by targeted NIPT. Women of advanced maternal age, or with increased fetal NT or abnormal biochemistry, have a higher risk of having a fetus affected by an atypical abnormal karyotype and need to be counseled accordingly when considering NIPT. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

The HPV-16 E7 oncoprotein induces centriole multiplication through deregulation of Polo-like kinase 4 expression

PubMed Central

2011-01-01

Background Infection with high-risk human papillomaviruses (HPVs) such as HPV-16 is intimately associated with squamous cell carcinomas (SCCs) of the anogenital tract and a subset of oropharyngeal carcinomas. Such lesions, including pre-invasive precursors, frequently show multipolar mitoses and aneuploidy. The high-risk HPV-16-encoded E7 oncoprotein has been shown to rapidly induce centrosome abnormalities thereby causing the formation of supernumerary mitotic spindle poles and increasing the risk for chromosome missegregation. HPV-16 E7 has been found to rapidly induce centriole overduplication, in part, through the simultaneous formation of more than one daughter centriole at single maternal centrioles (centriole multiplication). The precise molecular mechanism that underlies HPV-16 E7-induced centriole multiplication, however, remains poorly understood. Findings Here, we show that human keratinocytes engineered to stably express the HPV-16 E7 oncoprotein exhibit aberrant Polo-like kinase 4 (PLK4) protein expression at maternal centrioles. Real-time quantitative reverse transcriptase (qRT-PCR) analysis of these cells revealed an increase of PLK4 mRNA levels compared to control cells. Importantly, the ability of the HPV-16 E7 oncoprotein to induce centriole multiplication was found to correlate with its ability to activate the PLK4 promoter and to up-regulate PLK4 mRNA. Conclusions These results highlight the critical role of PLK4 transcriptional deregulation in centriole multiplication in HPV-16 E7-expressing cells. Our findings encourage further experiments to test transcriptional inhibitors or small molecules targeting PLK4 to prevent centriole abnormalities, mitotic infidelity and malignant progression in HPV-associated neoplasms and other tumors in which PLK4 regulation is disrupted. PMID:21609466

Multiple Biopsies and Detection of Cervical Cancer Precursors at Colposcopy

PubMed Central

Wentzensen, Nicolas; Walker, Joan L.; Gold, Michael A.; Smith, Katie M.; Zuna, Rosemary E.; Mathews, Cara; Dunn, S. Terence; Zhang, Roy; Moxley, Katherine; Bishop, Erin; Tenney, Meaghan; Nugent, Elizabeth; Graubard, Barry I.; Wacholder, Sholom; Schiffman, Mark

2015-01-01

Purpose Women with abnormal cervical cancer screening results are referred to colposcopy and biopsy for diagnosis of cervical cancer precursors (high-grade squamous intraepithelial lesions [HSILs]). Colposcopy with a single biopsy can miss identification of HSILs. No systematic study has quantified the improved detection of HSIL by taking multiple lesion-directed biopsies. Methods The Biopsy Study was an observational study of 690 women referred to colposcopy after abnormal cervical cancer screening results. Up to four directed biopsies were taken from distinct acetowhite lesions and ranked by colposcopic impression. A nondirected biopsy of a normal-appearing area was added if fewer than four directed biopsies were taken. HSIL identified by any biopsy was the reference standard of disease used to evaluate the incremental yield and sensitivity of multiple biopsies. Results In the overall population, sensitivities for detecting HSIL increased from 60.6% (95% CI, 54.8% to 66.6%) from a single biopsy to 85.6% (95% CI, 80.3% to 90.2%) after two biopsies and to 95.6% (95% CI, 91.3% to 99.2%) after three biopsies. A significant increase in sensitivity of multiple biopsies was observed in all subgroups. The highest increase in yield of HSIL was observed for women with a high-grade colposcopic impression, HSIL cytology, and human papillomavirus (HPV) type 16 positivity. Only 2% of all HSILs diagnosed in the participants were detected by biopsies of normal-appearing transformation zone. Conclusion Collection of additional lesion-directed biopsies during colposcopy increased detection of histologic HSIL, regardless of patient characteristics. Taking additional biopsies when multiple lesions are present should become the standard practice of colposcopic biopsy. PMID:25422481

Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism.

PubMed

Chen, Tzu-Ling; Yang, Hung-Chi; Hung, Cheng-Yu; Ou, Meng-Hsin; Pan, Yi-Yun; Cheng, Mei-Ling; Stern, Arnold; Lo, Szecheng J; Chiu, Daniel Tsun-Yee

2017-01-12

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos. The membrane-associated abnormalities were accompanied by impaired eggshell structure as evidenced by a transmission electron microscopic study. Such loss of membrane structural integrity was associated with abnormal lipid composition as lipidomic analysis revealed that lysoglycerophospholipids were significantly increased in G6PD-deficient embryos. Abnormal glycerophospholipid metabolism leading to defective embryonic development could be attributed to the increased activity of calcium-independent phospholipase A 2 (iPLA) in G6PD-deficient embryos. This notion is further supported by the fact that the suppression of multiple iPLAs by genetic manipulation partially rescued the embryonic defects in G6PD-deficient embryos. In addition, G6PD deficiency induced disruption of redox balance as manifested by diminished NADPH and elevated lipid peroxidation in embryos. Taken together, disrupted lipid metabolism due to abnormal redox homeostasis is a major factor contributing to abnormal embryonic development in G6PD-deficient C. elegans.

Continuous fetal head flexion as a marker for prenatal diagnosis of lethal multiple pterygium syndrome: a case report.

PubMed

Hasegawa, Akihiro; Hanaoka, Mieko; Murakoshi, Takeshi

2017-07-01

Lethal multiple pterygium syndrome (LMPS) is a fatal hereditary disease associated with abnormalities such as pterygium-induced congenital contractures. Fetal hydrops is present in more than half of all patients with LMPS, and all patients with LMPS are either stillborn or die in the early neonatal period. Ultrasonography findings for the prenatal diagnosis of LMPS include the detection of cutaneous webbing at multiple joints, multiple joint contractures, absent limb movement, and increased nuchal translucency. Here, we describe a patient who was diagnosed as having LMPS due to continuous fetal head flexion, despite the absence of the usual characteristics of the condition, including pterygium at the joints. Thus, continuous fetal head flexion can be a useful marker for prenatally diagnosing LMPS.

[Multiple gestation epidemiology--15 years survey].

PubMed

Rodrigues, Carla T; Branco, Miguel R; Ferreira, Isabel D; Nordeste, Ana; Fonseca, Margarida; Taborda, Adelaide; Silva, Isabel S; Almeida, Maria do Céu

2005-01-01

Between January of 1987 and December of 2001 were born 1243 twins related to 609 multiple pregnancies, in Maternidade Bissaya-Barreto. Data were grouped in periods of three years and several parameters were studied. The rate of multiple gestation has increased probably due to the contribution of the assisted conception techniques, and to the increase of the number of multiple fetal pregnancies (two or more) and to the increase of the mother age. These more frequent obstetric problems were preterm birth, gestational hypertension and abnormal sonographic data of fetal growth. The average age of delivery was 34 weeks and the birth weight has decreased. The most important factors for neonatal morbidity were hyaline membranous disease, intraventricular haemorrhage and the twin-twin transfusion syndrome. The neonatal mortality decreased in the last studied period.

Cumulative Impact of HIV and Multiple Concurrent Human Papillomavirus Infections on the Risk of Cervical Dysplasia

PubMed Central

Adler, David H.; Wallace, Melissa; Bennie, Thola; Abar, Beau; Meiring, Tracy L.; Williamson, Anna-Lise; Bekker, Linda-Gail

2016-01-01

Infection with HIV is known to increase the risk of cervical cancer. In addition, evidence suggests that concurrent infection with multiple human papillomavirus (HPV) genotypes increases the risk of cervical dysplasia more than infection with a single HPV genotype. However, the impact of the combination of HIV coinfection and presence of multiple concurrent HPV infections on the risk of cervical dysplasia is uncertain. We compared the results of HPV testing and Pap smears between HIV-infected and HIV-uninfected young women to assess the cumulative impact of these two conditions. We found that both HIV and the presence of multiple concurrent HPV infections are associated with increased risk of associated Pap smear abnormality and that the impact of these two risk factors may be additive. PMID:26997954

Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

PubMed Central

Israelashvili, Michal; Loewenstern, Yocheved

2015-01-01

Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

Segregation of a paternal insertional translocation results in partial 4q monosomy or 4q trisomy in two siblings

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

Hegmann, K.M.; Spikes, A.S.; Orr-Urtreger, A.

A genetics evaluation was requested for a 6-week-old infant with multiple congenital malformations including mild craniofacial anomalies, truncal hypotonia, hypospadias, and a ventriculoseptal defect. Blood obtained for chromosome analysis revealed an abnormal chromosome 4. Paternal chromosome analysis showed a 46,XY, inv ins (3;4)(p21.32;q25q21.2), inv(4)(p15.3q21.2) karyotype. Therefore, the proband`s chromosome 4 was the unbalanced product of this insertional translocation from the father resulting in partial monosomy 4q. Additionally, the derivative 4 had a pericentric inversion which was also seen in the father`s chromosome 4. During genetic counseling, the proband`s 2-year-old brother was evaluated. He was not felt to be abnormal inmore » appearance, but was described as having impulsive behavior. Chromosome analysis on this child revealed 46, XY, der(3) inv ins(3;4)(p21.32;q25q21.2)pat. This karyotype results in partial trisomy 4q. FISH using two-color {open_quotes}painting{close_quotes} probes for chromosomes 3 and 4 confirmed the G-banded interpretation in this family. The segregation seen in this family resulted in both reciprocal products being observed in the two children, with partial 4q monosomy showing multiple congenital anomalies, and partial 4q trisomy showing very few phenotypic abnormalities. 13 refs., 5 figs.« less

Mapping face encoding using functional MRI in multiple sclerosis across disease phenotypes.

PubMed

Rocca, Maria A; Vacchi, Laura; Rodegher, Mariaemma; Meani, Alessandro; Martinelli, Vittorio; Possa, Francesca; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

2017-10-01

Using fMRI during a face encoding (FE) task, we investigated the behavioral and fMRI correlates of FE in patients with relapse-onset multiple sclerosis (MS) at different stages of the disease and their relation with attentive-executive performance and structural MRI measures of disease-related damage. A fMRI FE task was administered to 75 MS patients (11 clinically isolated syndromes - CIS, 40 relapsing-remitting - RRMS - and 24 secondary progressive - SPMS) and 22 healthy controls (HC). fMRI activity during the face encoding condition was correlated with behavioral, clinical, neuropsychological and structural MRI variables. All study subjects activated brain regions belonging to face perception and encoding network, and deactivated areas of the default-mode network. Compared to HC, MS patients had the concomitant presence of areas of increased and decreased activations as well as increased and decreased deactivations. Compared to HC or RRMS, CIS patients experienced an increased recruitment of posterior-visual areas. Thalami, para-hippocampal gyri and right anterior cingulum were more activated in RRMS vs CIS or SPMS patients, while an increased recruitment of frontal areas was observed in SPMS vs RRMS. Areas of abnormal activations were significantly correlated with clinical, cognitive-behavioral and structural MRI measures. Abnormalities of FE network occur in MS and vary across disease clinical phenotypes. Early in the disease, an increased recruitment of areas typically devoted to face perception and encoding occurs. In SPMS patients, abnormal functional recruitment of frontal lobe areas might contribute to the severity of clinical manifestations.

Congenital hypertrophy of multiple intrinsic muscles of the foot.

PubMed

Shiraishi, Tomohiro; Park, Susam; Niu, Atushi; Hasegawa, Hiromi

2014-12-01

Congenital hypertrophy of a single intrinsic muscle of the foot is rare, and as far as we know, only six cases have been reported. We describe a case of congenital anomaly that showed hypertrophy of multiple intrinsic muscles of the foot; the affected muscles were all the intrinsic muscles of the foot except the extensor digitorum brevis or extensor hallucis. Other tissues such as adipose tissue, nervous tissue, or osseous tissue showed no abnormalities. To reduce the volume of the foot we removed parts of the enlarged muscles.

Hypophosphatemia in a Malnourished Child: When Renal Fanconi Syndrome Does Not Stand for Refeeding Syndrome.

PubMed

Runde, Joseph; Rivera-Rivera, Edgardo; Pompeii-Wolfe, Cecelia; Clardy, Christopher; Sentongo, Timothy

2018-05-10

Refeeding syndrome is diagnosed based on the onset of multiple laboratory abnormalities (most commonly hypophosphatemia) and clinical signs in the setting of nutrition rehabilitation of malnourished patients. Because definitions are not uniform, a broad differential diagnosis should always include renal tubular dysfunction. Our report details a 3 year-old child with undiagnosed renal tubular dysfunction who presented with the clinical picture of refeeding syndrome with refractory electrolyte abnormalities. A diagnosis of renal Fanconi syndrome was made after urinalysis that revealed glucosuria and urine electrolyte losses. Thus, urinalysis can aid in making a positive diagnosis of refeeding syndrome. © 2018 American Society for Parenteral and Enteral Nutrition.

CT arthrographic patterns in recurrent glenohumeral instability.

PubMed

Singson, R D; Feldman, F; Bigliani, L

1987-10-01

CT double-contrast arthrograms were performed on 54 shoulders in 53 patients with recurrent dislocation or subluxation to detect responsible underlying bony or soft-tissue abnormalities. Lesions of the anterior labrum in 52 (96%) of 54 cases and of the capsuloligamentous complex in 42 (78%) of 54 cases were the two most common abnormalities. There was no difference in the degree or number of labral lesions between subluxations and dislocations. However, more severe capsular lesions, subscapularis tendon tears, and widened subscapularis bursae were consistently found among patients with dislocations. Subsequent clinical, arthroscopic, and surgical findings showed that the use of CT double-contrast arthrograms resulted in improved definition of the multiple lesions associated with glenohumeral dysfunction.

Wolfram Syndrome presenting with optic atrophy and diabetes mellitus: two case reports

PubMed Central

2009-01-01

Wolfram syndrome is the constellation of juvenile onset diabetes mellitus and optic atrophy, known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). Patients demonstrate diabetes mellitus followed by optic atrophy in the first decade, diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow tracts early in the third decade, and multiple neurological abnormalities early in the fourth decade. This study reports two siblings with late diagnosed wolfram syndrome with diabetes insipidus, diabetes mellitus, optic atrophy, deafness and severe urological abnormalities. In conclusion, cases having early onset insulin-dependent diabetes mellitus and optic atrophy together need to be evaluated with respect to Wolfram. PMID:20062605

Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

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

Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.

1990-05-01

A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is oftenmore » needed for accurate differential diagnosis.« less

Genomics of Systemic Lupus Erythematosus: Insights Gained by Studying Monogenic Young-Onset Systemic Lupus Erythematosus.

PubMed

Hiraki, Linda T; Silverman, Earl D

2017-08-01

Systemic lupus erythematosus (SLE) is a systemic, autoimmune, multisystem disease with a heterogeneous clinical phenotype. Genome-wide association studies have identified multiple susceptibility loci, but these explain a fraction of the estimated heritability. This is partly because within the broad spectrum of SLE are monogenic diseases that tend to cluster in patients with young age of onset, and in families. This article highlights insights into the pathogenesis of SLE provided by these monogenic diseases. It examines genetic causes of complement deficiency, abnormal interferon production, and abnormalities of tolerance, resulting in monogenic SLE with overlapping clinical features, autoantibodies, and shared inflammatory pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Familial multiple ventricular extrasystoles, short stature, craniofacial abnormalities and digital hypoplasia: a further case of Stoll syndrome?

PubMed

Mercer, Catherine L; Keeton, Barry; Dennis, Nicolas R

2008-04-01

We report two brothers, their mother and a maternal cousin who had a distinctive facial phenotype, mild brachydactyly and prominence of the interphalangeal joints. One brother and the mother also had multiple ventricular extrasystoles. Six other relatives in four generations were probably affected on the basis of history and family photographs. We also report a further individual from a different family with a similar facial phenotype, Pierre-Robin sequence, tapering fingers and multiple ventricular extrasystoles. These families have some similarities to those reported by Stoll et al. in a single family, showing dominant inheritance. Our patients would seem to have the same or a related condition.

Osteoglophonic dwarfism in two generations.

PubMed Central

Kelley, R I; Borns, P F; Nichols, D; Zackai, E H

1983-01-01

A father and son, both affected by a skeletal dysplasia with severe craniofacial deformities, are reported and compared to three previously described isolated cases of the same dwarfism. The principal features are craniosynostosis, multiple lucent metaphyseal defects, flattening and anterior beaking of the vertebral bodies, and abnormal dentition. Autosomal dominant inheritance is suggested. Images PMID:6606709

The Role of Attention in Somatosensory Processing: A Multi-Trait, Multi-Method Analysis

ERIC Educational Resources Information Center

Wodka, Ericka L.; Puts, Nicolaas A. J.; Mahone, E. Mark; Edden, Richard A. E.; Tommerdahl, Mark; Mostofsky, Stewart H.

2016-01-01

Sensory processing abnormalities in autism have largely been described by parent report. This study used a multi-method (parent-report and measurement), multi-trait (tactile sensitivity and attention) design to evaluate somatosensory processing in ASD. Results showed multiple significant within-method (e.g., parent report of different…

Atypical Laterality of Resting Gamma Oscillations in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Maxwell, Christina R.; Villalobos, Michele E.; Schultz, Robert T.; Herpertz-Dahlmann, Beate; Konrad, Kerstin; Kohls, Gregor

2015-01-01

Abnormal brain oscillatory activity has been found in autism spectrum disorders (ASD) and proposed as a potential biomarker. While several studies have investigated gamma oscillations in ASD, none have examined resting gamma power across multiple brain regions. This study investigated resting gamma power using EEG in 15 boys with ASD and 18 age…

Alleviating Autonomic Dysreflexia after Spinal Cord Injury

DTIC Science & Technology

2017-12-01

autonomic disorders greatly influence the functional, psychological , and socioeconomic aspects of patients’ lives. Compared to numer- ous...The disruption of descending autonomic pathways renders abnormalities in multiple organ systems including cardiovascular function, respiration...the rise in blood pressure, the integration center in the brainstem transmits signals to the heart via parasympathetic pathways to reduce the heart

Severe Neurologic Disorders in 2 Fetuses with Zika Virus Infection, Colombia.

PubMed

Acosta-Reyes, Jorge; Navarro, Edgar; Herrera, Maria José; Goenaga, Eloina; Ospina, Martha L; Parra, Edgar; Mercado, Marcela; Chaparro, Pablo; Beltran, Mauricio; Gunturiz, Maria Luz; Pardo, Lissethe; Valencia, Catalina; Huertas, Sandra; Rodríguez, Jorge; Ruiz, Germán; Valencia, Diana; Haddad, Lisa B; Tinker, Sarah C; Moore, Cynthia A; Baquero, Hernando

2017-06-01

We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus.

Severe Neurologic Disorders in 2 Fetuses with Zika Virus Infection, Colombia

PubMed Central

Navarro, Edgar; Herrera, Maria José; Goenaga, Eloina; Ospina, Martha L.; Parra, Edgar; Mercado, Marcela; Chaparro, Pablo; Beltran, Mauricio; Gunturiz, Maria Luz; Pardo, Lissethe; Valencia, Catalina; Huertas, Sandra; Rodríguez, Jorge; Ruiz, Germán; Valencia, Diana; Haddad, Lisa B.; Tinker, Sarah C.; Moore, Cynthia A.; Baquero, Hernando

2017-01-01

We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus. PMID:28296632

Touch Processing and Social Behavior in ASD

ERIC Educational Resources Information Center

Miguel, Helga O.; Sampaio, Adriana; Martínez-Regueiro, Rocío; Gómez-Guerrero, Lorena; López-Dóriga, Cristina Gutiérrez; Gómez, Sonia; Carracedo, Ángel; Fernández-Prieto, Montse

2017-01-01

Abnormal patterns of touch processing have been linked to core symptoms in ASD. This study examined the relation between tactile processing patterns and social problems in 44 children and adolescents with ASD, aged 6-14 (M = 8.39 ± 2.35). Multiple linear regression indicated significant associations between touch processing and social problems. No…

Central hemodynamics and arterial stiffness in idiopathic and multiple system atrophy.

PubMed

Franzen, Klaas; Fliegen, Sabine; Koester, Jelena; Martin, Rafael Campos; Deuschl, Günther; Reppel, Michael; Mortensen, Kai; Schneider, Susanne A

2017-02-01

Blood pressure is commonly abnormal in parkinsonian disorders, but central hemodynamics and arterial stiffness, well-established predictors of total cardiovascular risk, have rarely been studied in these disorders. 32 patients [27 with idiopathic Parkinson's disease (iPD); 5 with multiple system atrophy (MSA)] and 15 controls matched for cardiac risk factors underwent 24 h-ambulatory blood pressure recordings using an I.E.M. device (Mobil-O-Graph™), measuring peripheral pressure and calculating central pressures and arterial stiffness. Mean augmentation indices corrected for heart rate (AIx@75) were significantly lower and pulse wave velocities were significantly elevated in patients compared to controls. Central systolic blood pressure, cardiac output and daytime total vascular resistance were significantly elevated in patients. Mean nocturnal systolic peripheral blood pressure and nocturnal heart rates were also significantly higher; 56.3% of patients had nocturnal hypertension (80% of the MSA group); 85.2% showed non-dipping. This supports previous findings of reduced vulnerability to systemic atherosclerosis and end-organ damage in treated PD. Yet, hemodynamic abnormalities were common and often remained asymptomatic.

Characterization of a complex chromosomal rearrangement using chromosome, FISH, and microarray assays in a girl with multiple congenital abnormalities and developmental delay.

PubMed

Hemmat, Morteza; Yang, Xiaojing; Chan, Patricia; McGough, Robert A; Ross, Leslie; Mahon, Loretta W; Anguiano, Arturo L; Boris, Wang T; Elnaggar, Mohamed M; Wang, Jia-Chi J; Strom, Charles M; Boyar, Fatih Z

2014-01-01

Complex chromosomal rearrangements (CCRs) are balanced or unbalanced structural rearrangements involving three or more cytogenetic breakpoints on two or more chromosomal pairs. The phenotypic anomalies in such cases are attributed to gene disruption, superimposed cryptic imbalances in the genome, and/or position effects. We report a 14-year-old girl who presented with multiple congenital anomalies and developmental delay. Chromosome and FISH analysis indicated a highly complex chromosomal rearrangement involving three chromosomes (3, 7 and 12), seven breakpoints as a result of one inversion, two insertions, and two translocations forming three derivative chromosomes. Additionally, chromosomal microarray study (CMA) revealed two submicroscopic deletions at 3p12.3 (467 kb) and 12q13.12 (442 kb). We postulate that microdeletion within the ROBO1 gene at 3p12.3 may have played a role in the patient's developmental delay, since it has potential activity-dependent role in neurons. Additionally, factors other than genomic deletions such as loss of function or position effects may also contribute to the abnormal phenotype in our patient.

Staging resection of multiple primary esophageal cancer by endoscopic submucosal dissection and esophagectomy: A case report.

PubMed

Yao, Yufeng; Wu, Yimin; Chai, Ying

2018-05-01

Multiple primary esophageal cancer pose great risks to patients and are always challenging to resect surgically. In order to reduce the risk of postoperative complication and meet the needs of minimally invasive and precision medicine, new treatment plans have been always developed for patients with multiple primary esophageal cancer. A 75-year-old man was admitted to our hospital for aggravated dysphagia. No significant abnormalities were identified on physical examination. Endoscopic examination detected 3 masses in the esophagus and biopsy confirmed multiple primary esophageal cancer. The patient received a new staging treatment procedure firstly and an innovative single-position, minimally invasive Ivor Lewis esophagectomy in our hospital. This patient discharged one week after the surgery and enjoyed a good health during our follow up for 30 month. We believe our procedure provides a beneficial new alternative approach for patients with multiple primary esophageal cancer.

Cranial Ultrasound Lesions in the NICU Predict Cerebral Palsy at Age 2 Years in Children Born at Extremely Low Gestational Age

PubMed Central

Kuban, Karl C. K.; Allred, Elizabeth N.; O’Shea, T. Michael; Paneth, Nigel; Pagano, Marcello; Dammann, Olaf; Leviton, Alan; Du Plessis, Adré; Westra, Sjirk J.; Miller, Cindy R.; Bassan, Haim; Krishnamoorthy, Kalpathy; Junewick, Joseph; Olomu, Nicholas; Romano, Elaine; Seibert, Joanna; Engelke, Steve; Karna, Padmani; Batton, Daniel; O’Connor, Sunila E.; Keller, Cecelia E.

2009-01-01

Our prospective cohort study of extremely low gestational age newborns evaluated the association of neonatal head ultrasound abnormalities with cerebral palsy at age 2 years. Cranial ultrasounds in 1053 infants were read with respect to intraventricular hemorrhage, ventriculomegaly, and echolucency, by multiple sonologists. Standardized neurological examinations classified cerebral palsy, and functional impairment was assessed. Forty-four percent with ventriculomegaly and 52% with echolucency developed cerebral palsy. Compared with no ultrasound abnormalities, children with echolucency were 24 times more likely to have quadriparesis and 29 times more likely to have hemiparesis. Children with ventriculomegaly were 17 times more likely to have quadriparesis or hemiparesis. Forty-three percent of children with cerebral palsy had normal head ultrasound. Focal white matter damage (echolucency) and diffuse damage (late ventriculomegaly) are associated with a high probability of cerebral palsy, especially quadriparesis. Nearly half the cerebral palsy identified at 2 years is not preceded by a neonatal brain ultrasound abnormality. PMID:19168819

Theo van Rens Prize. Arthroscopic assessment of the unstable shoulder.

PubMed

Hintermann, B; Gächter, A

1994-01-01

The purpose of this study was to evaluate prospectively the findings during shoulder arthroscopy in patients with recurrent anterior instability of the glenohumeral joint. One hundred and seventy-eight patients who fulfilled the criteria of having had at least one documented shoulder dislocation were included in the study. The pathological findings most frequently noted at arthroscopy were: anterior glenoid labral tears (85%), ventral capsule insufficiency (80%), Hill-Sachs compression fractures (67%), glenohumeral ligament insufficiency (55%), rotator cuff tears (20%), posterior glenoid labral tears (8%), and SLAP lesions (5%). Abnormalities were noted more frequently than expected, and there were significant differences between preoperative and postoperative diagnoses. Our study has taught us that a multiplicity of morphological changes are associated with instability of the glenohumeral joint, and that there is no single cause. The labrum and rim of the anterior inferior glenoid, for instance, showed typical abnormalities corresponding to different entities of anterior instability. In practice, this is very important, as the abnormalities visualized by imaging methods determine the surgical treatment.

Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders.

PubMed

Boronat, S; Vicente, M; Lainez, E; Sánchez-Montañez, A; Vázquez, E; Mangado, L; Martínez-Ribot, L; Del Campo, M

2017-01-01

Fetal alcohol spectrum disorders (FASD) cause neurodevelopmental abnormalities. However, publications about epilepsy and electroencephalographic features are scarce. In this study, we prospectively performed electroencephalography (EEG) and brain magnetic resonance (MR) imaging in 61 patients with diagnosis of FASD. One patient had multiple febrile seizures with normal EEGs. Fourteen children showed EEG anomalies, including slow background activity and interictal epileptiform discharges, focal and/or generalized, and 3 of them had epilepsy. In one patient, seizures were first detected during the EEG recording and one case had an encephalopathy with electrical status epilepticus during slow sleep (ESES). Focal interictal discharges in our patients did not imply the presence of underlying visible focal brain lesions in the neuroimaging studies, such as cortical dysplasia or polymicrogyria. However, they had nonspecific brain MR abnormalities, including corpus callosum hypoplasia, vermis hypoplasia or cavum septum pellucidum. The latter was significantly more frequent in the group with EEG abnormal findings (p < 0.01). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Implication of sperm chromosomal abnormalities in recurrent abortion and multiple implantation failure.

PubMed

Caseiro, Ana Lara; Regalo, Ana; Pereira, Elisa; Esteves, Telma; Fernandes, Fernando; Carvalho, Joaquim

2015-10-01

Currently, some infertility treatment centres provide sperm karyotype analysis, although the impact of sperm chromosomal abnormalities on fertility is not yet fully understood. Several studies using fluorescence in-situ hybridization (FISH) to analyse sperm chromosomal constitution discovered that the incidence of aneuploidy is increased in individuals with a history of repeated abortion or implantation failure and is even higher in cases of oligoasthenoteratozoospermia (OAT), abnormal somatic karyotype or in spermatozoa retrieved directly from the testis or epididymis, showing that the application of FISH in these cases may be of some benefit for improving the reproductive outcome. This article presents the results of clinical trials of FISH analysis on spermatozoa, the medical indications for performing this examination, its results in infertile patients and the advantages when performing genetic counselling prior to treatment. Also discussed is the possibility of applying the latest techniques of genetic analysis in these cases and the potential benefits for improving the prognosis of male infertility. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Co-localisation of abnormal brain structure and function in specific language impairment.

PubMed

Badcock, Nicholas A; Bishop, Dorothy V M; Hardiman, Mervyn J; Barry, Johanna G; Watkins, Kate E

2012-03-01

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. Copyright © 2011 Elsevier Inc. All rights reserved.

Mechanisms of developing post-traumatic stress disorder: new targets for drug development and other potential interventions.

PubMed

Wimalawansa, Sunil J

2014-01-01

The post-traumatic stress disorder (PTSD) is defined as a severe anxiety disorder that develops after exposure to an event with actual, threatened, or perceived death or serious injury, or a threat to the physical integrity of oneself or others that results in significant psychological trauma. Moreover, the ability of people to handle acute severe stress experiences varies among individuals. Depending on the underlying personality and resiliency, therefore, PTSD can occur in individuals exposed to exceedingly stressful incidences or those who have encountered seemingly less overwhelming stressors. In addition to severe stressful exposure, multiple other factors including genetic susceptibility; past experiences; cultural, spiritual, and personal beliefs; bullying and harassments; and lack of support at the workplace, social, and home environement may contribute to the development of PTSD. Author investigated multiple potential mechanisms for the development and sustenance of PTSD based on the recent literature and his own experiences and insight. Based on this search, author indicates that among other pathological and biochemical abnormalities, hormonal aberrations are most likely key mechanisms initiating and the maintenance of the PTSD. These pathophysiological neuro-hormonal changes instigate maladaptive learning processes caused by sustained high levels of anxiety and fear, through a hypo-responsive hypothalamic-pituitary axis and hyper-responsive catecholamine system (persistently elevated blood norepinephrine levels and lower than appropriate glucocorticoid levels). In addition to having inappropriately low serum cortisol levels and high epinephrine and norepinephrine levels, patients with PTSD also have mitochondrial dysfunctions and other hormonal abnormalities. Based on these data, author concluded that these pathological, biochemical and sustained neurohormonal abnormalities are likely to influence the structural brain changes, particularly in the amygdala and hippocampus, which are characteristics of patients with PTSD. Considering these abnormalities, neuroendocrine system needs to be considered as a key target for new drug development for prevention and treatment of PTSD.

Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders

PubMed Central

Ross, Fiona M.; Avet-Loiseau, Hervé; Ameye, Geneviève; Gutiérrez, Norma C.; Liebisch, Peter; O’Connor, Sheila; Dalva, Klara; Fabris, Sonia; Testi, Adele M.; Jarosova, Marie; Hodkinson, Clare; Collin, Anna; Kerndrup, Gitte; Kuglik, Petr; Ladon, Dariusz; Bernasconi, Paolo; Maes, Brigitte; Zemanova, Zuzana; Michalova, Kyra; Michau, Lucienne; Neben, Kai; Hermansen, N. Emil U.; Rack, Katrina; Rocci, Alberto; Protheroe, Rebecca; Chiecchio, Laura; Poirel, Hélène A; Sonneveld, Pieter; Nyegaard, Mette; Johnsen, Hans E.

2012-01-01

The European Myeloma Network has organized two workshops on fluorescence in situ hybridization in multiple myeloma. The first aimed to identify specific indications and consensus technical approaches of current practice. A second workshop followed a quality control exercise in which 21 laboratories analyzed diagnostic cases of purified plasma cells for recurrent abnormalities. The summary report was discussed at the EHA Myeloma Scientific Working Group Meeting 2010. During the quality control exercise, there was acceptable agreement on more than 1,000 tests. The conclusions from the exercise were that the primary clinical applications for FISH analysis were for newly diagnosed cases of MM or frank relapse cases. A range of technical recommendations included: 1) material should be part of the first draw of the aspirate; 2) samples should be sent at suitable times to allow for the lengthy processing procedure; 3) most importantly, PCs must be purified or specifically identified; 4) positive cut-off levels should be relatively conservative: 10% for fusion or break-apart probes, 20% for numerical abnormalities; 5) informative probes should be combined to best effect; 6) in specialist laboratories, a single experienced analyst is considered adequate; 7) at least 100 PC should be scored; 8) essential abnormalities to test for are t(4;14), t(14;16) and 17p13 deletions; 9) suitable commercial probes should be available for clinically relevant abnormalities; 10) the clinical report should be expressed clearly and must state the percentage of PC involved and the method used for identification; 11) a retrospective European based FISH data bank linked to clinical data should be generated; and 12) prospective analysis should be centralized for upcoming trials based on the recommendations made. The European Myeloma Network aims to build on these recommendations to establish standards for a common European data base to define subgroups with prognostic significance. PMID:22371180

Chromosome 13q deletion and IgH abnormalities may be both masked by near-tetraploidy in a high proportion of multiple myeloma patients: a combined morphology and I-FISH analysis.

PubMed

Koren-Michowitz, Maya; Hardan, Izhar; Berghoff, Janina; Yshoev, Galina; Amariglio, Ninette; Rechavi, Gideon; Nagler, Arnon; Trakhtenbrot, Luba

2007-10-08

Ploidy status and chromosomal aberrations involving chromosome 13q and the immunoglobulin heavy chain locus (IgH) are important prognostic features in multiple myeloma (MM). However, conventional cytogenetic studies are often not reveling and determination of plasma cells (PC) ploidy status in MM is technically difficult. We have used a combined cell morphology and interphase FISH (I-FISH) analysis in 184 consecutive BM samples from 136 MM patients for the diagnosis of chromosome 13q deletion [del (13q)] and IgH abnormalities. We have found a high prevalence (37%) of near-tetraploid (NT) PC in the BM samples studied. NT status of PC was verified with DNA index (DI) measurements. del (13q) was found in 69% and a total absence of one IgH copy (loss of IgH) in 20% of NT samples. We have shown that the presence of del (13q) and loss of IgH can be masked in NT cases: in 12 NT samples originally identified as normal for del (13q) the abnormality was obscured in the majority of plasma cells due to the presence of NT. Similarly, loss of IgH was masked in four samples with a large population of NT cells. Moreover, in one case the appearance of a 100% tetraploidy during disease progression masked the presence of del (13q), originally present, and could therefore falsely appear as disappearance of this prognostic marker. In conclusion, we have shown that a combination of three abnormalities, i.e., del (13q), loss of IgH and NT, all of potential prognostic significance, can be overlooked unless NT is specifically searched for and ruled out. Therefore, we suggest that a search for NT should be added to the routine BM assessment in MM patients.

Exploring brainstem function in multiple sclerosis by combining brainstem reflexes, evoked potentials, clinical and MRI investigations.

PubMed

Magnano, Immacolata; Pes, Giovanni Mario; Pilurzi, Giovanna; Cabboi, Maria Paola; Ginatempo, Francesca; Giaconi, Elena; Tolu, Eusebio; Achene, Antonio; Salis, Antonio; Rothwell, John C; Conti, Maurizio; Deriu, Franca

2014-11-01

To investigate vestibulo-masseteric (VMR), acoustic-masseteric (AMR), vestibulo-collic (VCR) and trigemino-collic (TCR) reflexes in patients with multiple sclerosis (MS); to relate abnormalities of brainstem reflexes (BSRs) to multimodal evoked potentials (EPs), clinical and Magnetic Resonance Imaging (MRI) findings. Click-evoked VMR, AMR and VCR were recorded from active masseter and sternocleidomastoid muscles, respectively; TCR was recorded from active sternocleidomastoid muscles, following electrical stimulation of the infraorbital nerve. EPs and MRI were performed with standard techniques. Frequencies of abnormal BSRs were: VMR 62.1%, AMR 55.1%, VCR 25.9%, TCR 58.6%. Brainstem dysfunction was identified by these tests, combined into a four-reflex battery, in 86.9% of cases, by EPs in 82.7%, MRI in 71.7% and clinical examination in 37.7% of cases. The sensitivity of paired BSRs/EPs (93.3%) was significantly higher than combined MRI/clinical testing (70%) in patients with disease duration ⩽6.4years. BSR alterations significantly correlated with clinical, EP and MRI findings. The four-BSR battery effectively increases the performance of standard EPs in early detection of brainstem impairment, otherwise undetected by clinical examination and neuroimaging. Multiple BSR assessment usefully supplements conventional testing and monitoring of brainstem function in MS, especially in newly diagnosed patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Three patients with Schaaf-Yang syndrome exhibiting arthrogryposis and endocrinological abnormalities.

PubMed

Enya, Takuji; Okamoto, Nobuhiko; Iba, Yoshinori; Miyazawa, Tomoki; Okada, Mitsuru; Ida, Shinobu; Naruto, Takuya; Imoto, Issei; Fujita, Atsushi; Miyake, Noriko; Matsumoto, Naomichi; Sugimoto, Keisuke; Takemura, Tsukasa

2018-03-01

MAGEL2 is the paternally expressed gene within Prader-Willi syndrome critical region at 15q11.2. We encountered three individuals in whom truncating mutations of MAGEL2 were identified. Patients 1 and 2, siblings born to healthy, non-consanguineous Japanese parents, showed generalized hypotonia, lethargy, severe respiratory difficulty, poor feeding, and multiple anomalies including arthrogryposis soon after birth. We carried out whole-exome sequencing, which detected a MAGEL2 mutation (c.1912C>T, p.Gln638*, heterozygous). The patients' father was heterozygous for the mutation. Patient 3 was a female infant, showed respiratory difficulty reflecting pulmonary hypoplasia, generalized hypotonia, feeding difficulty and multiple anomalies soon after birth. Targeted next-generation sequencing detected a novel heterozygous mutation in MAGEL2 (c.3131C>A, p.Ser1044*). This mutation was not found in the parents. MAGEL2 mutations, first reported to be the cause of the Prader-Willi like syndrome with autism by Schaaf et al. (2013) Nature Genetics, 45: 1405-1408 show the wide range of phenotypic spectrum from lethal arthrogryposis multiplex congenital to autism spectrum disorder (ASD) and mild intellectual disability (ID). Our results indicate that MAGEL2 mutations cause multiple congenital anomalies and intellectual disability accompanied by arthrogryposis multiplex congenita and various endocrinologic abnormalities, supporting that the view that clinical phenotypes of MAGEL2 mutations are variable. © 2018 Wiley Periodicals, Inc.

Abnormal Multiple Charge Memory States in Exfoliated Few-Layer WSe2 Transistors.

PubMed

Chen, Mikai; Wang, Yifan; Shepherd, Nathan; Huard, Chad; Zhou, Jiantao; Guo, L J; Lu, Wei; Liang, Xiaogan

2017-01-24

To construct reliable nanoelectronic devices based on emerging 2D layered semiconductors, we need to understand the charge-trapping processes in such devices. Additionally, the identified charge-trapping schemes in such layered materials could be further exploited to make multibit (or highly desirable analog-tunable) memory devices. Here, we present a study on the abnormal charge-trapping or memory characteristics of few-layer WSe 2 transistors. This work shows that multiple charge-trapping states with large extrema spacing, long retention time, and analog tunability can be excited in the transistors made from mechanically exfoliated few-layer WSe 2 flakes, whereas they cannot be generated in widely studied few-layer MoS 2 transistors. Such charge-trapping characteristics of WSe 2 transistors are attributed to the exfoliation-induced interlayer deformation on the cleaved surfaces of few-layer WSe 2 flakes, which can spontaneously form ambipolar charge-trapping sites. Our additional results from surface characterization, charge-retention characterization at different temperatures, and density functional theory computation strongly support this explanation. Furthermore, our research also demonstrates that the charge-trapping states excited in multiple transistors can be calibrated into consistent multibit data storage levels. This work advances the understanding of the charge memory mechanisms in layered semiconductors, and the observed charge-trapping states could be further studied for enabling ultralow-cost multibit analog memory devices.

Optic nerve size evaluated by magnetic resonance imaging in children with optic nerve hypoplasia, multiple pituitary hormone deficiency, isolated growth hormone deficiency, and idiopathic short stature.

PubMed

Birkebaek, Niels Holtum; Patel, Leena; Wright, Neville Bryce; Grigg, John Russell; Sinha, Smeeta; Hall, Catherine Margaret; Price, David Anthony; Lloyd, Ian Christopher; Clayton, Peter Ellis

2004-10-01

To objectively define criteria for intracranial optic nerve (ON) size in ON hypoplasia (ONH) on magnetic resonance imaging (MRI) scans. Intracranial ON sizes from MRI were compared between 46 children with ONH diagnosed by ophthalmoscopy (group 1, isolated ONH, 8 children; and group 2, ONH associated with abnormalities of the hypothalamic-pituitary axis and septum pellucidum, 38 children) and children with multiple pituitary hormone deficiency (group 3, multiple pituitary hormone deficiency, 14 children), isolated growth hormone deficiency (group 4, isolated growth hormone deficiency, 15 children), and idiopathic short stature (group 5, idiopathic short stature, 10 children). Intracranial ON size was determined by the cross-sectional area, calculated as [pi x (1/2) height x (1/2) width]. Groups 1 and 2 had lower intracranial ON size than did groups 3, 4, and 5 (P < .001). No patients in groups 3 through 5 who had MRI after 12 months of age (when 95% adult size of ONs is attained) had ONs <2.9 mm 2 . Visual acuity correlated significantly with ON size (P < .01). Magnetic resonance imaging of the ONs with cross-sectional area <2.9 mm 2 in a short child more than 12 months of age, with or without hypothalamic-pituitary axis abnormalities, confirms the clinical diagnosis of ONH.

Association of abnormal morphology and altered gene expression in human preimplantation embryos.

PubMed

Wells, Dagan; Bermúdez, Mercedes G; Steuerwald, Nury; Malter, Henry E; Thornhill, Alan R; Cohen, Jacques

2005-08-01

We set out to characterize the expression of nine genes in human preimplantation embryos and determine whether abnormal morphology is associated with altered gene activity. Reverse transcription and real-time polymerase chain reaction were used to quantify the expression of multiple genes in each embryo. The genes studied have various important cellular roles (e.g., cell cycle regulation, DNA repair, and apoptosis). Research laboratory working closely with a clinical IVF practice. Over 50 embryos were donated by infertile patients (various etiologies). Among these, all major stages of preimplantation development and a variety of common morphologic abnormalities were represented. None. Quantification of mRNA transcripts. We detected an association between certain forms of abnormal morphology and disturbances of gene activity. Cellular fragmentation was associated with altered expression of several genes, including TP53, suggesting that fragmenting blastomeres are suffering stress of a type monitored by p53, possibly as a consequence of suboptimal culture conditions. Appropriate gene expression is vital for the regulation of metabolic pathways and key developmental events. Our data indicates a possible causal relationship between changes in gene expression and the formation of clinically relevant abnormal embryo morphologies. We hypothesize that embryos with expression profiles characteristic of good morphology and appropriate for their developmental stage have the greatest potential for implantation. If confirmed, this could lead to a new generation of preimplantation genetic diagnosis (PGD) tests for assessing embryo viability and predicting implantation potential.

Longitudinal assessment of spirometry in the World Trade Center medical monitoring program.

PubMed

Skloot, Gwen S; Schechter, Clyde B; Herbert, Robin; Moline, Jacqueline M; Levin, Stephen M; Crowley, Laura E; Luft, Benjamin J; Udasin, Iris G; Enright, Paul L

2009-02-01

Multiple studies have demonstrated an initial high prevalence of spirometric abnormalities following World Trade Center (WTC) disaster exposure. We assessed prevalence of spirometric abnormalities and changes in spirometry between baseline and first follow-up evaluation in participants in the WTC Worker and Volunteer Medical Monitoring Program. We also determined the predictors of spirometric change between the two examinations. Prebronchodilator and postbronchodilator spirometry, demographics, occupational history, smoking status, and respiratory symptoms and exposure onset were obtained at both examinations (about 3 years apart). At the second examination, 24.1% of individuals had abnormal spirometry findings. The predominant defect was a low FVC without obstruction (16.1%). Between examinations, the majority of individuals did not have a greater-than-expected decline in lung function. The mean declines in prebronchodilator FEV(1) and FVC were 13 mL/yr and 2 mL/yr, respectively (postbronchodilator results were similar and not reported). Significant predictors of greater average decline between examinations were lack of bronchodilator responsiveness at examination 1 and weight gain [corrected]. Elevated rates of spirometric abnormalities were present at both examinations, with reduced FVC most common. Although the majority had a normal decline in lung function, lack of bronchodilator response at examination 1 and weight gain were significantly associated with greater-than-normal lung function declines [corrected]. Due to the presence of spirometric abnormalities > 5 years after the disaster in many exposed individuals, longer-term monitoring of WTC responders is essential.

Hydronephrosis in the Wnt5a-ablated kidney is caused by an abnormal ureter-bladder connection.

PubMed

Yun, Kangsun; Perantoni, Alan O

The Wnt5a null mouse is a complex developmental model which, among its several posterior-localized axis defects, exhibits multiple kidney phenotypes, including duplex kidney and loss of the medullary zone. We previously reported that ablation of Wnt5a in nascent mesoderm causes duplex kidney formation as a result of aberrant development of the nephric duct and abnormal extension of intermediate mesoderm. However, these mice also display a loss of the medullary region late in gestation. We have now genetically isolated duplex kidney formation from the medullary defect by specifically targeting the progenitors for both the ureteric bud and metanephric mesenchyme. The conditional mutants fail to form a normal renal medulla but no longer exhibit duplex kidney formation. Approximately 1/3 of the mutants develop hydronephrosis in the kidneys either uni- or bilaterally when using Dll1Cre. The abnormal kidney phenotype becomes prominent at E16.5, which approximates the time when urine production begins in the mouse embryonic kidney, and is associated with a dramatic increase in apoptosis only in mutant kidneys with hydronephrosis. Methylene blue dye injection and histologic examination reveal that aberrant cell death likely results from urine toxicity due to an abnormal ureter-bladder connection. This study shows that Wnt5a is not required for development of the renal medulla and that loss of the renal medullary region in the Wnt5a-deleted kidney is caused by an abnormal ureter-bladder connection. Published by Elsevier B.V.

Glutamatergic abnormalities of the thalamus in schizophrenia: a systematic review.

PubMed

Watis, L; Chen, S H; Chua, H C; Chong, S A; Sim, K

2008-01-01

The thalamus, a key information processing centre in facilitating sensory discrimination and cognitive processes, has been implicated in schizophrenia due to the increasing evidence showing structural and functional thalamic abnormalities. Glutamatergic abnormalities, in particular, have been examined since glutamate is one of the main neurotransmitters found in the thalamus. We aimed to review the existing literature (1978 till 2007) on post-mortem and in vivo studies of the various components of glutamatergic neurotransmission as well as studies of the glutamate receptor genes within the thalamus in schizophrenia. The literature search was done using multiple databases including Scopus, Web of Science, EBSCO host, Pubmed and ScienceDirect. Keywords used were "glutamate", "thalamus", "schizophrenia", "abnormalities", and "glutamatergic". Further searches were made using the bibliographies in the main journals and related papers were obtained. The extant data suggest that abnormalities of the glutamate receptors as well as other molecules involved in glutamatergic neurotransmission (including glutamate transporters and associated proteins, N-methyl D-aspartate (NMDA) receptor-associated intracellular signaling proteins, and glutamatergic enzymes) are found within the thalamus in schizophrenia. There is a pressing need for more rapid replication of findings from post mortem and genetic studies as well as the promotion of multi-component or multi-modality assessments of glutamatergic anomalies within the thalamus in order to allow a better appreciation of disruptions in these molecular networks in schizophrenia. These and future findings may represent potential novel targets for antipsychotic drugs to ameliorate the symptoms of schizophrenia.

Abnormal brain connectivity in first-episode psychosis: A diffusion MRI tractography study of the corpus callosum

PubMed Central

Price, Gary; Cercignani, Mara; Parker, Geoffrey J.M.; Altmann, Daniel R.; Barnes, Thomas R.E.; Barker, Gareth J.; Joyce, Eileen M.; Ron, Maria A.

2007-01-01

A model of disconnectivity involving abnormalities in the cortex and connecting white matter pathways may explain the clinical manifestations of schizophrenia. Recently, diffusion imaging tractography has made it possible to study white matter pathways in detail and we present here a study of patients with first-episode psychosis using this technique. We selected the corpus callosum for this study because there is evidence that it is abnormal in schizophrenia. In addition, the topographical organization of its fibers makes it possible to relate focal abnormalities to specific cortical regions. Eighteen patients with first-episode psychosis and 21 healthy subjects took part in the study. A probabilistic tractography algorithm (PICo) was used to study fractional anisotropy (FA). Seed regions were placed in the genu and splenium to track fiber tracts traversing these regions, and a multi-threshold approach to study the probability of connection was used. Multiple linear regressions were used to explore group differences. FA, a measure of tract coherence, was reduced in tracts crossing the genu, and to a lesser degree the splenium, in patients compared with controls. FA was also lower in the genu in females across both groups, but there was no gender-by-group interaction. The FA reduction in patients may be due to aberrant myelination or axonal abnormalities, but the similar tract volumes in the two groups suggest that severe axonal loss is unlikely at this stage of the illness. PMID:17275337

Bcr-Abl induces abnormal cytoskeleton remodeling, beta1 integrin clustering and increased cell adhesion to fibronectin through the Abl interactor 1 pathway.

PubMed

Li, Yingzhu; Clough, Nancy; Sun, Xiaolin; Yu, Weidong; Abbott, Brian L; Hogan, Christopher J; Dai, Zonghan

2007-04-15

Hematopoietic cells isolated from patients with Bcr-Abl-positive leukemia exhibit multiple abnormalities of cytoskeletal and integrin function. These abnormalities are thought to play a role in the pathogenesis of leukemia; however, the molecular events leading to these abnormalities are not fully understood. We show here that the Abi1 pathway is required for Bcr-Abl to stimulate actin cytoskeleton remodeling, integrin clustering and cell adhesion. Expression of Bcr-Abl induces tyrosine phosphorylation of Abi1. This is accompanied by a subcellular translocation of Abi1/WAVE2 to a site adjacent to membrane, where an F-actin-enriched structure containing the adhesion molecules such as beta1-integrin, paxillin and vinculin is assembled. Bcr-Abl-induced membrane translocation of Abi1/WAVE2 requires direct interaction between Abi1 and Bcr-Abl, but is independent of the phosphoinositide 3-kinase pathway. Formation of the F-actin-rich complex correlates with an increased cell adhesion to fibronectin. More importantly, disruption of the interaction between Bcr-Abl and Abi1 by mutations either in Bcr-Abl or Abi1 not only abolished tyrosine phosphorylation of Abi1 and membrane translocation of Abi1/WAVE2, but also inhibited Bcr-Abl-stimulated actin cytoskeleton remodeling, integrin clustering and cell adhesion to fibronectin. Together, these data define Abi1/WAVE2 as a downstream pathway that contributes to Bcr-Abl-induced abnormalities of cytoskeletal and integrin function.

Early Brain Vulnerability in Wolfram Syndrome

PubMed Central

Hershey, Tamara; Lugar, Heather M.; Shimony, Joshua S.; Rutlin, Jerrel; Koller, Jonathan M.; Perantie, Dana C.; Paciorkowski, Alex R.; Eisenstein, Sarah A.; Permutt, M. Alan

2012-01-01

Wolfram Syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development. PMID:22792385

The lipid accumulation product as a useful index for identifying abnormal glucose regulation in young Korean women.

PubMed

Oh, J-Y; Sung, Y-A; Lee, H J

2013-04-01

The lipid accumulation product, a combination of waist circumference and triglycerides concentration, has been suggested as a better marker for abnormal glucose regulation than BMI. We aimed to compare the lipid accumulation product and BMI as useful markers for abnormal glucose regulation in young Korean women. The lipid accumulation product was calculated using the formula [waist circumference (cm) - 58] × triglycerides (mmol/l). Glucose tolerance status was determined using a 75-g oral glucose tolerance test in 2810 Korean women aged 18-39 years from the general population. The prevalence of abnormal glucose regulation was 6.8% (isolated impaired fasting glucose 1.8%, isolated impaired glucose tolerance 4.0%; impaired fasting glucose + impaired glucose tolerance 0.4% and diabetes mellitus 0.6%). According to the quintile distributions of the lipid accumulation product and BMI, women with a lipid accumulation product quintile greater than their BMI quintile exhibited significantly greater areas under the curve and higher levels of 2-h post-load glucose, insulin, homeostasis model analysis of insulin resistance and lipid profiles than did women with a BMI quintile greater than their lipid accumulation product quintile. Multiple logistic regression revealed that the lipid accumulation product exhibited a higher odds ratio for abnormal glucose regulation than did BMI after adjusting for age, systolic blood pressure, HDL cholesterol, previous history of gestational diabetes and family history of diabetes (odds ratios 3.5 and 2.6 of the highest vs. the lowest quintiles of lipid accumulation product and BMI, respectively). The lipid accumulation product could be useful for identifying the young Korean women with abnormal glucose regulation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Patients who reattend after head injury: a high risk group.

PubMed Central

Voss, M.; Knottenbelt, J. D.; Peden, M. M.

1995-01-01

OBJECTIVE--To assess risk factors for important neurosurgical effects in patients who reattend after head injury. DESIGN--Retrospective study. SUBJECTS--606 patients who reattended a trauma unit after minor head injury. MAIN OUTCOME MEASURES--Intracranial abnormality detected on computed tomography or the need for neurosurgical intervention. RESULTS--Five patients died: two from unrelated causes and three from raised intracranial pressure. On multiple regression analysis the only significant predictor for both abnormality on computed tomography (14.4% of reattenders) and the need for operation (5% of reattenders) was vault fracture seen on the skull radiograph (P < 10(-6)); predictors for abnormal computed tomogram were a Glasgow coma scale score < 15 at either first or second attendance (P < 0.0001) and convulsion at second attendance (P < 0.05); predictive for operation only was penetrating injury of the skull (P < 10(-6)). On contingency table analysis these associations were confirmed. In addition significant associations with both abnormality on computed tomography and operation were focal neurological abnormality, weakness, or speech disturbance. Amnesia or loss of consciousness at the time of initial injury, personality change, and seizures were significantly associated only with abnormality on computed tomography. Headache, dizziness, nausea, and vomiting were common in reattenders but were found to have no independent significance. CONCLUSIONS--All patients who reattend after head injury should undergo computed tomography as at least 14% of scans can be expected to yield positive results. Where this facility is not available patients with predictors for operation should be urgently referred for neurosurgical opinion. Other patients can be readmitted and need referral only if symptoms persist despite symptomatic treatment or there is neurological deterioration while under observation. These patients are a high risk group and should be treated seriously. PMID:8520273

[Characteristics of pregnancy and delivery of fetuses affected by either central nervous system malformations or chromosomal abnormalities].

PubMed

Friedler, Jordana Mashiach; Mazor, Moshe; Shoham-Vardi, Ilana; Bashiri, Asher

2011-11-01

To determine whether fetuses affected by either chromosomal abnormalities or central nervous system (CNS) malformations are prone to complications during pregnancy and delivery. In this study, 320 singleton pregnancies with CNS malformations and 133 singleton pregnancies with chromosomal abnormaLities were compared with 149,112 singleton births without any known congenital anomalies. Exclusion criteria were: births with other congenital anomalies or malformations, pregnancies Lacking prenatal care and multiple pregnancies. Data was obtained using the computerized birth discharge records. The statistical analysis was performed with the SPSS package. There were no statistically significant differences in maternal age, ethnicity, uterine anomalies or parity. The ratio of general anesthesia was almost double in the study groups compared to the control group: 25% in the CNS malformation group (RR 2.617, CI 2.031-3.372) and 25.6% in the chromosomal abnormality group (RR 2.696, CI 1.825-3.982) and 11.3% in the control group (p < 0.001). There were nearly double cesarean sections (CS) rates in both study groups: 21.5% in the CNS malformation group, 20.3% in the chromosomal abnormaLity group and 12% in the control group. A logistic regression model that included previous CS, maLpresentation, non-reassuring fetal heart monitor (NRFHR) and presence of a malformation, concluded that the presence of a malformation was not an independent risk factor for CS. However, indirect causes, such as malpresentation (4.34 OR), were independently associated with the malformations. Fetuses affected by either CNS malformations or chromosomal abnormalities have a higher rate of pregnancy and delivery complications, including those which increase the risk of maternal morbidity and mortality.

Infant leukemia and congenital abnormalities: A Children’s Oncology Group study

PubMed Central

Johnson, Kimberly J.; Roesler, Michelle A.; Linabery, Amy M.; Hilden, Joanne M.; Davies, Stella M.; Ross, Julie A.

2010-01-01

Background Leukemia in infants is rare and has not been well-studied apart from leukemia in older children. Differences in survival and the molecular characteristics of leukemia in infants vs. older children suggest a distinct etiology, likely involving prenatal factors. Procedure We examined the association between eight categories of maternally-reported congenital abnormalities (CAs) (cleft lip or palate, spina bifida or other spinal defect, large or multiple birthmarks, other chromosomal abnormalities, small head or microcephaly, rib abnormalities, urogenital abnormalities, and other) and infant leukemia in a case-control study. The study included 443 cases diagnosed at <1 year of age at a Children’s Oncology Group institution in the United States or Canada from 1996-2006 and 324 controls. Controls were recruited from the cases’ geographic area either by random digit dialing (1999-2002) or through birth certificates (2003-2008) and were frequency-matched to cases on birth year. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression after adjustment for birth year and a measure of follow-up time to account for differences in the CA observation period. Results No statistically significant associations were observed between infant leukemia and any CA (OR=1.2; 95% CI 0.8-1.9), birthmarks (OR=1.4, 95% CI 0.7-2.5), urogenital abnormalities (OR=0.7; 95% CI 0.2-2.0), or other CA (OR=1.4; 95% CI 0.7-2.8). Results were similar for acute lymphoblastic and myeloid leukemia cases. Fewer than five subjects were in the remaining CA categories precluding analysis. Conclusions Overall, we did not find evidence to support an association between CAs and infant leukemia. PMID:20486175

Temporal and frontal cortical thickness associations with M100 auditory activity and attention in healthy controls and individuals with schizophrenia

PubMed Central

Edgar, J. Christopher; Hunter, Michael A.; Huang, Mingxiong; Smith, Ashley K.; Chen, Yuhan; Sadek, Joseph; Lu, Brett Y; Miller, Gregory A.; Cañive, José M.

2012-01-01

Background Although gray matter (GM) abnormalities are frequently observed in individuals with schizophrenia (SCZ), the functional consequences of these structural abnormalities are not yet understood. The present study sought to better understand GM abnormalities in SCZ by examining associations between GM and two putative functional SCZ biomarkers: weak 100 ms (M100) auditory responses and impairment on tests of attention. Methods Data were available from 103 subjects (healthy controls=52, SCZ=51). GM cortical thickness measures were obtained for superior temporal gyrus (STG) and prefrontal cortex (PFC). Magnetoencephalography (MEG) provided measures of left and right STG M100 source strength. Subjects were administered the Trail Making Test A and the Connors’ Continuous Performance Test to assess attention. Results A strong trend indicated less GM cortical thickness in SCZ than controls in both regions and in both hemispheres (p=0.06). Individuals with SCZ had weaker M100 responses than controls bilaterally, and individuals with SCZ performed more poorly than controls on tests of attention. Across groups, left STG GM was positively associated with left M00 source strength. In SCZ only, less left and right STG and PFC GM predicted poorer performance on tests of attention. After removing variance in attention associated with age, associations between GM and attention remained significant only in left and right STG. Conclusions Reduced GM cortical thickness may serve as a common substrate for multiple functional abnormalities in SCZ, with structural-functional abnormalities in STG GM especially prominent. As suggested by others, functional abnormalities in SCZ may be a consequence of elimination of the neuropil (dendritic arbors and associated synaptic infrastructure) between neuron bodies. PMID:22766129

Congenital Abnormalities and Hepatoblastoma: A Report from the Children’s Oncology Group (COG) and the Utah Population Database (UPDB)

PubMed Central

Venkatramani, Rajkumar; Spector, Logan G.; Georgieff, Michael; Tomlinson, Gail; Krailo, Mark; Malogolowkin, Marcio; Kohlmann, Wendy; Curtin, Karen; Fonstad, Rachel K.; Schiffman, Joshua D.

2014-01-01

Beckwith-Wiedemann Syndrome (BWS) and Familial Adenomatous Polyposis (FAP) are known to predispose to hepatoblastoma (HB). A case control study was conducted through the Children’s Oncology Group (COG) to study the association of HB with isolated congenital abnormalities. Cases (N = 383) were diagnosed between 2000 and 2008. Controls (N = 387) were recruited from state birth registries, frequency matched for sex, region, year of birth, and birth weight. Data on congenital abnormalities among subjects and covariates were obtained by maternal telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) describing the association between congenital abnormalities with HB, adjusted for sex, birth weight, maternal age and maternal education, were calculated using unconditional logistic regression. There was a significant association of HB with kidney, bladder, or sex organ abnormalities (OR = 4.75; 95% CI: 1.74–13) which appeared to be specific to kidney/bladder defects (OR = 4.3; 95% CI: 1.2–15.3) but not those of sex organs (OR = 1.24; 95% CI: 0.37–4.1). Elevated but non-significant ORs were found for spina bifida or other spinal defects (OR = 2.12; 95% CI: 0.39–11.7), large or multiple birthmarks (OR = 1.33; 95% CI: 0.81–2.21). The results were validated through the Utah Population Database (UPDB), a statewide population-based registry linking birth certificates, medical records, and cancer diagnoses. In the UPDB, there were 29 cases and 290 population controls matched 10:1 on sex and birth year. Consistent with the COG findings, kidney/bladder defects were associated with hepatoblastoma. These results confirm the association of HB with kidney/bladder abnormalities. PMID:24934283

Chronic Peripheral Inflammation is Associated With Cognitive Impairment in Schizophrenia: Results From the Multicentric FACE-SZ Dataset

PubMed Central

Bulzacka, Ewa; Boyer, Laurent; Schürhoff, Franck; Godin, Ophélia; Berna, Fabrice; Brunel, Lore; Andrianarisoa, Méja; Aouizerate, Bruno; Capdevielle, Delphine; Chéreau-Boudet, Isabelle; Chesnoy-Servanin, Gabrielle; Danion, Jean-Marie; Dubertret, Caroline; Dubreucq, Julien; Faget, Catherine; Gabayet, Franck; Le Gloahec, Tifenn; Llorca, Pierre-Michel; Mallet, Jasmina; Misdrahi, David; Rey, Romain; Richieri, Raphaëlle; Passerieux, Christine; Roux, Paul; Yazbek, Hanan; Leboyer, Marion; Fond, Guillaume

2016-01-01

Objectives: Inflammation, measured by abnormal blood C-reactive protein (CRP) level, has been described in schizophrenia (SZ), being inconsistently related to impaired cognitive functions. The aim of the present study is to investigate cognitive impairment associated with abnormal CRP levels in a large multi-centric sample of community-dwelling SZ patients, using a comprehensive neuropsychological battery. Method: Three hundred sixty-nine community-dwelling stable SZ subjects (76.2% men, mean age 32.7 y) were included and tested with a comprehensive battery of neuropsychological tests. Abnormal CRP level was defined as >3mg/L. Results: Multiple factor analysis revealed that abnormal CRP levels, found in 104 patients (28.2%), were associated with impaired General Intellectual Ability and Abstract Reasoning (aOR = 0.56, 95% CI 0.35–0.90, P = .014), independently of age, sex, education level, psychotic symptomatology, treatments, and addiction comorbidities. Abnormal CRP levels were also associated with the decline of all components of working memory (respectively effect size [ES] = 0.25, P = .033; ES = 0.27, P = .04; ES = 0.33, P = .006; and ES = 0.38, P = .004) and a wide range of other impaired cognitive functions, including memory (ES = 0.26, P = .026), learning abilities (ES = 0.28, P = .035), semantic memory (ES = 0.26, P = .026), mental flexibility (ES = 0.26, P = .044), visual attention (ES = 0.23, P = .004) and speed of processing (ES = 0.23, P = .043). Conclusion: Our results suggest that abnormal CRP level is associated with cognitive impairment in SZ. Evaluating the effectiveness of neuroprotective anti-inflammatory strategies is needed in order to prevent cognitive impairment in SZ. PMID:27143795

Repeated Blood Pressure Measurements in Childhood in Prediction of Hypertension in Adulthood.

PubMed

Oikonen, Mervi; Nuotio, Joel; Magnussen, Costan G; Viikari, Jorma S A; Taittonen, Leena; Laitinen, Tomi; Hutri-Kähönen, Nina; Jokinen, Eero; Jula, Antti; Cheung, Michael; Sabin, Matthew A; Daniels, Stephen R; Raitakari, Olli T; Juonala, Markus

2016-01-01

Hypertension may be predicted from childhood risk factors. Repeated observations of abnormal blood pressure in childhood may enhance prediction of hypertension and subclinical atherosclerosis in adulthood compared with a single observation. Participants (1927, 54% women) from the Cardiovascular Risk in Young Finns Study had systolic and diastolic blood pressure measurements performed when aged 3 to 24 years. Childhood/youth abnormal blood pressure was defined as above 90th or 95th percentile. After a 21- to 31-year follow-up, at the age of 30 to 45 years, hypertension (>140/90 mm Hg or antihypertensive medication) prevalence was found to be 19%. Carotid intima-media thickness was examined, and high-risk intima-media was defined as intima-media thickness >90th percentile or carotid plaques. Prediction of adulthood hypertension and high-risk intima-media was compared between one observation of abnormal blood pressure in childhood/youth and multiple observations by improved Pearson correlation coefficients and area under the receiver operating curve. When compared with a single measurement, 2 childhood/youth observations improved the correlation for adult systolic (r=0.44 versus 0.35, P<0.001) and diastolic (r=0.35 versus 0.17, P<0.001) blood pressure. In addition, 2 abnormal childhood/youth blood pressure observations increased the prediction of hypertension in adulthood (0.63 for 2 versus 0.60 for 1 observation, P=0.003). When compared with 2 measurements, third observation did not provide any significant improvement for correlation or prediction (P always >0.05). A higher number of childhood/youth observations of abnormal blood pressure did not enhance prediction of adult high-risk intima-media thickness. Compared with a single measurement, the prediction of adult hypertension was enhanced by 2 observations of abnormal blood pressure in childhood/youth. © 2015 American Heart Association, Inc.

Gorlin-Goltz syndrome.

PubMed

Jawa, Deepti Singh; Sircar, Keya; Somani, Rani; Grover, Neeraj; Jaidka, Shipra; Singh, Sanjeet

2009-07-01

Gorlin-Goltz syndrome is an autosomal dominant inherited disorder characterized by the presence of multiple odontogenic keratocysts along with various cutaneous, dental, osseous, ophthalmic, neurological, and sex organ abnormalities. Early diagnosis is essential as it may progress to aggressive basal cell carcinomas and neoplasias. Gorlin-Goltz syndrome has rarely been reported from India. We report here one such patient, diagnosed at a rural hospital.

Language Development in Down Syndrome: From the Prelinguistic Period to the Acquisition of Literacy

ERIC Educational Resources Information Center

Abbeduto, Leonard; Warren, Steven F.; Conners, Frances A.

2007-01-01

Down syndrome (DS) is associated with abnormalities in multiple organ systems and a characteristic phenotype that includes numerous behavioral features. Language, however, is among the most impaired domains of functioning in DS and, perhaps, also the greatest barrier to independent meaningful inclusion in the community. In this article, we review…

Linking cellular zinc status to body weight and fat mass: mapping quantitative trait loci in Znt7 knockout mice

USDA-ARS?s Scientific Manuscript database

Zinc transporter 7 (Znt7, Slc30a7) knockout (KO) mice display abnormalities in body weight gain and body adiposity. Regulation of body weight and fatness is complex, involving multiple genetic and environmental factors. To understand how zinc homeostasis influences body weight gain and fat deposit a...

Radiological features of late-onset lymphoedema in Noonan's syndrome.

PubMed

Ho, Wan-Ling; Wang, Jou-Kou; Li, Yiu-Wah

2003-03-01

Noonan's syndrome is a multiple congenital anomaly syndrome with diverse manifestations. Lymphatic abnormalities occur in less than 20% of patients. We report a 14-year-old boy who presented with swollen lower limbs and dysmorphic features characteristic of Noonan's syndrome. The radiological features of this unusual case of late-onset lymphoedema in association with Noonan's syndrome are presented.

[MLPA technique--principles and use in practice].

PubMed

Rusu, Cristina; Sireteanu, Adriana; Puiu, Maria; Skrypnyk, Cristina; Tomescu, E; Csep, Katalin; Creţ, Victoria; Barbarii, Ligia

2007-01-01

MLPA (Multiplex Ligation-dependent Probe Amplification) is a recently introduced method, based on PCR principle, useful for the detection of different genetic abnormalities (aneuploidies, gene deletions/duplications, subtelomeric rearrangements, methylation status etc). The technique is simple, reliable and cheap. We present this method to discuss its importance for a modern genetic service and to underline its multiple advantages.

Communication in the Early Stage of Language Development in Children with CHARGE Syndrome

ERIC Educational Resources Information Center

Peltokorpi, Sini; Huttunen, Kerttu

2008-01-01

CHARGE syndrome is characterized by multiple physical abnormalities, and impaired vision and hearing. In this pilot study, communication in the early stage of language development in three one- to eight-year-old children with CHARGE syndrome was explored using video recorded free-play interaction sessions and a parental questionnaire. The children…

Evidence of a Faster Posterior Dominant EEG Rhythm in Children with Autism

ERIC Educational Resources Information Center

Gregory, Michael D.; Mandelbaum, David E.

2012-01-01

Multiple electroencephalography (EEG) abnormalities have been associated with autism. In the course of clinical work, we have observed a posterior dominant EEG rhythm at higher frequency in children with autism. To test this observation, 56 EEG tracings of children with autism were compared to the EEGs of age-matched controls. Children with autism…

Ocular surgery in a child with Coffin Lowry syndrome: Anesthetic concerns.

PubMed

Singh, P M; Baidya, Dalim K; Govindarajan, Srinivasa; Trikha, Anjan

2013-01-01

Coffin Lowry syndrome is a rare disease involving multiple organ systems. From the anesthesiologists point of view it involves mental retardation, seizures, difficult airway, cardiac abnormalities (pediatric dilated cardiomyopathy) and skeletal deformities. We share our experience of management of a child with Coffin Lowry syndrome and also discuss the problems faced during perioperative period.

Effects of Quizzing Methodology on Student Outcomes: Reading Compliance, Retention, and Perceptions

ERIC Educational Resources Information Center

Dowling, Carey Bernini

2017-01-01

This study set out to replicate and extend research on students' reading compliance and examine the impact of daily quizzing methodology on students' reading compliance and retention. 98 students in two sections of Abnormal Psychology participated (mean age = 21.5, SD = 3.35; 72.4% Caucasian). Using a multiple baseline quasi-experimental design…

Structural Changes in the Somatosensory System Correlate with Tic Severity in Gilles de la Tourette Syndrome

ERIC Educational Resources Information Center

Thomalla, Gotz; Siebner, Hartwig R.; Jonas, Melanie; Baumer, Tobias; Biermann-Ruben, Katja; Hummel, Friedhelm; Gerloff, Christian; Muller-Vahl, Kirsten; Schnitzler, Alfons; Orth, Michael; Munchau, Alexander

2009-01-01

Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Previous structural MRI studies have identified regional abnormalities in grey matter, especially in the basal ganglia. These findings are consistent with the assumption of alterations in cortico-striato-thalamo-cortical circuits and…

Main Effects of Diagnoses, Brain Regions, and their Interaction Effects for Cerebral Metabolites in Bipolar and Unipolar Depressive Disorders

NASA Astrophysics Data System (ADS)

Tan, Hai-Zhu; Li, Hui; Liu, Chen-Feng; Guan, Ji-Tian; Guo, Xiao-Bo; Wen, Can-Hong; Ou, Shao-Min; Zhang, Yin-Nan; Zhang, Jie; Xu, Chong-Tao; Shen, Zhi-Wei; Wu, Ren-Hua; Wang, Xue-Qin

2016-11-01

Previous studies suggested patients with bipolar depressive disorder (BDd) or unipolar depressive disorder (UDd) have cerebral metabolites abnormalities. These abnormalities may stem from multiple sub-regions of gray matter in brain regions. Thirteen BDd patients, 20 UDd patients and 20 healthy controls (HC) were enrolled to investigate these abnormalities. Absolute concentrations of 5 cerebral metabolites (glutamate-glutamine (Glx), N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), parietal cortex (PC)) were measured from 4 subregions (the medial frontal cortex (mPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and parietal cortex (PC)) of gray matter. Main and interaction effects of cerebral metabolites across subregions of gray matter were evaluated. For example, the Glx was significantly higher in BDd compared with UDd, and so on. As the interaction analyses showed, some interaction effects existed. The concentrations of BDds’ Glx, Cho, Cr in the ACC and HCs’ mI and Cr in the PC were higher than that of other interaction effects. In addition, the concentrations of BDds’ Glx and Cr in the PC and HCs’ mI in the ACC were statistically significant lower than that of other interaction effects. These findings point to region-related abnormalities of cerebral metabolites across subjects with BDd and UDd.

Main Effects of Diagnoses, Brain Regions, and their Interaction Effects for Cerebral Metabolites in Bipolar and Unipolar Depressive Disorders.

PubMed

Tan, Hai-Zhu; Li, Hui; Liu, Chen-Feng; Guan, Ji-Tian; Guo, Xiao-Bo; Wen, Can-Hong; Ou, Shao-Min; Zhang, Yin-Nan; Zhang, Jie; Xu, Chong-Tao; Shen, Zhi-Wei; Wu, Ren-Hua; Wang, Xue-Qin

2016-11-21

Previous studies suggested patients with bipolar depressive disorder (BDd) or unipolar depressive disorder (UDd) have cerebral metabolites abnormalities. These abnormalities may stem from multiple sub-regions of gray matter in brain regions. Thirteen BDd patients, 20 UDd patients and 20 healthy controls (HC) were enrolled to investigate these abnormalities. Absolute concentrations of 5 cerebral metabolites (glutamate-glutamine (Glx), N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), parietal cortex (PC)) were measured from 4 subregions (the medial frontal cortex (mPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and parietal cortex (PC)) of gray matter. Main and interaction effects of cerebral metabolites across subregions of gray matter were evaluated. For example, the Glx was significantly higher in BDd compared with UDd, and so on. As the interaction analyses showed, some interaction effects existed. The concentrations of BDds' Glx, Cho, Cr in the ACC and HCs' mI and Cr in the PC were higher than that of other interaction effects. In addition, the concentrations of BDds' Glx and Cr in the PC and HCs' mI in the ACC were statistically significant lower than that of other interaction effects. These findings point to region-related abnormalities of cerebral metabolites across subjects with BDd and UDd.

An Autonomous Connectivity Restoration Algorithm Based on Finite State Machine for Wireless Sensor-Actor Networks.

PubMed

Zhang, Ying; Wang, Jun; Hao, Guan

2018-01-08

With the development of autonomous unmanned intelligent systems, such as the unmanned boats, unmanned planes and autonomous underwater vehicles, studies on Wireless Sensor-Actor Networks (WSANs) have attracted more attention. Network connectivity algorithms play an important role in data exchange, collaborative detection and information fusion. Due to the harsh application environment, abnormal nodes often appear, and the network connectivity will be prone to be lost. Network self-healing mechanisms have become critical for these systems. In order to decrease the movement overhead of the sensor-actor nodes, an autonomous connectivity restoration algorithm based on finite state machine is proposed. The idea is to identify whether a node is a critical node by using a finite state machine, and update the connected dominating set in a timely way. If an abnormal node is a critical node, the nearest non-critical node will be relocated to replace the abnormal node. In the case of multiple node abnormality, a regional network restoration algorithm is introduced. It is designed to reduce the overhead of node movements while restoration happens. Simulation results indicate the proposed algorithm has better performance on the total moving distance and the number of total relocated nodes compared with some other representative restoration algorithms.

An Autonomous Connectivity Restoration Algorithm Based on Finite State Machine for Wireless Sensor-Actor Networks

PubMed Central

Zhang, Ying; Wang, Jun; Hao, Guan

2018-01-01

With the development of autonomous unmanned intelligent systems, such as the unmanned boats, unmanned planes and autonomous underwater vehicles, studies on Wireless Sensor-Actor Networks (WSANs) have attracted more attention. Network connectivity algorithms play an important role in data exchange, collaborative detection and information fusion. Due to the harsh application environment, abnormal nodes often appear, and the network connectivity will be prone to be lost. Network self-healing mechanisms have become critical for these systems. In order to decrease the movement overhead of the sensor-actor nodes, an autonomous connectivity restoration algorithm based on finite state machine is proposed. The idea is to identify whether a node is a critical node by using a finite state machine, and update the connected dominating set in a timely way. If an abnormal node is a critical node, the nearest non-critical node will be relocated to replace the abnormal node. In the case of multiple node abnormality, a regional network restoration algorithm is introduced. It is designed to reduce the overhead of node movements while restoration happens. Simulation results indicate the proposed algorithm has better performance on the total moving distance and the number of total relocated nodes compared with some other representative restoration algorithms. PMID:29316702

Structural brain changes versus self-report: machine-learning classification of chronic fatigue syndrome patients.

PubMed

Sevel, Landrew S; Boissoneault, Jeff; Letzen, Janelle E; Robinson, Michael E; Staud, Roland

2018-05-30

Chronic fatigue syndrome (CFS) is a disorder associated with fatigue, pain, and structural/functional abnormalities seen during magnetic resonance brain imaging (MRI). Therefore, we evaluated the performance of structural MRI (sMRI) abnormalities in the classification of CFS patients versus healthy controls and compared it to machine learning (ML) classification based upon self-report (SR). Participants included 18 CFS patients and 15 healthy controls (HC). All subjects underwent T1-weighted sMRI and provided visual analogue-scale ratings of fatigue, pain intensity, anxiety, depression, anger, and sleep quality. sMRI data were segmented using FreeSurfer and 61 regions based on functional and structural abnormalities previously reported in patients with CFS. Classification was performed in RapidMiner using a linear support vector machine and bootstrap optimism correction. We compared ML classifiers based on (1) 61 a priori sMRI regional estimates and (2) SR ratings. The sMRI model achieved 79.58% classification accuracy. The SR (accuracy = 95.95%) outperformed both sMRI models. Estimates from multiple brain areas related to cognition, emotion, and memory contributed strongly to group classification. This is the first ML-based group classification of CFS. Our findings suggest that sMRI abnormalities are useful for discriminating CFS patients from HC, but SR ratings remain most effective in classification tasks.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) with multiple vascular complications misdiagnosed as Dubowitz syndrome.

PubMed

Dieks, Jana-Katharina; Baumer, Alessandra; Wilichowski, Ekkehard; Rauch, Anita; Sigler, Matthias

2014-09-01

To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. In microcephalic osteodysplastic primordial dwarfism type II (MOPD II; disproportionate short statue, microcephaly, facial abnormalities), however, cerebral aneurysms and other vascular abnormalities are frequent complications. MOPD II is a genetic disorder caused by mutations in the pericentrin (PCNT) gene (21q22). We report on a patient who came to our attention as a 22-year-old with subarachnoid bleeding due to a ruptured cranial aneurysm. Until then, the patient was thought and published to have Dubowitz syndrome; previously, he was treated with coronary bypass surgery for extensive coronary angiopathy. Consecutive genetic testing revealed MOPD II. After clinical stabilization, the patient was discharged to a specialized rehabilitation center where he died due to re-rupture of a cranial aneurysm. In patients with short stature-especially when clinical features are accompanied by vascular complications-MOPD II should be considered as a differential diagnosis leading to consecutive genetic testing. After detection of mutations in the PCNT gene, a full vascular status including cerebral imaging and cardiac evaluation needs to be determined in order to analyze vascular abnormalities and initiate prophylactic treatment.

Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome.

PubMed

Numakura, Chikahiko; Kitanaka, Sachiko; Kato, Mitsuhiro; Ishikawa, Shigeo; Hamamoto, Yoshioki; Katsushima, Yuriko; Kimura, Toshiyuki; Hayasaka, Kiyoshi

2010-09-01

SOX2 anophthalmia syndrome characteristically presents as anophthalmia or microphthalmia, with various extraocular symptoms, such as hypogonadotropic hypogonadism, brain anomaly, and esophageal abnormalities. In this report, we describe a patient with SOX2 anophthalmia syndrome complicated with a dental anomaly, multiple supernumerary impacted teeth, and persistence of deciduous teeth. Multiple supernumerary teeth are usually not solitary symptoms, but indicate systemic syndrome such as cleidocranial dysplasia. In odontogenesis, many transcriptional factors, such as BMPs, FGFs, and Wnts, play significant roles and SOX2 is known to interact with some of them. The role of SOX2 in dental development remains unknown, however, multiple supernumerary teeth can be considered as extraocular symptoms of SOX2 anophthalmia syndrome, rather than the coincidence of two rare diseases.

Osteomalacia: a case series of patients with atypical clinical orthopaedic presentations.

PubMed

Fok, A W M; Ng, T P

2010-12-01

Osteomalacia is uncommon in an affluent subtropical city like Hong Kong, where sunlight exposure is adequate and nutritional support is good. We present three patients who had osteomalacia with different presentations. A 74-year-old male with oncogenic osteomalacia presented with multiple bone pain. His biochemical markers returned to normal 4 days postoperatively after resection of a second toe giant cell tumour of tendon sheath. A 62-year-old woman with a history of liver problem and proximal muscle weakness was admitted with atraumatic fracture of the left distal humerus due to osteomalacia. An 81-year-old vegetarian woman with inadequate sun exposure complained of multiple bone pains. Subsequent investigation revealed dietary- and sunlight-deficient osteomalacia with multiple bony abnormalities including marked femur bowing.

Multiple acquired portosystemic shunts secondary to primary hypoplasia of the portal vein in a cat.

PubMed

Sugimoto, Satoko; Maeda, Shingo; Tsuboi, Masaya; Saeki, Kohei; Chambers, James K; Yonezawa, Tomohiro; Fukushima, Kenjiro; Fujiwara, Reina; Uchida, Kazuyuki; Tsujimoto, Hajime; Matsuki, Naoaki; Ohno, Koichi

2018-06-06

A 6-year 5-month-old spayed female Scottish Fold cat presented with a one-month history of gait abnormalities, increased salivation, and decreased activity. A blood test showed hyperammonemia and increased serum bile acids. Imaging tests revealed multiple shunt vessels indicating acquired portosystemic shunt. Histopathologic analysis of liver biopsy showed features consistent with liver hypoperfusion, such as a barely recognizable portal vein, increased numbers of small arterioles, and diffuse vacuolar degeneration of hepatocytes. These findings supported the diagnosis of primary hypoplasia of the portal vein/microvascular dysplasia, (PHPV/MVD). To our knowledge, this is the first case of feline PHPV/MVD that developed multiple acquired portosystemic shunts and presented with hepatic encephalopathy.

Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous in transgenic line TgN3261Rpw.

PubMed

Colitz, C M; Malarkey, D E; Woychik, R P; Wilkinson, J E

2000-09-01

Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous are congenital ocular anomalies that can lead to cataract formation. A line of insertional mutant mice, TgN3261Rpw, generated at the Oak Ridge National Laboratory in a large-scale insertional mutagenesis program was found to have a low incidence (8/243; 3.29%) of multiple developmental ocular abnormalities. The ocular abnormalities include persistent hyperplastic primary vitreous, persistent hyperplastic tunica vasculosa lentis, failure of cleavage of the anterior segment, retrolental fibrovascular membrane, posterior polar cataract, and detached retina. This transgenic mouse line provides an ontogenetic model because of the high degree of similarity of this entity in humans, dogs, and mice.

Heavy and Light chain amyloidosois presenting as complete heart block: A rare presentation of a rare disease.

PubMed

Priyamvada, P S; Morkhandikar, S; Srinivas, B H; Parameswaran, S

2015-01-01

Amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix, which results from abnormal protein folding. Even though more than 25 precursor proteins are identified, majority of systemic amyloidosis results from deposition of abnormal immunoglobulin (Ig) light chains. In heavy chain amyloidosis (AH), deposits are derived from both heavy chain alone, whereas in heavy and light chain amyloidosis (AHL), the deposits are derived from Ig heavy chains and light chains. Both AH and AHL are extremely rare diseases. Here, we report an unusual presentation of IgG (lambda) AHL amyloidosis in the background of multiple myeloma, where the initial clinical presentation was complete heart block, which preceded the definitive diagnosis by 18 months.

Congenital malformations of the inner ear and the vestibulocochlear nerve in children with sensorineural hearing loss: evaluation with CT and MRI.

PubMed

Westerhof, J P; Rademaker, J; Weber, B P; Becker, H

2001-01-01

The purpose of this work was to study the diagnostic value of CT and MRI in children with sensorineural hearing loss and to analyze anatomic abnormalities of the inner ear and the vestibulocochlear nerve in this patient group. We evaluated 42 inner ears in 21 children with congenital deafness who had congenital inner ear malformations and who were candidates for cochlear implants. All patients were studied with high resolution MR and helical CT examinations. The MR study included a T2-weighted 3D fast SE sequence. We describe and tabulate the anatomic abnormalities. Special attention was given to abnormalities of the vestibulocochlear nerve. The field of view in the plane according to the length axis of the internal auditory canal (IAC) was 4 cm. Additional continuous parasagittal reformations perpendicular to the length axis of the IAC were studied with a field of view of 3 cm. CT and MRI allowed accurate identification of malformations of the inner ear in children with congenital deafness. We identified 99 malformations, with a majority of patients demonstrating multiple abnormalities. Common imaging findings were Mondini abnormality and Mondini variants (12/42) and fusion of the lateral or superior semicircular canal with the vestibule (12/42). MRI demonstrated in 9 of 21 patients a rudimentary or absent vestibulocochlear nerve in the auditory canal. CT and MRI are important modalities to analyze the inner ear in children who are candidates for cochlear implants. MRI with an extremely small field of view should be used to study possible abnormalities of the vestibulocochlear nerves. This may alter clinical care and allow cochlear implant placement in patients whose electrodiagnostic studies suggest that the implant should not be performed. The detailed analysis of abnormalities of the inner ear might establish prognostic factors.

Is Multiple Sclerosis an Autoimmune Disease?

PubMed Central

Wootla, Bharath; Eriguchi, Makoto; Rodriguez, Moses

2012-01-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS. PMID:22666554

Early Prognostic Value of Monitoring Serum Free Light Chain in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

PubMed

Özkurt, Zübeyde Nur; Sucak, Gülsan Türköz; Akı, Şahika Zeynep; Yağcı, Münci; Haznedar, Rauf

2017-03-16

We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.

Familial pseudoxanthoma elasticum associated with multiple comedones.

PubMed

Maarouf, Melody; Sharon, Victoria R; Sivamani, Raja K; Prakash, Neha; Bipin, T H; Davis, Tracy; Shi, Vivian Y

2017-09-15

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized by atypical elastic fibers that causes connective tissue abnormalities of the skin, eyes, and heart, among other organs. The disorder is rare, with a classic presentation of yellow-orange cobblestone-like papules on flexural areas, lax skin, ocular degeneration, and moribund vasculature in multiple organs. There is wide variability in the presentation of the affected organs [1]. We present two sisters with classic cutaneous findings of PXE with the additional unusual findings of numerous open comedones on the neck. To our knowledge, this is the first report of numerous open comedones in familial PXE.

FDG PET/CT findings in acquired perforating dermatosis.

PubMed

Shinmura, Akiko; Abe, Koichiro; Baba, Shingo; Isoda, Takuro; Maruoka, Yasuhiro; Yasukawa, Fumiko; Kiryu, Hiromaro; Sasaki, Masayuki; Furue, Masutaka; Honda, Hiroshi

2012-10-01

Acquired perforating dermatosis (APD) is an uncommon cutaneous perforating disorder. We report a patient on hemodialysis who developed skin eruption and jaundice. He underwent FDG PET/CT under suspicion of biliary malignancies. PET/CT showed no significant abnormal uptake except of multiple FDG-avid nodules in the skin. The eruption he had was histopathologically diagnosed as APD by skin biopsy. His case suggests that APD should be considered as a differential diagnosis when multiple cutaneous FDG accumulations are found in a patient on hemodialysis. To the best of our knowledge, this is the first report showing the FDG PET/CT findings of APD.

Enhancement of multiple cranial and spinal nerves in vanishing white matter: expanding the differential diagnosis.

PubMed

Eluvathingal Muttikkal, Thomas Jose; Montealegre, Denia Ramirez; Matsumoto, Julie Ann

2018-03-01

Abnormal cranial or spinal nerve contrast enhancement on MRI in cases of suspected pediatric leukodystrophy is recognized as an important clue to the diagnosis of either metachromatic leukodystrophy or globoid cell leukodystrophy (Krabbe disease). We report a case of genetically confirmed childhood vanishing white matter with enhancement of multiple cranial and spinal nerves in addition to the more typical intracranial findings. This case expands the limited differential diagnosis of cranial nerve or spinal nerve enhancement in cases of suspected leukodystrophy and may aid in more efficient work-up and earlier diagnosis of vanishing white matter.

[The value of serum heavy/light chain immunoassay to assess therapeutic response in patients with multiple myeloma].

PubMed

Yu, X C; Su, W; Zhuang, J L

2018-04-14

Objective: To assess the value of immunoglobulin heavy/light chain (HLC) immunoassay on therapeutic response in patients with multiple myeloma(MM). Methods: A total of 45 newly diagnosed MM patients were retrospectively enrolled in Peking Union Medical College Hospital from 2013 to 2016, whose 115 serum samples were consecutively collected. HLC was tested to evaluate response and compare with other methods for M protein detection. Results: ①There were 30 males and 15 females in total of whom the monoclonal immunoglobulin was IgG in 27 (IgGκ∶IgGλ 12∶15) and IgA (IgAκ∶IgAλ 9∶9) in 18. The arerage age of the studied population was 59 (range 43-80) . ② In 34 patients with serum sample at diagnosis, 32 (94.1%) had abnormal HLC ratio (rHLC) while 2 patients with IgG had normal rHLC. The percentages of abnormal rHLC was 81.8% (18/22) at partial response、50.0%(9/18) at very good complete response and 16.0%(4/25) at complete response. ③In 25 patients reaching CR, there were 13 with IgG and 12 with IgA. 4 patients equally split of IgG and IgA had abnormal rHLC at complete response. ④By monitoring the rHLC of some patients consecutively, we found that the remission of rHLC was to some extent behind the remission of SPE and IEF, or even rFLC. Conclusion: Immunoglobulin HLC detection is one feasible method for minimal residual disease detection.

GABA receptor subunit distribution and FMRP-mGluR5 signaling abnormalities in the cerebellum of subjects with schizophrenia, mood disorders, and autism

PubMed Central

Fatemi, S. Hossein; Folsom, Timothy D.

2016-01-01

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. GABAergic receptor abnormalities have been documented in several major psychiatric disorders including schizophrenia, mood disorders, and autism. Abnormal expression of mRNA and protein for multiple GABA receptors has also been observed in multiple brain regions leading to alterations in the balance between excitatory/inhibitory signaling in the brain with potential profound consequences for normal cognition and maintenance of mood and perception. Altered expression of GABAA receptor subunits has been documented in Fragile X mental retardation 1 (FMR1) knockout mice, suggesting that loss of its protein product, fragile X mental retardation protein (FMRP), impacts GABAA subunit expression. Recent postmortem studies from our laboratory have shown reduced expression of FMRP in brains of subjects with schizophrenia, bipolar disorder, major depression, and autism. FMRP acts as a translational repressor and, under normal conditions, inhibits metabotropic glutamate receptor 5 (mGluR5)-mediated signaling. In fragile X syndrome (FXS), absence of FMRP is hypothesized to lead to unregulated mGluR5 signaling, ultimately resulting in the behavioral and intellectual impairments associated with this disorder. Our laboratory has identified changes in mGluR5 expression in autism, schizophrenia, and mood disorders. In the current review article, we discuss our postmortem data on GABA receptors, FMRP, and mGluR5 levels and compare our results with other laboratories. Finally, we discuss the interactions between these molecules and the potential for new therapeutic interventions that target these interconnected signaling systems. PMID:25432637

Aural symptoms in patients with temporomandibular joint disorders: multiple frequency tympanometry provides objective evidence of changes in middle ear impedance.

PubMed

Riga, Maria; Xenellis, John; Peraki, Eleni; Ferekidou, Elisa; Korres, Stavros

2010-12-01

The association of temporomandibular joint (TMJ) disorders with aural symptoms, such as tinnitus, otic fullness, and subjective decrease of hearing acuity, is a well-established clinical observation. Although several hypotheses have been made about the otic-conductive origin of these complaints, conventional 226-Hz tympanometry has failed to demonstrate any middle ear abnormalities. The aim of this study was to evaluate patients with TMJ disorders with multiple frequency tympanometry (MFT). Prospective clinical study. Outpatient clinic. The population of this study consisted of 40 patients with unilateral TMJ disorders diagnosed for longer than 1 month. After verifying that there were no abnormal otoscopic findings, 226-Hz tympanometry, conventional pure-tone audiometry, brainstem auditory evoked potentials, and MFT were performed. Resonant frequency (RF) values. With the exception of MFT, no abnormal audiologic findings were revealed. The ear ipsilateral to the lesion demonstrated significantly higher (p = 0.002) RF values in comparison to the contralateral ear. The difference in RF values was more obvious in patients aged 45 years or younger. The results of this study imply an increase in the stiffness of the middle ear, which has not been detected by conventional tympanometry. This represents the first concrete documentation of minor alterations in the conductive properties of the middle ear and seems to support the various hypotheses on the middle-ear origin of aural complaints in patients with TMJ disorders. Further studies are needed before a clear insight on the presumably multifactorial pathophysiology of these complaints can finally be reached.

Glutamatergic system abnormalities in posttraumatic stress disorder.

PubMed

Nishi, Daisuke; Hashimoto, Kenji; Noguchi, Hiroko; Hamazaki, Kei; Hamazaki, Tomohito; Matsuoka, Yutaka

2015-12-01

Accumulating evidence suggests involvement of the glutamatergic system in the biological mechanisms of posttraumatic stress disorder (PTSD), but few studies have demonstrated an association between glutamatergic system abnormalities and PTSD diagnosis or severity. We aimed to examine whether abnormalities in serum glutamate and in the glutamine/glutamate ratio were associated with PTSD diagnosis and severity in severely injured patients at risk for PTSD and major depressive disorder (MDD). This is a nested case-control study in TPOP (Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid) trial. Diagnosis and severity of PTSD were assessed 3 months after the accidents using the Clinician-Administered PTSD Scale. The associations of glutamate levels and the glutamine/glutamate ratio with diagnosis and severity of PTSD and MDD were investigated by univariate and multiple linear regression analyses. Ninety-seven of 110 participants (88 %) completed assessments at 3 months. Serum glutamate levels were significantly higher for participants with full or partial PTSD than for participants without PTSD (p = 0.049) and for participants with MDD than for participants without MDD (p = 0.048). Multiple linear regression analyses showed serum glutamate levels were significantly positively associated with PTSD severity (p = 0.02) and MDD severity (p = 0.03). The glutamine/glutamate ratio was also significantly inversely associated with PTSD severity (p = 0.03), but not with MDD severity (p = 0.07). These findings suggest that the glutamatergic system may play a major role in the pathogenesis of PTSD and the need for new treatments targeting the glutamatergic system to be developed for PTSD.

White and gray matter damage in primary progressive MS

PubMed Central

Chard, Declan; Altmann, Daniel R.; Tozer, Daniel; Miller, David H.; Thompson, Alan J.; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

2016-01-01

Objective: The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex (“primary WM damage model”); and (2) cortical abnormalities predict later changes in connected WM tracts (“primary GM damage model”). Methods: Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. Results: The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. Conclusion: These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. PMID:26674332

White and gray matter damage in primary progressive MS: The chicken or the egg?

PubMed

Bodini, Benedetta; Chard, Declan; Altmann, Daniel R; Tozer, Daniel; Miller, David H; Thompson, Alan J; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

2016-01-12

The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex ("primary WM damage model"); and (2) cortical abnormalities predict later changes in connected WM tracts ("primary GM damage model"). Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. © 2015 American Academy of Neurology.

MRI and magnetic resonance angiography findings in patients with multiple sclerosis mimicked by stroke.

PubMed

Khedr, Abdullatif Al; Canaple, Sandrine; Monet, Pauline; Godefroy, Olivier; Bugnicourt, Jean-Marc

2013-08-01

We report a 45-year-old woman who presented with a first demyelinating event with abnormalities seen on both MRI and magnetic resonance angiography that were highly suggestive of acute ischemic stroke. This report highlights the problem of differential diagnosis of acute neurological symptoms in adult subjects. Copyright © 2012 Elsevier Ltd. All rights reserved.

Quantitative Analysis of the Shape of the Corpus Callosum in Patients with Autism and Comparison Individuals

ERIC Educational Resources Information Center

Casanova, Manuel F.; El-Baz, Ayman; Elnakib, Ahmed; Switala, Andrew E.; Williams, Emily L.; Williams, Diane L.; Minshew, Nancy J.; Conturo, Thomas E.

2011-01-01

Multiple studies suggest that the corpus callosum in patients with autism is reduced in size. This study attempts to elucidate the nature of this morphometric abnormality by analyzing the shape of this structure in 17 high-functioning patients with autism and an equal number of comparison participants matched for age, sex, IQ, and handedness. The…

Congenital diaphragmatic hernia in a case of patau syndrome: a rare association.

PubMed

A, Jain; P, Kumar; A, Jindal; Yk, Sarin

2015-01-01

Congenital diaphragmatic hernia (CDH) occurs in 5-10% associated with chromosomal abnormalities like, Pallister Killian syndrome, Trisomy 18, and certain deletions.. Association of CDH with trisomy 13 (Patau syndromes) is very rare. Here, we report such an unusual association, where surgical repair was done, but eventually the case succumbed as a result of multiple fatal co-morbidities.

Congenital Diaphragmatic Hernia in a Case of Patau Syndrome: A Rare Association

PubMed Central

A, Jain; P, Kumar; A, Jindal; Yk, Sarin

2015-01-01

Congenital diaphragmatic hernia (CDH) occurs in 5-10% associated with chromosomal abnormalities like, Pallister Killian syndrome, Trisomy 18, and certain deletions.. Association of CDH with trisomy 13 (Patau syndromes) is very rare. Here, we report such an unusual association, where surgical repair was done, but eventually the case succumbed as a result of multiple fatal co-morbidities. PMID:26034714

Ga-67 positivity in sarcoidosis of the skin with coincident thyroid uptake of uncertain etiology

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

Moreno, A.J.; Brown, J.M.; Salinas, J.A.

1984-03-01

Gallium-67 citrate scintigraphy of a 26-year-old woman with systemic sarcoidosis demonstrated abnormal radiotracer uptake within multiple biopsy-proven sarcoidal cutaneous lesions and within both lobes of the thyroid gland. The etiology of the thyroidal uptake of the Ga-67 was uncertain but it may represent sarcoidal involvement of the gland.

Centriole overduplication through the concurrent formation of multiple daughter centrioles at single maternal templates.

PubMed

Duensing, A; Liu, Y; Perdreau, S A; Kleylein-Sohn, J; Nigg, E A; Duensing, S

2007-09-20

Abnormal centrosome numbers are detected in virtually all cancers. The molecular mechanisms that underlie centrosome amplification, however, are poorly characterized. Based on the model that each maternal centriole serves as a template for the formation of one and only one daughter centriole per cell division cycle, the prevailing view is that centriole overduplication arises from successive rounds of centriole reproduction. Here, we provide evidence that a single maternal centriole can concurrently generate multiple daughter centrioles. This mechanism was initially identified in cells treated with the peptide vinyl sulfone proteasome inhibitor Z-L(3)VS. We subsequently found that the formation of more than one daughter at maternal centrioles requires cyclin E/cyclin-dependent kinase 2 as well as Polo-like kinase 4 and that overexpression of these proteins mimics this phenotype in the absence of a proteasome inhibitor. Moreover, we show that the human papillomavirus type 16 E7 oncoprotein stimulates aberrant daughter centriole numbers in part through the formation of more than one daughter centriole at single maternal templates. These results help to explain how oncogenic stimuli can rapidly induce abnormal centriole numbers within a single cell-division cycle and provide insights into the regulation of centriole duplication.

Patient with confirmed LEOPARD syndrome developing multiple melanoma

PubMed Central

Colmant, Caroline; Franck, Deborah; Marot, Liliane; Matthijs, Gert; Sznajer, Yves; Blomme, Sandrine

2018-01-01

LEOPARD syndrome, also known as Gorlin syndrome II, cardiocutaneous syndrome, lentiginosis profusa syndrome, Moynahan syndrome, was more recently coined as Noonan syndrome with multiple lentigines (NSML), inside the RASopathies. Historically, the acronym LEOPARD refers to the presence of distinctive clinical features such as: lentigines (L), electrocardiographic/conduction abnormalities (E), ocular hypertelorism (O), pulmonary stenosis (P), genital abnormalities (A), retardation of growth (R), and sensorineural deafness (D). This condition is identified in 85% of patients with phenotype hallmarks caused by presence a germline point mutation in PTPN11 gene. Association of melanoma to NSML seems to be rare: to our knowledge, two patients so far were reported in the literature. We herein present a patient diagnosed with LEOPARD syndrome, in whom molecular investigation confirmed the presence of the c.1403C>T mutation in exon 12 of the PTPN11 gene, who developed four superficial spreading melanomas and three atypical lentiginous hyperplasias. Three of the melanomas were achromic or hypochromic, three were in situ, and one had a Breslow index under 0.5 mm. Dermoscopic examination showed some characteristic white structures in most of the lesions, which were a signature pattern and a key for the diagnosis. PMID:29445579

Patient with confirmed LEOPARD syndrome developing multiple melanoma.

PubMed

Colmant, Caroline; Franck, Deborah; Marot, Liliane; Matthijs, Gert; Sznajer, Yves; Blomme, Sandrine; Tromme, Isabelle

2018-01-01

LEOPARD syndrome, also known as Gorlin syndrome II, cardiocutaneous syndrome, lentiginosis profusa syndrome, Moynahan syndrome, was more recently coined as Noonan syndrome with multiple lentigines (NSML), inside the RASopathies. Historically, the acronym LEOPARD refers to the presence of distinctive clinical features such as: lentigines (L), electrocardiographic/conduction abnormalities (E), ocular hypertelorism (O), pulmonary stenosis (P), genital abnormalities (A), retardation of growth (R), and sensorineural deafness (D). This condition is identified in 85% of patients with phenotype hallmarks caused by presence a germline point mutation in PTPN11 gene. Association of melanoma to NSML seems to be rare: to our knowledge, two patients so far were reported in the literature. We herein present a patient diagnosed with LEOPARD syndrome, in whom molecular investigation confirmed the presence of the c.1403C>T mutation in exon 12 of the PTPN11 gene, who developed four superficial spreading melanomas and three atypical lentiginous hyperplasias. Three of the melanomas were achromic or hypochromic, three were in situ, and one had a Breslow index under 0.5 mm. Dermoscopic examination showed some characteristic white structures in most of the lesions, which were a signature pattern and a key for the diagnosis.

Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumor progression

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

Dracopoli, N.C.; Harnett, P.; Bale, S.J.

The gene for familial malignant melanoma and its precursor lesion, the dysplastic nevus, has been assigned to a region of the distal short arm of chromosome 1, which is frequently involved in karyotypic abnormalities in melanoma cells. The authors have examined loci on chromosome 1p for loss-of-constitutional heterozygosity in 35 melanomas and 21 melanoma cell lines to analyze the role of these abnormalities in melanocyte transformation. Loss-of-heterozygosity at loci on chromosome 1p was identified in 15/35 (43%) melanomas and 11/21 (52%) melanoma cell lines. Analysis of multiple metastases derived from the same patient and of melanoma and lymphoblastoid samples frommore » a family with hereditary melanoma showed that the loss-of-heterozygosity at loci on distal 1p is a late event in tumor progression, rather than the second mutation that would occur if melanoma were due to a cellular recessive mechanism. Comparisons with neuroblastoma and multiple endocrine neoplasia (MEN2) suggest that the frequent 1p loss-of-heterozygosity in these malignancies is a common late event of neuroectodermal tumor progression.« less

Mass screening of multiple abdominal solid organs using mobile helical computed tomography scanner--a preliminary report.

PubMed

Ishikawa, Susumu; Aoki, Jun; Ohwada, Susumu; Takahashi, Toru; Morishita, Yasuo; Ueda, Keisuke

2007-04-01

The possibility of a new screening procedure for multiple abdominal solid organs using a mobile helical computed tomography (CT) scanner was evaluated. A total of 4,543 residents, who were 40 years of age or older, received CT scanning without contrast medium. The mean age of participants was 64 years including 2,022 males and 2,521 females. A total of 2,105 abnormal findings were uniquely detected in 1,594 participants. Liver and kidney diseases including ureter occupied around 30% of total abnormal findings, respectively. Besides frequent cystic or calcified lesions, solid tumours were suspected in 56 lesions, which received further examination by specialized physicians. Five (9%) of them were confirmed as being malignant tumours including pancreatic cancer in two patients, and liver, lung and ovary cancers in one patient each, respectively. All five patients with each malignant lesion received curative operations. Small-sized abdominal aortic aneurysms and heart valve diseases were uniquely found in 22 and two patients, respectively. Qualitative diagnoses of solid tumours were difficult using CT findings without contrast medium. CT screening procedures require further investigation in aspect of the selection of examinees, CT scanning procedure, sensitivity and specificity, and cost-effectiveness.

A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a Common Cause?

PubMed

Morris, Gerwyn; Berk, Michael; Puri, Basant K

2018-04-01

There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis). Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes. Regional differences in neuronal resistance to oxidative and inflammatory insults and in the performance of antioxidant defences in the central nervous system may also play a role. Importantly, replicated experimental findings suggest that the use of high-resolution SPECT imaging may have the capacity to differentiate patients afforded a diagnosis of CFS from those with a diagnosis of depression. Further research involving this form of neuroimaging appears warranted in an attempt to overcome the problem of aetiologically heterogeneous cohorts which probably explain conflicting findings produced by investigative teams active in this field. However, the ionising radiation and relative lack of sensitivity involved probably preclude its use as a routine diagnostic tool.

Predictors of intractable childhood epilepsy.

PubMed

Seker Yilmaz, Berna; Okuyaz, Cetin; Komur, Mustafa

2013-01-01

Our study sought to identify early predictive factors of medically intractable childhood epilepsy. A cohort of epileptic children from the city of Mersin was retrospectively investigated. All patients received care from the same Department of Pediatric Neurology. The epileptic cohort was divided into a drug-responsive epilepsy group and an intractable epilepsy group. Intractable epilepsy is defined as continued seizures in children despite adequate therapy with two or more antiepileptic drugs for more than 18 months. Strong univariate association was observed between intractability and several factors: age of onset, high initial seizure frequency, symptomatic etiology, mixed seizure types, previous history of status epilepticus, febrile and neonatal seizures, mental and motor developmental delay, multiple seizures in 1 day, electroencephalogram abnormalities, magnetic resonance imaging findings, and specific epileptic syndromes. Logistic regression analysis revealed that a previous history of epilepticus status, abnormal electroencephalogram results, and multiple seizures in 1 day comprise independent predictors of medically intractable childhood epilepsy. We suggest that medical intractability in childhood epilepsy can be predicted by monitoring these factors. Along with early prediction, alternative therapies may be designed to provide patients better seizure control and quality of life. Copyright © 2013 Elsevier Inc. All rights reserved.

Zinc in Gut-Brain Interaction in Autism and Neurological Disorders

PubMed Central

Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M.

2015-01-01

A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life. PMID:25878905

Characterization of a complex chromosomal rearrangement using chromosome, FISH, and microarray assays in a girl with multiple congenital abnormalities and developmental delay

PubMed Central

2014-01-01

Complex chromosomal rearrangements (CCRs) are balanced or unbalanced structural rearrangements involving three or more cytogenetic breakpoints on two or more chromosomal pairs. The phenotypic anomalies in such cases are attributed to gene disruption, superimposed cryptic imbalances in the genome, and/or position effects. We report a 14-year-old girl who presented with multiple congenital anomalies and developmental delay. Chromosome and FISH analysis indicated a highly complex chromosomal rearrangement involving three chromosomes (3, 7 and 12), seven breakpoints as a result of one inversion, two insertions, and two translocations forming three derivative chromosomes. Additionally, chromosomal microarray study (CMA) revealed two submicroscopic deletions at 3p12.3 (467 kb) and 12q13.12 (442 kb). We postulate that microdeletion within the ROBO1 gene at 3p12.3 may have played a role in the patient’s developmental delay, since it has potential activity-dependent role in neurons. Additionally, factors other than genomic deletions such as loss of function or position effects may also contribute to the abnormal phenotype in our patient. PMID:25478007

Zinc in gut-brain interaction in autism and neurological disorders.

PubMed

Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M

2015-01-01

A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life.

The expanding universe of neurotrophic factors: therapeutic potential in aging and age-associated disorders.

PubMed

Lanni, C; Stanga, S; Racchi, M; Govoni, S

2010-01-01

Multiple molecular, cellular, structural and functional changes occur in the brain during aging. Neural cells may respond to these changes adaptively by employing multiple mechanisms in order to maintain the integrity of nerve cell circuits and to facilitate responses to environmental demands. Otherwise, they may succumb to neurodegenerative cascades that result in disorders such as Alzheimer's and Parkinson's diseases. An important role in this balancement is played by neurotrophic factors, which are central to many aspects of nervous system function since they regulate the development, maintenance and survival of neurons and neuron-supporting cells such as glia and oligodendrocytes. A vast amount of evidence indicates that alterations in levels of neurotrophic factors or their receptors can lead to neuronal death and contribute to aging as well as to the pathogenesis of diseases of abnormal trophic support (such as neurodegenerative diseases and depression) and diseases of abnormal excitability (such as epilepsy and central pain sensitization). Cellular and molecular mechanisms by which neurotrophic factors may influence cell survival and excitability are also critically examined to provide novel concepts and targets for the treatment of physiological changes bearing detrimental functional alterations and of different diseases affecting the central nervous system during aging.

Multiple tests for wind turbine fault detection and score fusion using two- level multidimensional scaling (MDS)

NASA Astrophysics Data System (ADS)

Ye, Xiang; Gao, Weihua; Yan, Yanjun; Osadciw, Lisa A.

2010-04-01

Wind is an important renewable energy source. The energy and economic return from building wind farms justify the expensive investments in doing so. However, without an effective monitoring system, underperforming or faulty turbines will cause a huge loss in revenue. Early detection of such failures help prevent these undesired working conditions. We develop three tests on power curve, rotor speed curve, pitch angle curve of individual turbine. In each test, multiple states are defined to distinguish different working conditions, including complete shut-downs, under-performing states, abnormally frequent default states, as well as normal working states. These three tests are combined to reach a final conclusion, which is more effective than any single test. Through extensive data mining of historical data and verification from farm operators, some state combinations are discovered to be strong indicators of spindle failures, lightning strikes, anemometer faults, etc, for fault detection. In each individual test, and in the score fusion of these tests, we apply multidimensional scaling (MDS) to reduce the high dimensional feature space into a 3-dimensional visualization, from which it is easier to discover turbine working information. This approach gains a qualitative understanding of turbine performance status to detect faults, and also provides explanations on what has happened for detailed diagnostics. The state-of-the-art SCADA (Supervisory Control And Data Acquisition) system in industry can only answer the question whether there are abnormal working states, and our evaluation of multiple states in multiple tests is also promising for diagnostics. In the future, these tests can be readily incorporated in a Bayesian network for intelligent analysis and decision support.

The relationship of trauma severity and mortality with cardiac enzymes and cytokines at multiple trauma patients.

PubMed

Karakuş, Ali; Kekeç, Zeynep; Akçan, Ramazan; Seydaoğlu, Gülşah

2012-07-01

In this study, we aimed to determine the effects of trauma severity on cardiac involvement through evaluating the trauma severity score together with diagnostic tests in multiple trauma patients. A trauma score was determined using various trauma severity scales. After obtaining the approval of the ethics committee of the faculty, this prospective study was performed through evaluating 100 multiple trauma patients, aged over 15 years, who applied to our Emergency Department (ED). After determining the trauma severity score using instruments such as the Injury Severity Score (ISS), Glasgow Coma Scale (GCS), and Revised Trauma Score (RTS), the cardiac condition was evaluated using biochemical and radiological diagnostic tests. During the study period, 100 patients were evaluated (78 male, 22 female; mean age: 33.2±15.4; range 15 to 70 years). It was determined that 92 (92%) were blunt trauma cases, and 77 (77%) of them were due to traffic accidents. The majority of cases showed electrocardiogram (ECG) abnormalities (63%) and sinus tachycardia (36%). Abnormal echocardiogram (ECHO) findings, mostly accompanied by ventricular defects (n=24), were determined in 31 of the cases. Nineteen cases with high trauma severity score resulted in death, and 14 of all deaths were secondary to traffic accidents. Trauma scores were found to show a significant difference between the two groups. The ISS trauma scale was determined to be the most effective in terms of indicating heart involvement in patients with multiple traumas. Close follow-up and cardiac monitoring should be applied to patients with high trauma severity scores considering possible cardiac rhythm changes and hemodynamic disturbances due to cardiac involvement.

Identification of a duplication of Xq28 associated with bilateral periventricular nodular heterotopia.

PubMed Central

Fink, J M; Dobyns, W B; Guerrini, R; Hirsch, B A

1997-01-01

Bilateral periventricular nodular heterotopia (BPNH) is a malformation of neuronal migration and is characterized by nodules of heterotopic gray matter lining the lateral ventricles of the brain. The majority of BPNH patients are female and have epilepsy as a sole clinical manifestation of their disease. Familial BPNH has been mapped to Xq28 by linkage analysis. A multiple congenital anomaly-mental retardation syndrome (BPNH/MR) was recently delineated in three unrelated boys with BPNH, cerebellar hypoplasia, severe mental retardation, epilepsy, and syndactyly. High-resolution chromosome analysis revealed a subtle abnormality of Xq28 in one of the boys with BPNH/MR syndrome. FISH with cosmids and YACs from Xq28 further characterized this abnormality as a 2.25-3.25-Mb inverted duplication. No abnormality of Xq28 was detected by G-banding or FISH in the other two boys. These data support the linkage assignment of BPNH to band Xq28 and narrow the critical region to the distal 2.25-3.25 Mb of Xq28. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:9311743

Asbestotic radiological abnormalities among United States merchant marine seamen.

PubMed

Selikoff, I J; Lilis, R; Levin, G

1990-05-01

There has been limited information concerning the prevalence of radiologically evident parenchymal and pleural fibrosis consistent with prior exposure to asbestos among merchant marine seamen, despite the wide use of asbestos in ship construction until the late 1970s and subsequent exposure of seamen to the asbestos that had been installed. A total of 3324 chest radiographs (1985-7) of long term United States seamen were reviewed. One third (34.8%) had parenchymal or pleural abnormalities, or both (ILO classification); pleural changes were predominant. Abnormalities increased with longer duration from onset of shipboard exposure (as defined by first year at sea). The prevalence of asbestotic changes was greater among seamen who had served in the engine department (391/420; 42.5%) compared with seamen in other departments, including deck (301/820; 36.6%), steward (278/981; 28.4%), or with service in multiple departments (167/541; 30.9%). Since many vessels, particularly those built before 1978, contain asbestos materials, appropriate engineering controls (including complete removal, if possible) are required as well as appropriate medical surveillance for those who served aboard such ships.

Asbestotic radiological abnormalities among United States merchant marine seamen.

PubMed Central

Selikoff, I J; Lilis, R; Levin, G

1990-01-01

There has been limited information concerning the prevalence of radiologically evident parenchymal and pleural fibrosis consistent with prior exposure to asbestos among merchant marine seamen, despite the wide use of asbestos in ship construction until the late 1970s and subsequent exposure of seamen to the asbestos that had been installed. A total of 3324 chest radiographs (1985-7) of long term United States seamen were reviewed. One third (34.8%) had parenchymal or pleural abnormalities, or both (ILO classification); pleural changes were predominant. Abnormalities increased with longer duration from onset of shipboard exposure (as defined by first year at sea). The prevalence of asbestotic changes was greater among seamen who had served in the engine department (391/420; 42.5%) compared with seamen in other departments, including deck (301/820; 36.6%), steward (278/981; 28.4%), or with service in multiple departments (167/541; 30.9%). Since many vessels, particularly those built before 1978, contain asbestos materials, appropriate engineering controls (including complete removal, if possible) are required as well as appropriate medical surveillance for those who served aboard such ships. PMID:2357448

Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries

PubMed Central

Talkowski, Michael E.; Rosenfeld, Jill A.; Blumenthal, Ian; Pillalamarri, Vamsee; Chiang, Colby; Heilbut, Adrian; Ernst, Carl; Hanscom, Carrie; Rossin, Elizabeth; Lindgren, Amelia; Pereira, Shahrin; Ruderfer, Douglas; Kirby, Andrew; Ripke, Stephan; Harris, David; Lee, Ji-Hyun; Ha, Kyungsoo; Kim, Hyung-Goo; Solomon, Benjamin D.; Gropman, Andrea L.; Lucente, Diane; Sims, Katherine; Ohsumi, Toshiro K.; Borowsky, Mark L.; Loranger, Stephanie; Quade, Bradley; Lage, Kasper; Miles, Judith; Wu, Bai-Lin; Shen, Yiping; Neale, Benjamin; Shaffer, Lisa G.; Daly, Mark J.; Morton, Cynthia C.; Gusella, James F.

2012-01-01

SUMMARY Balanced chromosomal abnormalities (BCAs) represent a reservoir of single gene disruptions in neurodevelopmental disorders (NDD). We sequenced BCAs in autism and related NDDs, revealing disruption of 33 loci in four general categories: 1) genes associated with abnormal neurodevelopment (e.g., AUTS2, FOXP1, CDKL5), 2) single gene contributors to microdeletion syndromes (MBD5, SATB2, EHMT1, SNURF-SNRPN), 3) novel risk loci (e.g., CHD8, KIRREL3, ZNF507), and 4) genes associated with later onset psychiatric disorders (e.g., TCF4, ZNF804A, PDE10A, GRIN2B, ANK3). We also discovered profoundly increased burden of copy number variants among 19,556 neurodevelopmental cases compared to 13,991 controls (p = 2.07×10−47) and enrichment of polygenic risk alleles from autism and schizophrenia genome-wide association studies (p = 0.0018 and 0.0009, respectively). Our findings suggest a polygenic risk model of autism incorporating loci of strong effect and indicate that some neurodevelopmental genes are sensitive to perturbation by multiple mutational mechanisms, leading to variable phenotypic outcomes that manifest at different life stages. PMID:22521361

Intraductal ultrasonographic anatomy of biliary varices in patients with portal hypertension.

PubMed

Takagi, Tadayuki; Irisawa, Atsushi; Shibukawa, Goro; Hikichi, Takuto; Obara, Katsutoshi; Ohira, Hiromasa

2015-01-01

The term, portal biliopathy, denotes various biliary abnormalities, such as stenosis and/or dilatation of the bile duct, in patients with portal hypertension. These vascular abnormalities sometimes bring on an obstructive jaundice, but they are not clear which vessels participated in obstructive jaundice. The aim of present study was clear the bile ductal changes in patients with portal hypertension in hopes of establishing a therapeutic strategy for obstructive jaundice caused by biliary varices. Three hundred and thirty-seven patients who underwent intraductal ultrasound (IDUS) during endoscopic retrograde cholangiography for biliary abnormalities were enrolled. Portal biliopathy was analyzed using IDUS. Biliary varices were identified in 11 (2.7%) patients. IDUS revealed biliary varices as multiple, hypoechoic features surrounding the bile duct wall. These varices could be categorized into one of two groups according to their location in the sectional image of bile duct: epicholedochal and paracholedochal. Epicholedochal varices were identified in all patients, but paracholedochal varices were observed only in patients with extrahepatic portal obstruction. IDUS was useful to characterize the anatomy of portal biliopathy in detail.

Gastrointestinal symptoms, motility, and transit after the Roux-en-Y operation

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

Perino, L.E.; Adcock, K.A.; Goff, J.S.

1988-04-01

Roux-en-Y patients have symptoms that vary from almost none to inability to tolerate oral feedings. This study was designed to determine whether there is a relationship between a patient's symptoms and the function of the gastric remnant or the Roux-limb. Gastric remnant and Roux-limb emptying were studied in eight patients with technetium-99m-labeled oatmeal and Roux-limb motor activity was measured with a water-perfused manometry system. We found that gastric emptying was rarely significantly slowed, but emptying of the Roux-limb was delayed in several patients. We also found that there was a rough correlation between the patient's symptoms and the degree ofmore » abnormal motility found in the Roux-limb. There is no known reason for these abnormalities in Roux-limb function in some patients after a Roux-en-Y, but our finding of worse abnormalities in those who had multiple previous gastric surgeries suggests that the symptoms and dysfunction may be related to the number of surgeries, as well as to the type of surgery.« less

Epidemiology of HPV Genotypes among HIV Positive Women in Kenya: A Systematic Review and Meta-Analysis.

PubMed

Menon, Sonia; Wusiman, Aibibula; Boily, Marie Claude; Kariisa, Mbabazi; Mabeya, Hillary; Luchters, Stanley; Forland, Frode; Rossi, Rodolfo; Callens, Steven; Vanden Broeck, Davy

2016-01-01

There is a scarcity of data on the distribution of human papillomavirus (HPV) genotypes in the HIV positive population and in invasive cervical cancer (ICC) in Kenya. This may be different from genotypes found in abnormal cytology. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18, and the nonavalent vaccine targeting 90% of all ICC cases, such HPV genotype distribution data are indispensable for predicting the impact of vaccination and HPV screening on prevention. Even with a successful vaccination program, vaccinated women will still require screening to detect those who will develop ICC from other High risk (HR) HPV genotypes not prevented by current vaccines. The aim of this review is to report on the prevalence of pHR/HR HPV types and multiple pHR/HR HPV genotypes in Kenya among HIV positive women with normal, abnormal cytology and ICC. PUBMED, EMBASE, SCOPUS, and PROQUEST were searched for articles on HPV infection up to August 2nd 2016. Search terms were HIV, HPV, Cervical Cancer, Incidence or Prevalence, and Kenya. The 13 studies included yielded a total of 2116 HIV-infected women, of which 89 had ICC. The overall prevalence of pHR/HR HPV genotypes among HIV-infected women was 64% (95%CI: 50%-77%). There was a borderline significant difference in the prevalence of pHR/HR HPV genotypes between Female Sex workers (FSW) compared to non-FSW in women with both normal and abnormal cytology. Multiple pHR/HR HPV genotypes were highly prominent in both normal cytology/HSIL and ICC. The most prevalent HR HPV genotypes in women with abnormal cytology were HPV 16 with 26%, (95%CI: 23.0%-30.0%) followed by HPV 35 and 52, with 21% (95%CI: 18%-25%) and 18% (95%CI: 15%-21%), respectively. In women with ICC, the most prevalent HPV genotypes were HPV 16 (37%; 95%CI: 28%-47%) and HPV 18 (24%; 95%CI: 16%-33%). HPV 16/18 gains prominence as the severity of cervical disease increases, with HPV 16/18 accounting for 61% (95%CI: 50.0%-70.0%) of all ICC cases. A secondary prevention program will be necessary as this population harbors multiple pHR/HR HPV co-infections, which may not be covered by current vaccines. A triage based on FSW as an indicator may be warranted.

Epidemiology of HPV Genotypes among HIV Positive Women in Kenya: A Systematic Review and Meta-Analysis

PubMed Central

Menon, Sonia; Wusiman, Aibibula; Boily, Marie Claude; Kariisa, Mbabazi; Mabeya, Hillary; Luchters, Stanley; Forland, Frode; Rossi, Rodolfo; Callens, Steven; vanden Broeck, Davy

2016-01-01

Background There is a scarcity of data on the distribution of human papillomavirus (HPV) genotypes in the HIV positive population and in invasive cervical cancer (ICC) in Kenya. This may be different from genotypes found in abnormal cytology. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18, and the nonavalent vaccine targeting 90% of all ICC cases, such HPV genotype distribution data are indispensable for predicting the impact of vaccination and HPV screening on prevention. Even with a successful vaccination program, vaccinated women will still require screening to detect those who will develop ICC from other High risk (HR) HPV genotypes not prevented by current vaccines. The aim of this review is to report on the prevalence of pHR/HR HPV types and multiple pHR/HR HPV genotypes in Kenya among HIV positive women with normal, abnormal cytology and ICC. Methods PUBMED, EMBASE, SCOPUS, and PROQUEST were searched for articles on HPV infection up to August 2nd 2016. Search terms were HIV, HPV, Cervical Cancer, Incidence or Prevalence, and Kenya. Results The 13 studies included yielded a total of 2116 HIV-infected women, of which 89 had ICC. The overall prevalence of pHR/HR HPV genotypes among HIV-infected women was 64% (95%CI: 50%-77%). There was a borderline significant difference in the prevalence of pHR/HR HPV genotypes between Female Sex workers (FSW) compared to non-FSW in women with both normal and abnormal cytology. Multiple pHR/HR HPV genotypes were highly prominent in both normal cytology/HSIL and ICC. The most prevalent HR HPV genotypes in women with abnormal cytology were HPV 16 with 26%, (95%CI: 23.0%-30.0%) followed by HPV 35 and 52, with 21% (95%CI: 18%-25%) and 18% (95%CI: 15%-21%), respectively. In women with ICC, the most prevalent HPV genotypes were HPV 16 (37%; 95%CI: 28%-47%) and HPV 18 (24%; 95%CI: 16%-33%). Conclusion HPV 16/18 gains prominence as the severity of cervical disease increases, with HPV 16/18 accounting for 61% (95%CI: 50.0%-70.0%) of all ICC cases. A secondary prevention program will be necessary as this population harbors multiple pHR/HR HPV co-infections, which may not be covered by current vaccines. A triage based on FSW as an indicator may be warranted. PMID:27764092

The Association of PTSD Symptom Severity with Localized Hippocampus and Amygdala Abnormalities

PubMed Central

Akiki, Teddy J.; Averill, Christopher L.; Wrocklage, Kristen M.; Schweinsburg, Brian; Scott, J. Cobb; Martini, Brenda; Averill, Lynnette A.; Southwick, Steven M.; Krystal, John H.; Abdallah, Chadi G.

2017-01-01

Background The hippocampus and amygdala have been repeatedly implicated in the psychopathology of posttraumatic stress disorder (PTSD). While numerous structural neuroimaging studies examined these two structures in PTSD, these analyses have largely been limited to volumetric measures. Recent advances in vertex-based neuroimaging methods have made it possible to identify specific locations of subtle morphometric changes within a structure of interest. Methods In this cross-sectional study, we used high-resolution magnetic resonance imaging to examine the relationship between PTSD symptomatology, as measured using the Clinician Administered PTSD Scale for the DSM-IV (CAPS), and structural shape of the hippocampus and amygdala using vertex-wise shape analyses in a group of combat-exposed US Veterans (N = 69). Results Following correction for multiple comparisons and controlling for age and cranial volume, we found that participants with more severe PTSD symptoms showed an indentation in the anterior half of the right hippocampus and an indentation in the dorsal region of the right amygdala (corresponding to the centromedial amygdala). Post hoc analysis using stepwise regression suggest that among PTSD symptom clusters, arousal symptoms explain most of the variance in the hippocampal abnormality, whereas re-experiencing symptoms explain most of the variance in the amygdala abnormality. Conclusion The results provide evidence of localized abnormalities in the anterior hippocampus and centromedial amygdala in combat-exposed US Veterans suffering from PTSD symptoms. This novel finding provides a more fine-grained analysis of structural abnormalities in PTSD and may be informative for understanding the neurobiology of the disorder. PMID:28825050

Fluorescence immunophenotyping and interphase cytogenetics (FICTION) detects BCL6 abnormalities, including gene amplification, in most cases of nodular lymphocyte-predominant Hodgkin lymphoma.

PubMed

Bakhirev, Alexei G; Vasef, Mohammad A; Zhang, Qian-Yun; Reichard, Kaaren K; Czuchlewski, David R

2014-04-01

BCL6 translocations are a frequent finding in B-cell lymphomas of diverse subtypes, including some cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). However, reliable analysis of BCL6 rearrangements using fluorescence in situ hybridization is difficult in NLPHL because of the relative paucity of neoplastic cells. Combined immunofluorescence microscopy and fluorescence in situ hybridization, or fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION), permits targeted analysis of neoplastic cells. To better define the spectrum of BCL6 abnormalities in NLPHL using FICTION analysis. We performed an optimized FICTION analysis of 24 lymph nodes, including 11 NLPHL, 5 follicular hyperplasia with prominent progressive transformation of germinal centers, and 8 follicular hyperplasia without progressive transformation of germinal centers. BCL6 rearrangement was identified in 5 of 11 cases of NLPHL (46%). In addition, BCL6 gene amplification, with large clusters of BCL6 signals in the absence of chromosome 3 aneuploidy, was detected in 3 of 11 cases of NLPHL (27%). One NLPHL showed extra copies of BCL6 present in conjunction with multiple copies of chromosome 3. Altogether, we detected BCL6 abnormalities in 9 of 11 cases of NLPHL (82%). None of the progressive transformation of germinal centers or follicular hyperplasia cases showed BCL6 abnormalities by FICTION. To our knowledge, this is the first report of BCL6 gene amplification in NLPHL. Our optimized protocol for FICTION permits detection of cytogenetic abnormalities in most NLPHL cases and may represent a useful ancillary diagnostic technique.

Frequency and Prognostic Significance of Abnormal Liver Function Tests in Patients With Cardiogenic Shock.

PubMed

Jäntti, Toni; Tarvasmäki, Tuukka; Harjola, Veli-Pekka; Parissis, John; Pulkki, Kari; Sionis, Alessandro; Silva-Cardoso, Jose; Køber, Lars; Banaszewski, Marek; Spinar, Jindrich; Fuhrmann, Valentin; Tolonen, Jukka; Carubelli, Valentina; diSomma, Salvatore; Mebazaa, Alexandre; Lassus, Johan

2017-10-01

Cardiogenic shock (CS) is a cardiac emergency often leading to multiple organ failure and death. Assessing organ dysfunction and appropriate risk stratification are central for the optimal management of these patients. The purpose of this study was to assess the prevalence of abnormal liver function tests (LFTs), as well as early changes of LFTs and their impact on outcome in CS. We measured LFTs in 178 patients in CS from serial blood samples taken at 0 hours, 12 hours, and 24 hours. The associations of LFT abnormalities and their early changes with all-cause 90-day mortality were estimated using Fisher's exact test and Cox proportional hazards regression analysis. Baseline alanine aminotransferase (ALT) was abnormal in 58% of the patients, more frequently in nonsurvivors. Abnormalities in other LFTs analyzed (alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin) were not associated with short-term mortality. An increase in ALT of >20% within 24 hours (ΔALT>+20%) was observed in 24% of patients. ΔALT>+20% was associated with a more than 2-fold increase in mortality compared with those with stable or decreasing ALT (70% and 28%, p <0.001). Multivariable regression analysis showed that ΔALT>+20% was associated with increased 90-day mortality independent of other known risk factors. In conclusion, an increase in ALT in the initial phase was seen in 1/4 of patients in CS and was independently associated with 90-day mortality. This finding suggests that serial ALT measurements should be incorporated in the clinical assessment of patients in CS. Copyright © 2017 Elsevier Inc. All rights reserved.

Dissociated functional connectivity profiles for motor and attention deficits in acute right-hemisphere stroke

PubMed Central

Ramsey, Lenny; Rengachary, Jennifer; Zinn, Kristi; Siegel, Joshua S.; Metcalf, Nicholas V.; Strube, Michael J.; Snyder, Abraham Z.; Corbetta, Maurizio; Shulman, Gordon L.

2016-01-01

Strokes often cause multiple behavioural deficits that are correlated at the population level. Here, we show that motor and attention deficits are selectively associated with abnormal patterns of resting state functional connectivity in the dorsal attention and motor networks. We measured attention and motor deficits in 44 right hemisphere-damaged patients with a first-time stroke at 1–2 weeks post-onset. The motor battery included tests that evaluated deficits in both upper and lower extremities. The attention battery assessed both spatial and non-spatial attention deficits. Summary measures for motor and attention deficits were identified through principal component analyses on the raw behavioural scores. Functional connectivity in structurally normal cortex was estimated based on the temporal correlation of blood oxygenation level-dependent signals measured at rest with functional magnetic resonance imaging. Any correlation between motor and attention deficits and between functional connectivity in the dorsal attention network and motor networks that might spuriously affect the relationship between each deficit and functional connectivity was statistically removed. We report a double dissociation between abnormal functional connectivity patterns and attention and motor deficits, respectively. Attention deficits were significantly more correlated with abnormal interhemispheric functional connectivity within the dorsal attention network than motor networks, while motor deficits were significantly more correlated with abnormal interhemispheric functional connectivity patterns within the motor networks than dorsal attention network. These findings indicate that functional connectivity patterns in structurally normal cortex following a stroke link abnormal physiology in brain networks to the corresponding behavioural deficits. PMID:27225794

Cerebrovascular risk factors and brain microstructural abnormalities on diffusion tensor images in HIV-infected individuals.

PubMed

Nakamoto, Beau K; Jahanshad, Neda; McMurtray, Aaron; Kallianpur, Kalpana J; Chow, Dominic C; Valcour, Victor G; Paul, Robert H; Marotz, Liron; Thompson, Paul M; Shikuma, Cecilia M

2012-08-01

HIV-associated neurocognitive disorder remains prevalent in HIV-infected individuals despite effective antiretroviral therapy. As these individuals age, comorbid cerebrovascular disease will likely impact cognitive function. Effective tools to study this impact are needed. This study used diffusion tensor imaging (DTI) to characterize brain microstructural changes in HIV-infected individuals with and without cerebrovascular risk factors. Diffusion-weighted MRIs were obtained in 22 HIV-infected subjects aged 50 years or older (mean age = 58 years, standard deviation = 6 years; 19 males, three females). Tensors were calculated to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps. Statistical comparisons accounting for multiple comparisons were made between groups with and without cerebrovascular risk factors. Abnormal glucose metabolism (i.e., impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) was associated with significantly higher MD (false discovery rate (FDR) critical p value = 0.008) and lower FA (FDR critical p value = 0.002) in the caudate and lower FA in the hippocampus (FDR critical p value = 0.004). Pearson correlations were performed between DTI measures in the caudate and hippocampus and age- and education-adjusted composite scores of global cognitive function, memory, and psychomotor speed. There were no detectable correlations between the neuroimaging measures and measures of cognition. In summary, we demonstrate that brain microstructural abnormalities are associated with abnormal glucose metabolism in the caudate and hippocampus of HIV-infected individuals. Deep gray matter structures and the hippocampus may be vulnerable in subjects with comorbid abnormal glucose metabolism, but our results should be confirmed in further studies.

Open bite as a risk factor for orthodontic root resorption.

PubMed

Motokawa, Masahide; Terao, Akiko; Kaku, Masato; Kawata, Toshitsugu; Gonzales, Carmen; Darendeliler, M Ali; Tanne, Kazuo

2013-12-01

The purpose of the present study was to clarify the prevalence and degree of root resorption induced by orthodontic treatment in patients with and without open bite. One hundred and eleven patients treated with multibracket appliances were retrospectively selected from the patients and divided into non-open bite (NOB) and open bite (OB) groups. The severity of root resorption and the root shape were classified into five groups on periapical radiographs before and after treatment. Moreover, only in the OB group, all teeth were sub-divided into functional and hypofunctional ones that are occluding and non-occluding. As the results of multiple linear regression analysis of patient characteristics and clinical variables with the number of overall root resorption, the independent variables that were found to contribute significantly to root resorption were bite and abnormal root shape. The prevalences of root resorption evaluated in the number of patients were significantly higher in OB group than in NOB group, and those in the number of teeth were significantly higher in OB group than in NOB group, in particular anterior and premolar teeth. The prevalence of resorbed teeth with abnormal root shapes was also significantly higher in OB group than in NOB group. On the other hand, in OB group, the prevalences of root resorption and teeth with abnormal root shape were significantly greater in hypofunctional teeth than in normal functional teeth. There are more teeth with root resorption and abnormal root shape in open bite cases than in normal bite cases, and more teeth with abnormal root shapes and root resorption in hypofunctional teeth than in functional teeth.

Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

PubMed Central

Chen, Lizhou; Huang, Xiaoqi; Lei, Du; He, Ning; Hu, Xinyu; Chen, Ying; Li, Yuanyuan; Zhou, Jinbo; Guo, Lanting; Kemp, Graham J.; Gong, Qiyong

2015-01-01

Background Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. Methods We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. Results Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. Limitations This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. Conclusion Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD. PMID:25853285

Relationship between pre-sarcopenia, sarcopenia and bone mineral density in elderly men.

PubMed

Pereira, Fernando Borges; Leite, André Ferreira; de Paula, Ana Patrícia

2015-02-01

Analyze the influence of sarcopenia in bone health of elderly men. This cross-sectional study evaluated 198 men aged over 60 years. Body composition was measured by dual energy X-ray absorptiometry. The BMD was measured at the femoral neck, total hip, lumbar spine and 33% radius. The diagnosis of abnormal BMD was defined for men who presented densitometric diagnosis of osteopenia or osteoporosis defined by T-score of femoral neck, total hip and lumbar spine. The pre-sarcopenia and sarcopenia were defined according to the European Working Group on Sarcopenia in Older People. The group diagnosed with normal BMD, compared to the group of abnormal BMD, have significantly higher body weight, body mass index, grip strength, lean mass, fat mass, and relative appendicular skeletal muscle mass (RASM). However, after multiple linear regression analysis, we found that only the RASM, lean mass, and handgrip strength in the dominant hand influenced the variability of the BMD after adjustment for age and weight. Regression analyzes showed a positive association between greater appendicular lean mass and a smaller number of elderly patients with abnormal BMD diagnostic. The regression analyzes showed that elderly men diagnosed with pre-sarcopenia and sarcopenia had more abnormal BMD than non-sarcopenic elderly men. We concluded that pre-sarcopenia and sarcopenia were associated with abnormal BMD. The lean mass, compared to fat mass, has a greater positive influence on the BMD of elderly men. This result suggests the importance of the increase in lean mass for the bone health of elderly men.

Electrophysiological Evaluation of Dysphagia in the Mild or Moderate Patients with Multiple Sclerosis: A Concept of Subclinical Dysphagia.

PubMed

Beckmann, Yesim; Gürgör, Nevin; Çakır, Ahmet; Arıcı, Şehnaz; İncesu, Tülay Kurt; Seçil, Yaprak; Ertekin, Cumhur

2015-06-01

Swallowing mechanism and neurogenic dysphagia in MS have been rarely studied by electromyographical (EMG) methods. This study aims to evaluate the presence of subclinical dysphagia in patients with mild multiple sclerosis (MS) using electrophysiological methods. A prospective study of 51 patients with relapsing remitting multiple sclerosis and 18 age-matched healthy adults was investigated. We used electromyography to measure the activity of the submental muscles during swallowing. Electrophysiological recordings of patients were obtained during relapse, after relapse, and at any time in remission period. Clinical dysphagia was found in 12% of MS patients, while electrophysiological swallowing abnormalities were encountered in 33% of patients. Subclinical dysphagia was determined in 35% of patients during an MS relapse, in 20% of patients after a relapse, and in 25% of all 51 patients in the remission period based on EMG findings. Duration of swallowing signal of submental muscles in all MS patients was found to be longer than in normal subjects (p = 0.001). During swallowing of 50 ml of sequential water, the compensatory respiratory cycles occurred more often in MS patients than normal subjects, especially during a relapse (p = 0.005). This is the first study investigating swallowing abnormalities and subclinical dysphagia from the electrophysiological aspect in MS patients with mild disability. The electrophysiological tests described in this study are useful to uncover subclinical dysphagia since they have the advantage of being rapid, easy to apply, non-invasive, and without risk for the patients.

Abnormality in catalase import into peroxisomes leads to severe neurological disorder

PubMed Central

Sheikh, Faruk G.; Pahan, Kalipada; Khan, Mushfiquddin; Barbosa, Ernest; Singh, Inderjit

1998-01-01

Peroxisomal disorders are lethal inherited diseases caused by either defects in peroxisome assembly or dysfunction of single or multiple enzymatic function(s). The peroxisomal matrix proteins are targeted to peroxisomes via the interaction of peroxisomal targeting signal sequences 1 and 2 (PTS1 or PTS2) with their respective cytosolic receptors. We have studied human skin fibroblast cell lines that have multiple peroxisomal dysfunctions with normal packaging of PTS1 and PTS2 signal-containing proteins but lack catalase in peroxisomes. To understand the defect in targeting of catalase to peroxisomes and the loss of multiple enzyme activities, we transfected the mutant cells with normal catalase modified to contain either PTS1 or PTS2 signal sequence. We demonstrate the integrity of these pathways by targeting catalase into peroxisomes via PTS1 or PTS2 pathways. Furthermore, restoration of peroxisomal functions by targeting catalase-SKL protein (a catalase fused to the PTS1 sequence) to peroxisomes indicates that loss of multiple functions may be due to their inactivation by H2O2 or other oxygen species in these catalase-negative peroxisomes. In addition to enzyme activities, targeting of catalase-SKL chimera to peroxisomes also corrected the in situ levels of fatty acids and plasmalogens in these mutant cell lines. In normal fibroblasts treated with aminotriazole to inhibit catalase, we found that peroxisomal functions were inhibited to the level found in mutant cells, an observation that supports the conclusion that multiple peroxisomal enzyme defects in these patients are caused by H2O2 toxicity in catalase-negative peroxisomes. Moreover, targeting of catalase to peroxisomes via PTS1 and PTS2 pathways in these mutant cell lines suggests that there is another pathway for catalase import into peroxisomes and that an abnormality in this pathway manifests as a peroxisomal disease. PMID:9501198

IgA-kappa type multiple myeloma affecting proximal and distal renal tubules.

PubMed

Minemura, K; Ichikawa, K; Itoh, N; Suzuki, N; Hara, M; Shigematsu, S; Kobayashi, H; Hiramatsu, K; Hashizume, K

2001-09-01

A 45-year-old male was admitted because of chest pain, lumbago, and bilateral ankle pain. Examination disclosed hypophosphatemic osteomalacia, acquired Fanconi syndrome, and abnormalities in distal nephron such as distal renal tubular acidosis and renal diabetes insipidus. Further exploration revealed IgA kappa multiple myeloma excreting urinary Bence Jones protein (kappa-light chain). Renal biopsy revealed thick basement membranes and elec-tron-dense crystals in proximal tubular epithelial cells. Immunofluorescent studies revealed deposition of kappa-light chain in renal tubular epithelial cells that caused the renal tubular damage. Although the osteomalacia was relieved by medical treatment, the urinary Bence Jones protein and the renal tubular defects were not improved by the chemotherapy for the myeloma. The patient died of exacerbation of multiple myeloma at 50 years of age.

Cherubism with multiple dental abnormalities: a rare presentation

PubMed Central

Misra, Satya Ranjan; Mishra, Lora; Mohanty, Neeta; Mohanty, Susant

2014-01-01

Cherubism is a progressive, hereditary fibro-osseous lesion exclusively affecting the jaw bones. It is caused by the abnormal functioning of osteoblasts and osteoclasts, leading to replacement of normal bone by cellular fibrous tissue and immature bone, which produces painless progressive growth of the jaw, with a round facial appearance. It was first described in 1933 by Jones as ‘familial multilocular cystic disease of the jaws’. The term ‘cherubism’ was later coined to describe the rounded facial appearance resulting from jaw hypertrophy that was reminiscent of cherubs depicted throughout Renaissance art. The bony lesions generally occur at an early age, affect one or both jaws symmetrically, and grow progressively until puberty. Spontaneous regression is seen in most cases, although surgical re-contouring may be required for others for aesthetic reasons. PMID:25301429

Noonan's syndrome with keratoconus and optic disc coloboma.

PubMed

Ascaso, F J; Del Buey, M A; Huerva, V; Latre, B; Palomar, A

1993-01-01

We report the case of a 14-year-old girl with multiple findings characteristic of Noonan's syndrome, including short stature, mild mental retardation, facial, skeletal and renal abnormalities. In addition, ophthalmic examination revealed a keratoconus in the left eye and a right optic disc coloboma. To date, only two cases of Noonan's syndrome with keratoconus have been reported, and this is the second case of this syndrome with optic disc coloboma. To our knowledge, this is the first report of Noonan's syndrome associated with unilateral keratoconus and contralateral optic disc coloboma. In view of the large number of patients with Noonan's syndrome reported to date and the rarity of these ocular abnormalities, it is most likely that this association is fortuitous. Ocular findings reported in patients with Noonan's syndrome are reviewed.

Resting state EEG abnormalities in autism spectrum disorders

PubMed Central

2013-01-01

Autism spectrum disorders (ASD) are a group of complex and heterogeneous developmental disorders involving multiple neural system dysfunctions. In an effort to understand neurophysiological substrates, identify etiopathophysiologically distinct subgroups of patients, and track outcomes of novel treatments with translational biomarkers, EEG (electroencephalography) studies offer a promising research strategy in ASD. Resting-state EEG studies of ASD suggest a U-shaped profile of electrophysiological power alterations, with excessive power in low-frequency and high-frequency bands, abnormal functional connectivity, and enhanced power in the left hemisphere of the brain. In this review, we provide a summary of recent findings, discuss limitations in available research that may contribute to inconsistencies in the literature, and offer suggestions for future research in this area for advancing the understanding of ASD. PMID:24040879

Congenital skeletal malformations and cleft palate induced in goats by ingestion of Lupinus, Conium and Nicotiana species.

PubMed

Panter, K E; Keeler, R F; Bunch, T D; Callan, R J

1990-01-01

Three piperidine alkaloid containing plants, Conium maculatum (poison-hemlock), Nicotiana glauca (tree tobacco) and Lupinus formosus (lunara lupine), induced multiple congenital contractures (MCC) and palatoschisis in goat kids when their dams were gavaged with the plant during gestation days 30-60. The skeletal abnormalities included fixed extension or flexure of the carpal, tarsal, and fetlock joints, scoliosis, lordosis, torticollis and rib cage abnormalities. Clinical signs of toxicity included those reported in sheep, cattle and pigs--ataxia, incoordination, muscular weakness, prostration and death. One quinolizidine alkaloid containing plant, Lupinus caudatus (tailcup lupine), on the other hand, which is also known to cause MCC in cows, caused only slight signs of toxicity in pregnant goats and no teratogenic effects in their offspring.

Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability.

PubMed

Gamba, Bruno F; Zechi-Ceide, Roseli M; Kokitsu-Nakata, Nancy M; Vendramini-Pittoli, Siulan; Rosenberg, Carla; Krepischi Santos, Ana C V; Ribeiro-Bicudo, Lucilene; Richieri-Costa, Antonio

2016-11-01

We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A , DUF1220 , and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date.

Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability

PubMed Central

Gamba, Bruno F.; Zechi-Ceide, Roseli M.; Kokitsu-Nakata, Nancy M.; Vendramini-Pittoli, Siulan; Rosenberg, Carla; Krepischi Santos, Ana C.V.; Ribeiro-Bicudo, Lucilene; Richieri-Costa, Antonio

2016-01-01

We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A, DUF1220, and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date. PMID:27920638

The Smith-Lemli-Opitz syndrome

PubMed Central

Kelley, R.; Hennekam, R.

2000-01-01

The Smith-Lemli-Opitz syndrome (SLOS) is one of the archetypical multiple congenital malformation syndromes. The recent discovery of the biochemical cause of SLOS and the subsequent redefinition of SLOS as an inborn error of cholesterol metabolism have led to important new treatment possibilities for affected patients. Moreover, the recent recognition of the important role of cholesterol in vertebrate embryogenesis, especially with regard to the hedgehog embryonic signalling pathway and its effects on the expression of homeobox genes, has provided an explanation for the abnormal morphogenesis in the syndrome. The well known role of cholesterol in the formation of steroid hormones has also provided a possible explanation for the abnormal behavioural characteristics of SLOS.


Keywords: Smith-Lemli-Opitz syndrome; cholesterol metabolism; 7-dehydrocholesterol reductase; clinical history; management PMID:10807690

The spleen in liver cirrhosis: revisiting an old enemy with novel targets.

PubMed

Li, Liang; Duan, Mubing; Chen, Weisan; Jiang, An; Li, Xiaoming; Yang, Jun; Li, Zongfang

2017-05-23

The spleen is a secondary lymphoid organ which can influence the progression of multiple diseases, notably liver cirrhosis. In chronic liver diseases, splenomegaly and hypersplenism can manifest following the development of portal hypertension. These splenic abnormalities correlate with and have been postulated to facilitate the progression of liver fibrosis to cirrhosis, although precise mechanisms remain poorly understood. In this review, we summarize the literature to highlight the mechanistic contributions of splenomegaly and hypersplenism to the development of liver cirrhosis, focusing on three key aspects: hepatic fibrogenesis, hepatic immune microenvironment dysregulation and liver regeneration. We conclude with a discussion of the possible therapeutic strategies for modulating splenic abnormalities, including the novel potential usage of nanomedicine in non-surgically targetting splenic disorders for the treatment of liver cirrhosis.

Neural control of renal function in health and disease.

PubMed

DiBona, G F

1994-04-01

The renal sympathetic innervation of the kidney exerts significant effects on multiple aspects of renal function, including renal haemodynamics, tubular sodium and water reabsorption and renin secretion. These effects constitute an important control system which is important in the physiological regulation of arterial pressure and total body fluid and sodium homeostasis. Abnormalities in this regulatory mechanism have pathophysiological consequences and are manifest in clinically relevant human disease states. Decreased renal sympathetic nerve activity results in impaired renin secretion, the inability to conserve sodium normally and an attenuated ability to dispose of both acute and chronic sodium loads. Increased renal sympathetic nerve activity contributes significantly to the excess renal sodium retention and related renal abnormalities observed in both hypertension and oedema forming conditions, such as cardiac failure, cirrhosis and nephrotic syndrome.

Molecular cytogenetic analysis consistently identifies translocations involving chromosomes 1, 2 and 15 in five embryonal rhabdomyosarcoma cell lines and a PAX-FOXO1A fusion gene negative alveolar rhabdomyosarcoma cell line.

PubMed

Roberts, I; Gordon, A; Wang, R; Pritchard-Jones, K; Shipley, J; Coleman, N

2001-01-01

Rhabdomyosarcoma in children is a "small round blue cell tumour" that displays skeletal muscle differentiation. Two main histological variants are recognised, alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma. Whereas consistent chromosome translocations characteristic of ARMS have been reported, no such cytogenetic abnormality has yet been described in ERMS. We have used multiple colour chromosome painting to obtain composite karyotypes for five ERMS cell lines and one PAX-FOXO1A fusion gene negative ARMS. The cell lines were assessed by spectral karyotyping (SKY), tailored multi-fluorophore fluorescence in situ hybridisation (M-FISH) using series of seven colour paint sets generated to examine specific abnormalities, and comparative genomic hybridisation (CGH). This approach enabled us to obtain karyotypes of the cell lines in greater detail than previously possible. Several recurring cytogenetic abnormalities were demonstrated, including translocations involving chromosomes 1 and 15 and chromosomes 2 and 15, in 4/6 and 2/6 cell lines respectively. All six cell lines demonstrated abnormalities of chromosome 15. Translocations between chromosomes 1 and 15 have previously been recorded in two primary cases of ERMS by conventional cytogenetics. Analysis of the translocation breakpoints may suggest mechanisms of ERMS tumourigenesis and may enable the development of novel approaches to the clinical management of this tumour. Copyright 2002 S. Karger AG, Basel

Fish consumption and risk of subclinical brain abnormalities on MRI in older adults.

PubMed

Virtanen, J K; Siscovick, D S; Longstreth, W T; Kuller, L H; Mozaffarian, D

2008-08-05

To investigate the association between fish consumption and subclinical brain abnormalities. In the population-based Cardiovascular Health Study, 3,660 participants age > or =65 underwent an MRI scan in 1992-1994. Five years later, 2,313 were scanned. Neuroradiologists assessed MRI scans in a standardized and blinded manner. Food frequency questionnaires were used to assess dietary intakes. Participants with known cerebrovascular disease were excluded from the analyses. After adjustment for multiple risk factors, the risk of having one or more prevalent subclinical infarcts was lower among those consuming tuna/other fish > or =3 times/week, compared to <1/month (relative risk 0.74, 95% CI = 0.54-1.01, p = 0.06, p trend = 0.03). Tuna/other fish consumption was also associated with trends toward lower incidence of subclinical infarcts. Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy. No significant associations were found between fried fish consumption and any subclinical brain abnormalities. Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits.

Clinical and molecular cytogenetic studies in ring chromosome 5: report of a child with congenital abnormalities.

PubMed

Basinko, Audrey; Giovannucci Uzielli, Maria Luisa; Scarselli, Gloria; Priolo, Manuela; Timpani, Giuseppina; De Braekeleer, Marc

2012-02-01

We report here a child with a ring chromosome 5 (r(5)) associated with facial dysmorphology and multiple congenital abnormalities. Fluorescent in situ hybridization (FISH) using bacterial artificial chromosome (BAC) clones was performed to determine the breakpoints involved in the r(5). The 5p deletion extended from 5p13.2-3 to 5pter and measured 34.61 Mb (range: 33.7-35.52 Mb) while the 5q deletion extended from 5q35.3 to 5qter and measured 2.44 Mb (range: 2.31-2.57 Mb). The patient presented signs such as microcephaly, hypertelorism, micrognathia and epicanthal folds, partially recalling those of a deletion of the short arm of chromosome 5 and the "cri-du-chat" syndrome. The most striking phenotypic features were the congenital heart abnormalities which have been frequently reported in deletions of the distal part of the long arm of chromosome 5 and in rings leading to a 5q35-5qter deletion. However, the NKX2-5 gene, which has been related to congenital heart defects, was not deleted in our patient, nor presumably to some other patients with 5q35.3-5qter deletion. We propose that VEGFR3, deleted in our patient, could be a candidate gene for the congenital heart abnormalities observed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Diffusion tensor imaging with tract-based spatial statistics reveals local white matter abnormalities in preterm infants.

PubMed

Anjari, Mustafa; Srinivasan, Latha; Allsop, Joanna M; Hajnal, Joseph V; Rutherford, Mary A; Edwards, A David; Counsell, Serena J

2007-04-15

Infants born preterm have a high incidence of neurodevelopmental impairment in later childhood, often associated with poorly defined cerebral white matter abnormalities. Diffusion tensor imaging quantifies the diffusion of water within tissues and can assess microstructural abnormalities in the developing preterm brain. Tract-based spatial statistics (TBSS) is an automated observer-independent method of aligning fractional anisotropy (FA) images from multiple subjects to allow groupwise comparisons of diffusion tensor imaging data. We applied TBSS to test the hypothesis that preterm infants have reduced fractional anisotropy in specific regions of white matter compared to term-born controls. We studied 26 preterm infants with no evidence of focal lesions on conventional magnetic resonance imaging (MRI) at term equivalent age and 6 healthy term-born control infants. We found that the centrum semiovale, frontal white matter and the genu of the corpus callosum showed significantly lower FA in the preterm group. Infants born at less than or equal to 28 weeks gestational age (n=11) displayed additional reductions in FA in the external capsule, the posterior aspect of the posterior limb of the internal capsule and the isthmus and middle portion of the body of the corpus callosum. This study demonstrates that TBSS provides an observer-independent method of identifying white matter abnormalities in the preterm brain at term equivalent age in the absence of focal lesions.

Ventilation/Perfusion distribution abnormalities in morbidly obese subjects before and after bariatric surgery.

PubMed

Rivas, Eva; Arismendi, Ebymar; Agustí, Alvar; Sanchez, Marcelo; Delgado, Salvadora; Gistau, Concepción; Wagner, Peter D; Rodriguez-Roisin, Roberto

2015-04-01

Obesity is a global and growing public health problem. Bariatric surgery (BS) is indicated in patients with morbid obesity. To our knowledge, the effects of morbid obesity and BS on ventilation/perfusion (V.a/Q.) ratio distributions using the multiple inert gas elimination technique have never before been explored. We compared respiratory and inert gas (V.a/Q. ratio distributions) pulmonary gas exchange, breathing both ambient air and 100% oxygen, in 19 morbidly obese women (BMI, 45 kg/m2), both before and 1 year after BS, and in eight normal-weight, never smoker, age-matched, healthy women. Before BS, morbidly obese individuals had reduced arterial Po2 (76 ± 2 mm Hg) and an increased alveolar-arterial Po2 difference (27 ± 2 mm Hg) caused by small amounts of shunt (4.3% ± 1.1% of cardiac output), along with abnormally broadly unimodal blood flow dispersion (0.83 ± 0.06). During 100% oxygen breathing, shunt increased twofold in parallel with a reduction of blood flow to low V.a/Q. units, suggesting the development of reabsorption atelectasis without reversion of hypoxic pulmonary vasoconstriction. After BS, body weight was reduced significantly (BMI, 31 kg/m2), and pulmonary gas exchange abnormalities were decreased. Morbid obesity is associated with mild to moderate shunt and V.a/Q. imbalance. These abnormalities are reduced after BS.

Corkscrew retinal vessels in neurofibromatosis type 1: report of 12 cases.

PubMed

Muci-Mendoza, R; Ramella, M; Fuenmayor-Rivera, D

2002-03-01

To describe a distinctive spectrum of retinal microvascular abnormalities in 12 patients with neurofibromatosis type 1 (NF-1). This is an observational prospective study of the ocular fundus evaluated by direct ophthalmoscopy with or without fluorescein angiography, to investigate retinal microvascular abnormalities in 32 patients with NF-1 and in 30 control subjects. The evaluation included a complete general and neurological physical examination and in some cases computed tomography, magnetic resonance imaging with gadolinium-DTPA, or both. The occurrence of a distinctive spectrum of retinal microvascular abnormalities is described in 12 patients with NF-1 (37.5%). At the lower end of the spectrum, present in 10 patients, the anomaly consisted of minuscule second or third order tortuous venules, which were called "corkscrew retinal vessels." These were usually isolated but in a few cases multiple. They flow towards the superior or inferior temporal veins. They had a length of one to two disc diameters. They ended either in a minute tuft or vanished on the retinal surface. The upper end of the spectrum was seen in only two patients. One of them had an exceptionally large venous anastomosis on the nasal retina and the other had an arteriovenous malformation extending over one retinal quadrant. None of the patients in the control group had such retinal microvascular abnormalities. The "corkscrew" retinal vessels described in this report constitute a broad spectrum of microvascular markers in NF-1 patients.

Multiple sclerosis pathogenesis: missing pieces of an old puzzle.

PubMed

Rahmanzadeh, Reza; Brück, Wolfgang; Minagar, Alireza; Sahraian, Mohammad Ali

2018-06-08

Traditionally, multiple sclerosis (MS) was considered to be a CD4 T cell-mediated CNS autoimmunity, compatible with experimental autoimmune encephalitis model, which can be characterized by focal lesions in the white matter. However, studies of recent decades revealed several missing pieces of MS puzzle and showed that MS pathogenesis is more complex than the traditional view and may include the following: a primary degenerative process (e.g. oligodendroglial pathology), generalized abnormality of normal-appearing brain tissue, pronounced gray matter pathology, involvement of innate immunity, and CD8 T cells and B cells. Here, we review these findings and discuss their implications in MS pathogenesis.

Angiostrongylus vasorum Causing Severe Granulomatous Hepatitis with Concurrent Multiple Acquired PSS.

PubMed

Cook, Simon; Priestnall, Simon L; Blake, Damer; Meeson, Richard L

2015-01-01

A 14 mo old female Jack Russell terrier presented with a 12 hr history of vomiting and inappetence. She was subsequently diagnosed with multiple acquired portosystemic shunts during an exploratory celiotomy. Gross and histopathological hepatic abnormalities were consistent with chronic disease, including features suggestive of portal hypertension that was potentially caused by migrating and resident Angiostrongylus vasorum larvae. Fecal analysis and polymerase chain reaction of hepatic tissue confirmed the presence of Angiostrongylus vasorum . The dog recovered clinically following empirical treatment and supportive care. A lack of parasite burden was confirmed 9 wk postdiagnosis; however, serum biochemical analysis at that time was suggestive of ongoing hepatic dysfunction.

Acoustical Detection Of Leakage In A Combustor

NASA Technical Reports Server (NTRS)

Puster, Richard L.; Petty, Jeffrey L.

1993-01-01

Abnormal combustion excites characteristic standing wave. Acoustical leak-detection system gives early warning of failure, enabling operating personnel to stop combustion process and repair spray bar before leak grows large enough to cause damage. Applicable to engines, gas turbines, furnaces, and other machines in which acoustic emissions at known frequencies signify onset of damage. Bearings in rotating machines monitored for emergence of characteristic frequencies shown in previous tests associated with incipient failure. Also possible to monitor for signs of trouble at multiple frequencies by feeding output of transducer simultaneously to multiple band-pass filters and associated circuitry, including separate trigger circuit set to appropriate level for each frequency.

Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis.

PubMed

Pardini, Matteo; Sudre, Carole H; Prados, Ferran; Yaldizli, Özgür; Sethi, Varun; Muhlert, Nils; Samson, Rebecca S; van de Pavert, Steven H; Cardoso, M Jorge; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

2016-11-01

To assess the association between proximity to the inner (ventricular and aqueductal) and outer (pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey matter (GM) abnormalities, and white matter (WM) lesions, in multiple sclerosis (MS). 67 people with relapse-onset MS and 30 healthy controls were included in the study. Volumetric T1 images and high-resolution (1 mm 3 ) magnetisation transfer ratio (MTR) images were acquired and segmented into 12 bands between the inner and outer surfaces of the brain. The first and last bands were discarded to limit partial volume effects with cerebrospinal fluid. MTR values were computed for all bands in supratentorial NAWM, cerebellar NAWM and brainstem NA tissue, and deep and cortical GM. Band WM lesion volumes were also measured. Proximity to the ventricular surfaces was associated with progressively lower MTR values in the MS group but not in controls in supratentorial and cerebellar NAWM, brainstem NA and in deep and cortical GM. The density of WM lesions was associated with proximity to the ventricles only in the supratentorial compartment, and no link was found with distance from the pial surfaces. In MS, MTR abnormalities in NAWM and GM are related to distance from the inner and outer surfaces of the brain, and this suggests that there is a common factor underlying their spatial distribution. A similar pattern was not found for WM lesions, raising the possibility that different factors promote their formation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Total alpha-fetoprotein and Lens culinaris agglutinin-reactive alpha-fetoprotein in fetal chromosomal abnormalities.

PubMed

Yamamoto, R; Azuma, M; Kishida, T; Yamada, H; Satomura, S; Fujimoto, S

2001-11-01

To examine the differences in multiples of the median (MoM) of total alpha-fetoprotein, and the proportion of Lens culinaris agglutinin reactive alpha-fetoprotein (% alpha-fetoprotein-L2 + L3) in the maternal serum and amniotic fluid of pregnant women whose fetuses were diagnosed with autosomal or sex chromosomal abnormalities. Prospective consecutive series. University hospital. Maternal sera and amniotic fluids from 46 pregnant women with trisomy 21 fetuses, 10 pregnant women with trisomy 18 fetuses, one pregnant woman with a trisomy 13 fetus, six pregnant women with fetal sex chromosomal abnormalities, and 100 pregnant women for whom the fetal karyotype was diagnosed as normal following a genetic amniocentesis. The proportion of alpha-fetoprotein-L2 + L3 in maternal serum for trisomy 21 (40.3%. P < 0.0001) and trisomy 18 (39.8%, P < 0.05) showed a significantly higher value compared with normal (32.6%). The proportion of alpha-fetoprotein-L2 + L3 in amniotic fluid was significantly higher (P < 0.0001) for trisomy 21 (46.6%) than for a normal karyotype (41.5%). Only for the trisomy 21 group was there a strong correlation in the % alpha-fetoprotein-L2 + L3 between maternal serum and amniotic fluid (r = 0.840, P < 0.0001). For all groups, there was no correlation between alpha-fetoprotein MoM and % alpha-fetoprotein-L2 + L3 in maternal serum and amniotic fluid. The proportion of alpha-fetoprotein-L2 + L3 in maternal serum is an appropriate choice for a trisomy 21 biochemical marker, and it is possible that combining alpha-fetoprotein-L2 + L3 analysis with assays of alpha-fetoprotein in maternal serum could further improve the sensitivity and specificity of multiple marker screening.

Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia.

PubMed

Kesby, James P; Cui, Xiaoying; Burne, Thomas H J; Eyles, Darryl W

2013-01-01

Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

Multiple Rapid Swallow Maneuver Enhances the Clinical Utility of High-Resolution Manometry in Patients Showing Ineffective Esophageal Motility

PubMed Central

Min, Yang Won; Shin, Inseub; Son, Hee Jung; Rhee, Poong-Lyul

2015-01-01

Abstract The clinical significance of ineffective esophageal motility (IEM) together with multiple rapid swallow (MRS) has not been yet evaluated in the Chicago Classification v3.0. This study evaluated the adjunctive role of MRS in IEM and determined the criteria of abnormal MRS to maximize the utility of IEM. We analyzed 186 patients showing IEM or normal esophageal motility (NEM), who underwent esophageal high-resolution impedance–manometry for esophageal symptoms. Two different criteria for abnormal MRS were applied to IEM subjects, resulting in 2 corresponding subgroups: IEM-A when distal contractile integral (DCI) ratio between an average wet swallows and MRS contraction was <1 and IEM-B when MRS contraction DCI was <450 mm Hg-s-cm. One IEM subject inadequately performed MRS. Among the remaining 52 IEM subjects, 18 (34.6%) were classified into IEM-A and 23 (44.2%) into IEM-B. IEM subjects showed less complete bolus transit (median 0.0%, interquartile range 0.0–20.0% vs 60.0%, 30.0–80.0; P < 0.001) resulting in higher impaired bolus transit than NEM subjects (98.1% vs 66.9%, P = 0.001). IEM-B subjects showed additionally higher pathologic bolus exposure than NEM subjects (55.6% vs 29.3%, P = 0.001), whereas IEM-A subjects could not. Although IEM-B subjects had the highest prevalence of gastroesophageal reflux disease among the subjects groups, it did not reach statistical significance. In conclusion, IEM patients with abnormal MRS contraction have an increased risk of prolonged bolus clearance, poor bolus transit, and pathologic bolus exposure. IEM patients need to be assessed concerning whether MRS contraction DCI is <450 mm Hg-s-cm to segregate clinically relevant patients. PMID:26448010

Dissection of the complex genetic basis of craniofacial anomalies using haploid genetics and interspecies hybrids in Nasonia wasps

PubMed Central

Werren, John H.; Cohen, Lorna B.; Gadau, Juergen; Ponce, Rita; Baudry, Emmanuelle; Lynch, Jeremy A.

2016-01-01

The animal head is a complex structure where numerous sensory, structural and alimentary structures are concentrated and integrated, and its ontogeny requires precise and delicate interactions among genes, cells, and tissues. Thus, it is perhaps unsurprising that craniofacial abnormalities are among the most common birth defects in people, or that these defects have a complex genetic basis involving interactions among multiple loci. Developmental processes that depend on such epistatic interactions become exponentially more difficult to study in diploid organisms as the number of genes involved increases. Here, we present hybrid haploid males of the wasp species pair Nasonia vitripennis and Nasonia giraulti, which have distinct male head morphologies, as a genetic model of craniofacial development that possesses the genetic advantages of haploidy, along with many powerful genomic tools. Viable, fertile hybrids can be made between the species, and quantitative trail loci related to shape differences have been identified. In addition, a subset of hybrid males show head abnormalities, including clefting at the midline and asymmetries. Crucially, epistatic interactions among multiple loci underlie several developmental differences and defects observed in the F2 hybrid males. Furthermore, we demonstrate an introgression of a chromosomal region from N. giraulti into N. vitripennis that shows an abnormality in relative eye size, which maps to a region containing a major QTL for this trait. Therefore, the genetic sources of head morphology can, in principle, be identified by positional cloning. Thus, Nasonia is well positioned to be a uniquely powerful model invertebrate system with which to probe both development and complex genetics of craniofacial patterning and defects. PMID:26721604

Abnormal functional connectivity and cortical integrity influence dominant hand motor disability in multiple sclerosis: a multimodal analysis.

PubMed

Zhong, Jidan; Nantes, Julia C; Holmes, Scott A; Gallant, Serge; Narayanan, Sridar; Koski, Lisa

2016-12-01

Functional reorganization and structural damage occur in the brains of people with multiple sclerosis (MS) throughout the disease course. However, the relationship between resting-state functional connectivity (FC) reorganization in the sensorimotor network and motor disability in MS is not well understood. This study used resting-state fMRI, T1-weighted and T2-weighted, and magnetization transfer (MT) imaging to investigate the relationship between abnormal FC in the sensorimotor network and upper limb motor disability in people with MS, as well as the impact of disease-related structural abnormalities within this network. Specifically, the differences in FC of the left hemisphere hand motor region between MS participants with preserved (n = 17) and impaired (n = 26) right hand function, compared with healthy controls (n = 20) was investigated. Differences in brain atrophy and MT ratio measured at the global and regional levels were also investigated between the three groups. Motor preserved MS participants had stronger FC in structurally intact visual information processing regions relative to motor impaired MS participants. Motor impaired MS participants showed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain compared with the other groups. Logistic regression analysis showed that regional MTR predicted motor disability beyond the impact of global atrophy whereas regional grey matter volume did not. More importantly, as the first multimodal analysis combining resting-state fMRI, T1-weighted, T2-weighted and MTR images in MS, we demonstrate how a combination of structural and functional changes may contribute to motor impairment or preservation in MS. Hum Brain Mapp 37:4262-4275, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Circadian abnormalities in mouse models of Smith-Magenis syndrome: evidence for involvement of RAI1.

PubMed

Lacaria, Melanie; Gu, Wenli; Lupski, James R

2013-07-01

Smith-Magenis syndrome (SMS; OMIM 182290) is a genomic disorder characterized by multiple congenital anomalies, intellectual disability, behavioral abnormalities, and disordered sleep resulting from an ~3.7 Mb deletion copy number variant (CNV) on chromosome 17p11.2 or from point mutations in the gene RAI1. The reciprocal duplication of this region results in another genomic disorder, Potocki-Lupski syndrome (PTLS; OMIM 610883), characterized by autism, intellectual disability, and congenital anomalies. We previously used chromosome-engineering and gene targeting to generate mouse models for PTLS (Dp(11)17/+), and SMS due to either deletion CNV or gene knock-out (Df(11)17-2/+ and Rai1(+/-) , respectively) and we observed phenotypes in these mouse models consistent with their associated human syndromes. To investigate the contribution of individual genes to the circadian phenotypes observed in SMS, we now report the analysis of free-running period lengths in Rai1(+/-) and Df(11)17-2/+ mice, as well as in mice deficient for another known circadian gene mapping within the commonly deleted/duplicated region, Dexras1, and we compare these results to those previously observed in Dp(11)17/+ mice. Reduced free-running period lengths were seen in Df(11)17-2/+, Rai1(+/-) , and Dexras1(-/-) , but not Dexras1(+/-) mice, suggesting that Rai1 may be the primary gene underlying the circadian defects in SMS. However, we cannot rule out the possibility that cis effects between multiple haploinsufficient genes in the SMS critical interval (e.g., RAI1 and DEXRAS1) either exacerbate the circadian phenotypes observed in SMS patients with deletions or increase their penetrance in certain environments. This study also confirms a previous report of abnormal circadian function in Dexras1(-/-) mice. Copyright © 2013 Wiley Periodicals, Inc.

GABA receptor subunit distribution and FMRP-mGluR5 signaling abnormalities in the cerebellum of subjects with schizophrenia, mood disorders, and autism.

PubMed

Fatemi, S Hossein; Folsom, Timothy D

2015-09-01

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. GABAergic receptor abnormalities have been documented in several major psychiatric disorders including schizophrenia, mood disorders, and autism. Abnormal expression of mRNA and protein for multiple GABA receptors has also been observed in multiple brain regions leading to alterations in the balance between excitatory/inhibitory signaling in the brain with potential profound consequences for normal cognition and maintenance of mood and perception. Altered expression of GABAA receptor subunits has been documented in fragile X mental retardation 1 (FMR1) knockout mice, suggesting that loss of its protein product, fragile X mental retardation protein (FMRP), impacts GABAA subunit expression. Recent postmortem studies from our laboratory have shown reduced expression of FMRP in the brains of subjects with schizophrenia, bipolar disorder, major depression, and autism. FMRP acts as a translational repressor and, under normal conditions, inhibits metabotropic glutamate receptor 5 (mGluR5)-mediated signaling. In fragile X syndrome (FXS), the absence of FMRP is hypothesized to lead to unregulated mGluR5 signaling, ultimately resulting in the behavioral and intellectual impairments associated with this disorder. Our laboratory has identified changes in mGluR5 expression in autism, schizophrenia, and mood disorders. In the current review article, we discuss our postmortem data on GABA receptors, FMRP, and mGluR5 levels and compare our results with other laboratories. Finally, we discuss the interactions between these molecules and the potential for new therapeutic interventions that target these interconnected signaling systems. Copyright © 2014 Elsevier B.V. All rights reserved.

Absence of CFAP69 Causes Male Infertility due to Multiple Morphological Abnormalities of the Flagella in Human and Mouse.

PubMed

Dong, Frederick N; Amiri-Yekta, Amir; Martinez, Guillaume; Saut, Antoine; Tek, Julie; Stouvenel, Laurence; Lorès, Patrick; Karaouzène, Thomas; Thierry-Mieg, Nicolas; Satre, Véronique; Brouillet, Sophie; Daneshipour, Abbas; Hosseini, Seyedeh Hanieh; Bonhivers, Mélanie; Gourabi, Hamid; Dulioust, Emmanuel; Arnoult, Christophe; Touré, Aminata; Ray, Pierre F; Zhao, Haiqing; Coutton, Charles

2018-04-05

The multiple morphological abnormalities of the flagella (MMAF) phenotype is among the most severe forms of sperm defects responsible for male infertility. The phenotype is characterized by the presence in the ejaculate of immotile spermatozoa with severe flagellar abnormalities including flagella being short, coiled, absent, and of irregular caliber. Recent studies have demonstrated that MMAF is genetically heterogeneous, and genes thus far associated with MMAF account for only one-third of cases. Here we report the identification of homozygous truncating mutations (one stop-gain and one splicing variant) in CFAP69 of two unrelated individuals by whole-exome sequencing of a cohort of 78 infertile men with MMAF. CFAP69 encodes an evolutionarily conserved protein found at high levels in the testis. Immunostaining experiments in sperm from fertile control individuals showed that CFAP69 localized to the midpiece of the flagellum, and the absence of CFAP69 was confirmed in both individuals carrying CFPA69 mutations. Additionally, we found that sperm from a Cfap69 knockout mouse model recapitulated the MMAF phenotype. Ultrastructural analysis of testicular sperm from the knockout mice showed severe disruption of flagellum structure, but histological analysis of testes from these mice revealed the presence of all stages of the seminiferous epithelium, indicating that the overall progression of spermatogenesis is preserved and that the sperm defects likely arise during spermiogenesis. Together, our data indicate that CFAP69 is necessary for flagellum assembly/stability and that in both humans and mice, biallelic truncating mutations in CFAP69 cause autosomal-recessive MMAF and primary male infertility. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Assisting People with Multiple Disabilities by Actively Keeping the Head in an Upright Position with a Nintendo Wii Remote Controller through the Control of an Environmental Stimulation

ERIC Educational Resources Information Center

Shih, Ching-Hsiang; Shih, Chia-Ju; Shih, Ching-Tien

2011-01-01

The latest researches have adopted software technology by applying the Nintendo Wii Remote Controller to the correction of hyperactive limb behavior. This study extended Wii Remote Controller functionality for improper head position (posture) correction (i.e. actively adjusting abnormal head posture) to assess whether two people with multiple…

Dysfunctions of the Iga system: a common link between intestinal and renal diseases

PubMed Central

Papista, Christina; Berthelot, Laureline; Monteiro, Renato C

2011-01-01

Immunoglobulin A (Iga)-isotype antibodies play an important role in immunity owing to their structure, glycosylation, localization and receptor interactions. Dysfunctions in this system can lead to multiple types of pathology. This review describes the characteristics of Iga and discusses the involvement of abnormalities in the Iga system on the development of celiac disease and Iga nephropathy. PMID:21278767

Celluloid Marginalization: Pedagogical Strategies for Increasing Students' Critical Thought through the Multiple (Re)Readings of Trans* Subjectivities in Film

ERIC Educational Resources Information Center

Nicolazzo, Z.

2014-01-01

Critically analyzing films allows for the interrogation of how such binaries as normal/abnormal, good/bad, and moral/immoral are culturally (re)inscribed, who sets the boundaries of what is deemed socially legible, and who gets to decide where these boundaries are set. This article utilizes critical discourse analysis to explore the transgender…

Proteomic Analysis of Trauma-Induced Heterotopic Ossification Formation

DTIC Science & Technology

2016-10-01

60% of these patients go on to form abnormal bone within the soft tissue of their injured limbs. This condition, known as Heterotopic Ossification... psychological and physical damage sustained as a result of multiple orthopaedic surgical procedures. As a result, the effort, time, and cost of wounded...third year of this research project has continued to integrate productive and complementary activities across four distinct campuses. Critical

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

Levy, H.M.; Smith, R.

Two cases of thalassemia major are presented in which bone scintigraphy demonstrated diffuse hepatic uptake of Tc-99m diphosphonate. Although abnormal splenic and renal uptake of Tc-99m phosphates has been reported in patients with thalassemia major, hepatic uptake has not been reported previously. This scintigraphic finding is presumably due to increased iron deposition in the liver, resulting from increased iron turnover and retention in these patients and from multiple previous blood transfusions.

The putaminal abnormalities on 3.0T magnetic resonance imaging: can they separate parkinsonism-predominant multiple system atrophy from Parkinson's disease?

PubMed

Feng, Jie-Ying; Huang, Biao; Yang, Wan-Qun; Zhang, Yu-Hu; Wang, Li-Min; Wang, Li-Juan; Zhong, Xiao-Ling

2015-03-01

The putaminal abnormalities detected on 1.5 T magnetic resonance imaging (MRI), such as putaminal atrophy, slit-like hyperintense rim, and hypointensity in the putamen on T2-weighted (T2W) imaging are important signs on differentiating multiple system atrophy with parkinsonism (MSA-P) from Parkinson's disease (PD). However, the putaminal abnormalities may have different manifestations on 3.0 T from those on 1.5 T. To investigate the diagnostic value of putaminal abnormalities on 3.0 T MRI for differentiating MSA-P from PD. The study included a MSA-P group (9 men, 9 women), a PD group (12 men, 14 women), and a control group (11 men, 13 women). All subjects were examined with 3.0 T MRI using the conventional protocol. Putaminal atrophy, T2-hypointensity in the dorsolateral putamenat, and a slit-like hyperintense rim on the lateral putamen were evaluated in each subject. There were no significant differences in the slit-like hyperintense rim (P = 0.782) or T2-hypointensity in the dorsolateral putamen (P = 0.338) among the three groups. Bilateral putaminal atrophy was found in 44.4% (8 of 18) of the MSA-P patients, in only 7.7% (2 of 26) of the PD patients, and in none of the controls. The proportion of subjects with putaminal atrophy was significantly higher in the MAS-P group (P = 0.008) and control group (P < 0.001). The specificity and sensitivity of putaminal atrophy for distinguishing MSA-P from PD was 92.3% and 44.4%, respectively. The signal changes in the putamen on T2W imaging on 3.0 T MRI, including slit-like hyperintense rim and putaminal hypointensity, are not specific signs for MSA-P. Putaminal atrophy is highly specific for differentiating MSA-P from PD and healthy controls, but its insufficient sensitivity limits its diagnostic value. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Reduced Integrity of Right Lateralized White Matter in Patients with Primary Insomnia: A Diffusion-Tensor Imaging Study.

PubMed

Li, Shumei; Tian, Junzhang; Bauer, Andreas; Huang, Ruiwang; Wen, Hua; Li, Meng; Wang, Tianyue; Xia, Likun; Jiang, Guihua

2016-08-01

Purpose To analyze the integrity of white matter (WM) tracts in primary insomnia patients and provide better characterization of abnormal WM integrity and its relationship with disease duration and clinical features of primary insomnia. Materials and Methods This prospective study was approved by the ethics committee of the Guangdong No. 2 Provincial People's Hospital. Tract-based spatial statistics were used to compare changes in diffusion parameters of WM tracts from 23 primary insomnia patients and 30 healthy control (HC) participants, and the accuracy of these changes in distinguishing insomnia patients from HC participants was evaluated. Voxel-wise statistics across subjects was performed by using a 5000-permutation set with family-wise error correction (family-wise error, P < .05). Multiple regressions were used to analyze the associations between the abnormal fractional anisotropy (FA) in WM with disease duration, Pittsburgh Sleep Quality Index, insomnia severity index, self-rating anxiety scale, and the self-rating depression scale in primary insomnia. Characteristics for abnormal WM were also investigated in tract-level analyses. Results Primary insomnia patients had lower FA values mainly in the right anterior limb of the internal capsule, right posterior limb of the internal capsule, right anterior corona radiata, right superior corona radiata, right superior longitudinal fasciculus, body of the corpus callosum, and right thalamus (P < .05, family-wise error correction). The receiver operating characteristic areas for the seven regions were acceptable (range, 0.60-0.74; 60%-74%). Multiple regression models showed abnormal FA values in the thalamus and body corpus callosum were associated with the disease duration, self-rating depression scale, and Pittsburgh Sleep Quality Index scores. Tract-level analysis suggested that the reduced FA values might be related to greater radial diffusivity. Conclusion This study showed that WM tracts related to regulation of sleep and wakefulness, and limbic cognitive and sensorimotor regions, are disrupted in the right brain in patients with primary insomnia. The reduced integrity of these WM tracts may be because of loss of myelination. (©) RSNA, 2016.

Improving the rates of electronic results acknowledgement at a tertiary eye care centre.

PubMed

Phua, Val; Au, Benjamin; Soh, Yu Qiang; Husain, Rahat

2017-01-01

Hundreds of thousands of tests are performed annually in hospitals worldwide. Safety Issues arise when abnormal results are not recognized promptly resulting in delayed treatment and increased morbidity and mortality. As a result Singapore's largest healthcare group, Singhealth introduced an electronic result acknowledgement system. This system was adopted by the Singapore National Eye Centre (SNEC) in February 2016. Baseline measurements show that weekly numbers of unacknowledged results ranged from 193 to 617. The current standards of electronic results acknowledgement posts a significant patient safety hazard. Root cause analysis was performed to identify contributory factors. Pareto principle was then used by the authors to identify the main contributory factors. We employed the rapid cycle improvement Plan-do-study-act (PDSA) strategy to test and evaluate implemented changes. Changes are implemented for 2 weeks and data collected prospectively. The data is analyzed the week after and the following PDSA actions are decided and instituted the following week. 3 PDSA cycles were undertaken in total. The first PDSA cycle focused on raising awareness of the problem at hand, the number of unacknowledged results drastically decreased during the 1 st week of implementation of our PDSA from 617 to 254. The second PDSA cycle targeted the lack of knowledge of doctors involved in the electronic result acknowledgement process. There was a trend downwards near the end of the cycle which continued through the week after. The third PDSA cycle targeted individual doctors and provided individual remedial training. Second line doctors were also equipped to better handle abnormal results. There was significant improvement with the number of unacknowledged abnormal results dropping to <5 a week. Multiple factors were identified to contribute to the low compliance to electronic acknowledgement of results. The role doctors play in the issue at hand was paramount and required careful handling in a professional manner with multiple reminders and emphasis on the importance of acknowledging and acting on the results.A significant improvement in the rates of acknowledgement of abnormal results was demonstrated with clear benefits to patient safety. Interventions can be replicated when implementing similar systems to other areas of healthcare.

Improving the rates of electronic results acknowledgement at a tertiary eye care centre

PubMed Central

Phua, Val; Au, Benjamin; Soh, Yu Qiang; Husain, Rahat

2017-01-01

Background Hundreds of thousands of tests are performed annually in hospitals worldwide. Safety Issues arise when abnormal results are not recognized promptly resulting in delayed treatment and increased morbidity and mortality. As a result Singapore’s largest healthcare group, Singhealth introduced an electronic result acknowledgement system. This system was adopted by the Singapore National Eye Centre (SNEC) in February 2016. Baseline measurements show that weekly numbers of unacknowledged results ranged from 193 to 617. The current standards of electronic results acknowledgement posts a significant patient safety hazard. Methods Root cause analysis was performed to identify contributory factors. Pareto principle was then used by the authors to identify the main contributory factors. We employed the rapid cycle improvement Plan-do-study-act (PDSA) strategy to test and evaluate implemented changes. Changes are implemented for 2 weeks and data collected prospectively. The data is analyzed the week after and the following PDSA actions are decided and instituted the following week. 3 PDSA cycles were undertaken in total. Results The first PDSA cycle focused on raising awareness of the problem at hand, the number of unacknowledged results drastically decreased during the 1stweek of implementation of our PDSA from 617 to 254. The second PDSA cycle targeted the lack of knowledge of doctors involved in the electronic result acknowledgement process. There was a trend downwards near the end of the cycle which continued through the week after. The third PDSA cycle targeted individual doctors and provided individual remedial training. Second line doctors were also equipped to better handle abnormal results. There was significant improvement with the number of unacknowledged abnormal results dropping to <5 a week. Conclusions Multiple factors were identified to contribute to the low compliance to electronic acknowledgement of results. The role doctors play in the issue at hand was paramount and required careful handling in a professional manner with multiple reminders and emphasis on the importance of acknowledging and acting on the results.A significant improvement in the rates of acknowledgement of abnormal results was demonstrated with clear benefits to patient safety. Interventions can be replicated when implementing similar systems to other areas of healthcare. PMID:29450290

Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries.

PubMed

Jehee, Fernanda Sarquis; Takamori, Jean Tetsuo; Medeiros, Paula F Vasconcelos; Pordeus, Ana Carolina B; Latini, Flavia Roche M; Bertola, Débora Romeo; Kim, Chong Ae; Passos-Bueno, Maria Rita

2011-01-01

Conventional karyotyping detects anomalies in 3-15% of patients with multiple congenital anomalies and mental retardation (MCA/MR). Whole-genome array screening (WGAS) has been consistently suggested as the first choice diagnostic test for this group of patients, but it is very costly for large-scale use in developing countries. We evaluated the use of a combination of Multiplex Ligation-dependent Probe Amplification (MLPA) kits to increase the detection rate of chromosomal abnormalities in MCA/MR patients. We screened 261 MCA/MR patients with two subtelomeric and one microdeletion kits. This would theoretically detect up to 70% of all submicroscopic abnormalities. Additionally we scored the de Vries score for 209 patients in an effort to find a suitable cut-off for MLPA screening. Our results reveal that chromosomal abnormalities were present in 87 (33.3%) patients, but only 57 (21.8%) were considered causative. Karyotyping detected 15 abnormalities (6.9%), while MLPA identified 54 (20.7%). Our combined MLPA screening raised the total detection number of pathogenic imbalances more than three times when compared to conventional karyotyping. We also show that using the de Vries score as a cut-off for this screening would only be suitable under financial restrictions. A decision analytic model was constructed with three possible strategies: karyotype, karyotype + MLPA and karyotype + WGAS. Karyotype + MLPA strategy detected anomalies in 19.8% of cases which account for 76.45% of the expected yield for karyotype + WGAS. Incremental Cost Effectiveness Ratio (ICER) of MLPA is three times lower than that of WGAS, which means that, for the same costs, we have three additional diagnoses with MLPA but only one with WGAS. We list all causative alterations found, including rare findings, such as reciprocal duplications of regions deleted in Sotos and Williams-Beuren syndromes. We also describe imbalances that were considered polymorphisms or rare variants, such as the new SNP that confounded the analysis of the 22q13.3 deletion syndrome. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Complex and Dynamic Chromosomal Rearrangements in a Family With Seemingly Non-Mendelian Inheritance of Dopa-Responsive Dystonia.

PubMed

Lohmann, Katja; Redin, Claire; Tönnies, Holger; Bressman, Susan B; Subero, Jose Ignacio Martin; Wiegers, Karin; Hinrichs, Frauke; Hellenbroich, Yorck; Rakovic, Aleksandar; Raymond, Deborah; Ozelius, Laurie J; Schwinger, Eberhard; Siebert, Reiner; Talkowski, Michael E; Saunders-Pullman, Rachel; Klein, Christine

2017-07-01

Chromosomal rearrangements are increasingly recognized to underlie neurologic disorders and are often accompanied by additional clinical signs beyond the gene-specific phenotypic spectrum. To elucidate the causal genetic variant in a large US family with co-occurrence of dopa-responsive dystonia as well as skeletal and eye abnormalities (ie, ptosis, myopia, and retina detachment). We examined 10 members of a family, including 5 patients with dopa-responsive dystonia and skeletal and/or eye abnormalities, from a US tertiary referral center for neurological diseases using multiple conventional molecular methods, including fluorescence in situ hybridization and array comparative genomic hybridization as well as large-insert whole-genome sequencing to survey multiple classes of genomic variations. Of note, there was a seemingly implausible transmission pattern in this family due to a mutation-negative obligate mutation carrier. Genetic diagnosis in affected family members and insight into the formation of large deletions. Four members were diagnosed with definite and 1 with probable dopa-responsive dystonia. All 5 affected individuals carried a large heterozygous deletion encompassing all 6 exons of GCH1. Additionally, all mutation carriers had congenital ptosis requiring surgery, 4 had myopia, 2 had retinal detachment, and 2 showed skeletal abnormalities of the hands, ie, polydactyly or syndactyly or missing a hand digit. Two individuals were reported to be free of any disease. Analyses revealed complex chromosomal rearrangements on chromosome 14q21-22 in unaffected individuals that triggered the expansion to a larger deletion segregating with affection status. The expansion occurred recurrently, explaining the seemingly non-mendelian inheritance pattern. These rearrangements included a deletion of GCH1, which likely contributes to the dopa-responsive dystonia, as well as a deletion of BMP4 as a potential cause of digital and eye abnormalities. Our findings alert neurologists to the importance of clinical red flags, ie, unexpected co-occurrence of clinical features that may point to the presence of chromosomal rearrangements as the primary disease cause. The clinical management and diagnostics of such patients requires an interdisciplinary approach in modern clinical-diagnostic care.

Health-related lifestyle behaviors among male and female rural-to-urban migrant workers in Shanghai, China.

PubMed

Yang, Hua; He, Fang; Wang, Tianhao; Liu, Yao; Shen, Yao; Gong, Jian; Dai, Wei; Zhou, Jing; Gu, Jie; Tu, Yimin; Wang, Tianying; Shen, Lei; Wu, Yumiao; Xia, Xiuping; Xu, Donghao; Pan, Zhigang; Zhu, Shanzhu

2015-01-01

Lifestyle behaviors significantly impact health, yet remain poorly defined in Chinese rural-to-urban migrants. In a cross-sectional study of health-related behaviors of 5484 rural-to-urban migrants who had worked in Shanghai for at least six months, we assessed the contribution of demographics and physical and mental health to lifestyle behaviors in male and female participants by multiple stepwise cumulative odds logistic regression. Respondents were 51.3% male. 9.9% exhibited abnormal blood pressure; 27.0% were overweight or obese; 11.2% reported abnormal mental health; 36.9% reported healthy lifestyle. Multiple stepwise cumulative odds logistic regression indicated that men working in manufacturing reported less unhealthy lifestyle than those in hospitality (cumulative odds ratio (COR) = 1.806, 95%CI 1.275-2.559) or recreation/leisure (COR = 3.248, 95%CI 2.379-4.435); and women working in manufacturing and construction reported less unhealthy lifestyle than those in all other sectors. Unhealthy lifestyle was associated with small workplaces for men (COR = 1.422, 95%CI 1.154-1.752), working more than 8 or 11 hours per day for women and men, respectively, and earning over 3500 RMB in women (COR = 1.618, 95%CI 1.137-2.303). Single women and women who had previously resided in three or more cities were more likely to report unhealthy lifestyle (COR = 2.023, 95%CI 1.664-2.461, and COR = 1.311, 95%CI 1.072-1.602, respectively). Abnormal mental status was also correlated with unhealthy lifestyle in men (COR = 3.105, 95%CI 2.454-3.930) and women (COR = 2.566, 95%CI 2.024-3.252). There were different risk factors of unhealthy lifestyle score in male and female rural-to-urban migrants, especially in number of cities experienced, salary, marital status, work place scale. Several demographic groups: employment sectors (e.g. hospitality and recreation/leisure), working conditions (e.g. long hours) and abnormal mental status were associated with unhealthy lifestyle behaviors in Chinese rural-to-urban migrants, and health interventions should be targeted to these groups.

Health-Related Lifestyle Behaviors among Male and Female Rural-to-Urban Migrant Workers in Shanghai, China

PubMed Central

Yang, Hua; He, Fang; Wang, Tianhao; Liu, Yao; Shen, Yao; Gong, Jian; Dai, Wei; Zhou, Jing; Gu, Jie; Tu, Yimin; Wang, Tianying; Shen, Lei; Wu, Yumiao; Xia, Xiuping; Xu, Donghao; Pan, Zhigang; Zhu, Shanzhu

2015-01-01

Background Lifestyle behaviors significantly impact health, yet remain poorly defined in Chinese rural-to-urban migrants. Methods In a cross-sectional study of health-related behaviors of 5484 rural-to-urban migrants who had worked in Shanghai for at least six months, we assessed the contribution of demographics and physical and mental health to lifestyle behaviors in male and female participants by multiple stepwise cumulative odds logistic regression. Results Respondents were 51.3% male. 9.9% exhibited abnormal blood pressure; 27.0% were overweight or obese; 11.2% reported abnormal mental health; 36.9% reported healthy lifestyle. Multiple stepwise cumulative odds logistic regression indicated that men working in manufacturing reported less unhealthy lifestyle than those in hospitality (cumulative odds ratio (COR) = 1.806, 95%CI 1.275–2.559) or recreation/leisure (COR = 3.248, 95%CI 2.379–4.435); and women working in manufacturing and construction reported less unhealthy lifestyle than those in all other sectors. Unhealthy lifestyle was associated with small workplaces for men (COR = 1.422, 95%CI 1.154–1.752), working more than 8 or 11 hours per day for women and men, respectively, and earning over 3500 RMB in women (COR = 1.618, 95%CI 1.137–2.303). Single women and women who had previously resided in three or more cities were more likely to report unhealthy lifestyle (COR = 2.023, 95%CI 1.664–2.461, and COR = 1.311, 95%CI 1.072–1.602, respectively). Abnormal mental status was also correlated with unhealthy lifestyle in men (COR = 3.105, 95%CI 2.454–3.930) and women (COR = 2.566, 95%CI 2.024–3.252). Conclusions There were different risk factors of unhealthy lifestyle score in male and female rural-to-urban migrants, especially in number of cities experienced, salary, marital status, work place scale. Several demographic groups: employment sectors (e.g. hospitality and recreation/leisure), working conditions (e.g. long hours) and abnormal mental status were associated with unhealthy lifestyle behaviors in Chinese rural-to-urban migrants, and health interventions should be targeted to these groups. PMID:25710464

Complications in multiple gestation pregnancy: A cross-sectional study of ten maternal-fetal medicine centers in China

PubMed Central

Wei, Jun; Wu, Qi-Jun; Zhang, Tie-Ning; Shen, Zi-Qi; Liu, Hao; Zheng, Dong-Ming; Cui, Hong; Liu, Cai-Xia

2016-01-01

Complications in women with multiple gestation pregnancy have not been studied in China. We aimed to establish a database of women with multiple gestation pregnancy and investigate the complications related to multiple pregnancy. We conducted a cross-sectional study that included 3246 women with multiple gestation pregnancy and who had multiple live-birth deliveries; the women were registered at ten maternal-fetal medicine centers in China in 2013. All participants completed a detailed questionnaire that included basic demographic information, history of gestation and abnormal fetal development, risk factors during pregnancy, and pregnancy outcomes. Overall, 1553 (47.8%) women experienced pregnancy complications; these women were more likely to have lower height and less education than women who did not experience complications. However, women who experienced complications had a higher twin birth rate and were more likely to have received regular antenatal care and assisted reproductive technology than women without complications (P < 0.05). Notably, preterm birth was a primary complication in multiple pregnancy (n = 960). In conclusion, pregnancy complications, especially preterm birth, were relatively common in women with multiple gestation pregnancy. The findings from this cross-sectional study in China may be used as a foundation for investigating risk factors for complications in women with multiple gestation pregnancy in the future. PMID:27127170

Complications in multiple gestation pregnancy: A cross-sectional study of ten maternal-fetal medicine centers in China.

PubMed

Wei, Jun; Wu, Qi-Jun; Zhang, Tie-Ning; Shen, Zi-Qi; Liu, Hao; Zheng, Dong-Ming; Cui, Hong; Liu, Cai-Xia

2016-05-24

Complications in women with multiple gestation pregnancy have not been studied in China. We aimed to establish a database of women with multiple gestation pregnancy and investigate the complications related to multiple pregnancy. We conducted a cross-sectional study that included 3246 women with multiple gestation pregnancy and who had multiple live-birth deliveries; the women were registered at ten maternal-fetal medicine centers in China in 2013. All participants completed a detailed questionnaire that included basic demographic information, history of gestation and abnormal fetal development, risk factors during pregnancy, and pregnancy outcomes. Overall, 1553 (47.8%) women experienced pregnancy complications; these women were more likely to have lower height and less education than women who did not experience complications. However, women who experienced complications had a higher twin birth rate and were more likely to have received regular antenatal care and assisted reproductive technology than women without complications (P < 0.05). Notably, preterm birth was a primary complication in multiple pregnancy (n = 960). In conclusion, pregnancy complications, especially preterm birth, were relatively common in women with multiple gestation pregnancy. The findings from this cross-sectional study in China may be used as a foundation for investigating risk factors for complications in women with multiple gestation pregnancy in the future.

Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis

PubMed Central

Solanky, Bhavana S.; Muhlert, Nils; Tur, Carmen; Edden, Richard A. E.; Wheeler-Kingshott, Claudia A. M.; Miller, David H.; Thompson, Alan J.; Ciccarelli, Olga

2015-01-01

Neurodegeneration is thought to be the major cause of ongoing, irreversible disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid is the principle inhibitory neurotransmitter in the brain. The aims of this study were to investigate if gamma-aminobutyric acid levels (i) are abnormal in patients with secondary progressive multiple sclerosis compared with healthy controls; and (ii) correlate with physical and cognitive performance in this patient population. Thirty patients with secondary progressive multiple sclerosis and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to quantify gamma-aminobutyric acid levels in the prefrontal cortex, right hippocampus and left sensorimotor cortex. All subjects were assessed clinically and underwent a cognitive assessment. Multiple linear regression models were used to compare differences in gamma-aminobutyric acid concentrations between patients and controls adjusting for age, gender and tissue fractions within each spectroscopic voxel. Regression was used to examine the relationships between the cognitive function and physical disability scores specific for these regions with gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl-aspartate and glutamine-glutamate complex levels. When compared with controls, patients performed significantly worse on all motor and sensory tests, and were cognitively impaired in processing speed and verbal memory. Patients had significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted difference = −0.403 mM, 95% confidence intervals −0.792, −0.014, P = 0.043) and sensorimotor cortex (adjusted difference = −0.385 mM, 95% confidence intervals −0.667, −0.104, P = 0.009) compared with controls. In patients, reduced motor function in the right upper and lower limb was associated with lower gamma-aminobutyric acid concentration in the sensorimotor cortex. Specifically for each unit decrease in gamma-aminobutyric acid levels (in mM), there was a predicted −10.86 (95% confidence intervals −16.786 to −4.482) decrease in grip strength (kg force) (P < 0.001) and −8.74 (95% confidence intervals −13.943 to −3.015) decrease in muscle strength (P < 0.006). This study suggests that reduced gamma-aminobutyric acid levels reflect pathological abnormalities that may play a role in determining physical disability. These abnormalities may include decreases in the pre- and postsynaptic components of gamma-aminobutyric acid neurotransmission and in the density of inhibitory neurons. Additionally, the reduced gamma-aminobutyric acid concentration may contribute to the neurodegenerative process, resulting in increased firing of axons, with consequent increased energy demands, which may lead to neuroaxonal degeneration and loss of the compensatory mechanisms that maintain motor function. This study supports the idea that modulation of gamma-aminobutyric acid neurotransmission may be an important target for neuroprotection in multiple sclerosis. See De Stefano and Giorgio (doi:10.1093/brain/awv213) for a scientific commentary on this article. PMID:26304151

Relationship between heart rate recovery and inflammatory markers in patients with polycystic ovary syndrome: a cross-sectional study.

PubMed

Giallauria, Francesco; Orio, Francesco; Lombardi, Gaetano; Colao, Annamaria; Vigorito, Carlo; Tafuri, Maria Giovanna; Palomba, Stefano

2009-02-02

Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk factors for cardiovascular disease. An abnormal heart rate recovery (HRR), an easily-obtained measure derived from exercise stress test and closely related to an increased risk for cardiovascular mortality, has been recently described in PCOS women. A subclinical increase of the inflammation markers has been also observed in the PCOS. This study was designed to study the relationships between HRR and inflammatory markers in PCOS women. Two-hundred forty-three young PCOS patients without known risk factors for cardiovascular risk were enrolled. All patients underwent hormonal and metabolic profile, white blood cells (WBCs) count and C-reactive protein (CRP). HRR was calculated as the difference between heart rate at peak exercise and heart rate at first minute of the cool-down period. Abnormal HRR was defined as

Exposure of spermatozoa to dibutyl phthalate induces abnormal embryonic development in a marine invertebrate Galeolaria caespitosa (Polychaeta: Serpulidae).

PubMed

Lu, Yonggang; Lin, Minjie; Aitken, Robert John

2017-10-01

In this study, we have investigated the impact of dibutyl phthalate (DBP) on early embryogenesis in a sessile marine invertebrate, Galeolaria caespitosa. DBP was found to induce sperm dysfunction as well as impaired and defective embryogenesis characterised by a particular pattern of abnormality. Thus, after the first cleavage, one blastomere in these abnormal embryos was able to carry out further mitoses, while the other arrested. Analysis of microtubules, chromosomes and actin filaments demonstrated that the mitotic spindles in the abnormal embryos were irregularly bent, shortened and unable to anchor to the cortex, resulting in the defective segregation of chromosomes. Within the non-dividing blastomeres, karyokinesis was found to continue at a slow pace as indicated by the presence of multiple sets of abnormal mitotic spindles. However, cytokinesis had been disrupted in these arrested cells due to a failure to assemble the contractile actin ring, as a result of which one pole of the embryos remained as one large, undivided cell. DBP was found to suppress the activity of superoxide dismutase in spermatozoa and, in association with this change, DBP-treated cells experienced oxidative stress as indicated by the presence of lipid aldehydes, such as 4-hydroxynonenal (4-HNE) in the sperm acrosome and neck. Adduction of lipid aldehydes at the level of the acrosome would be expected to impede the acrosome reaction and account for the significant decrease in fertilisation rates. 4-HNE generated as a consequence of lipid peroxidation in the sperm neck resulted in alkylation of the sperm centrioles. Such paternally damaged centrioles were inherited by the embryos and disrupted cytoskeletal protein organisation during early cleavage, generating the observed abnormalities in embryonic development. This research emphasises the vulnerability of spermatozoa to oxidative damage and highlights novel potential mechanisms for reproductive toxicity involving the alkylation of subcellular structures in spermatozoa by lipid aldehydes. Copyright © 2017 Elsevier B.V. All rights reserved.

The assessment of ovulation by a combination of ultrasound and detailed serial hormone profiles in 35 women with long-standing unexplained infertility.

PubMed

Petsos, P; Chandler, C; Oak, M; Ratcliffe, W A; Wood, R; Anderson, D C

1985-06-01

We have examined for the presence of subtle hormonal abnormalities in women with long-standing unexplained infertility. For a full cycle serum LH, FSH, progesterone and oestradiol levels were measured about three times a week, and serial ultrasound scans of the ovaries made until the time of apparent ovulation. The results on 45 cycles in 35 women with unexplained infertility and in three normal volunteers are presented. Normal ovulatory cycles were defined by a length of 26-32 d, and progressive follicular maturation followed by disappearance or abrupt reduction in size of a follicle within 48 h of the recorded LH peak, followed by progressive and sustained rise in serum progesterone levels to more than 25 nmol/l and a luteal phase length of greater than or equal to 13 d. Thirty spontaneous cycles (28 women) were clearly normal while 15 spontaneous cycles (12 women) were abnormal. Abnormalities included luteinization of an unruptured follicle (eight cycles), absence of follicular development (two cycles), poor follicular development (two cycles), persistence of a large ovarian cyst from the preceeding cycle (two cycles) and one aluteal cycle. Six of the abnormal cycles were characterized hormonally by inappropriate elevation of serum LH levels throughout. If this study had been based only on serial ultrasound scans, all results on abnormal cycles might have been misinterpreted. If it had been conducted only with (multiple) progesterone determinations and the level of greater than 25 nmol/l had been taken as indicative of ovulation nine clearly abnormal cycles would have been considered as normal. We conclude that the combination of the hormonal and ultrasound assessment of ovulation increases our confidence for confirmation of normality and reveals various ovulatory disorders which are possibly due to an endocrinological defect or defects.

A novel scoring system to measure radiographic abnormalities and related spirometric values in cured pulmonary tuberculosis.

PubMed

Báez-Saldaña, Renata; López-Arteaga, Yesenia; Bizarrón-Muro, Alma; Ferreira-Guerrero, Elizabeth; Ferreyra-Reyes, Leticia; Delgado-Sánchez, Guadalupe; Cruz-Hervert, Luis Pablo; Mongua-Rodríguez, Norma; García-García, Lourdes

2013-01-01

Despite chemotherapy, patients with cured pulmonary tuberculosis may result in lung functional impairment. To evaluate a novel scoring system based on the degree of radiographic abnormalities and related spirometric values in patients with cured pulmonary tuberculosis. One hundred and twenty seven patients with cured pulmonary tuberculosis were prospectively enrolled in a referral hospital specializing in respiratory diseases. Spirometry was performed and the extent of radiographic abnormalities was evaluated twice by each of two readers to generate a novel quantitative score. Scoring reproducibility was analyzed by the intra-class correlation coefficient (ICC) and the Bland-Altman method. Multiple linear regression models were performed to assess the association of the extent of radiographic abnormalities with spirometric values. The intra-observer agreement for scoring of radiographic abnormalities (SRA) showed an ICC of 0.81 (CI:95%, 0.67-0.95) and 0.78 (CI:95%, 0.65-0.92), for reader 1 and 2, respectively. Inter-observer reproducibility for the first measurement was 0.83 (CI:95%, 0.71-0.95), and for the second measurement was 0.74 (CI:95%, 0.58-0.90). The Bland-Altman analysis of the intra-observer agreement showed a mean bias of 0.87% and -0.55% and an inter-observer agreement of -0.35% and -1.78%, indicating a minor average systematic variability. After adjustment for age, gender, height, smoking status, pack-years of smoking, and degree of dyspnea, the scoring degree of radiographic abnormalities was significantly and negatively associated with absolute and percent predicted values of FVC: -0.07 (CI:95%, -0.01 to -0.04); -2.48 (CI:95%, -3.45 to -1.50); and FEV1 -0.07 (CI:95%, -0.10 to -0.05); -2.92 (CI:95%, -3.87 to -1.97) respectively, in the patients studied. The extent of radiographic abnormalities, as evaluated through our novel scoring system, was inversely associated with spirometric values, and exhibited good reliability and reproducibility. As intra-observer and inter-observer agreement of the SRA varied from good to excellent, the use of SRA in this setting appears acceptable.

A Novel Scoring System to Measure Radiographic Abnormalities and Related Spirometric Values in Cured Pulmonary Tuberculosis

PubMed Central

Báez-Saldaña, Renata; López-Arteaga, Yesenia; Bizarrón-Muro, Alma; Ferreira-Guerrero, Elizabeth; Ferreyra-Reyes, Leticia; Delgado-Sánchez, Guadalupe; Cruz-Hervert, Luis Pablo; Mongua-Rodríguez, Norma; García-García, Lourdes

2013-01-01

Background Despite chemotherapy, patients with cured pulmonary tuberculosis may result in lung functional impairment. Objective To evaluate a novel scoring system based on the degree of radiographic abnormalities and related spirometric values in patients with cured pulmonary tuberculosis. Methods One hundred and twenty seven patients with cured pulmonary tuberculosis were prospectively enrolled in a referral hospital specializing in respiratory diseases. Spirometry was performed and the extent of radiographic abnormalities was evaluated twice by each of two readers to generate a novel quantitative score. Scoring reproducibility was analyzed by the intra-class correlation coefficient (ICC) and the Bland-Altman method. Multiple linear regression models were performed to assess the association of the extent of radiographic abnormalities with spirometric values. Results The intra-observer agreement for scoring of radiographic abnormalities (SRA) showed an ICC of 0.81 (CI:95%, 0.67–0.95) and 0.78 (CI:95%, 0.65–0.92), for reader 1 and 2, respectively. Inter-observer reproducibility for the first measurement was 0.83 (CI:95%, 0.71–0.95), and for the second measurement was 0.74 (CI:95%, 0.58–0.90). The Bland-Altman analysis of the intra-observer agreement showed a mean bias of 0.87% and -0.55% and an inter-observer agreement of -0.35% and -1.78%, indicating a minor average systematic variability. After adjustment for age, gender, height, smoking status, pack-years of smoking, and degree of dyspnea, the scoring degree of radiographic abnormalities was significantly and negatively associated with absolute and percent predicted values of FVC: -0.07 (CI:95%, -0.01 to -0.04); -2.48 (CI:95%, -3.45 to -1.50); and FEV1 -0.07 (CI:95%, -0.10 to -0.05); -2.92 (CI:95%, -3.87 to -1.97) respectively, in the patients studied. Conclusion The extent of radiographic abnormalities, as evaluated through our novel scoring system, was inversely associated with spirometric values, and exhibited good reliability and reproducibility. As intra-observer and inter-observer agreement of the SRA varied from good to excellent, the use of SRA in this setting appears acceptable. PMID:24223865

Ocular Manifestations of Noonan Syndrome: A Prospective Clinical and Genetic Study of 25 Patients.

PubMed

van Trier, Dorothée C; Vos, Anna M C; Draaijer, Renske W; van der Burgt, Ineke; Draaisma, Jos M Th; Cruysberg, Johannes R M

2016-10-01

To determine the full spectrum of ocular manifestations in patients with Noonan syndrome (NS). Prospective cross-sectional clinical and genetic study in a tertiary referral center. Twenty-five patients with NS (mean age, 14 years; range, 8 months-25 years) clinically diagnosed by validated criteria. All patients were examined by the same team following a detailed study protocol. Genetic analyses were performed in 23 patients. Ocular abnormalities of vision and refraction, external ocular features, ocular position and motility, anterior segment, posterior segment, and intraocular pressure. Ocular features of vision and refraction were amblyopia (32%), myopia (40%), and astigmatism (52%). External ocular features were epicanthic folds (84%), hypertelorism (68%), ptosis (56%), high upper eyelid crease (64%), lower eyelid retraction (60%), abnormal upward slanting palpebral fissures (36%), downward slanting palpebral fissures (32%), and lagophthalmos (28%). Orthoptic abnormalities included strabismus (40%), abnormal stereopsis (44%), and limited ocular motility (40%). Anterior segment abnormalities included prominent corneal nerves (72%) and posterior embryotoxon (32%). Additional ocular features were found, including nonglaucomatous optic disc excavation (20%), relatively low (<10 mmHg) intraocular pressure (22%), and optic nerve hypoplasia (4%). Mutations were established in 22 patients: 19 PTPN11 mutations (76%), 1 SOS1 mutation, 1 BRAF mutation, and 1 KRAS mutation. The patient with the highest number of prominent corneal nerves had an SOS1 mutation. The patient with the lowest visual acuity, associated with bilateral optic nerve hypoplasia, had a BRAF mutation. Patients with severe ptosis and nearly total absence of levator muscle function had PTPN11 mutations. All patients showed at least 3 ocular features (range, 3-13; mean, 7), including at least 1 external ocular feature in more than 95% of the patients. Noonan syndrome is a clinical diagnosis with multiple genetic bases associated with an extensive variety of congenital ocular abnormalities. Ocular features of NS are characterized by 1 or more developmental anomalies of the eyelids (involving the position, opening, and closure) associated with various other ocular abnormalities in childhood, including amblyopia, myopia, astigmatism, strabismus, limited ocular motility, prominent corneal nerves, and posterior embryotoxon. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Detection and Type-Distribution of Human Papillomavirus in Vulva and Vaginal Abnormal Cytology Lesions and Cancer Tissues from Thai Women.

PubMed

Ngamkham, Jarunya; Boonmark, Krittika; Phansri, Thainsang

2016-01-01

Vulva and Vaginal cancers are rare among all gynecological cancers worldwide, including Thailand, and typically affect women in later life. Persistent high risk human papillomavirus (HR-HPV) infection is one of several important causes of cancer development. In this study, we focused on HPV investigation and specific type distribution from Thai women with abnormality lesions and cancers of the vulva and Vaginal. A total of ninety paraffin-embedded samples of vulva and Vaginal abnormalities and cancer cells with histologically confirmed were collected from Thai women, who were diagnosed in 2003-2012 at the National Cancer Institute, Thailand. HPV DNA was detected and genotyped using polymerase chain reaction and enzyme immunoassay with GP5+/ bio 6+ consensus specific primers and digoxigenin-labeled specific oligoprobes, respectively. The human β-globin gene was used as an internal control. Overall results represented that HPV frequency was 16/34 (47.1%) and 8/20 (40.0%) samples of vulva with cancer and abnormal cytology lesions, respectively, while, 3/5 (60%) and 16/33 (51.61%) samples of Vaginal cancer and abnormal cytology lesions, respectively, were HPV DNA positive. Single HPV type and multiple HPV type infection could be observed in both type of cancers and abnormal lesion samples in the different histological categorizes. HPV16 was the most frequent type in all cancers and abnormal cytology lesions, whereas HPV 18 was less frequent and could be detected as co-infection with other high risk HPV types. In addition, low risk types such as HPV 6, 11 and 70 could be detected in Vulva cancer and abnormal cytology lesion samples, whereas, all Vaginal cancer samples exhibited only high risk HPV types; HPV 16 and 31. In conclusion, from our results in this study we suggest that women with persistent high risk HPV type infection are at risk of developing vulva and Vaginal cancers and HPV 16 was observed at the highest frequent both of these, similar to the cervical cancer cases. Although the number of samples in this study was limited and might not represent the overall incidence and prevalence in Thai women, but the baseline data are of interest and suggest further study for primary cancer screening and/or developing the efficiency of prophylactic HPV vaccines in Thailand.

The effect of prothrombotic blood abnormalities on risk of deep vein thrombosis in users of hormone replacement therapy: a prospective case-control study.

PubMed

Douketis, Jim D; Julian, Jim A; Crowther, Mark A; Kearon, Clive; Bates, Shannon M; Barone, Marisa; Piovella, Franco; Middeldorp, Saskia; Prandoni, Paolo; Johnston, Marilyn; Costantini, Lorrie; Ginsberg, Jeffrey S

2011-01-01

Few studies have assessed the effect of prothrombotic blood abnormalities on the risk of deep vein thrombosis (DVT) with hormone replacement therapy (HRT). We studied postmenopausal women with suspected DVT in whom HRT use and prothrombotic blood abnormalities were sought. Cases had unprovoked DVT and controls had no DVT and without DVT risk factors. The risk of DVT was determined in women with and without prothrombotic abnormalities. A total of 510 postmenopausal women with suspected DVT were assessed; 57 cases and 283 controls were identified. Compared to HRT, nonusers without the factor V Leiden mutation, the risk of DVT was increased in estrogen-progestin HRT users (odds ratio [OR], 3.2; 95% confidence interval [CI]: 1.2-8.6) and in nonusers with the factor V Leiden mutation (OR, 5.3; 1.9-15.4) and appears multiplied in users of estrogen-progestin HRT with the factor V Leiden mutation (OR, 17.1; 3.7-78). Compared to HRT, nonusers with normal factor VIII, the risk of DVT was increased in estrogen-progestin HRT users with normal factor VIII (OR, 2.8; 1.0-7.9) and in HRT nonusers with the highest factor VIII quartile (OR, 6.0; 2.1-17), and appears to be multiplied in women who are users of estrogen-progestin HRT with the highest factor VIII quartile (OR, 17.0; 3.6-80). In postmenopausal women who are estrogen-progestin HRT users, the presence of the factor V Leiden mutation or an elevated factor VIII level appears to have a multiplicative effect on their overall risk of DVT, increasing it 17-fold compared to women without these blood abnormalities who are HRT nonusers.

Rapid Point-Of-Care Breath Test for Biomarkers of Breast Cancer and Abnormal Mammograms

PubMed Central

Phillips, Michael; Beatty, J. David; Cataneo, Renee N.; Huston, Jan; Kaplan, Peter D.; Lalisang, Roy I.; Lambin, Philippe; Lobbes, Marc B. I.; Mundada, Mayur; Pappas, Nadine; Patel, Urvish

2014-01-01

Background Previous studies have reported volatile organic compounds (VOCs) in breath as biomarkers of breast cancer and abnormal mammograms, apparently resulting from increased oxidative stress and cytochrome p450 induction. We evaluated a six-minute point-of-care breath test for VOC biomarkers in women screened for breast cancer at centers in the USA and the Netherlands. Methods 244 women had a screening mammogram (93/37 normal/abnormal) or a breast biopsy (cancer/no cancer 35/79). A mobile point-of-care system collected and concentrated breath and air VOCs for analysis with gas chromatography and surface acoustic wave detection. Chromatograms were segmented into a time series of alveolar gradients (breath minus room air). Segmental alveolar gradients were ranked as candidate biomarkers by C-statistic value (area under curve [AUC] of receiver operating characteristic [ROC] curve). Multivariate predictive algorithms were constructed employing significant biomarkers identified with multiple Monte Carlo simulations and cross validated with a leave-one-out (LOO) procedure. Results Performance of breath biomarker algorithms was determined in three groups: breast cancer on biopsy versus normal screening mammograms (81.8% sensitivity, 70.0% specificity, accuracy 79% (73% on LOO) [C-statistic value], negative predictive value 99.9%); normal versus abnormal screening mammograms (86.5% sensitivity, 66.7% specificity, accuracy 83%, 62% on LOO); and cancer versus no cancer on breast biopsy (75.8% sensitivity, 74.0% specificity, accuracy 78%, 67% on LOO). Conclusions A pilot study of a six-minute point-of-care breath test for volatile biomarkers accurately identified women with breast cancer and with abnormal mammograms. Breath testing could potentially reduce the number of needless mammograms without loss of diagnostic sensitivity. PMID:24599224

Using impedance cardiography to detect asymptomatic cardiovascular disease in prehypertensive adults with risk factors.

PubMed

DeMarzo, Arthur P

2013-06-01

Early detection of cardiovascular disease (CVD) in prehypertension could initiate appropriate treatment and prevent progression. Impedance cardiography (ICG) is a noninvasive technology that can be used to assess cardiovascular function. This study used ICG waveform analysis with postural change to detect CVD in asymptomatic prehypertensive adults over 40 years of age with no history of CVD and at least 2 cardiovascular risk factors: cigarette smoking, poor diet, physical inactivity, central obesity, family history of premature CVD, elevated blood glucose, and dyslipidemia. A study group of 25 apparently healthy adults was tested by ICG in standing and supine positions. Criteria for an age-matched control group of 16 healthy subjects included an active lifestyle, no risk factor, and no history of CVD. In addition to hemodynamic measurements of systemic vascular resistance (SVR) and cardiac index (CI), ICG used SVR to assess vascular resistive load, an index of arterial compliance and a widening of the systolic waveform to assess vascular pulsatile load, and waveform analysis and measured wave amplitude to detect ventricular dysfunction. All subjects in the study group had some abnormal ICG data, with an average of 2.9 ± 1.5 abnormalities per person. ICG indicated that 24 (96%) had elevated vascular load, 13 (52%) had some type of ventricular dysfunction, and 12 (48%) had abnormal hemodynamics. For the control group, ICG showed none (0%) with elevated vascular load, none (0%) with ventricular dysfunction, and 7 (44%) with high CI. Prehypertensives over 40 years of age with multiple risk factors have different cardiovascular abnormalities. This ICG test could be used as part of a prevention program for early detection of CVD. An abnormal ICG test could expedite the initiation of customized treatment that targets the subclinical CVD.

Increased patient communication using a process supplementing an electronic medical record.

PubMed

Garvey, Thomas D; Evensen, Ann E

2015-02-01

Importance: Patients with cervical cytology abnormalities may require surveillance for many years, which increases the risk of management error, especially in clinics with multiple managing clinicians. National Committee for Quality Assurance (NCQA) Patient-Centered Medical Home (PCMH) certification requires tracking of abnormal results and communicating effectively with patients. The purpose of this study was to determine whether a computer-based tracking system that is not embedded in the electronic medical record improves (1) accurate and timely communication of results and (2) patient adherence to follow-up recommendations. Design: Pre/post study using data from 2005-2012. Intervention implemented in 2008. Data collected via chart review for at least 18 months after index result. Participants: Pre-intervention: all women (N = 72) with first abnormal cytology result from 2005-2007. Post-intervention: all women (N = 128) with first abnormal cytology result from 2008-2010. Patients were seen at a suburban, university-affiliated, family medicine residency clinic. Intervention: Tracking spreadsheet reviewed monthly with reminders generated for patients not in compliance with recommendations. Main Outcome and Measures: (1) rates of accurate and timely communication of results and (2) rates of patient adherence to follow-up recommendations. Intervention decreased absent or erroneous communication from clinician to patient (6.4% pre- vs 1.6% post-intervention [P = 0.04]), but did not increase patient adherence to follow-up recommendations (76.1% pre- vs 78.0% post-intervention [ P= 0.78]). Use of a spreadsheet tracking system improved communication of abnormal results to patients, but did not significantly improve patient adherence to recommended care. Although the tracking system complies with NCQA PCMH requirements, it was insufficient to make meaningful improvements in patient-oriented outcomes.

Varenicline and Abnormal Sleep Related Events

PubMed Central

Savage, Ruth L.; Zekarias, Alem; Caduff-Janosa, Pia

2015-01-01

Study Objectives: To assess adverse drug reaction reports of “abnormal sleep related events” associated with varenicline, a partial agonist to the α4β2 subtype of nicotinic acetylcholine receptors on neurones, indicated for smoking cessation. Design: Twenty-seven reports of “abnormal sleep related events” often associated with abnormal dreams, nightmares, or somnambulism, which are known to be associated with varenicline use, were identified in the World Health Organisation (WHO) Global Individual Case Safety Reports Database. Original anonymous reports were obtained from the four national pharmacovigilance centers that submitted these reports and assessed for reaction description and causality. Measurements and Results: These 27 reports include 10 of aggressive activity occurring during sleep and seven of other sleep related harmful or potentially harmful activities, such as apparently deliberate self-harm, moving a child or a car, or lighting a stove or a cigarette. Assessment of these 17 reports of aggression or other actual or potential harm showed that nine patients recovered or were recovering on varenicline withdrawal and there were no consistent alternative explanations. Thirteen patients experienced single events, and two had multiple events. Frequency was not stated for the remaining two patients. Conclusions: The descriptions of the reports of aggression during sleep with violent dreaming are similar to those of rapid eye movement sleep behavior disorder and also nonrapid eye movement (NREM) sleep parasomnias in some adults. Patients who experience somnambulism or dreams of a violent nature while taking varenicline should be advised to consult their health providers. Consideration should be given to clarifying the term sleep disorders in varenicline product information and including sleep related harmful and potentially harmful events. Citation: Savage RL, Zekarias A, Caduff-Janosa P. Varenicline and abnormal sleep related events. SLEEP 2015;38(5):833–837. PMID:25409105

'They say Islam has a solution for everything, so why are there no guidelines for this?' Ethical dilemmas associated with the births and deaths of infants with fatal abnormalities from a small sample of Pakistani Muslim couples in Britain.

PubMed

Shaw, Alison

2012-11-01

This paper presents ethical dilemmas concerning the termination of pregnancy, the management of childbirth, and the withdrawal of life-support from infants in special care, for a small sample of British Pakistani Muslim parents of babies diagnosed with fatal abnormalities. Case studies illustrating these dilemmas are taken from a qualitative study of 66 families of Pakistani origin referred to a genetics clinic in Southern England. The paper shows how parents negotiated between the authoritative knowledge of their doctors, religious experts, and senior family members in response to the ethical dilemmas they faced. There was little knowledge or open discussion of the view that Islam permits the termination of pregnancy for serious or fatal abnormality within 120 days and there was considerable disquiet over the idea of ending a pregnancy. For some parents, whether their newborn baby would draw breath was a main worry, with implications for the baby's Muslim identity and for the recognition of loss the parents would receive from family and community. This concern sometimes conflicted with doctors' concerns to minimize risk to future pregnancies by not performing a Caesarean delivery if a baby is sure to die. The paper also identifies parents' concerns and feelings of wrong-doing regarding the withdrawal of artificial life-support from infants with multiple abnormalities. The conclusion considers some of the implications of these observations for the counselling and support of Muslim parents following the pre- or neo-natal diagnosis of fatal abnormalities in their children. © 2011 Blackwell Publishing Ltd.

Placental Histomorphology in a Case of Double Trisomy 48,XXX,+18.

PubMed

Shah, Sujal I; Dyer, Lisa; Stanek, Jerzy

2018-01-01

Approximately 50% of early spontaneous abortions are found to have chromosomal abnormalities. In these cases, certain histopathologic abnormalities are suggestive of, although not diagnostic for, the presence of chromosomal abnormalities. However, placental histomorphology in cases of complex chromosomal abnormalities, including double trisomies, is virtually unknown. We present the case of a 27-year-old G3P22002 female presenting at 19 weeks and 1 day of gestation by last menstrual period for scheduled prenatal visit. Ultrasound revealed a single fetus without heart tones and adequate amniotic fluid. Limited fetal measurements were consistent with estimated gestational age of 17 weeks. Labor was induced with misoprostol due to fetal demise. Autopsy revealed an immature female fetus with grade 1-2 maceration. The ears were low-set and posteriorly rotated. The fingers were short bilaterally, and the right foot showed absence of the second and third digits. Evaluation of the organs showed predominantly marked autolysis consistent with retained stillbirth. Placental examination revealed multiple findings, including focal pseudovillous papilliform trophoblastic proliferation of the undersurface of the chorionic plate and clustering of perpendicularly oriented sclerotic chorionic villi in the chorion laeve, which have not been previously reported in cases of chromosomal abnormalities. Karyotype of placental tissue revealed a 48,XXX,+18 karyotype and the same double trisomy of fetal thymic tissue by FISH. In addition to convoluted outlines of chorionic villi, villous trophoblastic pseudoinclusions, and clusters of villous cytotrophoblasts, the previously unreported focal pseudovillous papilliform trophoblastic proliferation of the undersurface of the chorionic plate and clustering of perpendicularly oriented sclerotic chorionic villi in the chorion laeve were observed in this double trisomy case. More cases have to be examined to show if the histology is specific for this double trisomy.

Placental Histomorphology in a Case of Double Trisomy 48,XXX,+18

PubMed Central

2018-01-01

Background Approximately 50% of early spontaneous abortions are found to have chromosomal abnormalities. In these cases, certain histopathologic abnormalities are suggestive of, although not diagnostic for, the presence of chromosomal abnormalities. However, placental histomorphology in cases of complex chromosomal abnormalities, including double trisomies, is virtually unknown. Case Report We present the case of a 27-year-old G3P22002 female presenting at 19 weeks and 1 day of gestation by last menstrual period for scheduled prenatal visit. Ultrasound revealed a single fetus without heart tones and adequate amniotic fluid. Limited fetal measurements were consistent with estimated gestational age of 17 weeks. Labor was induced with misoprostol due to fetal demise. Autopsy revealed an immature female fetus with grade 1-2 maceration. The ears were low-set and posteriorly rotated. The fingers were short bilaterally, and the right foot showed absence of the second and third digits. Evaluation of the organs showed predominantly marked autolysis consistent with retained stillbirth. Placental examination revealed multiple findings, including focal pseudovillous papilliform trophoblastic proliferation of the undersurface of the chorionic plate and clustering of perpendicularly oriented sclerotic chorionic villi in the chorion laeve, which have not been previously reported in cases of chromosomal abnormalities. Karyotype of placental tissue revealed a 48,XXX,+18 karyotype and the same double trisomy of fetal thymic tissue by FISH. Conclusion In addition to convoluted outlines of chorionic villi, villous trophoblastic pseudoinclusions, and clusters of villous cytotrophoblasts, the previously unreported focal pseudovillous papilliform trophoblastic proliferation of the undersurface of the chorionic plate and clustering of perpendicularly oriented sclerotic chorionic villi in the chorion laeve were observed in this double trisomy case. More cases have to be examined to show if the histology is specific for this double trisomy. PMID:29707399

Atypical sulcal anatomy in young children with autism spectrum disorder

PubMed Central

Auzias, G.; Viellard, M.; Takerkart, S.; Villeneuve, N.; Poinso, F.; Fonséca, D. Da; Girard, N.; Deruelle, C.

2014-01-01

Autism spectrum disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Nonetheless, atypical cortical folding provides lingering evidence of early disruptions in neurodevelopmental processes and identifying changes in the geometry of cortical sulci is of primary interest for characterizing these structural abnormalities in autism and their evolution over the first stages of brain development. Here, we applied state-of-the-art sulcus-based morphometry methods to a large highly-selective cohort of 73 young male children of age spanning from 18 to 108 months. Moreover, such large cohort was selected through extensive behavioral assessments and stringent inclusion criteria for the group of 59 children with autism. After manual labeling of 59 different sulci in each hemisphere, we computed multiple shape descriptors for each single sulcus element, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that the central, intraparietal and frontal medial sulci showed a significant and consistent pattern of abnormalities across our different geometrical indices. We also found that autistic and control children exhibited strikingly different relationships between age and structural changes in brain morphology. Lastly, the different measures of sulcus shapes were correlated with the CARS and ADOS scores that are specific to the autistic pathology and indices of symptom severity. Inherently, these structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD. In contrast to those previously reported in adults, it is very unlikely that these abnormalities originate from general compensatory mechanisms unrelated to the primary pathology. Rather, they most probably reflect an early disruption on developmental trajectory that could be part of the primary pathology. PMID:24936410

‘THEY SAY ISLAM HAS A SOLUTION FOR EVERYTHING, SO WHY ARE THERE NO GUIDELINES FOR THIS?’ ETHICAL DILEMMAS ASSOCIATED WITH THE BIRTHS AND DEATHS OF INFANTS WITH FATAL ABNORMALITIES FROM A SMALL SAMPLE OF PAKISTANI MUSLIM COUPLES IN BRITAIN

PubMed Central

SHAW, ALISON

2012-01-01

This paper presents ethical dilemmas concerning the termination of pregnancy, the management of childbirth, and the withdrawal of life-support from infants in special care, for a small sample of British Pakistani Muslim parents of babies diagnosed with fatal abnormalities. Case studies illustrating these dilemmas are taken from a qualitative study of 66 families of Pakistani origin referred to a genetics clinic in Southern England. The paper shows how parents negotiated between the authoritative knowledge of their doctors, religious experts, and senior family members in response to the ethical dilemmas they faced. There was little knowledge or open discussion of the view that Islam permits the termination of pregnancy for serious or fatal abnormality within 120 days and there was considerable disquiet over the idea of ending a pregnancy. For some parents, whether their newborn baby would draw breath was a main worry, with implications for the baby's Muslim identity and for the recognition of loss the parents would receive from family and community. This concern sometimes conflicted with doctors' concerns to minimize risk to future pregnancies by not performing a Caesarean delivery if a baby is sure to die. The paper also identifies parents' concerns and feelings of wrong-doing regarding the withdrawal of artificial life-support from infants with multiple abnormalities. The conclusion considers some of the implications of these observations for the counselling and support of Muslim parents following the pre- or neo-natal diagnosis of fatal abnormalities in their children. PMID:21649685

CHRONIC PERCHLORATE EXPOSURE CAUSES MORPHOLOGICAL ABNORMALITIES IN DEVELOPING STICKLEBACK

PubMed Central

Bernhardt, Richard R.; Von Hippel, Frank A.; O’Hara, Todd M.

2011-01-01

Few studies have examined the effects of chronic perchlorate exposure during growth and development, and fewer still have analyzed the effects of perchlorate over multiple generations. We describe morphological and developmental characteristics for threespine stickleback (Gasterosteus aculeatus) that were spawned and raised to sexual maturity in perchlorate-treated water (G1,2003) and for their offspring (G2,2004) that were not directly treated with perchlorate. The G1,2003 displayed a variety of abnormalities, including impaired formation of calcified traits, slower growth rates, aberrant sexual development, poor survivorship, and reduced pigmentation that allowed internal organs to be visible. Yet these conditions were absent when the offspring of contaminated fish (G2,2004) were raised in untreated water, suggesting a lack of transgenerational effects and that surviving populations may be able to recover following remediation of perchlorate-contaminated sites PMID:21465539

Role of epithelial cells in idiopathic pulmonary fibrosis: from innocent targets to serial killers.

PubMed

Selman, Moisés; Pardo, Annie

2006-06-01

Idiopathic pulmonary fibrosis (IPF), a progressive and relentless lung scarring of unknown etiology, has been recognized as the most lethal interstitial lung disease. Despite the growing interest in IPF, the precise molecular mechanisms underlying the development of fibrosis and leading to the irreversible destruction of the lung are still unknown. Recently, it has been proposed that IPF, instead of being a chronic inflammatory disorder, results from multiple cycles of epithelial cell injury and activation. In turn, active alveolar epithelial cells provoke the migration, proliferation, and activation of mesenchymal cells with the formation of fibroblastic/myofibroblastic foci and the exaggerated accumulation of extracellular matrix, mirroring abnormal wound repair. In this article, some characteristics of the alveolar epithelium are briefly outlined, and the fibrogenic mechanisms specifically operated by active abnormal epithelial cells are examined.

Urinary tract infection with Pasteurella multocida in a patient with cat exposure and abnormal urinary tract physiology: Case report and literature review.

PubMed

Costanzo, Joel T; Wojciechowski, Amy L; Bajwa, Rajinder P S

2017-01-01

Pasteurella multocida is a gram-negative organism that commonly colonizes the mouth of cats and dogs, and is known to cause infection in humans associated with animal bites or scratches. Sites of infection other than skin and soft tissue are rare, but have been reported in patients with specific risk factors including anatomical abnormalities or immunosuppression. Herein, we report a case of a symptomatic urinary tract infection caused by P. multocida in a 59 year old female who presented to the hospital with complaints of systemic symptoms including malaise, rigors, and chills, as well as thick, malodorous urine. The patient self-catheterized multiple times daily due to urostomy with Kock pouch. Treatment with piperacillin/tazobactam followed by amoxicillin resulted in resolution of the infection.

Female-to-male transsexual with 47,XXX karyotype.

PubMed

Turan, M T; Eşel, E; Dündar, M; Candemir, Z; Baştürk, M; Sofuoğlu, S; Ozkul, Y

2000-12-01

There are few reports describing chromosomal abnormalities in transsexuals. In rare cases, transsexualism and sexual chromosomal multiplicity coexist. Six cases of male-to-female transsexuals with 47,XYY chromosomal pattern have been previously reported. We have not encountered any female transsexual cases with 47,XXX karyotype in the literature. A 21-year-old female patient came to our outpatient department with depressive symptoms and suicidal thoughts. On psychiatric interview, she reported that she had feelings of discomfort with her gender identity and had desired to be male since her childhood. Then, we performed cytogenetic investigation using blood culture and G chromosome banding. Histology and DNA histograms of the patient revealed a chromosomal pattern of 47,XXX. We conclude that sexual chromosomal abnormalities in some transsexuals may cause a vulnerability to development of a gender identity disorder.

The Role of Attention in Somatosensory Processing: A Multi-trait, Multi-method Analysis

PubMed Central

Puts, Nicolaas A. J.; Mahone, E. Mark; Edden, Richard A. E.; Tommerdahl, Mark; Mostofsky, Stewart H.

2016-01-01

Sensory processing abnormalities in autism have largely been described by parent report. This study used a multi-method (parent-report and measurement), multi-trait (tactile sensitivity and attention) design to evaluate somatosensory processing in ASD. Results showed multiple significant within-method (e.g., parent report of different traits)/cross-trait (e.g., attention and tactile sensitivity) correlations, suggesting that parent-reported tactile sensory dysfunction and performance-based tactile sensitivity describe different behavioral phenomena. Additionally, both parent-reported tactile functioning and performance-based tactile sensitivity measures were significantly associated with measures of attention. Findings suggest that sensory (tactile) processing abnormalities in ASD are multifaceted, and may partially reflect a more global deficit in behavioral regulation (including attention). Challenges of relying solely on parent-report to describe sensory difficulties faced by children/families with ASD are also highlighted. PMID:27448580

Clinical image and pathology of hypertrophic cranial pachymeningitis.

PubMed

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

2014-12-12

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

Identification of faulty sensor using relative partial decomposition via independent component analysis

NASA Astrophysics Data System (ADS)

Wang, Z.; Quek, S. T.

2015-07-01

Performance of any structural health monitoring algorithm relies heavily on good measurement data. Hence, it is necessary to employ robust faulty sensor detection approaches to isolate sensors with abnormal behaviour and exclude the highly inaccurate data in the subsequent analysis. The independent component analysis (ICA) is implemented to detect the presence of sensors showing abnormal behaviour. A normalized form of the relative partial decomposition contribution (rPDC) is proposed to identify the faulty sensor. Both additive and multiplicative types of faults are addressed and the detectability illustrated using a numerical and an experimental example. An empirical method to establish control limits for detecting and identifying the type of fault is also proposed. The results show the effectiveness of the ICA and rPDC method in identifying faulty sensor assuming that baseline cases are available.

Congenital microcephaly: A diagnostic challenge during Zika epidemics.

PubMed

Alvarado-Socarras, Jorge L; Idrovo, Álvaro J; Contreras-García, Gustavo A; Rodriguez-Morales, Alfonso J; Audcent, Tobey A; Mogollon-Mendoza, Adriana C; Paniz-Mondolfi, Alberto

2018-02-19

The multiple, wide and diverse etiologies of congenital microcephaly are complex and multifactorial. Recent advances in genetic testing have improved understanding of novel genetic causes of congenital microcephaly. The recent Zika virus (ZIKV) epidemic in Latin America has highlighted the need for a better understanding of the underlying pathological mechanisms of microcephaly including both infectious and non-infectious causes. The diagnostic approach to microcephaly needs to include potential infectious and genetic etiologies, as well as environmental in-utero exposures such as alcohol, toxins, and medications. Emerging genetic alterations linked to microcephaly include abnormal mitotic microtubule spindle structure and abnormal function of centrosomes. We discuss the diagnostic challenge of congenital microcephaly in the context of understanding the links with ZIKV emergence as a new etiological factor involved in this birth defect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Child Maltreatment Among Singletons and Multiple Births in Japan: A Population-Based Study.

PubMed

Yokoyama, Yoshie; Oda, Terumi; Nagai, Noriyo; Sugimoto, Masako; Mizukami, Kenji

2015-12-01

The occurrence of multiple births has been recognized as a risk factor for child maltreatment. However, few population-based studies have examined the relationship between multiple births and child maltreatment. This study aimed to evaluate the degree of risk of child maltreatment among singletons and multiple births in Japan and to identify factors associated with increased risk. Using population-based data, we analyzed the database of records on child maltreatment and medical checkups for infants aged 1.5 years filed at Nishinomiya City Public Health Center between April 2007 and March 2011. To protect personal information, the data were transferred to anonymized electronic files for analysis. After adjusting by logistic regression for each associated factor and gestation number, multiples themselves were not associated with the risk of child maltreatment. However, compared with singletons, multiples had a significantly higher rate of risk factors for child maltreatment, including low birth weight and neural abnormality. Moreover, compared with mothers of singleton, mothers of twins had a significantly higher rate of poor health, which is a risk factor of child maltreatment. Multiples were not associated with the risk of child maltreatment. However, compared with singletons, multiples and their mothers had a significantly higher rate of risk factors of child maltreatment.

Active Duty- U.S. Army Noise-Induced Hearing Injury Quarterly Surveillance: Q1 2010 Thru Q2 2012

DTIC Science & Technology

2014-06-10

threshold shift, tinnitus , and Noise-Induced Hearing Loss. RECOMMENDATIONS: Commanders and Preventive Medicine assets at multiple levels should use...Humes LE, Jollenbeck LM, Durch JS: Noise and military service: Implications for hearing loss and tinnitus . Washington, DC: National Academy Press...NONSPECIFIC ABNORMAL AUDITORY FUNCTION STUDIES TINN Tinnitus 38830 TINNITUS UNSPECIFIED TINN Tinnitus 38831 SUBJECTIVE TINNITUS TINN Tinnitus 38832 OBJECTIVE

Determinants of spirometric abnormalities among silicotic patients in Hong Kong.

PubMed

Leung, Chi C; Chang, Kwok C; Law, Wing S; Yew, Wing W; Tam, Cheuk M; Chan, Chi K; Wong, Man Y

2005-09-01

Silicosis is the second commonest notified occupational disease in Hong Kong. To characterize the determinants of spirometric abnormalities in silicosis. The spirometric patterns of consecutive silicotic patients on confirmation by the Pneumoconiosis Medical Board from 1991 to 2002 were correlated with demographic characteristics, occupational history, smoking history, tuberculosis (TB) history and radiographic features by univariate and multiple regression analyses. Of 1576 silicotic patients included, 55.6% showed normal spirometry, 28.5% normal forced vital capacity (FVC>or=80% predicted) but reduced forced expiratory ratio (FER<70%), 7.6% reduced FVC but normal FER, and 8.4% reduced both FVC and FER. Age, ever-smoking, cigarette pack-years, industry, job type, history of TB, size of lung nodules and progressive massive fibrosis (PMF) were all significantly associated with airflow limitation on univariate analysis (all P<0.05), while sex and profusion of nodules were not. Only age, cigarette pack-years, history of TB, size of lung nodules and PMF remained as significant independent predictors of airflow obstruction in multiple logistic regression analysis. After controlling for airflow obstruction, only shorter exposure duration, history of TB and profusion of nodules were significant independent predictors of reduced FVC. As well as age, history of TB, cigarette pack-years, PMF and nodule size contributed comparable effects to airflow obstruction in multiple linear regression analyses, while profusion of nodules was the strongest factor for reduced vital capacity. In an occupational compensation setting, disease indices and history of tuberculosis are independent predictors of both airflow obstruction and reduced vital capacity for silicotic patients.

Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach

PubMed Central

Garner, Joseph P.; Thogerson, Collette M.; Dufour, Brett D.; Würbel, Hanno; Murray, James D.; Mench, Joy A.

2011-01-01

The NIMH's new strategic plan, with its emphasis on the “4P's” (Prediction, Preemption, Personalization, & Populations) and biomarker-based medicine requires a radical shift in animal modeling methodology. In particular 4P's models will be non-determinant (i.e. disease severity will depend on secondary environmental and genetic factors); and validated by reverse-translation of animal homologues to human biomarkers. A powerful consequence of the biomarker approach is that different closely-related disorders have a unique fingerprint of biomarkers. Animals can be validated as a highly-specific model of a single disorder by matching this `fingerprint'; or as a model of a symptom seen in multiple disorders by matching common biomarkers. Here we illustrate this approach with two Abnormal Repetitive Behaviors (ARBs) in mice: stereotypies; and barbering (hair pulling). We developed animal versions of the neuropsychological biomarkers that distinguish human ARBs, and tested the fingerprint of the different mouse ARBs. As predicted, the two mouse ARBs were associated with different biomarkers. Both barbering and stereotypy could be discounted as models of OCD (even though they are widely used as such), due to the absence of limbic biomarkers which are characteristic of OCD and hence are necessary for a valid model. Conversely barbering matched the fingerprint of trichotillomania (i.e. selective deficits in set-shifting), suggesting it may be a highly specific model of this disorder. In contrast stereotypies were correlated only with a biomarker (deficits in response shifting) correlated with stereotypies in multiple disorders, suggesting that animal stereotypies model stereotypies in multiple disorders. PMID:21219937

Prolonged striatal disinhibition as a chronic animal model of tic disorders.

PubMed

Vinner, Esther; Israelashvili, Michal; Bar-Gad, Izhar

2017-12-01

Experimental findings and theoretical models have associated Tourette syndrome with abnormal striatal inhibition. The expression of tics, the hallmark symptom of this disorder, has been transiently induced in non-human primates and rodents by the injection of GABA A antagonists into the striatum, leading to temporary disinhibition. The novel chronic model of tic expression utilizes mini-osmotic pumps implanted subcutaneously in the rat's back for prolonged infusion of bicuculline into the dorsolateral striatum. Tics were expressed on the contralateral side to the infusion over a period of multiple days. Tic expression was stable, and maintained similar properties throughout the infusion period. Electrophysiological recordings revealed the existence of tic-related local field potential spikes and individual neuron activity changes that remained stable throughout the infusion period. The striatal disinhibition model provides a unique combination of face validity (tic expression) and construct validity (abnormal striatal inhibition) but is limited to sub-hour periods. The new chronic model extends the period of tic expression to multiple days and thus enables the study of tic dynamics and the effects of behavior and pharmacological agents on tic expression. The chronic model provides similar behavioral and neuronal correlates of tics as the acute striatal disinhibition model but over prolonged periods of time, thus providing a unique, basal ganglia initiated model of tic expression. Chronic expression of symptoms is the key to studying the time varying properties of Tourette syndrome and the effects of multiple internal and external factors on this disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

An electrophysiological approach to the diagnosis of neurogenic dysphagia: implications for botulinum toxin treatment.

PubMed

Alfonsi, E; Merlo, I M; Ponzio, M; Montomoli, C; Tassorelli, C; Biancardi, C; Lozza, A; Martignoni, E

2010-01-01

Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle has been proposed for the treatment of neurogenic dysphagia due to CP hyperactivity. The aim was to determine whether an electrophysiological method exploring oropharyngeal swallowing could guide treatment and discriminate responders from non-responders, based on the association of CP dysfunction with other electrophysiological abnormalities of swallowing. Patients with different neurological disorders were examined: Parkinson disease, progressive supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system atrophy cerebellar variant, stroke, multiple sclerosis and ataxia telangiectasia. All patients presented with clinical dysphagia, and with complete absence of CP muscle inhibition during the hypopharyngeal phase of swallowing. Each patient underwent clinical and electrophysiological investigations before and after treatment with BTX into the CP muscle of one side (15 units of Botox). Clinical and electrophysiological procedures were performed in a blind manner by two different investigators. The following electrophysiological measures were analysed: (1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); (2) duration of laryngopharyngeal mechanogram (LPM-D); (3) duration of the inhibition of the CP muscle EMG activity (CPEMG-ID); and (4) interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngopharyngeal mechanogram (I-SHEMG-LPM). Two months after treatment, 50% of patients showed a significant improvement. Patients with prolonged or reduced SHEMG-D values and prolonged I-SHEMG-LPM values did not respond to BTX. Therefore, values for which BTX had no effect (warning values) were identified. This electrophysiological method can recognise swallowing abnormalities which may affect the outcome of the therapeutic approach to dysphagia with BTX treatment.

Basonuclin 2 has a function in the multiplication of embryonic craniofacial mesenchymal cells and is orthologous to disco proteins

PubMed Central

Vanhoutteghem, Amandine; Maciejewski-Duval, Anna; Bouche, Cyril; Delhomme, Brigitte; Hervé, Françoise; Daubigney, Fabrice; Soubigou, Guillaume; Araki, Masatake; Araki, Kimi; Yamamura, Ken-ichi; Djian, Philippe

2009-01-01

Basonuclin 2 is a recently discovered zinc finger protein of unknown function. Its paralog, basonuclin 1, is associated with the ability of keratinocytes to multiply. The basonuclin zinc fingers are closely related to those of the Drosophila proteins disco and discorelated, but the relation between disco proteins and basonuclins has remained elusive because the function of the disco proteins in larval head development seems to have no relation to that of basonuclin 1 and because the amino acid sequence of disco, apart from the zinc fingers, also has no similarity to that of the basonuclins. We have generated mice lacking basonuclin 2. These mice die within 24 h of birth with a cleft palate and abnormalities of craniofacial bones and tongue. In the embryonic head, expression of the basonuclin 2 gene is restricted to mesenchymal cells in the palate, at the periphery of the tongue, and in the mesenchymal sheaths that surround the brain and the osteocartilagineous structures. In late embryos, the rate of multiplication of these mesenchymal cells is greatly diminished. Therefore, basonuclin 2 is essential for the multiplication of craniofacial mesenchymal cells during embryogenesis. Non-Drosophila insect databases available since 2008 reveal that the basonuclins and the disco proteins share much more extensive sequence and gene structure similarity than noted when only Drosophila sequences were examined. We conclude that basonuclin 2 is both structurally and functionally the vertebrate ortholog of the disco proteins. We also note the possibility that some human craniofacial abnormalities are due to a lack of basonuclin 2. PMID:19706529

Sensitivity, specificity, and predictive values of pediatric metabolic syndrome components in relation to adult metabolic syndrome: the Princeton LRC follow-up study.

PubMed

Huang, Terry T-K; Nansel, Tonja R; Belsheim, Allen R; Morrison, John A

2008-02-01

To estimate the sensitivity, specificity, and predictive values of pediatric metabolic syndrome (MetS) components (obesity, fasting glucose, triglycerides, high-density lipoprotein, and blood pressure) at various cutoff points in relation to adult MetS. Data from the National Heart, Lung, and Blood Institute Lipid Research Clinics Princeton Prevalence Study (1973-1976) and the Princeton Follow-up Study (2000-2004) were used to calculate sensitivity, specificity, and positive and negative predictive values for each component at a given cutoff point and for aggregates of components. Individual pediatric components alone showed low to moderate sensitivity, high specificity, and moderate predictive values in relation to adult MetS. When all 5 pediatric MetS components were considered, the presence of at least 1 abnormality had higher sensitivity for adult MetS than individual components alone. When multiple abnormalities were mandatory for MetS, positive predictive value was high and sensitivity was low. Childhood body mass alone showed neither high sensitivity nor high positive predictive value for adult MetS. Considering multiple metabolic variables in childhood can improve the predictive usefulness for adult MetS, compared with each component or body mass alone. MetS variables may be useful for identifying some children who are at risk for prevention interventions.

Bone marrow mesenchymal stem cells are abnormal in multiple myeloma

PubMed Central

Corre, Jill; Mahtouk, Karène; Attal, Michel; Gadelorge, Mélanie; Huynh, Anne; Fleury-Cappellesso, Sandrine; Danho, Clotaire; Laharrague, Patrick; Klein, Bernard; Rème, Thierry; Bourin, Philippe

2007-01-01

Recent literature suggested that cell of the microenvironment of solid tumors could be abnormal as well. To address this hypothesis in multiple myeloma (MM), we studied bone marrow mesenchymal stem cells (BMMSCs), the only long-lived cells of the bone marrow microenvironment, by gene expression with Affymetrix arrays and phenotypic and functional study in 3 groups of individuals: patients with MM and those with monoclonal gamopathy of undefined significance (MGUS), and healthy aged-matched subjects. Gene expression profile independently classified the BMMSCs of these individuals in a normal and in a MM group. MGUS BMMSCs were interspersed between those 2 groups. Among the 145 distinct genes differentially expressed in MM and normal BMMSCs 46% were involved in tumor-microenvironment cross-talk. Known soluble factors involved in MM pathophysiologic features, (interleukin (IL)-6, IL-1β, DKK1 and amphiregulin, were revealed and new ones found. In particular, GDF-15 was found to induce dose-dependant growth of MOLP-6, a stromal cell-dependent myeloma cell line. Functionally, MM BMMSCs induced an over-growth of MOLP-6, and their capacity to differentiate into an osteoblastic lineage was impaired. Thus, BMMSCs from MM patients could create a very efficient niche to support the survival and proliferation of the myeloma stem cells. PMID:17344918

The contemporary spectrum of multiple sclerosis misdiagnosis: A multicenter study.

PubMed

Solomon, Andrew J; Bourdette, Dennis N; Cross, Anne H; Applebee, Angela; Skidd, Philip M; Howard, Diantha B; Spain, Rebecca I; Cameron, Michelle H; Kim, Edward; Mass, Michele K; Yadav, Vijayshree; Whitham, Ruth H; Longbrake, Erin E; Naismith, Robert T; Wu, Gregory F; Parks, Becky J; Wingerchuk, Dean M; Rabin, Brian L; Toledano, Michel; Tobin, W Oliver; Kantarci, Orhun H; Carter, Jonathan L; Keegan, B Mark; Weinshenker, Brian G

2016-09-27

To characterize patients misdiagnosed with multiple sclerosis (MS). Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS. Of 110 misdiagnosed patients, 51 (46%) were classified as "definite" and 59 (54%) "probable" misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%). Duration of misdiagnosis was 10 years or longer in 36 (33%) and an earlier opportunity to make a correct diagnosis was identified for 79 patients (72%). Seventy-seven (70%) received disease-modifying therapy and 34 (31%) experienced unnecessary morbidity because of misdiagnosis. Four (4%) participated in a research study of an MS therapy. Leading factors contributing to misdiagnosis were consideration of symptoms atypical for demyelinating disease, lack of corroborative objective evidence of a CNS lesion as satisfying criteria for MS attacks, and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms. Misdiagnosis of MS leads to unnecessary and potentially harmful risks to patients. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important contemporary contributors to misdiagnosis. © 2016 American Academy of Neurology.

Gait Profile Score in multiple sclerosis patients with low disability.

PubMed

Morel, Eric; Allali, Gilles; Laidet, Magali; Assal, Frédéric; Lalive, Patrice H; Armand, Stéphane

2017-01-01

Gait abnormalities are subtle in multiple sclerosis (MS) patients with low disability and need to be better determined. As a biomechanical approach, the Gait Profile Score (GPS) is used to assess gait quality by combining nine gait kinematic variables in one single value. This study aims i) to establish if the GPS can detect gait impairments and ii) to compare GPS with discrete spatiotemporal and kinematic parameters in low-disabled MS patients. Thirty-four relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score ≤2 (mean age 36.32±8.72 years; 12 men, 22 women; mean EDSS 1.19±0.8) and twenty-two healthy controls (mean age 36.85±7.87 years; 6 men, 16 women) matched for age, weight, height, body mass index and gender underwent an instrumented gait analysis. No significant difference in GPS values and in spatiotemporal parameters was found between patients and controls. However patients showed a significant alteration at the ankle and pelvis level. GPS fails to identify gait abnormalities in low-disabled MS patients, although kinematic analysis revealed subtle gait alterations. Future studies should investigate other methods to assess gait impairments with a gait score in low-disabled MS patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Detection of a complex translocation using fluorescent in situ hybridization (FISH)

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

Rosen, B.A.; Abuelo, D.N.; Mark, H.F.

1994-09-01

The use of fluorescent in situ hybridization (FISH) allowed the detection of a complex 3-way translocation in a patient with multiple congenital malformations and mental retardation. The patient was a 10-year-old girl with mental retardation, seizures, repaired cleft palate, esotropia, epicanthal folds, broad nasal bridge, upward slanting palpebral fissures, single transverse palmar crease, brachydactyly, hypoplastic nails, ectrodactyly between the third and fourth right toes, and hypoplasia of the left third toe. Chromosome analysis performed at birth was reported as normal. We performed high resolution banding analysis which revealed an apparently balanced translocation between chromosomes 2 and 9. However, because ofmore » her multiple abnormalities, further studies were ordered. Fluorescent in situ hybridization (FISH) using chromosome painting probes revealed a karyotype of 46,XX,t(2;8;9) (2pter{yields}q31::8q21.2{yields}8qter; 8pter{yields}q21.2::2q31{yields}q34::9q34{yields}qter; 9pter{yields}q34::2q34{yields}qter). The 3-way translocation appears to be de novo, as neither parent is a translocation carrier. This case illustrates the importance of using FISH to further investigate cases of apparently balanced translocations in the presence of phenotypic abnormalities and/or mental retardation.« less

Novel Phenotypic and Genotypic Findings in X-Linked Retinoschisis

PubMed Central

Tsang, Stephen H.; Vaclavik, Veronika; Bird, Alan C.; Robson, Anthony G.; Holder, Graham E.

2009-01-01

Objective To describe atypical phenotypes associated with the retinoschisis (X-linked, juvenile) 1 mutation (RS1). Methods Seven patients with multiple fine white dots at the macula and reduced visual acuity were evaluated. Six patients underwent pattern and full-field electroretinography (ERG). On-off ERG, optical coherence tomography, and fundus autofluorescence imaging were performed in some patients. Mutational screening of RS1 was prompted by the ERG findings. Results Fine white dots resembling drusenlike deposits and sometimes associated with retinal pigment epithelial abnormalities were present in the maculae. An electronegative bright-flash ERG configuration was present in all patients tested, and abnormal pattern ERG findings confirmed macular dysfunction. A parafoveal ring of high-density autofluorescence was present in 3 eyes; 1 patient showed high-density foci concordant with the white dots. Optical coherence tomography did not show foveal schisis in 3 of 4 eyes. All patients carried mutations in RS1, including 1 with a novel 206T→C mutation in exon 4. Conclusions Multiple fine white dots at the macula may be the initial fundus feature in RS1 mutation. Electrophysiologic findings suggest dysfunction after phototransduction and enable focused mutational screening. Autofluorescence imaging results suggest early retinal pigment epithelium involvement; a parafoveal ring of high-density autofluorescence has not previously been described in this disorder. PMID:17296904

Small Airway Dysfunction and Abnormal Exercise Responses

PubMed Central

Petsonk, Edward L.; Stansbury, Robert C.; Beeckman-Wagner, Lu-Ann; Long, Joshua L.; Wang, Mei Lin

2016-01-01

Rationale Coal mine dust exposure can cause symptoms and loss of lung function from multiple mechanisms, but the roles of each disease process are not fully understood. Objectives We investigated the implications of small airway dysfunction for exercise physiology among a group of workers exposed to coal mine dust. Methods Twenty coal miners performed spirometry, first breathing air and then helium-oxygen, single-breath diffusing capacity, and computerized chest tomography, and then completed cardiopulmonary exercise testing. Measurements and Main Results Six participants meeting criteria for small airway dysfunction were compared with 14 coal miners who did not. At submaximal workload, miners with small airway dysfunction used a higher proportion of their maximum voluntary ventilation and had higher ventilatory equivalents for both O2 and CO2. Regression modeling indicated that inefficient ventilation was significantly related to small airway dysfunction but not to FEV1 or diffusing capacity. At the end of exercise, miners with small airway dysfunction had 27% lower O2 consumption. Conclusions Small airway abnormalities may be associated with important inefficiency of exercise ventilation. In dust-exposed individuals with only mild abnormalities on resting lung function tests or chest radiographs, cardiopulmonary exercise testing may be important in defining causes of exercise intolerance. PMID:27073987

Multiple autism-like behaviors in a novel transgenic mouse model

PubMed Central

Hamilton, Shannon M.; Spencer, Corinne M.; Harrison, Wilbur R.; Yuva-Paylor, Lisa A.; Graham, Deanna F.; Daza, Ray A.M.; Hevner, Robert F.; Overbeek, Paul A.; Paylor, Richard

2011-01-01

Autism spectrum disorder (ASD) diagnoses are behaviorally-based with no defined universal biomarkers, occur at a 1:110 ratio in the population, and predominantly affect males compared to females at approximately a 4:1 ratio. One approach to investigate and identify causes of ASD is to use organisms that display abnormal behavioral responses that model ASD-related impairments. This study describes a novel transgenic mouse, MALTT, which was generated using a forward genetics approach. It was determined that the transgene integrated within a noncoding region on the X chromosome. The MALTT line exhibited a complete repertoire of ASD-like behavioral deficits in all three domains required for an ASD diagnosis: reciprocal social interaction, communication, and repetitive or inflexible behaviors. Specifically, MALTT male mice showed deficits in social interaction and interest, abnormalities in pup and juvenile ultrasonic vocalization communications, and exhibited a repetitive stereotypy. Abnormalities were also observed in the domain of sensory function, a secondary phenotype prevalently associated with ASD. Mapping and expression studies suggested that the Fam46 gene family may be linked to the observed ASD-related behaviors. The MALTT line provides a unique genetic model for examining the underlying biological mechanisms involved in ASD-related behaviors. PMID:21093492

Chronic Desipramine Treatment Rescues Depression-Related, Social and Cognitive Deficits in Engrailed-2 Knockout Mice

PubMed Central

Brielmaier, Jennifer; Senerth, Julia M.; Silverman, Jill L.; Matteson, Paul G.; Millonig, James H.; DiCicco-Bloom, Emanuel; Crawley, Jacqueline N.

2014-01-01

Engrailed-2 (En2) is a homeobox transcription factor that regulates neurodevelopmental processes including neuronal connectivity and elaboration of monoaminergic neurons in the ventral hindbrain. We previously reported abnormalities in brain noradrenergic concentrations in En2 null mutant mice that were accompanied by increased immobility in the forced swim test, relevant to depression. An EN2 genetic polymorphism has been associated with autism spectrum disorders (ASD), and mice with a deletion in En2 display social abnormalities and cognitive deficits that may be relevant to multiple neuropsychiatric conditions. The present study evaluated the ability of chronic treatment with desipramine (DMI), a selective norepinephrine reuptake inhibitor and classical antidepressant, to reverse behavioral abnormalities in En2 −/− mice. DMI treatment significantly reduced immobility in the tail suspension and forced swim tests, restored sociability in the three-chambered social approach task, and reversed impairments in contextual fear conditioning in En2 −/− mice. Our findings indicate that modulation of brain noradrenergic systems rescues the depression-related phenotype in En2 −/− mice and suggest new roles for norepinephrine in the pathophysiology of the social and cognitive deficits seen in neuropsychiatric disorders such as autism or schizophrenia. PMID:24730055

Blastulation rates decline in a linear fashion from euploid to aneuploid embryos with single versus multiple chromosomal errors.

PubMed

Vega, Mario; Breborowicz, Andrzej; Moshier, Erin L; McGovern, Peter G; Keltz, Martin D

2014-08-01

To test the hypothesis that the blastulation rate is higher in euploid embryos than in aneuploid embryos as assessed by cleavage-stage biopsy with array-comprehensive genomic hybridization (aCGH). Retrospective cohort study. University-affiliated institution. Forty-one patients with 48 in vitro fertilization (IVF) cycles and 385 embryos that underwent cleavage-stage preimplantation genetic screening (PGS) with aCGH at the Continuum Reproductive Center between January 2010 and September 2013. None. Probability of blastocyst and/or fully expanded or hatching blastocyst (FEHB) progression depending on number of chromosomal abnormalities. Euploid embryos are twice as likely to progress to blastocyst and three times as likely to progress to FEHB than aneuploid embryos: 76% versus 37% and 56% versus 18%, respectively. For every additional chromosomal abnormality, the likelihood of progressing to the blastocyst stage decreases by 22% and the likelihood of progressing to FEHB decreases by 33%. Euploid embryos are far more likely than aneuploid embryos to progress to the blastocyst and FEHB stages. There is a linear decrease in probability of blastulation with the increasing number of chromosomal abnormalities. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Gpr177 regulates pulmonary vasculature development.

PubMed

Jiang, Ming; Ku, Wei-yao; Fu, Jiang; Offermanns, Stefan; Hsu, Wei; Que, Jianwen

2013-09-01

Establishment of the functional pulmonary vasculature requires intimate interaction between the epithelium and mesenchyme. Previous genetic studies have led to inconsistent conclusions about the contribution of epithelial Wnts to pulmonary vasculature development. This discrepancy is possibly due to the functional redundancy among different Wnts. Here, we use Shh-Cre to conditionally delete Gpr177 (the mouse ortholog of Drosophila Wntless, Wls), a chaperon protein important for the sorting and secretion of Wnt proteins. Deletion of epithelial Gpr177 reduces Wnt signaling activity in both the epithelium and mesenchyme, resulting in severe hemorrhage and abnormal vasculature, accompanied by branching defects and abnormal epithelial differentiation. We then used multiple mouse models to demonstrate that Wnt/β-catenin signaling is not only required for the proliferation and differentiation of mesenchyme, but also is important for the maintenance of smooth muscle cells through the regulation of the transcription factor Kruppel-like factor 2 (Klf2). Together, our studies define a novel mechanism by which epithelial Wnts regulate the normal development and maintenance of pulmonary vasculature. These findings provide insight into the pathobiology of congenital lung diseases, such as alveolar capillary dysplasia (ACD), that have abnormal alveolar development and dysmorphic pulmonary vasculature.

Support Vector Machine Classification of Major Depressive Disorder Using Diffusion-Weighted Neuroimaging and Graph Theory

PubMed Central

Sacchet, Matthew D.; Prasad, Gautam; Foland-Ross, Lara C.; Thompson, Paul M.; Gotlib, Ian H.

2015-01-01

Recently, there has been considerable interest in understanding brain networks in major depressive disorder (MDD). Neural pathways can be tracked in the living brain using diffusion-weighted imaging (DWI); graph theory can then be used to study properties of the resulting fiber networks. To date, global abnormalities have not been reported in tractography-based graph metrics in MDD, so we used a machine learning approach based on “support vector machines” to differentiate depressed from healthy individuals based on multiple brain network properties. We also assessed how important specific graph metrics were for this differentiation. Finally, we conducted a local graph analysis to identify abnormal connectivity at specific nodes of the network. We were able to classify depression using whole-brain graph metrics. Small-worldness was the most useful graph metric for classification. The right pars orbitalis, right inferior parietal cortex, and left rostral anterior cingulate all showed abnormal network connectivity in MDD. This is the first use of structural global graph metrics to classify depressed individuals. These findings highlight the importance of future research to understand network properties in depression across imaging modalities, improve classification results, and relate network alterations to psychiatric symptoms, medication, and comorbidities. PMID:25762941

Support vector machine classification of major depressive disorder using diffusion-weighted neuroimaging and graph theory.

PubMed

Sacchet, Matthew D; Prasad, Gautam; Foland-Ross, Lara C; Thompson, Paul M; Gotlib, Ian H

2015-01-01

Recently, there has been considerable interest in understanding brain networks in major depressive disorder (MDD). Neural pathways can be tracked in the living brain using diffusion-weighted imaging (DWI); graph theory can then be used to study properties of the resulting fiber networks. To date, global abnormalities have not been reported in tractography-based graph metrics in MDD, so we used a machine learning approach based on "support vector machines" to differentiate depressed from healthy individuals based on multiple brain network properties. We also assessed how important specific graph metrics were for this differentiation. Finally, we conducted a local graph analysis to identify abnormal connectivity at specific nodes of the network. We were able to classify depression using whole-brain graph metrics. Small-worldness was the most useful graph metric for classification. The right pars orbitalis, right inferior parietal cortex, and left rostral anterior cingulate all showed abnormal network connectivity in MDD. This is the first use of structural global graph metrics to classify depressed individuals. These findings highlight the importance of future research to understand network properties in depression across imaging modalities, improve classification results, and relate network alterations to psychiatric symptoms, medication, and comorbidities.

Structural brain abnormalities in Cushing's syndrome.

PubMed

Bauduin, Stephanie E E C; van der Wee, Nic J A; van der Werff, Steven J A

2018-05-08

Alongside various physical symptoms, patients with Cushing's disease and Cushing's syndrome display a wide variety of neuropsychiatric and cognitive symptoms, which are indicative of involvement of the central nervous system. The aim of this review is to provide an overview of the structural brain abnormalities that are associated with Cushing's disease and Cushing's syndrome and their relation to behavioral and cognitive symptomatology. In this review, we discuss the gray matter structural abnormalities found in patients with active Cushing's disease and Cushing's syndrome, the reversibility and persistence of these changes and the white matter structural changes related to Cushing's syndrome. Recent findings are of particular interest because they provide more detailed information on localization of the structural changes as well as possible insights into the underlying biological processes. Active Cushing's disease and Cushing's syndrome is related to volume reductions of the hippocampus and in a prefrontal region involving the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG). Whilst there are indications that the reductions in hippocampal volume are partially reversible, the changes in the ACC and MFG appear to be more persistent. In contrast to the volumetric findings, changes in white matter connectivity are typically widespread involving multiple tracts.

A follow-up study of neurologic and radiographic findings in working German Shepherd Dogs with and without degenerative lumbosacral stenosis.

PubMed

Steffen, Frank; Hunold, Katharina; Scharf, Gernot; Roos, Malgorzata; Flückiger, Mark

2007-11-15

To identify radiographic abnormalities associated with degenerative lumbosacral stenosis (DLSS) in German Shepherd Dogs (GSDs) and determine whether specific radiographic abnormalities could be used to identify dogs at risk of developing DLSS. Cohort study. 33 GSDs working as police dogs. Results of physical, neurologic, and orthopedic examinations were used to identify dogs with DLSS. Survey radiography of the lumbosacral junction was performed, and radiographs were compared with radiographs obtained 3 years earlier. DLSS was diagnosed in 15 of the 33 (45%) dogs. Thirteen of the 15 dogs with DLSS and 14 of the 18 dogs without DLSS had radiographic abnormalities of the lumbosacral junction. Twenty-two (67%) dogs were able to perform unrestricted duties, including 3 dogs with suspected DLSS. Six (18%) dogs had been excluded from active duty during the period of surveillance because of DLSS. Significant progression in specific clinical and radiographic signs was detected, but multiple logistic regression analysis did not identify any radiographic signs that could be used to predict the development of DLSS. Results suggested that survey radiography cannot be used to predict development of DLSS in working GSDs.

[Microecological investigation of vaginal microflora in women with varying degree gynecologic symptoms in clinics].

PubMed

Xiao, Bing-bing; Liu, Zhao-hui; Liao, Qin-ping

2009-01-01

To investigate the microecological status of vaginal microflora in the women with different vaginal symptoms. From March 2006 to October 2007, 6982 cases with varying degree vaginal symptoms including pruritus, increaseed leucorrhea, the leucorrhea having unusual smell, in the gynecology outpatient department were studied. The vagina secretions were examined in terms of the pH value, the hydrogen peroxide test, and Gram dyeing inspection of vaginal bacteria and microecology appraisal for colony's density, the multiplicity, the superiority fungus, and the inflammatory response. Among 6982 patients, normal vaginal microecology was identified in 750 (10.74%, 750/6982); abnormal microecology was found in 6232 (89.26%, 6232/6982); bacterial vaginosis (BV) was detected in 729 (10.44%, 729/6982); vulvovaginal candidiasis (VVC) was in 1527 (21.87%, 1527/6982). Ninety five patients (1.36%, 95/6982) were with both BV and VVC. Abnormal bacteria colonies were found in 1229 (17.60%, 1229/6982), and others were found in 2652 (37.98%, 2652/6982). The vaginal microecology in the women with different vaginal symptoms can be either normal or abnormal. Microecology clinical evaluation system can assess the vaginal microecosystem.

Errors in radiographic interpretation made by veterinary students.

PubMed

Lamb, C R; Pfeiffer, D U; Mantis, P

2007-01-01

As a means of identifying student weaknesses in radiographic interpretation that could be used as foci for teaching, a cohort of 96 students joining the final-year radiology rotation were randomly allocated to one of three radiographic interpretation quizzes, each based on radiographs of small-animal patients together with the signalment and a brief, relevant history. Students' quiz scores were analyzed by multiple logistic regression, using an outcome variable with the score for each item as numerator and maximum possible mark as denominator. Students' median quiz score was 49% of the maximum (range 23-80%). Students were more likely to gain a mark for items based on abnormal radiographs than for those based on normal radiographs (odds ratio 3.4, p < 0.001). Skeletal radiographs were associated with lower scores (OR 0.75, p = 0.03). The fewest marks were awarded for interpretation of a radiograph of a normal canine stifle and interpretation of a radiograph of a normal canine pelvis; these items were misinterpreted as abnormal by 86% and 80% of the students, respectively. Students' tendency to over-interpret normal radiographs may reflect a lack of knowledge of radiographic anatomy or an unrealistically high expectation that the radiographs are abnormal.

Crouzon's Syndrome: A Case Report.

PubMed

Kumar, G Ravi; Jyothsna, M; Ahmed, Syed Basheer; Lakshmi, K Sree

2013-01-01

Crouzon's syndrome (CS) is a rare autosomal dominant condition with multiple mutations of the fibroblast growth factor receptor (FGFR2) gene, which accounts for 4.8% of all cases of craniosynostosis. It is characterized by premature closure of cranial sutures, cranial deformities, midface hypoplasia, relative mandibular prognathism, hypertelorism, proptosis, strabismus and short upper lip, crowding of teeth, pseudocleft or sometimes cleft palate and other associated abnormalities. The CS can vary in severity from mild presentation to severe forms involving multiple cranial sutures. We report a case of CS in 11-year-old boy. How to cite this article: Kumar GR, Jyothsna M, Ahmed SB, Lakshmi KS, Crouzon's Syndrome: A Case Report. Int J Clin Pediatr Dent 2013;6(1):33-37.

Multimodal noninvasive and invasive imaging of extracranial venous abnormalities indicative of CCSVI: Results of the PREMiSe pilot study

PubMed Central

2013-01-01

Background There is no established noninvasive or invasive diagnostic imaging modality at present that can serve as a ‘gold standard’ or “benchmark” for the detection of the venous anomalies, indicative of chronic cerebrospinal venous insufficiency (CCSVI). We investigated the sensitivity and specificity of 2 invasive vs. 2 noninvasive imaging techniques for the detection of extracranial venous anomalies in the internal jugular veins (IJVs) and azygos vein/vertebral veins (VVs) in patients with multiple sclerosis (MS). Methods The data for this multimodal imaging comparison pilot study was collected in phase 2 of the “Prospective Randomized Endovascular therapy in Multiple Sclerosis” (PREMiSe) study using standardized imaging techniques. Thirty MS subjects were screened initially with Doppler sonography (DS), out of which 10 did not fulfill noninvasive screening procedure requirements on DS that consisted of ≥2 venous hemodynamic extracranial criteria. Accordingly, 20 MS patients with relapsing MS were enrolled into the multimodal diagnostic imaging study. For magnetic resonance venography (MRV), IJVs abnormal findings were considered absent or pinpoint flow, whereas abnormal VVs flow was classified as absent. Abnormalities of the VVs were determined only using non-invasive testing. Catheter venography (CV) was considered abnormal when ≥50% lumen restriction was detected, while intravascular ultrasound (IVUS) was considered abnormal when ≥50% restriction of the lumen or intra-luminal defects or reduced pulsatility was found. Non-invasive and invasive imaging modality comparisons between left, right and total IJVs and between the VVs and azygos vein were performed. Because there is no reliable way of non-invasively assessing the azygos vein, the VVs abnormalities detected by the non-invasive testing were compared to the azygos abnormalities detected by the invasive testing. All image modalities were analyzed in a blinded manner by more than one viewer, upon which consensus was reached. The sensitivity and specificity were calculated using contingency tables denoting the presence or absence of vein-specific abnormality findings between all imaging modalities used individually as the benchmark. Results The sensitivity of CV + IVUS was 68.4% for the right and 90% for the left IJV and 85.7% for the azygos vein/VVs, compared to venous anomalies detected on DS. Compared to the venous anomalies detected on MRV, the sensitivity of CV + IVUS was 71.4% in right and 100% in left IJVs and 100% in the azygos vein/VVs; however, the specificity was 38.5%, 38.9% and 11.8%, respectively. The sensitivity between the two invasive imaging techniques, used as benchmarks, ranged from 72.7% for the right IJV to 90% for the azygos vein but the IVUS showed a higher rate of venous anomalies than the CV. There was excellent correspondence between identifying collateral veins on MRV and CV. Conclusions Noninvasive DS screening for the detection of venous anomalies indicative of CCSVI may be a reliable approach for identifying patients eligible for further multimodal invasive imaging testing of the IJVs. However, the noninvasive screening methods were inadequate to depict the total amount of azygos vein/VVs anomalies identified with invasive testing. This pilot study, with limited sample size, shows that both a non-invasive and invasive multimodal imaging diagnostic approach should be recommended to depict a range of extracranial venous anomalies indicative of CCSVI. However, lack of invasive testing on the study subjects whose results were negative on the DS screening and of healthy controls, limits further generalizibility of our findings. In addition, the findings from the 2 invasive techniques confirmed the existence of severe extracranial venous anomalies that significantly impaired normal blood outflow from the brain in this group of MS patients. PMID:24139135

Investigation of confined placental mosaicism (CPM) at multiple sites in post-delivery placentas derived through intracytoplasmic sperm injection (ICSI).

PubMed

Minor, Agata; Harmer, Karynn; Peters, Nicole; Yuen, Basil Ho; Ma, Sai

2006-01-01

Although earlier studies on pregnancies derived through intracytoplasmic sperm injection (ICSI) reported increased non-mosaic aneuploidy among ICSI children, undetected mosaicism, such as confined placental mosaicism (CPM) has not been evaluated. We investigated the incidence of CPM in post-delivery placentas derived from ICSI, evaluated whether CPM was increased and whether it was a contributing factor to negative pregnancy outcome. [Fifty-one post-delivery placentas were collected from patients who underwent ICSI with a normal or negative pregnancy outcome]. Trophoblast and chorionic stroma from three sites were analyzed by comparative genomic hybridization (CGH) and flow cytometry. Detected abnormalities were confirmed by fluorescence in situ hybridization (FISH). The incidence of CPM in the ICSI population was compared to the general population from published data. We detected three cases of CPM in our study. One abnormality was found by CGH analysis; partial trisomy 7q and a partial monosomy Xp limited to the trophoblast at two sites. The abnormality was associated with a child affected by spina bifida. Two cases of mosaic tetraploidy were observed by flow cytometry in pregnancies with a normal outcome. All three abnormalities were confirmed by FISH analysis. The incidence of CPM in the ICSI study population was 5.88% (3/51), which was not statistically different from published reports in the general population (5.88% (42/714), Chi square, P > 0.05). The post-ICSI population was not at risk for CPM in this study. (c) 2005 Wiley-Liss, Inc.

Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications.

PubMed

Sardinha, Aline; Freire, Rafael Christophe da Rocha; Zin, Walter Araújo; Nardi, Antonio Egidio

2009-07-01

Multiple respiratory abnormalities can be found in anxiety disorders, especially in panic disorder (PD). Individuals with PD experience unexpected panic attacks, characterized by anxiety and fear, resulting in a number of autonomic and respiratory symptoms. Respiratory stimulation is a common event during panic attacks. The respiratory abnormality most often reported in PD patients is increased CO2 sensitivity, which has given rise to the hypothesis of fundamental abnormalities in the physiological mechanisms that control breathing in PD. There is evidence that PD patients with dominant respiratory symptoms are more sensitive to respiratory tests than are those who do not manifest such symptoms, and that the former group constitutes a distinct subtype. Patients with PD tend to hyperventilate and to panic in response to respiratory stimulants such as CO2, triggering the activation of a hypersensitive fear network. Although respiratory physiology seems to remain normal in these subjects, recent evidence supports the idea that they present subclinical abnormalities in respiration and in other functions related to body homeostasis. The fear network, composed of the hippocampus, the medial prefrontal cortex, the amygdala and its brain stem projections, might be oversensitive in PD patients. This theory might explain why medication and cognitive-behavioral therapy are both clearly effective. Our aim was to review the relationship between respiration and PD, addressing the respiratory subtype of PD and the hyperventilation syndrome, with a focus on respiratory challenge tests, as well as on the current mechanistic concepts and the pharmacological implications of this relationship.

Abnormal hippocampal shape in offenders with psychopathy.

PubMed

Boccardi, Marina; Ganzola, Rossana; Rossi, Roberta; Sabattoli, Francesca; Laakso, Mikko P; Repo-Tiihonen, Eila; Vaurio, Olli; Könönen, Mervi; Aronen, Hannu J; Thompson, Paul M; Frisoni, Giovanni B; Tiihonen, Jari

2010-03-01

Posterior hippocampal volumes correlate negatively with the severity of psychopathy, but local morphological features are unknown. The aim of this study was to investigate hippocampal morphology in habitually violent offenders having psychopathy. Manual tracings of hippocampi from magnetic resonance images of 26 offenders (age: 32.5 +/- 8.4), with different degrees of psychopathy (12 high, 14 medium psychopathy based on the Psychopathy Checklist Revised), and 25 healthy controls (age: 34.6 +/- 10.8) were used for statistical modelling of local changes with a surface-based radial distance mapping method. Both offenders and controls had similar hippocampal volume and asymmetry ratios. Local analysis showed that the high psychopathy group had a significant depression along the longitudinal hippocampal axis, on both the dorsal and ventral aspects, when compared with the healthy controls and the medium psychopathy group. The opposite comparison revealed abnormal enlargement of the lateral borders in both the right and left hippocampi of both high and medium psychopathy groups versus controls, throughout CA1, CA2-3 and the subicular regions. These enlargement and reduction effects survived statistical correction for multiple comparisons in the main contrast (26 offenders vs. 25 controls) and in most subgroup comparisons. A statistical check excluded a possible confounding effect from amphetamine and polysubstance abuse. These results indicate that habitually violent offenders exhibit a specific abnormal hippocampal morphology, in the absence of total gray matter volume changes, that may relate to different autonomic modulation and abnormal fear-conditioning. 2009 Wiley-Liss, Inc.

Sequencing of a Patient with Balanced Chromosome Abnormalities and Neurodevelopmental Disease Identifies Disruption of Multiple High Risk Loci by Structural Variation

PubMed Central

Blake, Jonathon; Riddell, Andrew; Theiss, Susanne; Gonzalez, Alexis Perez; Haase, Bettina; Jauch, Anna; Janssen, Johannes W. G.; Ibberson, David; Pavlinic, Dinko; Moog, Ute; Benes, Vladimir; Runz, Heiko

2014-01-01

Balanced chromosome abnormalities (BCAs) occur at a high frequency in healthy and diseased individuals, but cost-efficient strategies to identify BCAs and evaluate whether they contribute to a phenotype have not yet become widespread. Here we apply genome-wide mate-pair library sequencing to characterize structural variation in a patient with unclear neurodevelopmental disease (NDD) and complex de novo BCAs at the karyotype level. Nucleotide-level characterization of the clinically described BCA breakpoints revealed disruption of at least three NDD candidate genes (LINC00299, NUP205, PSMD14) that gave rise to abnormal mRNAs and could be assumed as disease-causing. However, unbiased genome-wide analysis of the sequencing data for cryptic structural variation was key to reveal an additional submicroscopic inversion that truncates the schizophrenia- and bipolar disorder-associated brain transcription factor ZNF804A as an equally likely NDD-driving gene. Deep sequencing of fluorescent-sorted wild-type and derivative chromosomes confirmed the clinically undetected BCA. Moreover, deep sequencing further validated a high accuracy of mate-pair library sequencing to detect structural variants larger than 10 kB, proposing that this approach is powerful for clinical-grade genome-wide structural variant detection. Our study supports previous evidence for a role of ZNF804A in NDD and highlights the need for a more comprehensive assessment of structural variation in karyotypically abnormal individuals and patients with neurocognitive disease to avoid diagnostic deception. PMID:24625750

Cervical Dysplasia and High-Risk Human Papillomavirus Infections among HIV-Infected and HIV-Uninfected Adolescent Females in South Africa

PubMed Central

Mrubata, Megan; Williamson, Anna-Lise; Bekker, Linda-Gail

2014-01-01

Background. HIV-infected adolescents may be at higher risk for high-grade cervical lesions than HIV-uninfected adolescents. The purpose of this study was to compare the prevalence of high-risk HPV (HR-HPV) infections and Pap smear abnormalities between these two groups. Methods. In this cross-sectional study, we compared the HPV DNA and Pap smear results between 35 HIV-infected and 50 HIV-uninfected adolescents in order to determine the prevalence of HR-HPV genotypes and cervical cytological abnormalities. Comparisons were made using Pearson χ 2 and independent-samples t-tests analyses, and associations between demographic and behavioral characteristics and HPV infections were examined. Results. HIV-infected participants were more likely to be infected with any HPV (88.6% versus 48.0%; P < 0.001) and with at least one HR-HPV (60.0% versus 24.0%; P = 0.001), and to have multiple concurrent HPV infections (68.6% versus 22.0%; P < 0.001). HPV 16 and 18 were relatively underrepresented among HR-HPV infections. Abnormal Pap test results were more common among HIV-infected participants (28.8% versus 12.0%; P = 0.054). A history of smoking was associated with HR-HPV infection. Conclusions. HIV-infected adolescents have an increased risk of infection with HR-HPV and of Pap test abnormalities. The majority of HR-HPV infections among our participants would not be prevented by the currently available vaccinations against HPV. PMID:25389377

Impact of cytogenetic abnormalities in adults with Ph-negative B-cell precursor acute lymphoblastic leukemia.

PubMed

Lafage-Pochitaloff, Marina; Baranger, Laurence; Hunault, Mathilde; Cuccuini, Wendy; Lefebvre, Christine; Bidet, Audrey; Tigaud, Isabelle; Eclache, Virginie; Delabesse, Eric; Bilhou-Nabéra, Chrystèle; Terré, Christine; Chapiro, Elise; Gachard, Nathalie; Mozziconacci, Marie-Joelle; Ameye, Geneviève; Porter, Sarah; Grardel, Nathalie; Béné, Marie C; Chalandon, Yves; Graux, Carlos; Huguet, Françoise; Lhéritier, Véronique; Ifrah, Norbert; Dombret, Hervé

2017-10-19

Multiple cytogenetic subgroups have been described in adult Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), often comprising small numbers of patients. In this study, we aimed to reassess the prognostic value of cytogenetic abnormalities in a large series of 617 adult patients with Ph-negative BCP-ALL (median age, 38 years), treated in the intensified Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/2005 trials. Combined data from karyotype, DNA index, fluorescence in situ hybridization, and polymerase chain reaction screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in 10 exclusive primary cytogenetic subgroups and in secondary subgroups, including complex and monosomal karyotypes. Prognostic analyses focused on cumulative incidence of failure (including primary refractoriness and relapse), event-free survival, and overall survival. Only 2 subgroups, namely t(4;11)/ KMT2A-AFF1 and 14q32/ IGH translocations, displayed a significantly worse outcome in this context, still observed after adjustment for age and after censoring patients who received allogeneic stem cell transplantation (SCT) in first remission at SCT time. A worse outcome was also observed in patients with low hypodiploidy/near triploidy, but this was likely related to their higher age and worse tolerance to therapy. The other cytogenetic abnormalities, including complex and monosomal karyotypes, had no prognostic value in these intensive protocols designed for adult patients up to the age of 60 years. © 2017 by The American Society of Hematology.

Corkscrew retinal vessels in neurofibromatosis type 1: report of 12 cases

PubMed Central

Muci-Mendoza, R; Ramella, M; Fuenmayor-Rivera, D

2002-01-01

Aim: To describe a distinctive spectrum of retinal microvascular abnormalities in 12 patients with neurofibromatosis type 1 (NF-1). Methods: This is an observational prospective study of the ocular fundus evaluated by direct ophthalmoscopy with or without fluorescein angiography, to investigate retinal microvascular abnormalities in 32 patients with NF-1 and in 30 control subjects. The evaluation included a complete general and neurological physical examination and in some cases computed tomography, magnetic resonance imaging with gadolinium-DTPA, or both. Results: The occurrence of a distinctive spectrum of retinal microvascular abnormalities is described in 12 patients with NF-1 (37.5%). At the lower end of the spectrum, present in 10 patients, the anomaly consisted of minuscule second or third order tortuous venules, which were called “corkscrew retinal vessels.” These were usually isolated but in a few cases multiple. They flow towards the superior or inferior temporal veins. They had a length of one to two disc diameters. They ended either in a minute tuft or vanished on the retinal surface. The upper end of the spectrum was seen in only two patients. One of them had an exceptionally large venous anastomosis on the nasal retina and the other had an arteriovenous malformation extending over one retinal quadrant. None of the patients in the control group had such retinal microvascular abnormalities. Conclusion: The “corkscrew” retinal vessels described in this report constitute a broad spectrum of microvascular markers in NF-1 patients. PMID:11864883

Vision and vision-related outcome measures in multiple sclerosis

PubMed Central

Balcer, Laura J.; Miller, David H.; Reingold, Stephen C.

2015-01-01

Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis. PMID:25433914

An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis

PubMed Central

Brown, J William L; Pardini, Matteo; Brownlee, Wallace J; Fernando, Kryshani; Samson, Rebecca S; Prados Carrasco, Ferran; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

2017-01-01

Abstract In established multiple sclerosis, tissue abnormality—as assessed using magnetization transfer ratio—increases close to the lateral ventricles. We aimed to determine whether or not (i) these changes are present from the earliest clinical stages of multiple sclerosis; (ii) they occur independent of white matter lesions; and (iii) they are associated with subsequent conversion to clinically definite multiple sclerosis and disability. Seventy-one subjects had MRI scanning a median of 4.6 months after a clinically isolated optic neuritis (49 females, mean age 33.5 years) and were followed up clinically 2 and 5 years later. Thirty-seven healthy controls (25 females, mean age 34.4 years) were also scanned. In normal-appearing white matter, magnetization transfer ratio gradients were measured 1–5 mm and 6–10 mm from the lateral ventricles. In control subjects, magnetization transfer ratio was highest adjacent to the ventricles and decreased with distance from them; in optic neuritis, normal-appearing white matter magnetization transfer ratio was lowest adjacent to the ventricles, increased over the first 5 mm, and then paralleled control values. The magnetization transfer ratio gradient over 1–5 mm differed significantly between the optic neuritis and control groups [+0.059 percentage units/mm (pu/mm) versus −0.033 pu/mm, P = 0.010], and was significantly steeper in those developing clinically definite multiple sclerosis within 2 years compared to those who did not (0.132 pu/mm versus 0.016 pu/mm, P = 0.020). In multivariate binary logistic regression the magnetization transfer ratio gradient was independently associated with the development of clinically definite multiple sclerosis within 2 years (magnetization transfer ratio gradient odds ratio 61.708, P = 0.023; presence of T2 lesions odds ratio 8.500, P = 0.071). At 5 years, lesional measures overtook magnetization transfer ratio gradients as significant predictors of conversion to multiple sclerosis. The magnetization transfer ratio gradient was not significantly affected by the presence of brain lesions [T2 lesions (P = 0.918), periventricular T2 lesions (P = 0.580) or gadolinium-enhancing T1 lesions (P = 0.724)]. The magnetization transfer ratio gradient also correlated with Expanded Disability Status Scale score 5 years later (Spearman r = 0.313, P = 0.027). An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis, is clinically relevant, and may arise from one or more mechanisms that are at least partly independent of lesion formation. PMID:28043954

Syndromic odontogenic keratocyst: A case report and review of literature

PubMed Central

Arshad, Fazil

2016-01-01

Odontogenic keratocysts (OKCs) may occur in two different forms, either as solitary (nonsyndromic OKCs) or as multiple OKCs (syndromic OKCs). Multiple OKCs usually occur as one of the findings in Gorlin–Goltz syndrome with other features such as skin carcinomas and rib, eye, and neurologic abnormalities. We report a rare case of Gorlin–Goltz syndrome in a 20-year-old male patient who presented with a slow growing swelling on lower right and left back teeth region since 2 months. Apart from these, other findings were frontal bossing, depressed nasal bridge, ocular hypertelorism, prominent supra orbital ridge, and mild mandibular prognathism. Excision was done and microscopic study revealed OKC and the follow-up could not be carried out for the complete management. We also presented a review of its pathogenesis, criterion, and differences between syndromic and nonsyndromic OKCs and suggest to thoroughly examine any patient who presents with multiple OKCs to rule out syndromic variety. PMID:27011939

Recent advances in multiple myeloma.

PubMed

Sjak-Shie, N N; Vescio, R A; Berenson, J R

2000-07-01

Multiple myeloma is the second most common hematologic malignancy, with approximately 15,000 new cases each year in the United States. Our understanding of the pathophysiology underlying myeloma continues to expand, but the cause of this plasma cell dyscrasia remains unclear. Though controversy remains regarding a possible viral cause of myeloma, evidence suggesting a role for the human herpesvirus-8 is mounting. The roles of cytogenetic abnormalities as well as aberrant angiogenesis and cytokine expression in the etiology of myeloma continue to be explored and may lead to future therapeutic strategies. Transplantation in myeloma is rarely curative but offers clinical benefit not only for young but possibly for older myeloma patients as well. Newer bisphosphonates may offer greater ease of administration, improved efficacy, and possibly even enhanced antitumor effect. Finally, thalidomide offers significant clinical benefit to patients with myeloma previously refractory to multiple agents, and its role in early stages of the disease is under investigation.

Extranodal posttransplant plasmacytic hyperplasia with subsequent posttransplant plasmacytic malignancy: six-year interval case report and review of the literature.

PubMed

Dunphy, Cherie H; Galambos, Csaba; Polski, Jacek M; Evans, H Lance; Gardner, Laura J; Grosso, Leonard E; Montone, Kathleen T

2002-03-01

Posttransplant lymphoproliferative disorders (PTLDs) represent a morphologic, immunophenotypic, and genotypic spectrum of disease. Most recently, Knowles et al divided PTLDs into 3 distinct categories: (1) plasmacytic hyperplasia, (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma, and (3) immunoblastic lymphoma and multiple myeloma. Although one form of PTLD may progress to another form, only 1 previous case has been reported in which multiple myeloma developed 14 months after an original diagnosis of plasmacytic hyperplasia. The type of solid organ transplant was not specified in that case. We report a post--cardiac transplant plasmacytic hyperplasia developing 7 years posttransplant. Six years subsequent to the plasmacytic hyperplasia, the patient developed a posttransplant plasmacytic malignancy, supported by morphology, flow cytometric immunophenotyping, and genotypic studies. Since we have no data to support disseminated bony disease or an abnormal serum protein, we have not used the term "multiple myeloma" for this case.

Multiple Low Energy Long Bone Fractures in the Setting of Rothmund-Thomson Syndrome.

PubMed

Beckmann, Nicholas

2015-01-01

Rothmund-Thomson syndrome is a rare autosomal recessive genodermatosis characterized by a poikilodermatous rash starting in infancy as well as various skeletal anomalies, juvenile cataracts, and predisposition to certain cancers. Although Rothmund-Thomson syndrome is associated with diminished bone mineral density in addition to multiple skeletal abnormalities, there are few reports of the association with stress fractures or pathologic fractures in low energy trauma or delayed healing of fractures. Presented is a case of a young adult male with Rothmund-Thomson syndrome presenting with multiple episodes of long bone fractures caused by low energy trauma with one of the fractures exhibiting significantly delayed healing. The patient was also found to have an asymptomatic stress fracture of the lower extremity, another finding of Rothmund-Thomson syndrome rarely reported in the literature. A thorough review of the literature and comprehensive presentation of Rothmund-Thomson syndrome is provided in conjunction with our case.

[A case of MEWDS. "The multiple evanescent white-dot syndrome"].

PubMed

Lefrançois, A; Hamard, H; Corbe, C; Schmitt, A; Badelon, I; Vidal, A

1989-01-01

A young white man developed acute bilateral visual loss with no previous general illness. Ophthalmoscopic examination showed multiple small yellow-white lesions scattered throughout the posterior poles and mild periphery fundus. There was also fine granularity of two foveal areas and one optic disc margin was blurred. Fluorescein angiography showed early hyperfluorescence of the lesions and late staining of the retinal pigment epithelium. Electrophysiologic abnormalities were transient, asymmetric, more marked in photopic than in scotopic. The origin could be in retinal bipolar cells. These lesions regressed, with return of normal visual function within several weeks. These clinical findings are different from others acute inflammatory diseases primarily involving retinal pigment epithelium and photoreceptors. This aspect is usually described as "multiple evanescent white dot syndrome". The etiology of this syndrome remains unknown with no evidence of systemic disease. A history of flulike illness is rare.

Role of Proangiogenic Factors in Immunopathogenesis of Multiple Sclerosis.

PubMed

Hamid, Kabir Magaji; Mirshafiey, Abbas

2016-02-01

Angiogenesis is a complex and balanced process in which new blood vessels form from preexisting ones by sprouting, splitting, growth and remodeling. This phenomenon plays a vital role in many physiological and pathological processes. However, the disturbance in physiological process can play a role in pathogenesis of some chronic inflammatory diseases, including multiple sclerosis (MS) in human and its animal model. Although the relation between abnormal blood vessels and MS lesions was established in previous studies, but the role of pathological angiogenesis remains unclear. In this study, the link between proangiogenic factors and multiple sclerosis pathogenesis was examined by conducting a systemic review. Thus we searched the English medical literature via PubMed, ISI web of knowledge, Medline and virtual health library (VHL) databases. In this review, we describe direct and indirect roles of some proangiogenic factors in MS pathogenesis and report the association of these factors with pathological and inflammatory angiogenesis.

Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves.

PubMed

Kim, Soo Ryang; Kanda, Fumio; Kobessho, Hiroshi; Sugimoto, Koji; Matsuoka, Toshiyuki; Kudo, Masatoshi; Hayashi, Yoshitake

2006-11-07

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Implant rehabilitation for a patient with Hallerman-Streiff syndrome: a case report.

PubMed

Abadi, Behruz J; Van Sickels, Joseph E; McConnell, Thomas A; Kluemper, G Thomas

2009-01-01

Hallermann-Streiff syndrome is a rare genetic disorder characterized by craniofacial malformations, sparse hair, eye abnormalities, dental defects, degenerative skin changes, and short stature. The syndrome has many implications for dental treatment. Patients typically present with multiple missing and poorly formed teeth. The purpose of this case report is to discuss the overall management of a patient with Hallermann-Streiff syndrome by oral maxillofacial surgery, orthodontic treatment, and prosthodontic reconstruction.

Human detection and motion analysis at security points

NASA Astrophysics Data System (ADS)

Ozer, I. Burak; Lv, Tiehan; Wolf, Wayne H.

2003-08-01

This paper presents a real-time video surveillance system for the recognition of specific human activities. Specifically, the proposed automatic motion analysis is used as an on-line alarm system to detect abnormal situations in a campus environment. A smart multi-camera system developed at Princeton University is extended for use in smart environments in which the camera detects the presence of multiple persons as well as their gestures and their interaction in real-time.

Gorlin-Goltz syndrome.

PubMed

Joshi, Priya Shirish; Deshmukh, Vijay; Golgire, Someshwar

2012-01-01

Gorlin-Goltz syndrome is an uncommon autosomal dominant inherited disorder, which is characterized by multiple odontogenic Keratocysts and basal cell carcinomas, skeletal, dental, ophthalmic, and neurological abnormalities, intracranial ectopic calcifications of the falx cerebri, and facial dysmorphism. Pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 (q22.3-q31) and loss or mutations of human patched gene (PTCH1 gene). Diagnosis is based upon established major and minor clinical and radiological criteria and ideally confirmed by deoxyribo nucleic acid analysis. We report a case of a 9-year-old girl presenting with three major and one minor feature of Gorlin-Goltz syndrome. Radiologic findings of the syndrome are easily identifiable on Orthopantomogram, chest X-ray, and Computed tomography scans. These investigations prompt an early verification of the disease, which is very important to prevent recurrence and better survival rates from the coexistent diseases.

Gorlin-Goltz syndrome

PubMed Central

Joshi, Priya Shirish; Deshmukh, Vijay; Golgire, Someshwar

2012-01-01

Gorlin-Goltz syndrome is an uncommon autosomal dominant inherited disorder, which is characterized by multiple odontogenic Keratocysts and basal cell carcinomas, skeletal, dental, ophthalmic, and neurological abnormalities, intracranial ectopic calcifications of the falx cerebri, and facial dysmorphism. Pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 (q22.3-q31) and loss or mutations of human patched gene (PTCH1 gene). Diagnosis is based upon established major and minor clinical and radiological criteria and ideally confirmed by deoxyribo nucleic acid analysis. We report a case of a 9-year-old girl presenting with three major and one minor feature of Gorlin-Goltz syndrome. Radiologic findings of the syndrome are easily identifiable on Orthopantomogram, chest X-ray, and Computed tomography scans. These investigations prompt an early verification of the disease, which is very important to prevent recurrence and better survival rates from the coexistent diseases. PMID:22363371

Dose-related cerebellar abnormality in rats with prenatal exposure to X-irradiation by magnetic resonance imaging volumetric analysis.

PubMed

Sawada, Kazuhiko; Saito, Shigeyoshi; Horiuchi-Hirose, Miwa; Mori, Yuki; Yoshioka, Yoshichika; Murase, Kenya

2013-09-01

Cerebellar abnormalities in 4-week-old rats with a single whole body X-irradiation at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 were examined by magnetic resonance imaging (MRI) volumetry. A 3D T2 W-MRI anatomical sequence with high-spatial resolution at 11.7-tesla was acquired from the fixed rat heads. By MRI volumetry, whole cerebellar volumes decreased dose-dependently. Multiple linear regression analysis revealed that the cortical volume (standardized β=0.901; P<0.001) was a major explanatory variable for the whole cerebellar volume, whereas both volumes of the white matter and deep cerebellar nuclei also decreased depending on the X-irradiation dose. The present MRI volumetric analysis revealed a dose-related cerebellar cortical hypoplasia by prenatal exposure to X-irradiation on E15. © 2013 The Authors. Congenital Anomalies © 2013 Japanese Teratology Society.

Neurocutaneous melanocytosis presenting in a teenager: A case report and review of the literature.

PubMed

Monica, I; Kumar, L Pavan; Uppin, Megha S; Jagannath Rao Naidu, Kotiyala V

2015-01-01

Neuro cutaneous melanocytosis (NCM) is a non-familial, congenital disorder characterized by multiple congenital nevi and brain or leptomeningeal abnormal melanin deposits. Here, we present an adult onset NCM. A 17-year-old boy presented with headache and double vision for 1 month. Magnetic resonance imaging of the brain showed hydrocephalus and abnormal meningeal hyper intensities in supra and infratentorial regions predominantly in the posterior fossa. Para medullary region showed an 11×10 mm nodular contrast enhancing nodule. Resection of an intramedullary central nervous system lesion revealed melanoma while skin biopsy was benign melanocytic nevus. As per Kadonaga and Frieden criteria, a diagnosis of NCM was made. Planned for craniospinal irradiation by three-dimensional conformal radiotherapy with a dose of 36 Gy, in 18 fractions (2 Gy/fraction and 5 days in a week) along with steroids however patient progressed and developed quadriplegia with intradural metastasis.

Reversible MRI lesions after seizures.

PubMed

Aykut-Bingol, C; Tekin, S; Ince, D; Aktan, S

1997-06-01

After generalized or partial seizures, transient lesions may appear on magnetic resonance (MR) images. The mechanisms of MR changes might be a defect in cerebral autoregulation and blood-brain permeability. We report a patient with partial and secondary generalized tonic-clonic seizures. After her first seizure which was generalized tonic-clonic in nature, we detected multiple high signal intensities over the frontal cortical area on proton density images which were enhanced with gadolinium on T1-weighted images. The first and repeated EEGs showed no abnormalities or epileptic discharges. We started carbamezapine (600 mg/d) and excluded systemic diseases like vasculitis, infections, aetiological factors causing cerebrovascular diseases. In the follow-up, she was seizure free under antiepileptic therapy and no other neurological deficit. Repeated MR scans after 24 months from her first seizure revealed no pathologic signal intensities. Although the pathophysiology is unknown, recognition of reversible lesions helps diagnostic and therapeutic approaches to abnormal MR findings after seizures.

Pathophysiologically based drug treatment of sickle cell disease.

PubMed

Steinberg, Martin H

2006-04-01

Sickle cell disease is a systemic disorder that is caused by a mutation (Glu6Val) in the gene that encodes beta globin. The sickle hemoglobin molecule (HbS) is a tetramer of two alpha-globin chains and two sickle beta-globin chains, and has the tendency to polymerize when deoxygenated. HbS facilitates abnormal interactions between the sickle erythrocyte and leukocytes and endothelial cells, which trigger a complex pathobiology. This multifaceted pathophysiology provides the opportunity to interrupt the disease at multiple sites, including polymerization of HbS, erythrocyte density and cell-cell interactions. For example, it is possible to induce higher concentrations of fetal hemoglobin, which disrupts the pathology-initiating step of HbS polymerization. Furthermore, it is possible to improve the hydration of sickle erythrocytes and it might be feasible to counteract the endothelial, inflammatory and oxidative abnormalities of sickle cell disease. A therapeutic approach that targets several sites of pathobiology might be most promising.

Embryonic mortality and abnormalities of aquatic birds: Apparent impacts of selenium from irrigation drainwater

USGS Publications Warehouse

Ohlendorf, H.M.; Hoffman, D.J.; Saiki, M.K.; Aldrich, T.W.

1986-01-01

Severe reproductive impacts were found in aquatic birds nesting on irrigation drainwater ponds in the San Joaquin Valley of California. Of 347 nests studied to late incubation or to hatching, 40.6% had at least one dead embryo and 19.6% had at least one embryo or chick with an obvious external anomaly. The deformities were often multiple and included missing or abnormal eyes, beaks, wings, legs and feet. Brain, heart, liver and skeletal anomalies were also present. Mean selenium concentrations in plants, invertebrates, and fish from the ponds were 22?175 ppm (dry weight), about 12 to 130 times those found at a nearby control area. Bird eggs (2.2?110 ppm) and livers (19?130 ppm) also contained elevated levels of selenium. Aquatic birds may experience similar problems in other areas where selenium occurs at elevated levels.

USE OF GLUE-ON SHOES TO IMPROVE CONFORMATIONAL ABNORMALITIES IN TWO ASIAN ELEPHANTS ( ELEPHAS MAXIMUS).

PubMed

Johnson, Gary; Smith, Joanne; Peddie, Jim; Peddie, Linda; DeMarco, Joe; Wiedner, Ellen

2018-03-01

This report describes the use of custom-made, glue-on shoes for the front feet of two female adult Asian elephants ( Elephas maximus) with conformational abnormalities. Both elephants had unequal leg lengths. The first elephant also had bilateral fetlock varus causing recurrent nail infections of the fourth digits of the front feet. The second elephant displayed weight shifting. Over several years, multiple shoe prototypes were tested. The current version is made of two types of shoe rubber, glued together and attached to the pad of the shorter leg with a liquid adhesive. The first elephant also has bilateral wedge pads to offload pressure from the fourth nails. The shoes are removed each month for foot care, then replaced. Within several months of wearing shoes, the first elephant's nail infections healed and the second elephant stopped weight shifting. Both elephants' gaits became smoother. This is the first description of corrective shoeing in elephants.

The first case of Niikawa-Kuroki syndrome in Kazakhstan associated with café au lait spots.

PubMed

Al Mosawi, A J; Fewin, L

2009-10-01

Niikawa-Kuroki syndrome (Kabuki syndrome) is a multiple congenital anomaly syndrome of unknown etiology with a very wide spectrum of abnormalities and severity. The aim of this paper was to report the first case of the syndrome in Kazakhstan associated café au lait. Five year and half old boy from Kazakhstan (Uzbek-of Turk ethnicity) presented with dysmorphic facial features (long palpebral fissures, a broad and depressed nasal tip, large prominent earlobes, small head, epicanthic folds short stature, delayed language development, hypotonia, bilateral developmental dysplasia of the hip (DDH), large ears and triangular chin, café au lait spots. The clinical diagnosis was based on the triad of characteristic facial abnormalities (long palpebral fissures, a broad and depressed nasal tip, large prominent earlobes, small head), growth retardation, (DDH). In this paper the authors report the first case of Kabuki syndrome associated with café au lait spots.

Optic disc dysplasia in poland syndrome.

PubMed

Maxfield, Steven D; Strominger, Mitchell B

2014-06-01

To report optic disc dysplasia in a case of Poland syndrome. Non-interventional case report. A 2-year-old boy with Poland syndrome was referred for ophthalmic evaluation after abnormal optic discs were found on exam. Physical exam at birth revealed right-sided aplasia of the pectoralis major muscle, symbrachydactyly, hypoplastic scapula, and an abnormal third rib. On dilated examination the optic nerve heads were dysplastic. The findings included multiple cilioretinal vessels, situs inversus, inferotemporal excavation, and surrounding pigmentary disturbances. Only one case of optic disc anomaly has been reported in Poland syndrome and was described as morning glory syndrome. The optic discs in our patient do not fit well with other optic disc excavation syndromes but are most reminiscent of those in papillorenal syndrome. As both Poland syndrome and papillorenal syndrome share vascular dysfunction as a possible etiology, this case adds to the literature of vascular dysgenesis in Poland syndrome.

Interbrachial Pinch by Trapezius Transfer in Amyoplasia Congenita: A Case Report

PubMed Central

Thione, Alessandro; Cavadas, Pedro C.; Rubi, Carlo G.

2017-01-01

Summary: Amyoplasia congenita, or “classic distal arthrogryposis,” is the most common disorder among the congenital, non-progressive, multiple joint contractural conditions named arthrogryposis. The cause remains unknown, and it occurs sporadically. Abnormal neurological examination indicates that movement in utero was diminished as a result of an abnormality of the central or peripheral nervous system, the motor end plate, or muscle. The absence of central neural pathology indicates the origin in akinetic fetal condition. Three weeks are enough to cause muscle weakness and joint fibrosis. Joint contractures in amyoplasia are often rigid and refractory to nonoperative treatment such as passive stretching. Surgery is focused on each patient's need respecting adaptive maneuvers to accomplish daily tasks. We present a case in which pectoral major muscle had no strength for pinching; a trapezius muscle transfer was planned to obtain an interbrachial pinch useful for grasping. PMID:28607845

Inactivation of the mouse Magel2 gene results in growth abnormalities similar to Prader-Willi syndrome.

PubMed

Bischof, Jocelyn M; Stewart, Colin L; Wevrick, Rachel

2007-11-15

Prader-Willi syndrome (PWS) is an imprinted genetic obesity disorder characterized by abnormalities of growth and metabolism. Multiple mouse models with deficiency of one or more PWS candidate genes have partially correlated individual genes with aspects of the PWS phenotype, although the genetic origin of defects in growth and metabolism has not been elucidated. Gene-targeted mutation of the PWS candidate gene Magel2 in mice causes altered circadian rhythm output and reduced motor activity. We now report that Magel2-null mice exhibit neonatal growth retardation, excessive weight gain after weaning, and increased adiposity with altered metabolism in adulthood, recapitulating fundamental aspects of the PWS phenotype. Magel2-null mice provide an important opportunity to examine the physiological basis for PWS neonatal failure to thrive and post-weaning weight gain and for the relationships among circadian rhythm, feeding behavior, and metabolism.

Genetics of inherited cardiocutaneous syndromes: a review

PubMed Central

Bardawil, Tara; Khalil, Samar; Bergqvist, Christina; Abbas, Ossama; Kibbi, Abdul Ghani; Bitar, Fadi; Nemer, Georges; Kurban, Mazen

2016-01-01

The life of a human being originates as a single cell which, under the influence of certain factors, divides sequentially into multiple cells that subsequently become committed to develop and differentiate into the different structures and organs. Alterations occurring early on in the development process may lead to fetal demise in utero. Conversely, abnormalities at later stages may result in structural and/or functional abnormalities of varying severities. The cardiovascular system and skin share certain developmental and structural factors; therefore, it is not surprising to find several inherited syndromes with both cardiac and skin manifestations. Here, we will review the overlapping pathways in the development of the skin and heart, as well as the resulting syndromes. We will also highlight several cutaneous clues that may help physicians screen and uncover cardiac anomalies that may be otherwise hidden and result in sudden cardiac death. PMID:27933191

Immunological modes of pregnancy loss: inflammation, immune effectors, and stress.

PubMed

Kwak-Kim, Joanne; Bao, Shihua; Lee, Sung Ki; Kim, Joon Woo; Gilman-Sachs, Alice

2014-08-01

Inflammatory immune response plays a key role in reproductive failures such as multiple implantation failures (MIF), early pregnancy loss, and recurrent pregnancy losses (RPL). Cellular immune responses particularly mediated by natural killer (NK), and T cells are often dysregulated in these conditions. Excessive or inappropriate recruitment of peripheral blood NK cells to the uterus may lead to cytotoxic environment in utero, in which proliferation and differentiation of trophoblast is hampered. In addition, inadequate angiogenesis by uterine NK cells often leads to abnormal vascular development and blood flow patterns, which, in turn, leads to increased oxidative stress or ischemic changes in the invading trophoblast. T-cell abnormalities with increased Th1 and Th17 immunity, and decreased Th2 and T regulatory immune responses may play important roles in RPL and MIF. A possible role of stress in inflammatory immune response is also reviewed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis.

PubMed

Cawley, Niamh; Solanky, Bhavana S; Muhlert, Nils; Tur, Carmen; Edden, Richard A E; Wheeler-Kingshott, Claudia A M; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2015-09-01

Neurodegeneration is thought to be the major cause of ongoing, irreversible disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid is the principle inhibitory neurotransmitter in the brain. The aims of this study were to investigate if gamma-aminobutyric acid levels (i) are abnormal in patients with secondary progressive multiple sclerosis compared with healthy controls; and (ii) correlate with physical and cognitive performance in this patient population. Thirty patients with secondary progressive multiple sclerosis and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to quantify gamma-aminobutyric acid levels in the prefrontal cortex, right hippocampus and left sensorimotor cortex. All subjects were assessed clinically and underwent a cognitive assessment. Multiple linear regression models were used to compare differences in gamma-aminobutyric acid concentrations between patients and controls adjusting for age, gender and tissue fractions within each spectroscopic voxel. Regression was used to examine the relationships between the cognitive function and physical disability scores specific for these regions with gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl-aspartate and glutamine-glutamate complex levels. When compared with controls, patients performed significantly worse on all motor and sensory tests, and were cognitively impaired in processing speed and verbal memory. Patients had significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted difference = -0.403 mM, 95% confidence intervals -0.792, -0.014, P = 0.043) and sensorimotor cortex (adjusted difference = -0.385 mM, 95% confidence intervals -0.667, -0.104, P = 0.009) compared with controls. In patients, reduced motor function in the right upper and lower limb was associated with lower gamma-aminobutyric acid concentration in the sensorimotor cortex. Specifically for each unit decrease in gamma-aminobutyric acid levels (in mM), there was a predicted -10.86 (95% confidence intervals -16.786 to -4.482) decrease in grip strength (kg force) (P < 0.001) and -8.74 (95% confidence intervals -13.943 to -3.015) decrease in muscle strength (P < 0.006). This study suggests that reduced gamma-aminobutyric acid levels reflect pathological abnormalities that may play a role in determining physical disability. These abnormalities may include decreases in the pre- and postsynaptic components of gamma-aminobutyric acid neurotransmission and in the density of inhibitory neurons. Additionally, the reduced gamma-aminobutyric acid concentration may contribute to the neurodegenerative process, resulting in increased firing of axons, with consequent increased energy demands, which may lead to neuroaxonal degeneration and loss of the compensatory mechanisms that maintain motor function. This study supports the idea that modulation of gamma-aminobutyric acid neurotransmission may be an important target for neuroprotection in multiple sclerosis.See De Stefano and Giorgio (doi:10.1093/brain/awv213) for a scientific commentary on this article. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Visual Impairment Screening at the Geriatric Frailty Clinic for Assessment of Frailty and Prevention of Disability at the Gérontopôle.

PubMed

Soler, V; Sourdet, S; Balardy, L; Abellan van Kan, G; Brechemier, D; Rougé-Bugat, M E; Tavassoli, N; Cassagne, M; Malecaze, F; Nourhashémi, F; Vellas, B

2016-01-01

To evaluate visual performance and factors associated with abnormal vision in patients screened for frailty at the Geriatric Frailty Clinic (GFC) for Assessment of Frailty and Prevention of Disability at Toulouse University Hospital. Retrospective, observational cross-sectional, single-centre study. Institutional practice. Patients were screened for frailty during a single-day hospital stay between October 2011 and October 2014 (n = 1648). Collected medical records included sociodemographic data (including living environment and educational level), anthropometric data, and clinical data. The general evaluation included the patient's functional status using the Activities of Daily Living (ADL) scale and the Instrumental Activity of Daily Living (IADL) scale, the Mini-Mental State Examination (MMSE) for cognition testing, and the Short Physical Performance Battery (SPPB) for physical performance. We also examined Body Mass Index (BMI), the Mini-Nutritional Assessment (MNA), and the Hearing Handicap Inventory for the Elderly Screening (HHIE-S) tool. The ophthalmologic evaluation included assessing visual acuity using the Snellen decimal chart for distant vision, and the Parinaud chart for near vision. Patients were divided into groups based on normal distant/near vision (NDV and NNV groups) and abnormal distant/near vision (ADV and ANV groups). Abnormal distant or near vision was defined as visual acuity inferior to 20/40 or superior to a Parinaud score of 2, in at least one eye. Associations with frailty-associated factors were evaluated in both groups. The mean age of the population was 82.6 ± 6.2 years. The gender distribution was 1,061 females (64.4%) and 587 males (35.6%). According to the Fried criteria, 619 patients (41.1%) were pre-frail and 771 (51.1%) were frail. Distant and near vision data were available for 1425 and 1426 patients, respectively. Distant vision was abnormal for 437 patients (30.7%). Near vision was abnormal for 199 patients (14%). Multiple regression analysis showed that abnormal distant vision as well as abnormal near vision were independently associated with greater age (P < 0.01), lower educational level (P < 0.05), lower performance on the MMSE (P < 0.001), and lower autonomy (P < 0.02), after controlling for age, gender, educational level, Fried criteria, and MMSE score. The high prevalence of visual disorders observed in the study population and their association with lower autonomy and cognitive impairment emphasises the need for systematic screening of visual impairments in the elderly. Frailty was not found to be independently associated with abnormal vision.

Higher educational attainment associated with reduced likelihood of abnormal cervical lesions among Zambian women - a cross sectional study.

PubMed

Hamoonga, Twaambo Euphemia; Likwa, Rosemary Ndonyo; Musonda, Patrick; Michelo, Charles

2017-10-13

The high burden of cervical cancer in Zambia prompted the Ministry of Health and partners to develop the cervical cancer prevention program in Zambia (CCPPZ) in 2006. Despite this intervention more women continue to die from the disease and there is little understanding of factors that may be linked with abnormal cervical lesions in the general population. We therefore examined if educational attainment is associated with abnormal cervical lesions among Zambian women aged 15 to 49 years. This study used data from the cervical cancer prevention program in Zambia, where a total of 14,294 women aged 15 to 49 years were screened for cervical cancer at nine health facilities between October 2013 and September 2014. The data represents women from six provinces of Zambia, namely Southern, Central, Copperbelt, Luapula, North-western and Eastern provinces. Step-wise logistic regression analysis using the Statistical Package for the Social Sciences (SPSS) version 21 was used to estimate adjusted odds ratios (AOR) and 95% confidence intervals (CIs) for educational attainment with presence of abnormal cervical lesions as outcome. Multiple imputation was further used to obtain the imputed stabilized estimates for educational attainment. The prevalence of abnormal cervical lesions, using the Visual Inspection with Acetic-acid (VIA) test was 10.7% (n = 1523). Educational attainment was inversely associated with abnormal cervical lesions (AOR = 0.75; 95% CI:0.70-0.81, AOR = 0.74; 95% CI:0.68-0.81 and AOR = 0.46; 95% CI:0.41-0.51) among women with primary, secondary and tertiary education, respectively, compared to those with no formal education. We find reduced likelihood of abnormal cervical lesions in educated women, suggesting a differential imbalance with women who have no formal education. These findings may be a reflection of inequalities associated with access to cervical cancer screening, making the service inadequately accessible for lower educated groups. This might also indicate serious limitations in awareness efforts instituted in the formative phases of the program. These findings underline the prevailing need for urgent concerted efforts in repackaging cervical cancer awareness programs targeting women with low or no formal education in whom the risk may be even higher.

Diagnostic Yield of Recommendations for Chest CT Examination Prompted by Outpatient Chest Radiographic Findings

PubMed Central

Harvey, H. Benjamin; Gilman, Matthew D.; Wu, Carol C.; Cushing, Matthew S.; Halpern, Elkan F.; Zhao, Jing; Pandharipande, Pari V.; Shepard, Jo-Anne O.

2015-01-01

Purpose To evaluate the diagnostic yield of recommended chest computed tomography (CT) prompted by abnormalities detected on outpatient chest radiographic images. Materials and Methods This HIPAA-compliant study had institutional review board approval; informed consent was waived. Reports of all outpatient chest radiographic examinations performed at a large academic center during 2008 (n = 29 138) were queried to identify studies that included a recommendation for a chest CT imaging. The radiology information system was queried for these patients to determine if a chest CT examination was obtained within 1 year of the index radiographic examination that contained the recommendation. For chest CT examinations obtained within 1 year of the index chest radiographic examination and that met inclusion criteria, chest CT images were reviewed to determine if there was an abnormality that corresponded to the chest radiographic finding that prompted the recommendation. All corresponding abnormalities were categorized as clinically relevant or not clinically relevant, based on whether further work-up or treatment was warranted. Groups were compared by using t test and Fisher exact test with a Bonferroni correction applied for multiple comparisons. Results There were 4.5% (1316 of 29138 [95% confidence interval {CI}: 4.3%, 4.8%]) of outpatient chest radiographic examinations that contained a recommendation for chest CT examination, and increasing patient age (P < .001) and positive smoking history (P = .001) were associated with increased likelihood of a recommendation for chest CT examination. Of patients within this subset who met inclusion criteria, 65.4% (691 of 1057 [95% CI: 62.4%, 68.2%) underwent a chest CT examination within the year after the index chest radiographic examination. Clinically relevant corresponding abnormalities were present on chest CT images in 41.4% (286 of 691 [95% CI: 37.7%, 45.2%]) of cases, nonclinically relevant corresponding abnormalities in 20.6% (142 of 691 [95% CI: 17.6%, 23.8%]) of cases, and no corresponding abnormalities in 38.1% (263 of 691 [95% CI: 34.4%, 41.8%]) of cases. Newly diagnosed, biopsy-proven malignancies were detected in 8.1% (56 of 691 [95% CI: 6.2%, 10.4%]) of cases. Conclusion A radiologist recommendation for chest CT to evaluate an abnormal finding on an outpatient chest radiographic examination has a high yield of clinically relevant findings. © RSNA, 2014 PMID:25531242

Temporal assessment of radiomic features on clinical mammography in a high-risk population

NASA Astrophysics Data System (ADS)

Mendel, Kayla R.; Li, Hui; Lan, Li; Chan, Chun-Wai; King, Lauren M.; Tayob, Nabihah; Whitman, Gary; El-Zein, Randa; Bedrosian, Isabelle; Giger, Maryellen L.

2018-02-01

Extraction of high-dimensional quantitative data from medical images has become necessary in disease risk assessment, diagnostics and prognostics. Radiomic workflows for mammography typically involve a single medical image for each patient although medical images may exist for multiple imaging exams, especially in screening protocols. Our study takes advantage of the availability of mammograms acquired over multiple years for the prediction of cancer onset. This study included 841 images from 328 patients who developed subsequent mammographic abnormalities, which were confirmed as either cancer (n=173) or non-cancer (n=155) through diagnostic core needle biopsy. Quantitative radiomic analysis was conducted on antecedent FFDMs acquired a year or more prior to diagnostic biopsy. Analysis was limited to the breast contralateral to that in which the abnormality arose. Novel metrics were used to identify robust radiomic features. The most robust features were evaluated in the task of predicting future malignancies on a subset of 72 subjects (23 cancer cases and 49 non-cancer controls) with mammograms over multiple years. Using linear discriminant analysis, the robust radiomic features were merged into predictive signatures by: (i) using features from only the most recent contralateral mammogram, (ii) change in feature values between mammograms, and (iii) ratio of feature values over time, yielding AUCs of 0.57 (SE=0.07), 0.63 (SE=0.06), and 0.66 (SE=0.06), respectively. The AUCs for temporal radiomics (ratio) statistically differed from chance, suggesting that changes in radiomics over time may be critical for risk assessment. Overall, we found that our two-stage process of robustness assessment followed by performance evaluation served well in our investigation on the role of temporal radiomics in risk assessment.

Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach.

PubMed

Garner, Joseph P; Thogerson, Collette M; Dufour, Brett D; Würbel, Hanno; Murray, James D; Mench, Joy A

2011-06-01

The NIMH's new strategic plan, with its emphasis on the "4P's" (Prediction, Pre-emption, Personalization, and Populations) and biomarker-based medicine requires a radical shift in animal modeling methodology. In particular 4P's models will be non-determinant (i.e. disease severity will depend on secondary environmental and genetic factors); and validated by reverse-translation of animal homologues to human biomarkers. A powerful consequence of the biomarker approach is that different closely related disorders have a unique fingerprint of biomarkers. Animals can be validated as a highly specific model of a single disorder by matching this 'fingerprint'; or as a model of a symptom seen in multiple disorders by matching common biomarkers. Here we illustrate this approach with two Abnormal Repetitive Behaviors (ARBs) in mice: stereotypies and barbering (hair pulling). We developed animal versions of the neuropsychological biomarkers that distinguish human ARBs, and tested the fingerprint of the different mouse ARBs. As predicted, the two mouse ARBs were associated with different biomarkers. Both barbering and stereotypy could be discounted as models of OCD (even though they are widely used as such), due to the absence of limbic biomarkers which are characteristic of OCD and hence are necessary for a valid model. Conversely barbering matched the fingerprint of trichotillomania (i.e. selective deficits in set-shifting), suggesting it may be a highly specific model of this disorder. In contrast stereotypies were correlated only with a biomarker (deficits in response shifting) correlated with stereotypies in multiple disorders, suggesting that animal stereotypies model stereotypies in multiple disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

Central nervous system involvement in adults with haemophagocytic lymphohistiocytosis: a single-center study.

PubMed

Cai, Guilan; Wang, Yini; Liu, Xiaojing; Han, Yanfei; Wang, Zhao

2017-08-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder characterized by proliferation and diffuse infiltration multiple organs with histiocytes, including the central nervous system (CNS). Neurological manifestations of HLH have been recognized in different studies with children, but they remain relatively ill-defined in adults with HLH. From March 2008 to October 2014, 289 adult patients with HLH were admitted to our center. Clinical, radiological, and cerebral spinal fluid (CSF) data of the patients with CNS involvement were reviewed, and a retrospective study in our single-center was carried out. CNS involvement was observed in 29 patients (10%) either in their diagnosis process or during disease course. CNS symptoms included disturbance of consciousness, cranial nerve palsies, seizures, headache, limb paralysis, irritability, meningism, and memory loss. CSF analysis was conducted in 17 patients (59%). Among them, 11 patients (65%) were reported as having abnormal CSF. Neuroradiological studies were performed in 25 patients (86%). Among the 13 cases that underwent CT scan, one patient hemorrhaged. Single or multiple hypodense foci were detected in the other 2 patients. Magnetic resonance imaging (MRI) abnormalities were found in 15 patients, including focal lesions in cortical and adjacent subcortical regions with or without variable nodular or ring contrast-enhancement, multiple lesions in white matter, diffuse white matter signal changes, and meningeal enhancement. Basal ganglia, cerebellum, and brainstem lesions were also observed. CNS involvement could also be found in adult patients with HLH, but not as frequent as it was in children. The clinical manifestations could be diversified. By carrying out rigorous CNS examinations, an early diagnosis could be made and it was of the utmost importance for the prevention of further lesions.

VoxelStats: A MATLAB Package for Multi-Modal Voxel-Wise Brain Image Analysis.

PubMed

Mathotaarachchi, Sulantha; Wang, Seqian; Shin, Monica; Pascoal, Tharick A; Benedet, Andrea L; Kang, Min Su; Beaudry, Thomas; Fonov, Vladimir S; Gauthier, Serge; Labbe, Aurélie; Rosa-Neto, Pedro

2016-01-01

In healthy individuals, behavioral outcomes are highly associated with the variability on brain regional structure or neurochemical phenotypes. Similarly, in the context of neurodegenerative conditions, neuroimaging reveals that cognitive decline is linked to the magnitude of atrophy, neurochemical declines, or concentrations of abnormal protein aggregates across brain regions. However, modeling the effects of multiple regional abnormalities as determinants of cognitive decline at the voxel level remains largely unexplored by multimodal imaging research, given the high computational cost of estimating regression models for every single voxel from various imaging modalities. VoxelStats is a voxel-wise computational framework to overcome these computational limitations and to perform statistical operations on multiple scalar variables and imaging modalities at the voxel level. VoxelStats package has been developed in Matlab(®) and supports imaging formats such as Nifti-1, ANALYZE, and MINC v2. Prebuilt functions in VoxelStats enable the user to perform voxel-wise general and generalized linear models and mixed effect models with multiple volumetric covariates. Importantly, VoxelStats can recognize scalar values or image volumes as response variables and can accommodate volumetric statistical covariates as well as their interaction effects with other variables. Furthermore, this package includes built-in functionality to perform voxel-wise receiver operating characteristic analysis and paired and unpaired group contrast analysis. Validation of VoxelStats was conducted by comparing the linear regression functionality with existing toolboxes such as glim_image and RMINC. The validation results were identical to existing methods and the additional functionality was demonstrated by generating feature case assessments (t-statistics, odds ratio, and true positive rate maps). In summary, VoxelStats expands the current methods for multimodal imaging analysis by allowing the estimation of advanced regional association metrics at the voxel level.

The role of transvaginal power Doppler ultrasound in the differential diagnosis of benign intrauterine focal lesions.

PubMed

Cogendez, Ebru; Eken, Meryem Kurek; Bakal, Nuray; Gun, Ismet; Kaygusuz, Ecmel Isik; Karateke, Ates

2015-10-01

The purpose of this prospective study was to assess the role of power Doppler imaging in the differential diagnosis of benign intrauterine focal lesions such as endometrial polyps and submucous myomas using the characteristics of power Doppler flow mapping. A total of 480 premenopausal patients with abnormal uterine bleeding were evaluated by transvaginal ultrasonography (TVS) searching for intrauterine pathology. Sixty-four patients with a suspicious focal endometrial lesion received saline infusion sonography (SIS) after TVS. Fifty-eight patients with focal endometrial lesions underwent power Doppler ultrasound (PDUS). Three different vascular flow patterns were defined: Single vessel pattern, multiple vessel pattern, and circular flow pattern. Finally, hysteroscopic resection was performed in all cases, and Doppler flow characteristics were then compared with the final histopathological findings. Histopathological results were as follows: endometrial polyp: 40 (69 %), submucous myoma: 18 (31 %). Of the cases with endometrial polyps, 80 % demonstrated a single vessel pattern, 7.5 % a multiple vessel pattern, and 0 % a circular pattern. Vascularization was not observed in 12.5 % of patients with polyps. Of the cases with submucousal myomas, 72.2 % demonstrated a circular flow pattern, 27.8 % a multiple vessel pattern, and none of them showed a single vessel pattern. The sensitivity, specificity, and positive and negative predictive values of the single vessel pattern in diagnosing endometrial polyps were 80, 100, 100, and 69.2 %, respectively; and for the circular pattern in diagnosing submucous myoma, these were 72.2, 100, 100, and 88.9 %, respectively. Power Doppler blood flow mapping is a useful, practical, and noninvasive diagnostic method for the differential diagnosis of benign intrauterine focal lesions. Especially in cases of recurrent abnormal uterine bleeding, recurrent abortion, and infertility, PDUS can be preferred as a first-line diagnostic method.

Characteristics of pediatric multiple sclerosis: The Turkish pediatric multiple sclerosis database.

PubMed

Yılmaz, Ünsal; Anlar, Banu; Gücüyener, Kıvılcım

2017-11-01

To document the clinical and paraclinical features of pediatric multiple sclerosis (MS) in Turkey. Data of MS patients with onset before age 18 years (n = 193) were collected from 27 pediatric neurology centers throughout Turkey. Earlier-onset (<12 years) and later-onset (≥12 years) groups were compared. There were 123 (63.7%) girls and 70 (36.3%) boys aged 4-17 years, median 14 years at disease onset. Family history of MS was 6.5%. The first presentation was polysymptomatic in 55.4% of patients, with brainstem syndromes (50.3%), sensory disturbances (44%), motor symptoms (33.2%), and optic neuritis (26.4%) as common initial manifestations. Nineteen children had facial paralysis and 10 had epileptic seizures at first attack; 21 (11%) were initially diagnosed with acute disseminated encephalomyelitis (ADEM). Oligoclonal bands were identified in 68% of patients. Magnetic resonance imaging revealed periventricular (96%), cortical/juxtacortical (64.2%), brainstem (63%), cerebellum (51.4%), and spinal cord (67%) involvement. Visual evoked potentials (VEP) were abnormal in 52%; serum 25-hydroxyvitamin D levels were low in 68.5% of patients. The earlier-onset group had a higher rate of infection/vaccination preceding initial attack, initial diagnosis of ADEM, longer interval between first 2 attacks, and more disability accumulating in the first 3 years of the disease. Brainstem and cerebellum are common sites of clinical and radiological involvement in pediatric-onset MS. VEP abnormalities are frequent even in patients without history of optic neuropathy. Vitamin D status does not appear to affect the course in early disease. MS beginning before 12 years of age has certain characteristics in history and course. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis.

PubMed

Tur, C; Penny, S; Khaleeli, Z; Altmann, D R; Cipolotti, L; Ron, M; Thompson, A J; Ciccarelli, O

2011-11-01

To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS). Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported. Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance (p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline (p < 0.001, PCC = -0.62), and executive function (p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing (p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory (p = 0.007, PCC = -0.55). The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS.

Institutional Protocol to Manage Consanguinity Detected by Genetic Testing in Pregnancy in a Minor

PubMed Central

Chen, Laura P.; Beck, Anita E.; Tsuchiya, Karen D.; Chow, Penny M.; Mirzaa, Ghayda M.; Wiester, Rebecca T.

2015-01-01

Single-nucleotide polymorphism arrays and other types of genetic tests have the potential to detect first-degree consanguinity and uncover parental rape in cases of minor teenage pregnancy. We present 2 cases in which genetic testing identified parental rape of a minor teenager. In case 1, single-nucleotide polymorphism array in a patient with multiple developmental abnormalities demonstrated multiple long stretches of homozygosity, revealing parental rape of a teenage mother. In case 2, a vague maternal sexual assault history and diagnosis of Pompe disease by direct gene sequencing identified parental rape of a minor. Given the medical, legal, and ethical implications of such revelations, a protocol was developed at our institution to manage consanguinity identified via genetic testing. PMID:25687148

Crouzon's Syndrome: A Case Report

PubMed Central

Jyothsna, M; Ahmed, Syed Basheer; Lakshmi, K Sree

2013-01-01

ABSTRACT Crouzon's syndrome (CS) is a rare autosomal dominant condition with multiple mutations of the fibroblast growth factor receptor (FGFR2) gene, which accounts for 4.8% of all cases of craniosynostosis. It is characterized by premature closure of cranial sutures, cranial deformities, midface hypoplasia, relative mandibular prognathism, hypertelorism, proptosis, strabismus and short upper lip, crowding of teeth, pseudocleft or sometimes cleft palate and other associated abnormalities. The CS can vary in severity from mild presentation to severe forms involving multiple cranial sutures. We report a case of CS in 11-year-old boy. How to cite this article: Kumar GR, Jyothsna M, Ahmed SB, Lakshmi KS, Crouzon's Syndrome: A Case Report. Int J Clin Pediatr Dent 2013;6(1):33-37. PMID:25206185

Stroke in Primary Hyperoxaluria Type I

PubMed Central

Rao, Neal M.; Yallapragada, Anil; Winden, Kellen D.; Saver, Jeffrey; Liebeskind, David S.

2014-01-01

We report the case of a 27-year-old man with a history of previously undiagnosed renal disease that presented with multiple cerebrovascular infarctions. Workup for traditional causes of cerebrovascular infarction including cardiac telemetry, multiple echocardiograms, and hypercoagulative workup was negative. However, a transcranial Doppler detected circulating microemboli at the rate of 14 per hour. A serum oxalate level greater than the supersaturation point of calcium oxalate was detected, providing a potential source of the microemboli. Furthermore, serial imaging recorded rapid mineralization of the infarcted territories. In the absence of any proximal vessel irregularities, atherosclerosis, valvular abnormalities, arrhythmias, or systemic shunt as potential stroke etiology in this patient, we propose that circulating oxalate precipitate may be a potential mechanism for stroke in patients with primary oxalosis. PMID:23551880